Direct immunosensing by spectral correlation interferometry: assay characteristics versus antibody immobilization chemistry.

PubMed

Burenin, Alexandr G; Urusov, Alexandr E; Betin, Alexei V; Orlov, Alexey V; Nikitin, Maxim P; Ksenevich, Tatiana I; Gorshkov, Boris G; Zherdev, Anatoly V; Dzantiev, Boris B; Nikitin, Petr I

2015-05-01

A 3-channel biosensor based on spectral correlation interferometry (SCI) has been adapted for direct optical detection of antigens by measuring changes in thickness of a biolayer on functionalized glass slips employed as affordable single-use sensor chips. The instrument is insensitive to the bulk refractive index of a solution under test and provides signals in metrological units (pm or nm). Using real-time monitoring with the SCI, protocols for fabrication of sensor chips with different functional (epoxylated, carboxylated, and biotinylated) surfaces for antibody immobilization have been developed and optimized to minimize chip-to-chip variations and achieve better limit of detection (LOD), shorter assay time, and longer shelf life. The optimized coupling surfaces have been compared for detection of human serum albumin (HSA) used as a model agent of medical significance. The dynamic ranges for measuring the HSA concentration were 0.07-20, 0.12-30, and 0.25-10 μg/ml, and the assay durations were less than 20, 15, and 30 min for the epoxylated, carboxylated, and biotinylated chips, respectively. The advantages of each type of sensor chip have been shown, namely, the carboxylated chips feature the shortest assay time, the epoxylated ones demonstrate the best LOD, and the biotinylated chips exhibit the longest shelf life in an unprotected environment. The developed protocols of antibody immobilization can be used in different biosensors and assay techniques including those based on fluorescent, magnetic or plasmonic labels, etc. The SCI is well compatible with various partially transparent layers used in biosensing and with microarrays for multi-analyte detection.

Imaging and chemical surface analysis of biomolecular functionalization of monolithically integrated on silicon Mach-Zehnder interferometric immunosensors

NASA Astrophysics Data System (ADS)

Gajos, Katarzyna; Angelopoulou, Michailia; Petrou, Panagiota; Awsiuk, Kamil; Kakabakos, Sotirios; Haasnoot, Willem; Bernasik, Andrzej; Rysz, Jakub; Marzec, Mateusz M.; Misiakos, Konstantinos; Raptis, Ioannis; Budkowski, Andrzej

2016-11-01

Time-of-flight secondary ion mass spectrometry (imaging, micro-analysis) has been employed to evaluate biofunctionalization of the sensing arm areas of Mach-Zehnder interferometers monolithically integrated on silicon chips for the immunochemical (competitive) detection of bovine κ-casein in goat milk. Biosensor surfaces are examined after: modification with (3-aminopropyl)triethoxysilane, application of multiple overlapping spots of κ-casein solutions, blocking with 100-times diluted goat milk, and reaction with monoclonal mouse anti-κ-casein antibodies in blocking solution. The areas spotted with κ-casein solutions of different concentrations are examined and optimum concentration providing homogeneous coverage is determined. Coverage of biosensor surfaces with biomolecules after each of the sequential steps employed in immunodetection is also evaluated with TOF-SIMS, supplemented by Atomic force microscopy and X-ray photoelectron spectroscopy. Uniform molecular distributions are observed on the sensing arm areas after spotting with optimum κ-casein concentration, blocking and immunoreaction. The corresponding biomolecular compositions are determined with a Principal Component Analysis that distinguished between protein amino acids and milk glycerides, as well as between amino acids characteristic for Mabs and κ-casein, respectively. Use of the optimum conditions (κ-casein concentration) for functionalization of chips with arrays of ten Mach-Zehnder interferometers provided on-chips assays with dramatically improved both intra-chip response repeatability and assay detection sensitivity.

Quantitative Investigation of Protein-Nucleic Acid Interactions by Biosensor Surface Plasmon Resonance.

PubMed

Wang, Shuo; Poon, Gregory M K; Wilson, W David

2015-01-01

Biosensor-surface plasmon resonance (SPR) technology has emerged as a powerful label-free approach for the study of nucleic acid interactions in real time. The method provides simultaneous equilibrium and kinetic characterization for biomolecular interactions with low sample requirements and without the need for external probes. A detailed and practical guide for protein-DNA interaction analyses using biosensor-SPR methods is presented. Details of SPR technology and basic fundamentals are described with recommendations on the preparation of the SPR instrument, sensor chips and samples, experimental design, quantitative and qualitative data analyses and presentation. A specific example of the interaction of a transcription factor with DNA is provided with results evaluated by both kinetic and steady-state SPR methods.

Handheld analyzer with on-chip molecularly-imprinted biosensors for electrical detection of propofol in plasma samples.

PubMed

Hong, Chien-Chong; Lin, Chih-Chung; Hong, Chian-Lang; Lin, Zi-Xiang; Chung, Meng-Hua; Hsieh, Pei-Wen

2016-12-15

This paper proposes a novel handheld analyzer with disposable lab-on-a-chip technology for the electrical detection of the anesthetic propofol in human plasma samples for clinical diagnoses. The developed on-chip biosensors are based on the conduction of molecularly imprinted polymers (MIPs) that employ label-free electrical detection techniques. Propofol in total intravenous anesthesia is widely used with a target-controlled infusion system. At present, the methods employed for detecting blood propofol concentrations in hospitals comprise high-performance liquid chromatography and ion mobility spectrometry. These conventional instruments are bulky, expensive, and difficult to access. In this study, we developed a novel plastic microfluidic biochip with an on-chip anesthetic biosensor that was characterized for the rapid detection of propofol concentrations. The experimental results revealed that the response time of the developed propofol biosensors was 25s. The specific binding of an MIP to a nonimprinted polymer (NIP) reached up to 560%. Moreover, the detection limit of the biosensors was 0.1μg/mL, with a linear detection range of 0.1-30μg/mL. The proposed disposable microfluidic biochip with an on-chip anesthetic biosensor using MIPs exhibited excellent performance in the separation and sensing of propofol molecules in the human plasma samples. Compared with large-scale conventional instruments, the developed microfluidic biochips with on-chip MIP biosensors present the advantages of a compact size, high selectivity, low cost, rapid response, and single-step detection. Copyright © 2016 Elsevier B.V. All rights reserved.

Recent advances in surface functionalization techniques on polymethacrylate materials for optical biosensor applications.

PubMed

Hosseini, Samira; Ibrahim, Fatimah; Djordjevic, Ivan; Koole, Leo H

2014-06-21

Biosensor chips for immune-based assay systems have been investigated for their application in early diagnostics. The development of such systems strongly depends on the effective protein immobilization on polymer substrates. In order to achieve this complex heterogeneous interaction the polymer surface must be functionalized with chemical groups that are reactive towards proteins in a way that surface functional groups (such as carboxyl, -COOH; amine, -NH2; and hydroxyl, -OH) chemically or physically anchor the proteins to the polymer platform. Since the proteins are very sensitive towards their environment and can easily lose their activity when brought in close proximity to the solid surface, effective surface functionalization and high level of control over surface chemistry present the most important steps in the fabrication of biosensors. This paper reviews recent developments in surface functionalization and preparation of polymethacrylates for protein immobilization. Due to their versatility and cost effectiveness, this particular group of plastic polymers is widely used both in research and in industry.

Hybridization-based biosensor containing hairpin probes and use thereof

DOEpatents

Miller, Benjamin L.; Strohsahl, Christopher M.

2010-10-12

A sensor chip that includes: a fluorescence quenching surface; a nucleic acid probe that contains first and second ends with the first end bound to the fluorescence quenching surface, and is characterized by being able to self-anneal into a hairpin conformation; and a first fluorophore bound to the second end of the first nucleic acid molecule. When the first nucleic acid molecule is in the hairpin conformation, the fluorescence quenching surface substantially quenches fluorescent emissions by the first fluorophore; and when the first nucleic acid molecule is in a non-hairpin conformation, fluorescent emissions by the fluorophore are substantially free of quenching by the fluorescence quenching surface. Various nucleic acid probes, methods of making the sensor chip, biological sensor devices that contain the sensor chip, and their methods of use are also disclosed.

Phase sensitive spectral domain interferometry for label free biomolecular interaction analysis and biosensing applications

NASA Astrophysics Data System (ADS)

Chirvi, Sajal

Biomolecular interaction analysis (BIA) plays vital role in wide variety of fields, which include biomedical research, pharmaceutical industry, medical diagnostics, and biotechnology industry. Study and quantification of interactions between natural biomolecules (proteins, enzymes, DNA) and artificially synthesized molecules (drugs) is routinely done using various labeled and label-free BIA techniques. Labeled BIA (Chemiluminescence, Fluorescence, Radioactive) techniques suffer from steric hindrance of labels on interaction site, difficulty of attaching labels to molecules, higher cost and time of assay development. Label free techniques with real time detection capabilities have demonstrated advantages over traditional labeled techniques. The gold standard for label free BIA is surface Plasmon resonance (SPR) that detects and quantifies the changes in refractive index of the ligand-analyte complex molecule with high sensitivity. Although SPR is a highly sensitive BIA technique, it requires custom-made sensor chips and is not well suited for highly multiplexed BIA required in high throughput applications. Moreover implementation of SPR on various biosensing platforms is limited. In this research work spectral domain phase sensitive interferometry (SD-PSI) has been developed for label-free BIA and biosensing applications to address limitations of SPR and other label free techniques. One distinct advantage of SD-PSI compared to other label-free techniques is that it does not require use of custom fabricated biosensor substrates. Laboratory grade, off-the-shelf glass or plastic substrates of suitable thickness with proper surface functionalization are used as biosensor chips. SD-PSI is tested on four separate BIA and biosensing platforms, which include multi-well plate, flow cell, fiber probe with integrated optics and fiber tip biosensor. Sensitivity of 33 ng/ml for anti-IgG is achieved using multi-well platform. Principle of coherence multiplexing for multi-channel label-free biosensing applications is introduced. Simultaneous interrogation of multiple biosensors is achievable with a single spectral domain phase sensitive interferometer by coding the individual sensograms in coherence-multiplexed channels. Experimental results demonstrating multiplexed quantitative biomolecular interaction analysis of antibodies binding to antigen coated functionalized biosensor chip surfaces on different platforms are presented.

Dual functional extracellular recording using a light-addressable potentiometric sensor for bitter signal transduction.

PubMed

Du, Liping; Wang, Jian; Chen, Wei; Zhao, Luhang; Wu, Chunsheng; Wang, Ping

2018-08-31

This paper presents a dual functional extracellular recording biosensor based on a light-addressable potentiometric sensor (LAPS). The design and fabrication of this biosensor make it possible to record both extracellular membrane potential changes and ATP release from a single taste bud cell for the first time. For detecting ATP release, LAPS chip was functionalized with ATP-sensitive DNA aptamer by covalent immobilization. Taste bud cells isolated from rat were cultured on LAPS surface. When the desired single taste bud cell was illuminated by modulated light, ATP release from single taste bud cells can be measured by recording the shifts of bias voltage-photocurrent curves (I-V curves) when the LAPS chip is working in discrete mode. On the other hand, extracellular membrane potential changes can be monitored by recording the fluctuation of LAPS photocurrent when the LAPS chip is working in continuous mode. The results show this biosensor can effectively record the enhancive effect of the bitter substance and inhibitory effect of the carbenoxolone (CBX) on the extracellular membrane potential changes and ATP release of single taste bud cells. In addition, the inhibitory effect of CBX also confirms LAPS extracellular recordings are originated from bitter signal transduction. It is proved this biosensor is suitable for extracellular recording of ATP release and membrane potential changes of single taste bud cells. It is suggested this biosensor could be applied to investigating taste signal transduction at the single-cell level as well as applied to other types of cells which have similar functions to taste bud cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Magnetic particles for in vitro molecular diagnosis: From sample preparation to integration into microsystems.

PubMed

Tangchaikeeree, Tienrat; Polpanich, Duangporn; Elaissari, Abdelhamid; Jangpatarapongsa, Kulachart

2017-10-01

Colloidal magnetic particles (MPs) have been developed in association with molecular diagnosis for several decades. MPs have the great advantage of easy manipulation using a magnet. In nucleic acid detection, these particles can act as a capture support for rapid and simple biomolecule separation. The surfaces of MPs can be modified by coating with various polymer materials to provide functionalization for different applications. The use of MPs enhances the sensitivity and specificity of detection due to the specific activity on the surface of the particles. Practical applications of MPs demonstrate greater efficiency than conventional methods. Beyond traditional detection, MPs have been successfully adopted as a smart carrier in microfluidic and lab-on-a-chip biosensors. The versatility of MPs has enabled their integration into small single detection units. MPs-based biosensors can facilitate rapid and highly sensitive detection of very small amounts of a sample. In this review, the application of MPs to the detection of nucleic acids, from sample preparation to analytical readout systems, is described. State-of-the-art integrated microsystems containing microfluidic and lab-on-a-chip biosensors for the nucleic acid detection are also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Biosensors in Health Care: The Milestones Achieved in Their Development towards Lab-on-Chip-Analysis

PubMed Central

Patel, Suprava; Nanda, Rachita; Sahoo, Sibasish; Mohapatra, Eli

2016-01-01

Immense potentiality of biosensors in medical diagnostics has driven scientists in evolution of biosensor technologies and innovating newer tools in time. The cornerstone of the popularity of biosensors in sensing wide range of biomolecules in medical diagnostics is due to their simplicity in operation, higher sensitivity, ability to perform multiplex analysis, and capability to be integrated with different function by the same chip. There remains a huge challenge to meet the demands of performance and yield to its simplicity and affordability. Ultimate goal stands for providing point-of-care testing facility to the remote areas worldwide, particularly the developing countries. It entails continuous development in technology towards multiplexing ability, fabrication, and miniaturization of biosensor devices so that they can provide lab-on-chip-analysis systems to the community. PMID:27042353

Paralytic shellfish poisoning (PSP) toxin binders for optical biosensor technology: problems and possibilities for the future: a review

PubMed Central

Campbell, K.; Rawn, D.F.K.; Niedzwiadek, B.; Elliott, C.T.

2011-01-01

This review examines the developments in optical biosensor technology, which uses the phenomenon of surface plasmon resonance, for the detection of paralytic shellfish poisoning (PSP) toxins. Optical biosensor technology measures the competitive biomolecular interaction of a specific biological recognition element or binder with a target toxin immobilised onto a sensor chip surface against toxin in a sample. Different binders such as receptors and antibodies previously employed in functional and immunological assays have been assessed. Highlighted are the difficulties in detecting this range of low molecular weight toxins, with analogues differing at four chemical substitution sites, using a single binder. The complications that arise with the toxicity factors of each toxin relative to the parent compound, saxitoxin, for the measurement of total toxicity relative to the mouse bioassay are also considered. For antibodies, the cross-reactivity profile does not always correlate to toxic potency, but rather to the toxin structure to which it was produced. Restrictions and availability of the toxins makes alternative chemical strategies for the synthesis of protein conjugate derivatives for antibody production a difficult task. However, when two antibodies with different cross-reactivity profiles are employed, with a toxin chip surface generic to both antibodies, it was demonstrated that the cross-reactivity profile of each could be combined into a single-assay format. Difficulties with receptors for optical biosensor analysis of low molecular weight compounds are discussed, as are the potential of alternative non-antibody-based binders for future assay development in this area. PMID:21623494

Paralytic shellfish poisoning (PSP) toxin binders for optical biosensor technology: problems and possibilities for the future: a review.

PubMed

Campbell, K; Rawn, D F K; Niedzwiadek, B; Elliott, C T

2011-06-01

This review examines the developments in optical biosensor technology, which uses the phenomenon of surface plasmon resonance, for the detection of paralytic shellfish poisoning (PSP) toxins. Optical biosensor technology measures the competitive biomolecular interaction of a specific biological recognition element or binder with a target toxin immobilised onto a sensor chip surface against toxin in a sample. Different binders such as receptors and antibodies previously employed in functional and immunological assays have been assessed. Highlighted are the difficulties in detecting this range of low molecular weight toxins, with analogues differing at four chemical substitution sites, using a single binder. The complications that arise with the toxicity factors of each toxin relative to the parent compound, saxitoxin, for the measurement of total toxicity relative to the mouse bioassay are also considered. For antibodies, the cross-reactivity profile does not always correlate to toxic potency, but rather to the toxin structure to which it was produced. Restrictions and availability of the toxins makes alternative chemical strategies for the synthesis of protein conjugate derivatives for antibody production a difficult task. However, when two antibodies with different cross-reactivity profiles are employed, with a toxin chip surface generic to both antibodies, it was demonstrated that the cross-reactivity profile of each could be combined into a single-assay format. Difficulties with receptors for optical biosensor analysis of low molecular weight compounds are discussed, as are the potential of alternative non-antibody-based binders for future assay development in this area.

Single-nucleotide polymorphism genotyping on optical thin-film biosensor chips.

PubMed

Zhong, Xiao-Bo; Reynolds, Robert; Kidd, Judith R; Kidd, Kenneth K; Jenison, Robert; Marlar, Richard A; Ward, David C

2003-09-30

Single-nucleotide polymorphisms (SNPs) constitute the bulk of human genetic variation and provide excellent markers to identify genetic factors contributing to complex disease susceptibility. A rapid, sensitive, and inexpensive assay is important for large-scale SNP scoring. Here we report the development of a multiplex SNP detection system using silicon chips coated to create a thin-film optical biosensor. Allele-discriminating, aldehyde-labeled oligonucleotides are arrayed and covalently attached to a hydrazinederivatized chip surface. Target sequences (e.g., PCR amplicons) then are hybridized in the presence of a mixture of biotinylated detector probes, one for each SNP, and a thermostable DNA ligase. After a stringent wash (0.01 M NaOH), ligation of biotinylated detector probes to perfectly matched capture oligomers is visualized as a color change on the chip surface (gold to blue/purple) after brief incubations with an anti-biotin IgG-horseradish peroxidase conjugate and a precipitable horseradish peroxidase substrate. Testing of PCR fragments is completed in 30-40 min. Up to several hundred SNPs can be assayed on a 36-mm2 chip, and SNP scoring can be done by eye or with a simple digital-camera system. This assay is extremely robust, exhibits high sensitivity and specificity, and is format-flexible and economical. In studies of mutations associated with risk for venous thrombosis and genotyping/haplotyping of African-American samples, we document high-fidelity analysis with 0 misassignments in 500 assays performed in duplicate.

Photosensitive biosensor array system using optical addressing without an addressing circuit on array biochips

NASA Astrophysics Data System (ADS)

Ahn, Chang-Geun; Ah, Chil Seong; Kim, Tae-Youb; Park, Chan Woo; Yang, Jong-Heon; Kim, Ansoon; Sung, Gun Yong

2010-09-01

This paper introduces a photosensitive biosensor array system with a simple photodiode array that detects photocurrent changes caused by reactions between probe and target molecules. Using optical addressing, the addressing circuit on the array chip is removed for low-cost application, and real cell addressing is achieved using an externally located computer-controllable light-emitting diode array module. The fabricated biosensor array chip shows a good dynamic range of 1-100 ng/mL under prostate-specific antigen detection, with an on-chip resolution of roughly 1 ng/mL.

Engineering the bioelectrochemical interface using functional nanomaterials and microchip technique toward sensitive and portable electrochemical biosensors.

PubMed

Jia, Xiaofang; Dong, Shaojun; Wang, Erkang

2016-02-15

Electrochemical biosensors have played active roles at the forefront of bioanalysis because they have the potential to achieve sensitive, specific and low-cost detection of biomolecules and many others. Engineering the electrochemical sensing interface with functional nanomaterials leads to novel electrochemical biosensors with improved performances in terms of sensitivity, selectivity, stability and simplicity. Functional nanomaterials possess good conductivity, catalytic activity, biocompatibility and high surface area. Coupled with bio-recognition elements, these features can amplify signal transduction and biorecognition events, resulting in highly sensitive biosensing. Additionally, microfluidic electrochemical biosensors have attracted considerable attention on account of their miniature, portable and low-cost systems as well as high fabrication throughput and ease of scaleup. For example, electrochemical enzymetic biosensors and aptamer biosensors (aptasensors) based on the integrated microchip can be used for portable point-of-care diagnostics and environmental monitoring. This review is a summary of our recent progress in the field of electrochemical biosensors, including aptasensors, cytosensors, enzymatic biosensors and self-powered biosensors based on biofuel cells. We presented the advantages that functional nanomaterials and microfluidic chip technology bring to the electrochemical biosensors, together with future prospects and possible challenges. Copyright © 2015 Elsevier B.V. All rights reserved.

Ultra-low fouling and high antibody loading zwitterionic hydrogel coatings for sensing and detection in complex media.

PubMed

Chou, Ying-Nien; Sun, Fang; Hung, Hsiang-Chieh; Jain, Priyesh; Sinclair, Andrew; Zhang, Peng; Bai, Tao; Chang, Yung; Wen, Ten-Chin; Yu, Qiuming; Jiang, Shaoyi

2016-08-01

For surface-based diagnostic devices to achieve reliable biomarker detection in complex media such as blood, preventing nonspecific protein adsorption and incorporating high loading of biorecognition elements are paramount. In this work, a novel method to produce nonfouling zwitterionic hydrogel coatings was developed to achieve these goals. Poly(carboxybetaine acrylamide) (pCBAA) hydrogel thin films (CBHTFs) prepared with a carboxybetaine diacrylamide crosslinker (CBAAX) were coated on gold and silicon dioxide surfaces via a simple spin coating process. The thickness of CBHTFs could be precisely controlled between 15 and 150nm by varying the crosslinker concentration, and the films demonstrated excellent long-term stability. Protein adsorption from undiluted human blood serum onto the CBHTFs was measured with surface plasmon resonance (SPR). Hydrogel thin films greater than 20nm exhibited ultra-low fouling (<5ng/cm(2)). In addition, the CBHTFs were capable of high antibody functionalization for specific biomarker detection without compromising their nonfouling performance. This strategy provides a facile method to modify SPR biosensor chips with an advanced nonfouling material, and can be potentially expanded to a variety of implantable medical devices and diagnostic biosensors. In this work, we developed an approach to realize ultra-low fouling and high ligand loading with a highly-crosslinked, purely zwitterionic, carboxybetaine thin film hydrogel (CBHTF) coating platform. The CBHTF on a hydrophilic surface demonstrated long-term stability. By varying the crosslinker content in the spin-coated hydrogel solution, the thickness of CBHTFs could be precisely controlled. Optimized CBHTFs exhibited ultra-low nonspecific protein adsorption below 5ng/cm(2) measured by a surface plasmon resonance (SPR) sensor, and their 3D architecture allowed antibody loading to reach 693ng/cm(2). This strategy provides a facile method to modify SPR biosensor chips with an advanced nonfouling material, and can be potentially expanded to a variety of implantable medical devices and diagnostic biosensors. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Real-time and label-free analysis of binding thermodynamics of carbohydrate-protein interactions on unfixed cancer cell surfaces using a QCM biosensor

PubMed Central

Li, Xueming; Song, Siyu; Shuai, Qi; Pei, Yihan; Aastrup, Teodor; Pei, Yuxin; Pei, Zhichao

2015-01-01

A novel approach to the study of binding thermodynamics and kinetics of carbohydrate-protein interactions on unfixed cancer cell surfaces using a quartz crystal microbalance (QCM) biosensor was developed, in which binding events take place at the cell surface, more closely mimicking a biologically relevant environment. In this study, colon adenocarcinoma cells (KM-12) and ovary adenocarcinoma cells (SKOV-3) grew on the optimized polystyrene-coated biosensor chip without fixation. The association and dissociation between the cell surface carbohydrates and a range of lectins, including WGA, Con A, UEA-I, GS-II, PNA and SBA, were monitored in real time and without label for evaluation of cell surface glycosylation. Furthermore, the thermodynamic and kinetic parameters of the interaction between lectins and cell surface glycan were studied, providing detailed information about the interactions, such as the association rate constant, dissociation rate constant, affinity constant, as well as the changes of entropy, enthalpy and Gibbs free energy. This application provides an insight into the cell surface glycosylation and the complex molecular recognition on the intact cell surface, which may have impacts on disease diagnosis and drug discovery. PMID:26369583

Environmental Stability of Plasmonic Biosensors Based on Natural versus Artificial Antibody.

PubMed

Luan, Jingyi; Xu, Ting; Cashin, John; Morrissey, Jeremiah J; Kharasch, Evan D; Singamaneni, Srikanth

2018-06-13

Plasmonic biosensors based on the refractive index sensitivity of localized surface plasmon resonance (LSPR) are considered to be highly promising for on-chip and point-of-care biodiagnostics. However, most of the current plasmonic biosensors employ natural antibodies as biorecognition elements, which can easily lose their biorecognition ability upon exposure to environmental stressors (e.g., temperature and humidity). Plasmonic biosensors relying on molecular imprints as recognition elements (artificial antibodies) are hypothesized to be an attractive alternative for applications in resource-limited settings due to their excellent thermal, chemical, and environmental stability. In this work, we provide a comprehensive comparison of the stability of plasmonic biosensors based on natural and artificial antibodies. Although the natural antibody-based plasmonic biosensors exhibit superior sensitivity, their stability (temporal, thermal, and chemical) was found to be vastly inferior to those based on artificial antibodies. Our results convincingly demonstrate that these novel classes of artificial antibody-based plasmonic biosensors are highly attractive for point-of-care and resource-limited conditions where tight control over transport, storage, and handling conditions is not possible.

Rapid analysis of protein interactions: On-chip micropurification of recombinant protein expressed in Esherichia coli.

PubMed

Natsume, Tohru; Taoka, Masato; Manki, Hiroshi; Kume, Shouen; Isobe, Toshiaki; Mikoshiba, Katsuhiko

2002-09-01

We describe a rapid analysis of interactions between antibodies and a recombinant protein present in total cell lysates. Using a surface plasmon resonance biosensor, a low concentration of glutathione-S-transferase (GST) fused protein expressed in small scale Esherichia coli culture was purified on an anti-GST antibody immobilized sensor chip. The 'on-chip purification' was verified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry by measuring the molecular masses of recombinant proteins purified on the sensor chip. The specific binding of monoclonal antibodies for the on-chip micropurified recombinant proteins can then be monitored, thus enabling kinetic analysis and epitope mapping of the bound antibodies. This approach reduced time, resources and sample consumption by avoiding conventional steps related to concentration and purification.

A fractal analysis of protein to DNA binding kinetics using biosensors.

PubMed

Sadana, Ajit

2003-08-01

A fractal analysis of a confirmative nature only is presented for the binding of estrogen receptor (ER) in solution to its corresponding DNA (estrogen response element, ERE) immobilized on a sensor chip surface [J. Biol. Chem. 272 (1997) 11384], and for the cooperative binding of human 1,25-dihydroxyvitamin D(3) receptor (VDR) to DNA with the 9-cis-retinoic acid receptor (RXR) [Biochemistry 35 (1996) 3309]. Ligands were also used to modulate the first reaction. Data taken from the literature may be modeled by using a single- or a dual-fractal analysis. Relationships are presented for the binding rate coefficient as a function of either the analyte concentration in solution or the fractal dimension that exists on the biosensor surface. The binding rate expressions developed exhibit a wide range of dependence on the degree of heterogeneity that exists on the surface, ranging from sensitive (order of dependence equal to 1.202) to very sensitive (order of dependence equal to 12.239). In general, the binding rate coefficient increases as the degree of heterogeneity or the fractal dimension of the surface increases. The predictive relationships presented provide further physical insights into the reactions occurring on the biosensor surface. Even though these reactions are occurring on the biosensor surface, the relationships presented should assist in understanding and in possibly manipulating the reactions occurring on cellular surfaces.

A new type of glucose biosensor based on surface acoustic wave resonator using Mn-doped ZnO multilayer structure.

PubMed

Luo, Jingting; Luo, Pingxiang; Xie, Min; Du, Ke; Zhao, Bixia; Pan, Feng; Fan, Ping; Zeng, Fei; Zhang, Dongping; Zheng, Zhuanghao; Liang, Guangxing

2013-11-15

This work reports a high-performance Mn-doped ZnO multilayer structure Love mode surface acoustic wave (SAW) biosensor for the detection of blood sugar. The biosensor was functionalized via immobilizing glucose oxidase onto a pH-sensitive polymer which was attached on Mn-doped ZnO biosensor. The fabricated SAW glucose biosensor is highly sensitive, accurate and fast with good anti-interference. The sensitivity of the SAW glucose biosensor is 7.184 MHz/mM and the accuracy is 6.96 × 10(-3)mM, which is sensitive and accurate enough for glucose monitoring. A good degree of reversibility and stability of the glucose sensor is also demonstrated, which keeps a constant differential frequency shift up to 32 days. Concerning the time response to human serum, the glucose sensor shows a value of 4.6 ± 0.4 min when increasing glucose concentrations and 7.1 ± 0.6 min when decreasing, which is less than 10 min and reach the fast response requirement for medical applications. The Mn-doped ZnO Love mode SAW biosensor can be fully integrated with CMOS Si chips and developed as a portable, passive and wireless real time detection system for blood sugar monitoring in human serum. Copyright © 2013 Elsevier B.V. All rights reserved.

Optical fiber LPG biosensor integrated microfluidic chip for ultrasensitive glucose detection

PubMed Central

Yin, Ming-jie; Huang, Bobo; Gao, Shaorui; Zhang, A. Ping; Ye, Xuesong

2016-01-01

An optical fiber sensor integrated microfluidic chip is presented for ultrasensitive detection of glucose. A long-period grating (LPG) inscribed in a small-diameter single-mode fiber (SDSMF) is employed as an optical refractive-index (RI) sensor. With the layer-by-layer (LbL) self-assembly technique, poly (ethylenimine) (PEI) and poly (acrylic acid) (PAA) multilayer film is deposited on the SDSMF-LPG sensor for both supporting and signal enhancement, and then a glucose oxidase (GOD) layer is immobilized on the outer layer for glucose sensing. A microfluidic chip for glucose detection is fabricated after embedding the SDSMF-LPG biosensor into the microchannel of the chip. Experimental results reveal that the SDSMF-LPG biosensor based on such a hybrid sensing film can ultrasensitively detect glucose concentration as low as 1 nM. After integration into the microfluidic chip, the detection range of the sensor is extended from 2 µM to 10 µM, and the response time is remarkablely shortened from 6 minutes to 70 seconds. PMID:27231643

Quantitative analysis of small molecule-nucleic acid interactions with a biosensor surface and surface plasmon resonance detection.

PubMed

Liu, Yang; Wilson, W David

2010-01-01

Surface plasmon resonance (SPR) technology with biosensor surfaces has become a widely-used tool for the study of nucleic acid interactions without any labeling requirements. The method provides simultaneous kinetic and equilibrium characterization of the interactions of biomolecules as well as small molecule-biopolymer binding. SPR monitors molecular interactions in real time and provides significant advantages over optical or calorimetic methods for systems with strong binding coupled to small spectroscopic signals and/or reaction heats. A detailed and practical guide for nucleic acid interaction analysis using SPR-biosensor methods is presented. Details of the SPR technology and basic fundamentals are described with recommendations on the preparation of the SPR instrument, sensor chips, and samples, as well as extensive information on experimental design, quantitative and qualitative data analysis and presentation. A specific example of the interaction of a minor-groove-binding agent with DNA is evaluated by both kinetic and steady-state SPR methods to illustrate the technique. Since the molecules that bind cooperatively to specific DNA sequences are attractive for many applications, a cooperative small molecule-DNA interaction is also presented.

Inkjet-printed microelectrodes on PDMS as biosensors for functionalized microfluidic systems.

PubMed

Wu, Jianwei; Wang, Ridong; Yu, Haixia; Li, Guijun; Xu, Kexin; Tien, Norman C; Roberts, Robert C; Li, Dachao

2015-02-07

Microfluidic systems based on polydimethylsiloxane (PDMS) have gained popularity in recent years. However, microelectrode patterning on PDMS to form biosensors in microchannels remains a worldwide technical issue due to the hydrophobicity of PDMS and its weak adhesion to metals. In this study, an additive technique using inkjet-printed silver nanoparticles to form microelectrodes on PDMS is presented. (3-Mercaptopropyl)trimethoxysilane (MPTMS) was used to modify the surface of PDMS to improve its surface wettability and its adhesion to silver. The modified surface of PDMS is rendered relatively hydrophilic, which is beneficial for the silver droplets to disperse and thus effectively avoids the coalescence of adjacent droplets. Additionally, a multilevel matrix deposition (MMD) method is used to further avoid the coalescence and yield a homogeneous pattern on the MPTMS-modified PDMS. A surface wettability comparison and an adhesion test were conducted. The resulting silver pattern exhibited good uniformity, conductivity and excellent adhesion to PDMS. A three-electrode electrochemical biosensor was fabricated successfully using this method and sealed in a PDMS microchannel, forming a lab-on-a-chip glucose biosensing system.

Reusable and Mediator-Free Cholesterol Biosensor Based on Cholesterol Oxidase Immobilized onto TGA-SAM Modified Smart Bio-Chips

PubMed Central

Rahman, Mohammed M.

2014-01-01

A reusable and mediator-free cholesterol biosensor based on cholesterol oxidase (ChOx) was fabricated based on self-assembled monolayer (SAM) of thioglycolic acid (TGA) (covalent enzyme immobilization by dropping method) using bio-chips. Cholesterol was detected with modified bio-chip (Gold/Thioglycolic-acid/Cholesterol-oxidase i.e., Au/TGA/ChOx) by reliable cyclic voltammetric (CV) technique at room conditions. The Au/TGA/ChOx modified bio-chip sensor demonstrates good linearity (1.0 nM to 1.0 mM; R = 0.9935), low-detection limit (∼0.42 nM, SNR∼3), and higher sensitivity (∼74.3 µAµM−1cm−2), lowest-small sample volume (50.0 μL), good stability, and reproducibility. To the best of our knowledge, this is the first statement with a very high sensitivity, low-detection limit, and low-sample volumes are required for cholesterol biosensor using Au/TGA/ChOx-chips assembly. The result of this facile approach was investigated for the biomedical applications for real samples at room conditions with significant assembly (Au/TGA/ChOx) towards the development of selected cholesterol biosensors, which can offer analytical access to a large group of enzymes for wide range of biomedical applications in health-care fields. PMID:24949733

Label-free silicon photonic biosensor system with integrated detector array.

PubMed

Yan, Rongjin; Mestas, Santano P; Yuan, Guangwei; Safaisini, Rashid; Dandy, David S; Lear, Kevin L

2009-08-07

An integrated, inexpensive, label-free photonic waveguide biosensor system with multi-analyte capability has been implemented on a silicon photonics integrated circuit from a commercial CMOS line and tested with nanofilms. The local evanescent array coupled (LEAC) biosensor is based on a new physical phenomenon that is fundamentally different from the mechanisms of other evanescent field sensors. Increased local refractive index at the waveguide's upper surface due to the formation of a biological nanofilm causes local modulation of the evanescent field coupled into an array of photodetectors buried under the waveguide. The planar optical waveguide biosensor system exhibits sensitivity of 20%/nm photocurrent modulation in response to adsorbed bovine serum albumin (BSA) layers less than 3 nm thick. In addition to response to BSA, an experiment with patterned photoresist as well as beam propagation method simulations support the evanescent field shift principle. The sensing mechanism enables the integration of all optical and electronic components for a multi-analyte biosensor system on a chip.

Label-free silicon photonic biosensor system with integrated detector array

PubMed Central

Yan, Rongjin; Mestas, Santano P.; Yuan, Guangwei; Safaisini, Rashid; Dandy, David S.

2010-01-01

An integrated, inexpensive, label-free photonic waveguide biosensor system with multi-analyte capability has been implemented on a silicon photonics integrated circuit from a commercial CMOS line and tested with nanofilms. The local evanescent array coupled (LEAC) biosensor is based on a new physical phenomenon that is fundamentally different from the mechanisms of other evanescent field sensors. Increased local refractive index at the waveguide’s upper surface due to the formation of a biological nanofilm causes local modulation of the evanescent field coupled into an array of photodetectors buried under the waveguide. The planar optical waveguide biosensor system exhibits sensitivity of 20%/nm photocurrent modulation in response to adsorbed bovine serum albumin (BSA) layers less than 3 nm thick. In addition to response to BSA, an experiment with patterned photoresist as well as beam propagation method simulations support the evanescent field shift principle. The sensing mechanism enables the integration of all optical and electronic components for a multi-analyte biosensor system on a chip. PMID:19606292

Rapid, sensitive, and reusable detection of glucose by a robust radiofrequency integrated passive device biosensor chip.

PubMed

Kim, Nam-Young; Adhikari, Kishor Kumar; Dhakal, Rajendra; Chuluunbaatar, Zorigt; Wang, Cong; Kim, Eun-Soo

2015-01-15

Tremendous demands for sensitive and reliable label-free biosensors have stimulated intensive research into developing miniaturized radiofrequency resonators for a wide range of biomedical applications. Here, we report the development of a robust, reusable radiofrequency resonator based integrated passive device biosensor chip fabricated on a gallium arsenide substrate for the detection of glucose in water-glucose solutions and sera. As a result of the highly concentrated electromagnetic energy between the two divisions of an intertwined spiral inductor coupled with an interdigital capacitor, the proposed glucose biosensor chip exhibits linear detection ranges with high sensitivity at center frequency. This biosensor, which has a sensitivity of up to 199 MHz/mgmL(-1) and a short response time of less than 2 sec, exhibited an ultralow detection limit of 0.033 μM and a reproducibility of 0.61% relative standard deviation. In addition, the quantities derived from the measured S-parameters, such as the propagation constant (γ), impedance (Z), resistance (R), inductance (L), conductance (G) and capacitance (C), enabled the effective multi-dimensional detection of glucose.

Rapid, Sensitive, and Reusable Detection of Glucose by a Robust Radiofrequency Integrated Passive Device Biosensor Chip

PubMed Central

Kim, Nam-Young; Adhikari, Kishor Kumar; Dhakal, Rajendra; Chuluunbaatar, Zorigt; Wang, Cong; Kim, Eun-Soo

2015-01-01

Tremendous demands for sensitive and reliable label-free biosensors have stimulated intensive research into developing miniaturized radiofrequency resonators for a wide range of biomedical applications. Here, we report the development of a robust, reusable radiofrequency resonator based integrated passive device biosensor chip fabricated on a gallium arsenide substrate for the detection of glucose in water-glucose solutions and sera. As a result of the highly concentrated electromagnetic energy between the two divisions of an intertwined spiral inductor coupled with an interdigital capacitor, the proposed glucose biosensor chip exhibits linear detection ranges with high sensitivity at center frequency. This biosensor, which has a sensitivity of up to 199 MHz/mgmL−1 and a short response time of less than 2 sec, exhibited an ultralow detection limit of 0.033 μM and a reproducibility of 0.61% relative standard deviation. In addition, the quantities derived from the measured S-parameters, such as the propagation constant (γ), impedance (Z), resistance (R), inductance (L), conductance (G) and capacitance (C), enabled the effective multi-dimensional detection of glucose. PMID:25588958

Nanophotonic label-free biosensors for environmental monitoring.

PubMed

Chocarro-Ruiz, Blanca; Fernández-Gavela, Adrián; Herranz, Sonia; Lechuga, Laura M

2017-06-01

The field of environmental monitoring has experienced a substantial progress in the last years but still the on-site control of contaminants is an elusive problem. In addition, the growing number of pollutant sources is accompanied by an increasing need of having efficient early warning systems. Several years ago biosensor devices emerged as promising environmental monitoring tools, but their level of miniaturization and their fully operation outside the laboratory prevented their use on-site. In the last period, nanophotonic biosensors based on evanescent sensing have emerged as an outstanding choice for portable point-of-care diagnosis thanks to their capability, among others, of miniaturization, multiplexing, label-free detection and integration in lab-on-chip platforms. This review covers the most relevant nanophotonic biosensors which have been proposed (including interferometric waveguides, grating-couplers, microcavity resonators, photonic crystals and localized surface plasmon resonance sensors) and their recent application for environmental surveillance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study of endothelial cell apoptosis using fluorescence resonance energy transfer (FRET) biosensor cell line with hemodynamic microfluidic chip system.

PubMed

Yu, J Q; Liu, X F; Chin, L K; Liu, A Q; Luo, K Q

2013-07-21

To better understand how hyperglycemia induces endothelial cell dysfunction under the diabetic conditions, a hemodynamic microfluidic chip system was developed. The system combines a caspase-3-based fluorescence resonance energy transfer (FRET) biosensor cell line which can detect endothelial cell apoptosis in real-time, post-treatment effect and with a limited cell sample, by using a microfluidic chip which can mimic the physiological pulsatile flow profile in the blood vessel. The caspase-3-based FRET biosensor endothelial cell line (HUVEC-C3) can produce a FRET-based sensor protein capable of probing caspase-3 activation. When the endothelial cells undergo apoptosis, the color of the sensor cells changes from green to blue, thus sensing apoptosis. A double-labeling fluorescent technique (yo pro-1 and propidium iodide) was used to validate the findings revealed by the FRET-based caspase sensor. The results show high rates of apoptosis and necrosis of endothelial cells when high glucose concentration was applied in our hemodynamic microfluidic chip combined with an exhaustive pulsatile flow profile. The two apoptosis detection techniques (fluorescent method and FRET biosensor) are comparable; but FRET biosensor offers more advantages such as real-time observation and a convenient operating process to generate more accurate and reliable data. Furthermore, the activation of the FRET biosensor also confirms the endothelial cell apoptosis induced by the abnormal pulsatile shear stress and high glucose concentration is through caspase-3 pathway. A 12% apoptotic rate (nearly a 4-fold increase compared to the static condition) was observed when the endothelial cells were exposed to a high glucose concentration of 20 mM under 2 h exhaustive pulsatile shear stress of 30 dyne cm(-2) and followed with another 10 h normal pulsatile shear stress of 15 dyne cm(-2). Therefore, the most important finding of this study is to develop a novel endothelial cell apoptosis detection method, which combines the microfluidic chip system and FRET biosensor. This finding may provide new insight into how glucose causes endothelial cell dysfunction, which is the major cause of diabetes-derived complications.

Analysis of Mycotoxins in Beer Using a Portable Nanostructured Imaging Surface Plasmon Resonance Biosensor.

PubMed

Joshi, Sweccha; Annida, Rumaisha M; Zuilhof, Han; van Beek, Teris A; Nielen, Michel W F

2016-11-02

A competitive inhibition immunoassay is described for the mycotoxins deoxynivalenol (DON) and ochratoxin A (OTA) in beer using a portable nanostructured imaging surface plasmon resonance (iSPR) biosensor, also referred to as imaging nanoplasmonics. The toxins were directly and covalently immobilized on a 3-dimensional carboxymethylated dextran (CMD) layer on a nanostructured iSPR chip. The assay is based on competition between the immobilized mycotoxins and free mycotoxins in the solution for binding to specific antibodies. The chip surface was regenerated after each cycle, and the combination of CMD and direct immobilization of toxins allowed the chips to be used for more than 450 cycles. The limits of detection (LODs) in beer were 17 ng/mL for DON and 7 ng/mL for OTA (or 0.09 ng/mL after 75 times enrichment). These LODs allowed detection of even less than 10% depletion of the tolerable daily intake of DON and OTA by beer. Significant cross-reactivity of anti-DON was observed toward DON-3-glucoside and 3-acetyl-DON, while no cross-reactivity was seen for 15-acetyl-DON. A preliminary in-house validation with 20 different batches of beer showed that both toxins can be detected at the considered theoretical safe level for beer. The assay can be used for in-field or at-line detection of DON in beer and also in barley without preconcentration, while OTA in beer requires an additional enrichment step, thus making the latter in its present form less suitable for field applications.

Quantum dot-based microfluidic biosensor for cancer detection

NASA Astrophysics Data System (ADS)

Ghrera, Aditya Sharma; Pandey, Chandra Mouli; Ali, Md. Azahar; Malhotra, Bansi Dhar

2015-05-01

We report results of the studies relating to fabrication of an impedimetric microfluidic-based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium-tin-oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir-Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system has been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10-15 M to 10-11 M.

Biosensors and bioelectronics on smartphone for portable biochemical detection.

PubMed

Zhang, Diming; Liu, Qingjun

2016-01-15

Smartphone has been widely integrated with sensors, such as test strips, sensor chips, and hand-held detectors, for biochemical detections due to its portability and ubiquitous availability. Utilizing built-in function modules, smartphone is often employed as controller, analyzer, and displayer for rapid, real-time, and point-of-care monitoring, which can significantly simplify design and reduce cost of the detecting systems. This paper presents a review of biosensors and bioelectronics on smartphone for portable biochemical detections. The biosensors and bioelectronics based on smartphone can mainly be classified into biosensors using optics, surface plasmon resonance, electrochemistry, and near-field communication. The developments of these biosensors and bioelectronics on smartphone are reviewed along with typical biochemical detecting cases. Sensor strategies, detector attachments, and coupling methods are highlighted to show designs of the compact, lightweight, and low-cost sensor systems. The performances and advantages of these designs are introduced with their applications in healthcare diagnosis, environment monitoring, and food evaluation. With advances in micro-manufacture, sensor technology, and miniaturized electronics, biosensor and bioelectronic devices on smartphone can be used to perform biochemical detections as common and convenient as electronic tag readout in foreseeable future. Copyright © 2015 Elsevier B.V. All rights reserved.

Wavelength dispersion characteristics of integrated silicon avalanche LEDs: potential applications in futuristic on-chip micro- and nano-biosensors

NASA Astrophysics Data System (ADS)

Okhai, Timothy A.; Snyman, Lukas W.; Polleux, Jean-Luc

2016-02-01

Si Av LEDs are easily integrated in on-chip integrated circuitry. They have high modulation frequencies into the GHz range and can be fabricated to sub-micron dimensions. Due to subsurface light generation in the silicon device itself, and the high refractive index differences between silicon and the device environment, the exiting light radiation has interesting dispersion characteristics. Three junction micro p+-np+ Silicon Avalanche based Light Emitting Devices (Si Av LEDs) have been analyzed in terms of dispersion characteristics, generally resulting in different wavelengths of light (colors) being emitted at different angles and solid angles from the surfaces of these devices. The emission wavelength is in the 450 - 850 nm range. The devices are of micron dimension and operate at 8 - 10V, 1μA - 2mA. The emission spot sizes are about 1 micron square. Emission intensities are up to 500 nW.μm-2. The observed dispersion characteristics range from 0.05 degrees per nm per degree at emission angle of 5 degrees, to 0.15 degrees per nm at emission angles of 30 degrees. It is believed that the dispersion characteristics can find interesting and futuristic on-chip electro-optic applications involving particularly a ranging from on chip micro optical wavelength dispersers, communication de-multiplexers, and novel bio-sensor applications. All of these could penetrate into the nanoscale dimensions.

Real-time, multiplexed electrochemical DNA detection using an active complementary metal-oxide-semiconductor biosensor array with integrated sensor electronics.

PubMed

Levine, Peter M; Gong, Ping; Levicky, Rastislav; Shepard, Kenneth L

2009-03-15

Optical biosensing based on fluorescence detection has arguably become the standard technique for quantifying extents of hybridization between surface-immobilized probes and fluorophore-labeled analyte targets in DNA microarrays. However, electrochemical detection techniques are emerging which could eliminate the need for physically bulky optical instrumentation, enabling the design of portable devices for point-of-care applications. Unlike fluorescence detection, which can function well using a passive substrate (one without integrated electronics), multiplexed electrochemical detection requires an electronically active substrate to analyze each array site and benefits from the addition of integrated electronic instrumentation to further reduce platform size and eliminate the electromagnetic interference that can result from bringing non-amplified signals off chip. We report on an active electrochemical biosensor array, constructed with a standard complementary metal-oxide-semiconductor (CMOS) technology, to perform quantitative DNA hybridization detection on chip using targets conjugated with ferrocene redox labels. A 4 x 4 array of gold working electrodes and integrated potentiostat electronics, consisting of control amplifiers and current-input analog-to-digital converters, on a custom-designed 5 mm x 3 mm CMOS chip drive redox reactions using cyclic voltammetry, sense DNA binding, and transmit digital data off chip for analysis. We demonstrate multiplexed and specific detection of DNA targets as well as real-time monitoring of hybridization, a task that is difficult, if not impossible, with traditional fluorescence-based microarrays.

Biosensor system-on-a-chip including CMOS-based signal processing circuits and 64 carbon nanotube-based sensors for the detection of a neurotransmitter.

PubMed

Lee, Byung Yang; Seo, Sung Min; Lee, Dong Joon; Lee, Minbaek; Lee, Joohyung; Cheon, Jun-Ho; Cho, Eunju; Lee, Hyunjoong; Chung, In-Young; Park, Young June; Kim, Suhwan; Hong, Seunghun

2010-04-07

We developed a carbon nanotube (CNT)-based biosensor system-on-a-chip (SoC) for the detection of a neurotransmitter. Here, 64 CNT-based sensors were integrated with silicon-based signal processing circuits in a single chip, which was made possible by combining several technological breakthroughs such as efficient signal processing, uniform CNT networks, and biocompatible functionalization of CNT-based sensors. The chip was utilized to detect glutamate, a neurotransmitter, where ammonia, a byproduct of the enzymatic reaction of glutamate and glutamate oxidase on CNT-based sensors, modulated the conductance signals to the CNT-based sensors. This is a major technological advancement in the integration of CNT-based sensors with microelectronics, and this chip can be readily integrated with larger scale lab-on-a-chip (LoC) systems for various applications such as LoC systems for neural networks.

Design and simulation of MEMS microvalves for silicon photonic biosensor chip

NASA Astrophysics Data System (ADS)

Amemiya, Yoshiteru; Nakashima, Yuuto; Maeda, Jun; Yokoyama, Shin

2018-04-01

For the early and easy diagnosis of diseases, we have proposed a silicon photonic biosensor chip with two kinds of MEMS microvalves for a multiple-item detection system. The driving voltage of the vertical type with the circular-plate capacitor structure and that of the lateral type with the comb-shaped electrode are investigated. From mechanical calculations, the driving voltage of the vertical type is estimated to be 30 V and that of the lateral type to be 15 V. The propagation loss at the intersecting waveguides of arrayed ring-resonator biosensors is also estimated. In the case of optimized intersecting waveguides, more than 67% transmittance of TE-mode light is simulated for the series connection of 20 intersecting waveguides. It is confirmed that it is possible to fabricate an 8 × 12 arrayed biosensor chip in an area of 1 × 1.5 mm2 taking the device size of the microvalves into consideration. We have, for the first time, designed a whole system, including sensors and a fluid channel with MEMS microvalves.

Highly sensitive quartz crystal microbalance based biosensor using Au dendrite structure

NASA Astrophysics Data System (ADS)

Asai, Naoto; Terasawa, Hideaki; Shimizu, Tomohiro; Shingubara, Shoso; Ito, Takeshi

2018-02-01

A Au dendrite structure was obtained by only electroplating under a suitable potential. A blanch like nanostructure was formed along the crystal orientation. In this study, we attempted to fabricate a Au dendrite structure on the electrode of a quartz crystal by electroplating to increase the specific surface area. We estimated the effective surface area by cyclic voltammetry (CV) and monitored the frequency shift induced by antigen-antibody interaction by the quartz crystal microbalance (QCM) method. The dendrite structure with the largest surface area was formed under -0.95 V for 5 min. In the measurement of the antigen-antibody interaction, the frequency shifts of 40, 80, and 110 Hz were obtained with the dendrite structured QCM chips formed at the above potential for 1, 1.5, and 2.0 min, respectively. The sensitivity was improved compared with that QCM chip having a flat surface electrode.

Nanophotonics for Lab-on-Chip Applications

NASA Astrophysics Data System (ADS)

Seitz, Peter

Optical methods are the preferred measurement techniques for biosensors and lab-on-chip applications. Their key properties are sensitivity, selectivity and robustness. To simplify the systems and their operation, it is desirable to employ label-free optical methods, requiring the functionalization of interfaces. Evanescent electromagnetic waves are probing the optical proper ties near the interfaces, a few 100 nm deep into the sample fluid. The sensitivity of these measurements can be improved with optical micro-resonators, in particular whispering gallery mode devices. Q factors as high as 2x108 have been achieved in practice. The resulting narrow-linewidth resonances and an unexpected thermo-optic effect make it possible to detect single biomolecules using a label-free biosensor principle. Future generations of biosensors and labs-on-chip for point-of-care and high-troughput screening applications will require large numbers of parallel measurement channels, necessitating optical micro-resonators in array format produced very cost-effectively.

Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms

PubMed Central

Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A.

2016-01-01

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with “open” digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions. PMID:27089377

Droplet-based Biosensing for Lab-on-a-Chip, Open Microfluidics Platforms.

PubMed

Dak, Piyush; Ebrahimi, Aida; Swaminathan, Vikhram; Duarte-Guevara, Carlos; Bashir, Rashid; Alam, Muhammad A

2016-04-14

Low cost, portable sensors can transform health care by bringing easily available diagnostic devices to low and middle income population, particularly in developing countries. Sample preparation, analyte handling and labeling are primary cost concerns for traditional lab-based diagnostic systems. Lab-on-a-chip (LoC) platforms based on droplet-based microfluidics promise to integrate and automate these complex and expensive laboratory procedures onto a single chip; the cost will be further reduced if label-free biosensors could be integrated onto the LoC platforms. Here, we review some recent developments of label-free, droplet-based biosensors, compatible with "open" digital microfluidic systems. These low-cost droplet-based biosensors overcome some of the fundamental limitations of the classical sensors, enabling timely diagnosis. We identify the key challenges that must be addressed to make these sensors commercially viable and summarize a number of promising research directions.

Off surface matrix based on-chip electrochemical biosensor platform for protein biomarker detection in undiluted serum.

PubMed

Arya, Sunil K; Kongsuphol, Patthara; Park, Mi Kyoung

2017-06-15

The manuscript describes a concept of using off surface matrix modified with capturing biomolecule for on-chip electrochemical biosensing. 3D matrix made by laser engraving of polymethyl methacrylate (PMMA) sheet as off surface matrix was integrated in very close vicinity of the electrode surface. Laser engraving and holes in PMMA along with spacing from surface provide fluidic channel and incubation chamber. Covalent binding of capturing biomolecule (anti-TNF-α antibody) on off-surface matrix was achieved via azide group activity of 4-fluoro-3-nitro-azidobenzene (FNAB), which act as cross-linker and further covalently binds to anti-TNF-α antibody via thermal reaction. Anti-TNF-α/FNAB/PMMA matrix was then integrated over comb structured gold electrode array based sensor chip. Separate surface modification followed by integration of sensor helped to prevent the sensor chip surface from fouling during functionalization. Nonspecific binding was prevented using starting block T20 (PBS). Results for estimating protein biomarker (TNF-α) in undiluted serum using Anti-TNF-α/FNAB/PMMA/Au reveal that system can detect TNF-α in 100pg/ml to 100ng/ml range with high sensitivity of 119nA/(ng/ml), with negligible interference from serum proteins and other cytokines. Thus, use of off surface matrix may provide the opportunity to electrochemically sense biomarkers sensitively to ng/ml range with negligible nonspecific binding and false signal in undiluted serum. Copyright © 2016 Elsevier B.V. All rights reserved.

Mannose glycoconjugates functionalized at positions 1 and 6. Binding analysis to DC-SIGN using biosensors.

PubMed

Reina, José J; Maldonado, Olivia S; Tabarani, Georges; Fieschi, Franck; Rojo, Javier

2007-01-01

The design of glycoconjugates to allow the generation of multivalent ligands capable of interacting with the receptor DC-SIGN is a topic of high interest due to the role played by this lectin in pathogen infections. Mannose, a ligand of this lectin, could be conjugated at two different positions, 1 and 6, not implicated in the binding process. We have prepared mannose conjugates at these two positions with a long spacer to allow their attachment to a biosensor chip surface. Analysis of the interaction between these surfaces and the tetravalent extracellular domain (ECD) of DC-SIGN by SPR biosensor has demonstrated that both positions are available for this conjugation without affecting the protein binding process. These results emphasize the possibility to conjugate mannose at position 6, allowing the incorporation of hydrophobic groups at the anomeric position to interact with hydrophobic residues in the carbohydrate recognition domain of DC-SIGN, increasing binding affinities. This fact is relevant for the future design of new ligands and the corresponding multivalent systems for DC-SIGN.

Preparation of surface plasmon resonance biosensor based on magnetic core/shell Fe3O4/SiO2 and Fe3O4/Ag/SiO2 nanoparticles.

PubMed

Wang, Liying; Sun, Ying; Wang, Jing; Wang, Jian; Yu, Aimin; Zhang, Hanqi; Song, Daqian

2011-06-01

In this paper, surface plasmon resonance biosensors based on magnetic core/shell Fe(3)O(4)/SiO(2) and Fe(3)O(4)/Ag/SiO(2) nanoparticles were developed for immunoassay. With Fe(3)O(4) and Fe(3)O(4)/Ag nanoparticles being used as seeding materials, Fe(3)O(4)/SiO(2) and Fe(3)O(4)/Ag/SiO(2) nanoparticles were formed by hydrolysis of tetraethyl orthosilicate. The aldehyde group functionalized magnetic nanoparticles provide organic functionality for bioconjugation. The products were characterized by scanning electronic microscopy (SEM), transmission electronic microscopy (TEM), FTIR and UV-vis absorption spectrometry. The magnetic nanoparticles possess the unique superparamagnetism property, exceptional optical properties and good compatibilities, and could be used as immobilization matrix for goat anti-rabbit IgG. The magnetic nanoparticles can be easily immobilized on the surface of SPR biosensor chip by a magnetic pillar. The effects of Fe(3)O(4)/SiO(2) and Fe(3)O(4)/Ag/SiO(2) nanoparticles on the sensitivity of SPR biosensors were also investigated. As a result, the SPR biosensors based on Fe(3)O(4)/SiO(2) nanoparticles and Fe(3)O(4)/Ag/SiO(2) nanoparticles exhibit a response for rabbit IgG in the concentration range of 1.25-20.00 μg ml(-1) and 0.30-20.00 μg ml(-1), respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

Hybrid optofluidic biosensors

NASA Astrophysics Data System (ADS)

Parks, Joshua W.

Optofluidics, born of the desire to create a system containing microfluidic environments with integrated optical elements, has seen dramatic increases in popularity over the last 10 years. In particular, the application of this technology towards chip based molecular sensors has undergone significant development. The most sensitive of these biosensors interface liquid- and solid-core antiresonant reflecting optical waveguides (ARROWs). These sensor chips are created using conventional silicon microfabrication. As such, ARROW technology has previously been unable to utilize state-of-the-art microfluidic developments because the technology used--soft polydimethyl siloxane (PDMS) micromolded chips--is unamenable to the silicon microfabrication workflows implemented in the creation of ARROW detection chips. The original goal of this thesis was to employ hybrid integration, or the connection of independently designed and fabricated optofluidic and microfluidic chips, to create enhanced biosensors with the capability of processing and detecting biological samples on a single hybrid system. After successful demonstration of this paradigm, this work expanded into a new direction--direct integration of sensing and detection technologies on a new platform with dynamic, multi-dimensional photonic re-configurability. This thesis reports a number of firsts, including: • 1,000 fold optical transmission enhancement of ARROW optofluidic detection chips through thermal annealing, • Detection of single nucleic acids on a silicon-based ARROW chip, • Hybrid optofluidic integration of ARROW detection chips and passive PDMS microfluidic chips, • Hybrid optofluidic integration of ARROW detection chips and actively controllable PDMS microfluidic chips with integrated microvalves, • On-chip concentration and detection of clinical Ebola nucleic acids, • Multimode interference (MMI) waveguide based wavelength division multiplexing for detection of single influenza virions, • All PDMS platform created from monolithically integrated solid- and liquid-core waveguides with single particle detection efficiency and directly integrated microvalves, featuring: ∘ Tunable/tailorable PDMS MMI waveguides, ∘ Lightvalves (optical switch/fluidic microvalve) with the ability to dynamically control light and fluid flow simultaneously, ∘ Lightvalve trap architecture with the ability to physically trap, detect, and analyze single biomolecules.

Towards an integrated optofluidic system for highly sensitive detection of antibiotics in seawater incorporating bimodal waveguide photonic biosensors and complex, active microfluidics

NASA Astrophysics Data System (ADS)

Szydzik, C.; Gavela, A. F.; Roccisano, J.; Herranz de Andrés, S.; Mitchell, A.; Lechuga, L. M.

2016-12-01

We present recent results on the realisation and demonstration of an integrated optofluidic lab-on-a-chip measurement system. The system consists of an integrated on-chip automated microfluidic fluid handling subsystem, coupled with bimodal nano-interferometer waveguide technology, and is applied in the context of detection of antibiotics in seawater. The bimodal waveguide (BMWG) is a highly sensitive label-free biosensor. Integration of complex microfluidic systems with bimodal waveguide technology enables on-chip sample handling and fluid processing capabilities and allows for significant automation of experimental processes. The on-chip fluid-handling subsystem is realised through the integration of pneumatically actuated elastomer pumps and valves, enabling high temporal resolution sample and reagent delivery and facilitating multiplexed detection processes.

Toward a solid-phase nucleic acid hybridization assay within microfluidic channels using immobilized quantum dots as donors in fluorescence resonance energy transfer.

PubMed

Chen, Lu; Algar, W Russ; Tavares, Anthony J; Krull, Ulrich J

2011-01-01

The optical properties and surface area of quantum dots (QDs) have made them an attractive platform for the development of nucleic acid biosensors based on fluorescence resonance energy transfer (FRET). Solid-phase assays based on FRET using mixtures of immobilized QD-oligonucleotide conjugates (QD biosensors) have been developed. The typical challenges associated with solid-phase detection strategies include non-specific adsorption, slow kinetics of hybridization, and sample manipulation. The new work herein has considered the immobilization of QD biosensors onto the surfaces of microfluidic channels in order to address these challenges. Microfluidic flow can be used to dynamically control stringency by adjustment of the potential in an electrokinetic-based microfluidics environment. The shearing force, Joule heating, and the competition between electroosmotic and electrophoretic mobilities allow the optimization of hybridization conditions, convective delivery of target to the channel surface to speed hybridization, amelioration of adsorption, and regeneration of the sensing surface. Microfluidic flow can also be used to deliver (for immobilization) and remove QD biosensors. QDs that were conjugated with two different oligonucleotide sequences were used to demonstrate feasibility. One oligonucleotide sequence on the QD was available as a linker for immobilization via hybridization with complementary oligonucleotides located on a glass surface within a microfluidic channel. A second oligonucleotide sequence on the QD served as a probe to transduce hybridization with target nucleic acid in a sample solution. A Cy3 label on the target was excited by FRET using green-emitting CdSe/ZnS QD donors and provided an analytical signal to explore this detection strategy. The immobilized QDs could be removed under denaturing conditions by disrupting the duplex that was used as the surface linker and thus allowed a new layer of QD biosensors to be re-coated within the channel for re-use of the microfluidic chip.

Quantum dot-based microfluidic biosensor for cancer detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghrera, Aditya Sharma; School of Engineering and Technology, ITM University, Gurgaon-122017; Pandey, Chandra Mouli

2015-05-11

We report results of the studies relating to fabrication of an impedimetric microfluidic–based nucleic acid sensor for quantification of DNA sequences specific to chronic myelogenous leukemia (CML). The sensor chip is prepared by patterning an indium–tin–oxide (ITO) coated glass substrate via wet chemical etching method followed by sealing with polydimethylsiloxane (PDMS) microchannel for fluid control. The fabricated microfluidic chip comprising of a patterned ITO substrate is modified by depositing cadmium selenide quantum dots (QCdSe) via Langmuir–Blodgett technique. Further, the QCdSe surface has been functionalized with specific DNA probe for CML detection. The probe DNA functionalized QCdSe integrated miniaturized system hasmore » been used to monitor target complementary DNA concentration by measuring the interfacial charge transfer resistance via hybridization. The presence of complementary DNA in buffer solution significantly results in decreased electro-conductivity of the interface due to presence of a charge barrier for transport of the redox probe ions. The microfluidic DNA biosensor exhibits improved linearity in the concentration range of 10{sup −15} M to 10{sup −11} M.« less

Wireless poly(dimethylsiloxane) quartz-crystal-microbalance biosensor chip fabricated by nanoimprint lithography for micropump integration aiming at application in lab-on-a-chip

NASA Astrophysics Data System (ADS)

Kato, Fumihito; Noguchi, Hiroyuki; Kodaka, Yukinari; Oshida, Naoya; Ogi, Hirotsugu

2018-07-01

We developed a quartz-crystal-microbalance (QCM) biosensor chip that operates wirelessly via electromagnetic waves, using poly(dimethylsiloxane) (PDMS). An AT-cut quartz oscillator (22–30 µm) is packaged in a microchannel, where it is supported by micropillars without mechanical fixing. As a result, the quartz oscillator is little affected by the thermal stress caused by the difference in the thermal expansion coefficients of the components, and the leakage of the vibration energy of the quartz oscillator is reduced. Consequently, high-frequency (∼56 MHz) measurement with a stable baseline (±∼2 ppm) is realized. We succeeded in repeatedly monitoring the binding reaction between immunoglobulin G (IgG) and Staphylococcus aureus protein A (SPA) with the quartz oscillator on which SPA molecules were immobilized nonspecifically. In addition, the affinity between SPA and IgG was calculated from the association and dissociation curves, and the usefulness of our wireless PDMS QCM biosensor was demonstrated.

ADMET biosensors: up-to-date issues and strategies.

PubMed

Fang, Yan; Offenhaeusser, Andrease

2004-12-01

This insight review introduces the new concepts, theories, technology, instruments, frontier issues, and key strategies of ADMET (absorption, distribution, metabolism, elimination, and toxicity) biosensors, from the fermi to the quantum levels. Information about ADMET, originating from one author's invention, a patented pharmacotherapy for rescuing cardio-cerebral vascular stunning and regulating vascular endothelial growth-factor signaling at the post-genomic level, can be detected by a new generation of ADMET biosensor. This is a single-cell/single-molecule field-effect transistor (FET) hybrid system, where single molecules or single cells are assembled at the FET surface in a high density array manner via complementary metal-oxide-semiconductor (CMOS)-compatible technologies. Within a given nanometer distance, ADMET-mediated oxidation-reduction (redox) potentials, electrochemistry responses, and electron transfer processes can be simultaneously and directly probed by the gates of field-effect transistor arrays. The nanometer details of the functional coupling principles and characterization technologies of DNA single-molecule/single-cell FETs, as well as the design of lab-on-a-chip instruments, are indicated. Four frontier issues and key strategies are elucidated in detail. This can lead to innovative technology for high-throughout screening of labs-on-chips to resolve the pharmaceutical industry's current bottleneck via novel, FET-based drug discovery and single-molecule/single-cell screening methods, which can bring about a pharmaceutical industry revolution in the 21st century.

Lab-on-a-Chip Pathogen Sensors for Food Safety

PubMed Central

Yoon, Jeong-Yeol; Kim, Bumsang

2012-01-01

There have been a number of cases of foodborne illness among humans that are caused by pathogens such as Escherichia coli O157:H7, Salmonella typhimurium, etc. The current practices to detect such pathogenic agents are cell culturing, immunoassays, or polymerase chain reactions (PCRs). These methods are essentially laboratory-based methods that are not at all real-time and thus unavailable for early-monitoring of such pathogens. They are also very difficult to implement in the field. Lab-on-a-chip biosensors, however, have a strong potential to be used in the field since they can be miniaturized and automated; they are also potentially fast and very sensitive. These lab-on-a-chip biosensors can detect pathogens in farms, packaging/processing facilities, delivery/distribution systems, and at the consumer level. There are still several issues to be resolved before applying these lab-on-a-chip sensors to field applications, including the pre-treatment of a sample, proper storage of reagents, full integration into a battery-powered system, and demonstration of very high sensitivity, which are addressed in this review article. Several different types of lab-on-a-chip biosensors, including immunoassay- and PCR-based, have been developed and tested for detecting foodborne pathogens. Their assay performance, including detection limit and assay time, are also summarized. Finally, the use of optical fibers or optical waveguide is discussed as a means to improve the portability and sensitivity of lab-on-a-chip pathogen sensors. PMID:23112625

On-Chip Synthesis of Protein Microarrays from DNA Microarrays Via Coupled In Vitro Transcription and Translation for Surface Plasmon Resonance Imaging Biosensor Applications

PubMed Central

Seefeld, Ting H.; Halpern, Aaron R.; Corn, Robert M.

2012-01-01

Protein microarrays are fabricated from double-stranded DNA (dsDNA) microarrays by a one-step, multiplexed enzymatic synthesis in an on-chip microfluidic format and then employed for antibody biosensing measurements with surface plasmon resonance imaging (SPRI). A microarray of dsDNA elements (denoted as generator elements) that encode either a His-tagged green fluorescent protein (GFP) or a His-tagged luciferase protein is utilized to create multiple copies of messenger RNA (mRNA) in a surface RNA polymerase reaction; the mRNA transcripts are then translated into proteins by cell-free protein synthesis in a microfluidic format. The His-tagged proteins diffuse to adjacent Cu(II)-NTA microarray elements (denoted as detector elements) and are specifically adsorbed. The net result is the on-chip, cell-free synthesis of a protein microarray that can be used immediately for SPRI protein biosensing. The dual element format greatly reduces any interference from the nonspecific adsorption of enzyme or proteins. SPRI measurements for the detection of the antibodies anti-GFP and anti-luciferase were used to verify the formation of the protein microarray. This convenient on-chip protein microarray fabrication method can be implemented for multiplexed SPRI biosensing measurements in both clinical and research applications. PMID:22793370

Discrimination of peptides by using a molecularly imprinted piezoelectric biosensor.

PubMed

Lin, Chung-Yin; Tai, Dar-Fu; Wu, Tzong-Zeng

2003-10-17

Based on the direct formation of a molecularly imprinted polymer on gold electrodes, we have developed a peptide sensor for the detection of low-molecular-weight peptides. A new cross-linking monomer, (N-Acr-L-Cys-NHBn)(2), was employed to attach the surface of the chip and to copolymerize with other monomers. Interestingly, N-benzylacrylamide participates in the polymerization and recognition is carried out in an aqueous environment. By using quartz crystal microbalance detection, short peptides can be monitored by their interaction with plastic antibodies specific for the target peptides. The selectivity of molecularly imprinted polymers and the sensitivity of such artificial biosensors have been combined to differentiate between traces of oxytocin and vasopressin to the ng mL(-1) scale.

Deposition of chemically reactive and repellent sites on biosensor chips for reduced non-specific binding.

PubMed

Gandhiraman, R P; Gubala, V; Le, N C H; Nam, Le Cao Hoai; Volcke, C; Doyle, C; James, B; Daniels, S; Williams, D E

2010-08-01

The performances of new polymeric materials with excellent optical properties and good machinability have led the biomedical diagnostics industry to develop cheap disposable biosensor platforms appropriate for point of care applications. Zeonor, a type of cycloolefin polymer (COP), is one such polymer that presents an excellent platform for biosensor chips. These polymer substrates have to be modified to have suitable physico-chemical properties for immobilizing proteins. In this work, we have demonstrated the amine functionalization of COP substrates, by plasma enhanced chemical vapour deposition (PECVD), through codeposition of ethylene diamine and 3-aminopropyltriethoxysilane precursors, for building chemistries on the plastic chip. The elemental composition, adhesion, ageing and reactivity of the plasma polymerized film were examined. The Si-O functionality present in amino silane contributed for a good interfacial adhesion of the coating to COP substrates and also acted as a network building layer for plasma polymerization. Wet chemical modification was then carried out on the amine functionalized chips to create chemically reactive isothiocyanate sites and protein repellent fluorinated sites on the same chip. The density of the reactive and repellent sites was altered by choosing appropriate mixtures of homofunctional phenyldiisothiocyanate (PDITC), pentafluoroisothiocyanate (5FITC) and phenylisothiocyanate (PITC) compounds. By tailoring the density of reactive binding sites and protein repellent sites, the non-specific binding of ssDNA has been decreased to a significant extent. Copyright 2010 Elsevier B.V. All rights reserved.

Biotinylated lipid bilayer disks as model membranes for biosensor analyses.

PubMed

Lundquist, Anna; Hansen, Søren B; Nordström, Helena; Danielson, U Helena; Edwards, Katarina

2010-10-15

The aim of this study was to investigate the potential of polyethylene glycol (PEG)-stabilized lipid bilayer disks as model membranes for surface plasmon resonance (SPR)-based biosensor analyses. Nanosized bilayer disks that included 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethylene glycol)(2000)] (DSPE-PEG(2000)-biotin) were prepared and structurally characterized by cryo-transmission electron microscopy (cryo-TEM) imaging. The biotinylated disks were immobilized via streptavidin to three different types of sensor chips (CM3, CM4, and CM5) varying in their degree of carboxymethylation and thickness of the dextran matrix. The bilayer disks were found to interact with and bind stably to the streptavidin-coated sensor surfaces. As a first step toward the use of these bilayer disks as model membranes in SPR-based studies of membrane proteins, initial investigations were carried out with cyclooxygenases 1 and 2 (COX 1 and COX 2). Bilayer disks were preincubated with the respective protein and thereafter allowed to interact with the sensor surface. The signal resulting from the interaction was, in both cases, significantly enhanced as compared with the signal obtained when disks alone were injected over the surface. The results of the study suggest that bilayer disks constitute a new and promising type of model membranes for SPR-based biosensor studies. Copyright 2010 Elsevier Inc. All rights reserved.

Computational analysis of integrated biosensing and shear flow in a microfluidic vascular model

NASA Astrophysics Data System (ADS)

Wong, Jeremy F.; Young, Edmond W. K.; Simmons, Craig A.

2017-11-01

Fluid flow and flow-induced shear stress are critical components of the vascular microenvironment commonly studied using microfluidic cell culture models. Microfluidic vascular models mimicking the physiological microenvironment also offer great potential for incorporating on-chip biomolecular detection. In spite of this potential, however, there are few examples of such functionality. Detection of biomolecules released by cells under flow-induced shear stress is a significant challenge due to severe sample dilution caused by the fluid flow used to generate the shear stress, frequently to the extent where the analyte is no longer detectable. In this work, we developed a computational model of a vascular microfluidic cell culture model that integrates physiological shear flow and on-chip monitoring of cell-secreted factors. Applicable to multilayer device configurations, the computational model was applied to a bilayer configuration, which has been used in numerous cell culture applications including vascular models. Guidelines were established that allow cells to be subjected to a wide range of physiological shear stress while ensuring optimal rapid transport of analyte to the biosensor surface and minimized biosensor response times. These guidelines therefore enable the development of microfluidic vascular models that integrate cell-secreted factor detection while addressing flow constraints imposed by physiological shear stress. Ultimately, this work will result in the addition of valuable functionality to microfluidic cell culture models that further fulfill their potential as labs-on-chips.

Imaging label-free biosensor with microfluidic system

NASA Astrophysics Data System (ADS)

Jahns, S.; Glorius, P.; Hansen, M.; Nazirizadeh, Y.; Gerken, M.

2015-06-01

We present a microfluidic system suitable for parallel label-free detection of several biomarkers utilizing a compact imaging measurement system. The microfluidic system contains a filter unit to separate the plasma from human blood and a functionalized, photonic crystal slab sensor chip. The nanostructure of the photonic crystal slab sensor chip is fabricated by nanoimprint lithography of a period grating surface into a photoresist and subsequent deposition of a TiO2 layer. Photonic crystal slabs are slab waveguides supporting quasi-guided modes coupling to far-field radiation, which are sensitive to refractive index changes due to biomarker binding on the functionalized surface. In our imaging read-out system the resulting resonance shift of the quasi-guided mode in the transmission spectrum is converted into an intensity change detectable with a simple camera. By continuously taking photographs of the sensor surface local intensity changes are observed revealing the binding kinetics of the biomarker to its specific target. Data from two distinct measurement fields are used for evaluation. For testing the sensor chip, 1 μM biotin as well as 1 μM recombinant human CD40 ligand were immobilized in spotsvia amin coupling to the sensor surface. Each binding experiment was performed with 250 nM streptavidin and 90 nM CD40 ligand antibody dissolved in phosphate buffered saline. In the next test series, a functionalized sensor chip was bonded onto a 15 mm x 15 mm opening of the 75 mm x 25 mm x 2 mm microfluidic system. We demonstrate the functionality of the microfluidic system for filtering human blood such that only blood plasma was transported to the sensor chip. The results of first binding experiments in buffer with this test chip will be presented.

Oriented antibody immobilization on self-assembled monolayers applied as impedance biosensors

NASA Astrophysics Data System (ADS)

Tsugimura, Kaiki; Ohnuki, Hitoshi; Wu, Haiyun; Endo, Hideaki; Tsuya, Daiju; Izumi, Mitsuru

2017-11-01

Oriented immobilization of antibodies on a sensor chip is crucial for enhancing both the sensitivity and antigen-binding capacity of immunosensors. Here, we report a comparative study of the effect of oriented and random antibody immobilization on the binding efficiency by electrochemical impedance spectroscopy (EIS). Oriented immobilization of anti-myoglobin immunoglobulin G (anti-Myo IgG) was achieved by bonding to an Fc receptor of protein G (PrG) on a self-assembled monolayer (SAM), which results in the myoglobin (Myo) binding sites being exposed outside the sensing surface. Random immobilization of anti-Myo IgG was achieved by direct covalent attachment to the SAM surface. Both immobilizations were applied to interdigitated electrodes to enhance the electrochemical signal, and the Myo biosensor performance was then evaluated by a series of EIS measurements. We found that (i) the rate of the normalized charge transfer resistance for the oriented sample was 3 times higher than that for the random sample and (ii) the detection limit was 0.001 ng/mL, which is the lowest recorded detection limit among Myo immunosensors based on EIS. These findings indicate that oriented antibody immobilization is crucial for preparing highly sensitive EIS-based biosensors.

Selective functionalisation of PDMS-based photonic lab on a chip for biosensing.

PubMed

Ibarlucea, Bergoi; Fernández-Sánchez, César; Demming, Stefanie; Büttgenbach, Stephanus; Llobera, Andreu

2011-09-07

A comparative study of different approaches for the selective immobilisation of biomolecules on the surface of poly(dimethylsiloxane) (PDMS) is reported. The motivation of this work is to set a robust and reliable protocol for the easy implementation of a biosensor device in a PDMS-based photonic lab-on-a-chip (PhLoC). A hollow prism configuration, previously reported for the colorimetric detection of analytes was chosen for this study. Here, the inner walls of the hollow prism were initially modified by direct adsorption of either polyethylene glycol (PEG) or polyvinyl alcohol (PVA) linear polymers as well as by carrying out a light chemical oxidation step. All these processes introduced hydroxyl groups on the PDMS surface to a different extent. The hydroxyl groups were further silanised using a silane containing an aldehyde end-group. The interaction between this group and a primary amine moiety enabled the selective covalent attachment of a biomolecule on the PDMS surface. A thorough structural characterisation of the resulting modified-PDMS substrates was carried out by contact angle measurements, X-ray photoelectron spectroscopic (XPS) analysis and atomic force microscopy (AFM) imaging. Using horseradish peroxidase as a model recognition element, different biosensor approaches based on each modification process were developed for the detection of hydrogen peroxide target analyte in a concentration range from 0.1 µM to 100 µM. The analytical performance was similar in all cases, a linear concentration range between 0.1 µM and 24.2 µM, a sensitivity of 0.02 a.u. µM(-1) and a limit of detection around 0.1 µM were achieved. However, important differences were observed in the reproducibility of the devices as well as in their operational stability, which was studied over a period of up to two months. Considering all these studies, the PVA-modified approach appeared to be the most suitable one for the simple fabrication of a biosensor device integrated in a PDMS PhLoC.

Lab-on-fiber technology: a new vision for chemical and biological sensing.

PubMed

Ricciardi, Armando; Crescitelli, Alessio; Vaiano, Patrizio; Quero, Giuseppe; Consales, Marco; Pisco, Marco; Esposito, Emanuela; Cusano, Andrea

2015-12-21

The integration of microfluidics and photonic biosensors has allowed achievement of several laboratory functions in a single chip, leading to the development of photonic lab-on-a-chip technology. Although a lot of progress has been made to implement such sensors in small and easy-to-use systems, many applications such as point-of-care diagnostics and in vivo biosensing still require a sensor probe able to perform measurements at precise locations that are often hard to reach. The intrinsic property of optical fibers to conduct light to a remote location makes them an ideal platform to meet this demand. The motivation to combine the good performance of photonic biosensors on chips with the unique advantages of optical fibers has thus led to the development of the so-called lab-on-fiber technology. This emerging technology envisages the integration of functionalized materials on micro- and nano-scales (i.e. the labs) with optical fibers to realize miniaturized and advanced all-in-fiber probes, especially useful for (but not limited to) label-free chemical and biological applications. This review presents a broad overview of lab-on-fiber biosensors, with particular reference to lab-on-tip platforms, where the labs are integrated on the optical fiber facet. Light-matter interaction on the fiber tip is achieved through the integration of thin layers of nanoparticles or nanostructures supporting resonant modes, both plasmonic and photonic, highly sensitive to local modifications of the surrounding environment. According to the physical principle that is exploited, different configurations - such as localized plasmon resonance probes, surface enhanced Raman scattering probes and photonic probes - are classified, while various applications are presented in context throughout. For each device, the surface chemistry and the related functionalization protocols are reviewed. Moreover, the implementation strategies and fabrication processes, either based on bottom-up or top-down approaches, are discussed. In conclusion we highlight some of the further development opportunities, including lab-in-a-needle technology, which could have a direct and disruptive impact in localized cancer treatment applications.

System-on-Chip Considerations for Heterogeneous Integration of CMOS and Fluidic Bio-Interfaces.

PubMed

Datta-Chaudhuri, Timir; Smela, Elisabeth; Abshire, Pamela A

2016-12-01

CMOS chips are increasingly used for direct sensing and interfacing with fluidic and biological systems. While many biosensing systems have successfully combined CMOS chips for readout and signal processing with passive sensing arrays, systems that co-locate sensing with active circuits on a single chip offer significant advantages in size and performance but increase the complexity of multi-domain design and heterogeneous integration. This emerging class of lab-on-CMOS systems also poses distinct and vexing technical challenges that arise from the disparate requirements of biosensors and integrated circuits (ICs). Modeling these systems must address not only circuit design, but also the behavior of biological components on the surface of the IC and any physical structures. Existing tools do not support the cross-domain simulation of heterogeneous lab-on-CMOS systems, so we recommend a two-step modeling approach: using circuit simulation to inform physics-based simulation, and vice versa. We review the primary lab-on-CMOS implementation challenges and discuss practical approaches to overcome them. Issues include new versions of classical challenges in system-on-chip integration, such as thermal effects, floor-planning, and signal coupling, as well as new challenges that are specifically attributable to biological and fluidic domains, such as electrochemical effects, non-standard packaging, surface treatments, sterilization, microfabrication of surface structures, and microfluidic integration. We describe these concerns as they arise in lab-on-CMOS systems and discuss solutions that have been experimentally demonstrated.

On-chip surface-enhanced Raman spectroscopy (SERS)-linked immuno-sensor assay (SLISA) for rapid environmental-surveillance of chemical toxins

NASA Astrophysics Data System (ADS)

Bhardwaj, Vinay; Srinivasan, Supriya; McGoron, Anthony J.

2005-05-01

The increasing threat of an intentional (attack) or accidental release of toxins, in particular chemical toxins, including chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) has increased public fear. The major problem in such attacks/accidents is to detect toxins present in very low levels. Indeed, several detection techniques are currently being used for the same. However, none of them meet the most critical requirements of a RISE (Rapid, Inexpensive, Simple and Effective) detect-to-protect class of biosensors. To address this critical demand our group has developed a prototype lab-on-a-chip (LOC) using a colloidal silver-based, surface-enhanced Raman spectroscopy (SERS)-linked immuno-sensor assay (SLISA). The LOC-SLISA was tested for the measurement of RAD54, a stress-marker protein expressed by yeast in response to hydrogen peroxide (H2O2), a toxin in the EPA priority list of chemical toxins. We found SLISA has good correlation in accuracy with the traditional ELISA technique and outperforms the latter by being rapid and easy-to-use. SLISA is more sensitive, provides qualitative information on immuno-sensor's chemical characterization and antigen-antibody binding, and allows direct detection with minimal or no chance of uncertainty, which is a stringent limitation of all label-based biosensor technologies including ELISA. For translational significance of our work, we correlated our results to U.S. EPA (environmental protection agency) defined risk exposure guideline levels of H2O2 to validate the commercial potential of our on-chip SLISA. The label-free, cell-based and RISE detection offered by SERS can allow development of biomedical and environmental sensor technology (BEST) needed for direct, rapid and continuous monitoring of human health and environment

A Highly Responsive Silicon Nanowire/Amplifier MOSFET Hybrid Biosensor

DTIC Science & Technology

2015-07-21

biosensor. The insets show a magnified view of the SiNW channel region (W = 55 nm). ( c ) Photograph of the biosensor chip fabricated via a top-down method...of the SiNW FET is 147 mV/decade. (b) VT and ( c ) ISINW at different pH levels; these values were extracted from Fig. 2a. VT was extracted using the...function of pH level in the hybrid biosensor. The extracted current change is 5.5 × 105 (=5.74 decade per pH). ( c ) Transient response of IMOSFET while

Nanostructure-enhanced surface plasmon resonance imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Špašková, Barbora; Lynn, Nicholas S.; Slabý, Jiří Bocková, Markéta; Homola, Jiří

2017-06-01

There remains a need for the multiplexed detection of biomolecules at extremely low concentrations in fields of medical diagnostics, food safety, and security. Surface plasmon resonance imaging is an established biosensing approach in which the measurement of the intensity of light across a sensor chip is correlated with the amount of target biomolecules captured by the respective areas on the chip. In this work, we present a new approach for this method allowing for enhanced bioanalytical performance via the introduction of nanostructured sensing chip and polarization contrast measurement, which enable the exploitation of both amplitude and phase properties of plasmonic resonances on the nanostructures. Here we will discuss a complex theoretical analysis of the sensor performance, whereby we investigate aspects related to both the optical performance as well as the transport of the analyte molecules to the functionalized surfaces. This analysis accounts for the geometrical parameters of the nanostructured sensing surface, the properties of functional coatings, and parameters related to the detection assay. Based on the results of the theoretical analysis, we fabricated sensing chips comprised of arrays of gold nanoparticles (by electron-beam lithography), which were modified by a biofunctional coating to allow for the selective capturing of the target biomolecules in the regions with high sensitivity. In addition, we developed a compact optical reader with an integrated microfluidic cell, allowing for the measurement from 50 independent sensing channels. The performance of this biosensor is demonstrated through the sensitive detection of short oligonucleotides down to the low picomolar level.

Tapered Optical Fiber Sensor for Label-Free Detection of Biomolecules

PubMed Central

Tian, Ye; Wang, Wenhui; Wu, Nan; Zou, Xiaotian; Wang, Xingwei

2011-01-01

This paper presents a fast, highly sensitive and low-cost tapered optical fiber biosensor that enables the label-free detection of biomolecules. The sensor takes advantage of the interference effect between the fiber’s first two propagation modes along the taper waist region. The biomolecules bonded on the taper surface were determined by demodulating the transmission spectrum phase shift. Because of the sharp spectrum fringe signals, as well as a relatively long biomolecule testing region, the sensor displayed a fast response and was highly sensitive. To better understand the influence of various biomolecules on the sensor, a numerical simulation that varied biolayer parameters such as thickness and refractive index was performed. The results showed that the spectrum fringe shift was obvious to be measured even when the biolayer was only nanometers thick. A microchannel chip was designed and fabricated for the protection of the sensor and biotesting. Microelectromechanical systems (MEMS) fabrication techniques were used to precisely control the profile and depth of the microchannel on the silicon chip with an accuracy of 2 μm. A tapered optical fiber biosensor was fabricated and evaluated with an Immune globulin G (IgG) antibody-antigen pair. PMID:22163821

Tapered optical fiber sensor for label-free detection of biomolecules.

PubMed

Tian, Ye; Wang, Wenhui; Wu, Nan; Zou, Xiaotian; Wang, Xingwei

2011-01-01

This paper presents a fast, highly sensitive and low-cost tapered optical fiber biosensor that enables the label-free detection of biomolecules. The sensor takes advantage of the interference effect between the fiber's first two propagation modes along the taper waist region. The biomolecules bonded on the taper surface were determined by demodulating the transmission spectrum phase shift. Because of the sharp spectrum fringe signals, as well as a relatively long biomolecule testing region, the sensor displayed a fast response and was highly sensitive. To better understand the influence of various biomolecules on the sensor, a numerical simulation that varied biolayer parameters such as thickness and refractive index was performed. The results showed that the spectrum fringe shift was obvious to be measured even when the biolayer was only nanometers thick. A microchannel chip was designed and fabricated for the protection of the sensor and biotesting. Microelectromechanical systems (MEMS) fabrication techniques were used to precisely control the profile and depth of the microchannel on the silicon chip with an accuracy of 2 μm. A tapered optical fiber biosensor was fabricated and evaluated with an Immune globulin G (IgG) antibody-antigen pair.

Design and process development of a photonic crystal polymer biosensor for point-of-care diagnostics

NASA Astrophysics Data System (ADS)

Dortu, F.; Egger, H.; Kolari, K.; Haatainen, T.; Furjes, P.; Fekete, Z.; Bernier, D.; Sharp, G.; Lahiri, B.; Kurunczi, S.; Sanchez, J.-C.; Turck, N.; Petrik, P.; Patko, D.; Horvath, R.; Eiden, S.; Aalto, T.; Watts, S.; Johnson, N. P.; De La Rue, R. M.; Giannone, D.

2011-07-01

In this work, we report advances in the fabrication and anticipated performance of a polymer biosensor photonic chip developed in the European Union project P3SENS (FP7-ICT4-248304). Due to the low cost requirements of point-ofcare applications, the photonic chip is fabricated from nanocomposite polymeric materials, using highly scalable nanoimprint- lithography (NIL). A suitable microfluidic structure transporting the analyte solutions to the sensor area is also fabricated in polymer and adequately bonded to the photonic chip. We first discuss the design and the simulated performance of a high-Q resonant cavity photonic crystal sensor made of a high refractive index polyimide core waveguide on a low index polymer cladding. We then report the advances in doped and undoped polymer thin film processing and characterization for fabricating the photonic sensor chip. Finally the development of the microfluidic chip is presented in details, including the characterisation of the fluidic behaviour, the technological and material aspects of the 3D polymer structuring and the stable adhesion strategies for bonding the fluidic and the photonic chips, with regards to the constraints imposed by the bioreceptors supposedly already present on the sensors.

Fast and simultaneous monitoring of organic pollutants in a drinking water treatment plant by a multi-analyte biosensor followed by LC-MS validation.

PubMed

Rodriguez-Mozaz, Sara; de Alda, Maria J López; Barceló, Damià

2006-04-15

This work describes the application of an optical biosensor (RIver ANALyser, RIANA) to the simultaneous analysis of three relevant environmental organic pollutants, namely, the pesticides atrazine and isoproturon and the estrogen estrone, in real water samples. This biosensor is based on an indirect inhibition immunoassay which takes place at a chemically modified optical transducer chip. The spatially resolved modification of the transducer surface allows the simultaneous determination of selected target analytes by means of "total internal reflection fluorescence" (TIRF). The performance of the immunosensor method developed was evaluated against a well accepted traditional method based on solid-phase extraction followed by liquid chromatography-mass spectrometry (LC-MS). The chromatographic method was superior in terms of linearity, sensitivity and accuracy, and the biosensor method in terms of repeatability, speed, cost and automation. The application of both methods in parallel to determine the occurrence and removal of atrazine, isoproturon and estrone throughout the treatment process (sand filtration, ozonation, activated carbon filtration and chlorination) in a waterworks showed an overestimation of results in the case of the biosensor, which was partially attributed to matrix and cross-reactivity effects, in spite of the addition of ovalbumin to the sample to minimize matrix interferences. Based on the comparative performance of both techniques, the biosensor emerges as a suitable tool for fast, simple and automated screening of water pollutants without sample pretreatment. To the author's knowledge, this is the first description of the application of the biosensor RIANA in the multi-analyte configuration to the regular monitoring of pollutants in a waterworks.

A hard-soft microfluidic-based biosensor flow cell for SPR imaging application.

PubMed

Liu, Changchun; Cui, Dafu; Li, Hui

2010-09-15

An ideal microfluidic-based biosensor flow cell should have not only a "soft" interface for high strength sealing with biosensing chips, but also "hard" macro-to-micro interface for tubing connection. Since these properties are exclusive of each other, no one material can provide the advantages of both. In this paper, we explore the application of a SiO(2) thin film, deposited by plasma-enhanced chemical vapor deposition (PECVD) technology, as an intermediate layer for irreversibly adhering polydimethylsiloxane (PDMS) to plastic substrate, and develop a hard-soft, compact, robust microfluidic-based biosensor flow cell for the multi-array immunoassay application of surface plasmon resonance (SPR) imaging. This hard-soft biosensor flow cell consists of one rigid, computer numerically controlled (CNC)-machined poly(methyl methacrylate) (PMMA) base coated with a 200 nm thick SiO(2) thin film, and one soft PDMS microfluidic layer. This novel microfluidic-based biosensor flow cell does not only keep the original advantage of conventional PDMS-based biosensor flow cell such as the intrinsically soft interface, easy-to-fabrication, and low cost, but also has a rigid, robust, easy-to-use interface to tubing connection and can be operated up to 185 kPa in aqueous environments without failure. Its application was successfully demonstrated with two types of experiments by coupling with SPR imaging biosensor: the real-time monitoring of the immunoglobulin G (IgG) interaction, as well as the detection of sulfamethoxazole (SMOZ) and sulfamethazine (SMZ) with the sensitivity of 3.5 and 0.6 ng/mL, respectively. This novel hard-soft microfluidic device is also useful for a variety of other biosensor flow cells. Copyright 2010 Elsevier B.V. All rights reserved.

Last Advances in Silicon-Based Optical Biosensors.

PubMed

Fernández Gavela, Adrián; Grajales García, Daniel; Ramirez, Jhonattan C; Lechuga, Laura M

2016-02-24

We review the most important achievements published in the last five years in the field of silicon-based optical biosensors. We focus specially on label-free optical biosensors and their implementation into lab-on-a-chip platforms, with an emphasis on developments demonstrating the capability of the devices for real bioanalytical applications. We report on novel transducers and materials, improvements of existing transducers, new and improved biofunctionalization procedures as well as the prospects for near future commercialization of these technologies.

Fabrication Localized Surface Plasmon Resonance sensor chip of gold nanoparticles and detection lipase-osmolytes interaction

NASA Astrophysics Data System (ADS)

Ghodselahi, T.; Hoornam, S.; Vesaghi, M. A.; Ranjbar, B.; Azizi, A.; Mobasheri, H.

2014-09-01

Co-deposition of RF-sputtering and RF-PECVD from acetylene gas and Au target were used to prepare sensor chip of gold nanoparticles (Au NPs). Deposition conditions were optimized to reach a Localized Surface Plasmon Resonance (LSPR) sensor chip of Au NPs with particle size less than 10 nm. The RF power was set at 180 W and the initial gas pressure was set at 0.035 mbar. Transmission Electron Microscopy (TEM) images and Atomic Force Microscopy (AFM) data were used to investigate particles size and surface morphology of LSPR sensor chip. The Au and C content of the LSPR sensor chip of Au NPs was obtained from X-ray photoelectron spectroscopy (XPS). The hydrogenated amorphous carbon (a-C:H) thin film was used as intermediate material to immobilize Au NPs on the SiO2 substrate. The interaction between two types of osmolytes, i.e. sorbitol and trehalose, with Pseudomonas cepacia lipase (PCL) were detected by the prepared LSPR biosensor chip. The detection mechanism is based on LSPR spectroscopy in which the wavelength of absorption peak is sensitive to the refractive index of the environment of the Au NPs. This mechanism eliminates the use of a probe or immobilization of PCL on the Au NPs of LSPR sensor chip. The interaction between PCL and osmolytes can change refractive index of the mixture or solution. We found that unlike to trehalose, sorbitol interacts with the PCL. This interaction increases refractive index of the PCL and sorbitol mixture. Refractive index of PCL in the presence of different concentration of sorbitol was obtained by Mie theory modeling of LSPR peaks. This modeling stated that the present LSPR sensor chip has sensitivity as high as wavelength shift of 175 nm per refractive index. Moreover, the detection of such weakly interaction between bio-molecules cannot be achieved by other analysis.

Towards a subcutaneous optical biosensor based on thermally hydrocarbonised porous silicon.

PubMed

Tong, Wing Yin; Sweetman, Martin J; Marzouk, Ezzat R; Fraser, Cara; Kuchel, Tim; Voelcker, Nicolas H

2016-01-01

Advanced biosensors in future medicine hinge on the evolvement of biomaterials. Porous silicon (pSi), a generally biodegradable and biocompatible material that can be fabricated to include environment-responsive optical characteristics, is an excellent candidate for in vivo biosensors. However, the feasibility of using this material as a subcutaneously implanted optical biosensor has never been demonstrated. Here, we investigated the stability and biocompatibility of a thermally-hydrocarbonised (THC) pSi optical rugate filter, and demonstrated its optical functionality in vitro and in vivo. We first compared pSi films with different surface chemistries and observed that the material was cytotoxic despite the outstanding stability of the THC pSi films. We then showed that the cytotoxicity correlates with reactive oxygen species levels, which could be mitigated by pre-incubation of THC pSi (PITHC pSi). PITHC pSi facilitates normal cellular phenotypes and is biocompatible in vivo. Importantly, the material also possesses optical properties capable of responding to microenvironmental changes that are readable non-invasively in cell culture and subcutaneous settings. Collectively, we demonstrate, for the first time, that PITHC pSi rugate filters are both biocompatible and optically functional for lab-on-a-chip and subcutaneous biosensing scenarios. We believe that this study will deepen our understanding of cell-pSi interactions and foster the development of implantable biosensors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetically engineered microbial biosensors for in situ monitoring of environmental pollution.

PubMed

Shin, Hae Ja

2011-02-01

Microbial biosensors are compact, portable, cost effective, and simple to use, making them seem eminently suitable for the in situ monitoring of environmental pollution. One promising approach for such applications is the fusion of reporter genes with regulatory genes that are dose-dependently responsive to the target chemicals or physiological signals. Their biosensor capabilities, such as target range and sensitivity, could be improved by modification of regulatory genes. Recent uses of such genetically engineered microbial biosensors include the development of portable biosensor kits and high-throughput cell arrays on chips, optic fibers, or other platforms for on-site and on-line monitoring of environmental pollution. This mini-review discusses recent advances in microbial biosensors and their future prospects, with a focus on the development and application of genetically modified microbial biosensors for in situ environmental monitoring.

A Conductometric Indium Oxide Semiconducting Nanoparticle Enzymatic Biosensor Array

PubMed Central

Lee, Dongjin; Ondrake, Janet; Cui, Tianhong

2011-01-01

We report a conductometric nanoparticle biosensor array to address the significant variation of electrical property in nanomaterial biosensors due to the random network nature of nanoparticle thin-film. Indium oxide and silica nanoparticles (SNP) are assembled selectively on the multi-site channel area of the resistors using layer-by-layer self-assembly. To demonstrate enzymatic biosensing capability, glucose oxidase is immobilized on the SNP layer for glucose detection. The packaged sensor chip onto a ceramic pin grid array is tested using syringe pump driven feed and multi-channel I–V measurement system. It is successfully demonstrated that glucose is detected in many different sensing sites within a chip, leading to concentration dependent currents. The sensitivity has been found to be dependent on the channel length of the resistor, 4–12 nA/mM for channel lengths of 5–20 μm, while the apparent Michaelis-Menten constant is 20 mM. By using sensor array, analytical data could be obtained with a single step of sample solution feeding. This work sheds light on the applicability of the developed nanoparticle microsensor array to multi-analyte sensors, novel bioassay platforms, and sensing components in a lab-on-a-chip. PMID:22163696

Chemical Functionalization of Plasmonic Surface Biosensors: A Tutorial Review on Issues, Strategies, and Costs

PubMed Central

2017-01-01

In an ideal plasmonic surface sensor, the bioactive area, where analytes are recognized by specific biomolecules, is surrounded by an area that is generally composed of a different material. The latter, often the surface of the supporting chip, is generally hard to be selectively functionalized, with respect to the active area. As a result, cross talks between the active area and the surrounding one may occur. In designing a plasmonic sensor, various issues must be addressed: the specificity of analyte recognition, the orientation of the immobilized biomolecule that acts as the analyte receptor, and the selectivity of surface coverage. The objective of this tutorial review is to introduce the main rational tools required for a correct and complete approach to chemically functionalize plasmonic surface biosensors. After a short introduction, the review discusses, in detail, the most common strategies for achieving effective surface functionalization. The most important issues, such as the orientation of active molecules and spatial and chemical selectivity, are considered. A list of well-defined protocols is suggested for the most common practical situations. Importantly, for the reported protocols, we also present direct comparisons in term of costs, labor demand, and risk vs benefit balance. In addition, a survey of the most used characterization techniques necessary to validate the chemical protocols is reported. PMID:28796479

Label‐Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes

PubMed Central

Kilic, Tugba; Zhang, Yu Shrike; Avci, Huseyin; Hu, Ning; Kim, Duckjin; Branco, Cristina; Aleman, Julio; Massa, Solange; Silvestri, Antonia; Kang, Jian; Desalvo, Anna; Hussaini, Mohammed Abdullah; Chae, Su‐Kyoung; Polini, Alessandro; Bhise, Nupura; Hussain, Mohammad Asif; Lee, HeaYeon

2017-01-01

Development of an efficient sensing platform capable of continual monitoring of biomarkers is needed to assess the functionality of the in vitro organoids and to evaluate their biological responses toward pharmaceutical compounds or chemical species over extended periods of time. Here, a novel label‐free microfluidic electrochemical (EC) biosensor with a unique built‐in on‐chip regeneration capability for continual measurement of cell‐secreted soluble biomarkers from an organoid culture in a fully automated manner without attenuating the sensor sensitivity is reported. The microfluidic EC biosensors are integrated with a human liver‐on‐a‐chip platform for continual monitoring of the metabolic activity of the organoids by measuring the levels of secreted biomarkers for up to 7 d, where the metabolic activity of the organoids is altered by a systemically applied drug. The variations in the biomarker levels are successfully measured by the microfluidic regenerative EC biosensors and agree well with cellular viability and enzyme‐linked immunosorbent assay analyses, validating the accuracy of the unique sensing platform. It is believed that this versatile and robust microfluidic EC biosensor that is capable of automated and continual detection of soluble biomarkers will find widespread use for long‐term monitoring of human organoids during drug toxicity studies or efficacy assessments of in vitro platforms. PMID:28546915

An automated optofluidic biosensor platform combining interferometric sensors and injection moulded microfluidics.

PubMed

Szydzik, C; Gavela, A F; Herranz, S; Roccisano, J; Knoerzer, M; Thurgood, P; Khoshmanesh, K; Mitchell, A; Lechuga, L M

2017-08-08

A primary limitation preventing practical implementation of photonic biosensors within point-of-care platforms is their integration with fluidic automation subsystems. For most diagnostic applications, photonic biosensors require complex fluid handling protocols; this is especially prominent in the case of competitive immunoassays, commonly used for detection of low-concentration, low-molecular weight biomarkers. For this reason, complex automated microfluidic systems are needed to realise the full point-of-care potential of photonic biosensors. To fulfil this requirement, we propose an on-chip valve-based microfluidic automation module, capable of automating such complex fluid handling. This module is realised through application of a PDMS injection moulding fabrication technique, recently described in our previous work, which enables practical fabrication of normally closed pneumatically actuated elastomeric valves. In this work, these valves are configured to achieve multiplexed reagent addressing for an on-chip diaphragm pump, providing the sample and reagent processing capabilities required for automation of cyclic competitive immunoassays. Application of this technique simplifies fabrication and introduces the potential for mass production, bringing point-of-care integration of complex automated microfluidics into the realm of practicality. This module is integrated with a highly sensitive, label-free bimodal waveguide photonic biosensor, and is demonstrated in the context of a proof-of-concept biosensing assay, detecting the low-molecular weight antibiotic tetracycline.

Direct biosensor detection of botulinum neurotoxin endopeptidase activity in sera from patients with type A botulism.

PubMed

Lévêque, Christian; Ferracci, Géraldine; Maulet, Yves; Mazuet, Christelle; Popoff, Michel; Seagar, Michael; El Far, Oussama

2014-07-15

Botulinum neurotoxin A (BoNT/A) has intrinsic endoprotease activity specific for SNAP-25, a key protein for presynaptic neurotransmitter release. The inactivation of SNAP-25 by BoNT/A underlies botulism, a rare but potentially fatal disease. There is a crucial need for a rapid and sensitive in vitro serological test for BoNT/A to replace the current in vivo mouse bioassay. Cleavage of SNAP-25 by BoNT/A generates neo-epitopes which can be detected by binding of a monoclonal antibody (mAb10F12) and thus measured by surface plasmon resonance (SPR). We have explored two SPR assay formats, with either mAb10F12 or His6-SNAP-25 coupled to the biosensor chip. When BoNT/A was incubated with SNAP-25 in solution and the reaction products were captured on a mAb-coated chip, a sensitivity of 5 fM (0.1LD50/ml serum) was obtained. However, this configuration required prior immunoprecipitation of BoNT/A. A sensitivity of 0.5 fM in 10% serum (0.1 LD50/ml serum) was attained when SNAP-25 was coupled directly to the chip, followed by sequential injection of BoNT/A samples and mAb10F12 into the flow system to achieve on-chip cleavage and detection, respectively. This latter format detected BoNT/A endoprotease activity in 50-100 µl serum samples from all patients (11/11) with type A botulism within 5h. No false positives occurred in sera from healthy subjects or patients with other neurological diseases. The automated chip-based procedure has excellent specificity and sensitivity, with significant advantages over the mouse bioassay in terms of rapidity, required sample volume and animal ethics. Copyright © 2014 Elsevier B.V. All rights reserved.

Last Advances in Silicon-Based Optical Biosensors

PubMed Central

Fernández Gavela, Adrián; Grajales García, Daniel; Ramirez, Jhonattan C.; Lechuga, Laura M.

2016-01-01

We review the most important achievements published in the last five years in the field of silicon-based optical biosensors. We focus specially on label-free optical biosensors and their implementation into lab-on-a-chip platforms, with an emphasis on developments demonstrating the capability of the devices for real bioanalytical applications. We report on novel transducers and materials, improvements of existing transducers, new and improved biofunctionalization procedures as well as the prospects for near future commercialization of these technologies. PMID:26927105

Bloch Surface Waves Biosensors for High Sensitivity Detection of Soluble ERBB2 in a Complex Biological Environment.

PubMed

Sinibaldi, Alberto; Sampaoli, Camilla; Danz, Norbert; Munzert, Peter; Sonntag, Frank; Centola, Fabio; Occhicone, Agostino; Tremante, Elisa; Giacomini, Patrizio; Michelotti, Francesco

2017-08-17

We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of the cancer biomarker ERBB2 in cell lysates. Overexpression of the ERBB2 protein is associated with aggressive breast cancer subtypes. To detect soluble ERBB2, we developed an optical set-up which operates in both label-free and fluorescence modes. The detection approach makes use of a sandwich assay, in which the one-dimensional photonic crystals sustaining Bloch surface waves are modified with monoclonal antibodies, in order to guarantee high specificity during the biological recognition. We present the results of exemplary protein G based label-free assays in complex biological matrices, reaching an estimated limit of detection of 0.5 ng/mL. On-chip and chip-to-chip variability of the results is addressed too, providing repeatability rates. Moreover, results on fluorescence operation demonstrate the capability to perform high sensitive cancer biomarker assays reaching a resolution of 0.6 ng/mL, without protein G assistance. The resolution obtained in both modes meets international guidelines and recommendations (15 ng/mL) for ERBB2 quantification assays, providing an alternative tool to phenotype and diagnose molecular cancer subtypes.

Future of biosensors: a personal view.

PubMed

Scheller, Frieder W; Yarman, Aysu; Bachmann, Till; Hirsch, Thomas; Kubick, Stefan; Renneberg, Reinhard; Schumacher, Soeren; Wollenberger, Ulla; Teller, Carsten; Bier, Frank F

2014-01-01

Biosensors representing the technological counterpart of living senses have found routine application in amperometric enzyme electrodes for decentralized blood glucose measurement, interaction analysis by surface plasmon resonance in drug development, and to some extent DNA chips for expression analysis and enzyme polymorphisms. These technologies have already reached a highly advanced level and need minor improvement at most. The dream of the "100-dollar" personal genome may come true in the next few years provided that the technological hurdles of nanopore technology or of polymerase-based single molecule sequencing can be overcome. Tailor-made recognition elements for biosensors including membrane-bound enzymes and receptors will be prepared by cell-free protein synthesis. As alternatives for biological recognition elements, molecularly imprinted polymers (MIPs) have been created. They have the potential to substitute antibodies in biosensors and biochips for the measurement of low-molecular-weight substances, proteins, viruses, and living cells. They are more stable than proteins and can be produced in large amounts by chemical synthesis. Integration of nanomaterials, especially of graphene, could lead to new miniaturized biosensors with high sensitivity and ultrafast response. In the future individual therapy will include genetic profiling of isoenzymes and polymorphic forms of drug-metabolizing enzymes especially of the cytochrome P450 family. For defining the pharmacokinetics including the clearance of a given genotype enzyme electrodes will be a useful tool. For decentralized online patient control or the integration into everyday "consumables" such as drinking water, foods, hygienic articles, clothing, or for control of air conditioners in buildings and cars and swimming pools, a new generation of "autonomous" biosensors will emerge.

Sensitive detection of capsaicinoids using a surface plasmon resonance sensor with anti-homovanillic Acid polyclonal antibodies.

PubMed

Nakamura, Shingo; Yatabe, Rui; Onodera, Takeshi; Toko, Kiyoshi

2013-11-13

Recently, highly functional biosensors have been developed in preparation for possible large-scale terrorist attacks using chemical warfare agents. Practically applicable sensors are required to have various abilities, such as high portability and operability, the capability of performing rapid and continuous measurement, as well as high sensitivity and selectivity. We developed the detection method of capsaicinoids, the main component of some lachrymators, using a surface plasmon resonance (SPR) immunosensor as an on-site detection sensor. Homovanillic acid, which has a vanillyl group similar to capsaicinoids such as capsaicin and dihydrocapsaicin, was bound to Concholepas concholepas hemocyanin (CCH) for use as an immunogen to generate polyclonal antibodies. An indirect competitive assay was carried out to detect capsaicinoids using SPR sensor chips on which different capsaicin analogues were immobilized. For the sensor chip on which 4-hydroxy-3-methoxybenzylamine hydrochloride was immobilized, a detection limit of 150 ppb was achieved. We found that the incubation time was not required and the detection can be completed in five minutes.

Simulations and design of microfabricated interdigitated electrodes for use in a gold nanoparticle enhanced biosensor.

PubMed

Hermansen, Peter; MacKay, Scott; Wishart, David; Jie Chen

2016-08-01

Microfabricated interdigitated electrode chips have been designed for use in a unique gold-nanoparticle based biosensor system. The use of these electrodes will allow for simple, accurate, inexpensive, and portable biosensing, with potential applications in diagnostics, medical research, and environmental testing. To determine the optimal design for these electrodes, finite element analysis simulations were carried out using COMSOL Multiphysics software. The results of these simulations determined some of the optimal design parameters for microfabricating interdigitated electrodes as well as predicting the effects of different electrode materials. Finally, based on the results of these simulations two different kinds of interdigitated electrode chips were made using photolithography.

Near Field Radiation Characteristics of Implantable Square Spiral Chip Inductor Antennas for Bio-Sensors

NASA Technical Reports Server (NTRS)

Nessel, James A.; Simons, Rainee N.; Miranda, Felix A.

2007-01-01

The near field radiation characteristics of implantable Square Spiral Chip Inductor Antennas (SSCIA) for Bio-Sensors have been measured. Our results indicate that the measured near field relative signal strength of these antennas agrees with simulated results and confirm that in the near field region the radiation field is fairly uniform in all directions. The effects of parameters such as ground-plane, number of turns and microstrip-gap width on the performance of the SSCIA are presented. Furthermore, the SSCIA antenna with serrated ground plane produce a broad radiation pattern, with a relative signal strength detectable at distances within the range of operation of hand-held devices for self-diagnosis.

Recovery Based Nanowire Field-Effect Transistor Detection of Pathogenic Avian Influenza DNA

NASA Astrophysics Data System (ADS)

Lin, Chih-Heng; Chu, Chia-Jung; Teng, Kang-Ning; Su, Yi-Jr; Chen, Chii-Dong; Tsai, Li-Chu; Yang, Yuh-Shyong

2012-02-01

Fast and accurate diagnosis is critical in infectious disease surveillance and management. We proposed a DNA recovery system that can easily be adapted to DNA chip or DNA biosensor for fast identification and confirmation of target DNA. This method was based on the re-hybridization of DNA target with a recovery DNA to free the DNA probe. Functionalized silicon nanowire field-effect transistor (SiNW FET) was demonstrated to monitor such specific DNA-DNA interaction using high pathogenic strain virus hemagglutinin 1 (H1) DNA of avian influenza (AI) as target. Specific electric changes were observed in real-time for AI virus DNA sensing and device recovery when nanowire surface of SiNW FET was modified with complementary captured DNA probe. The recovery based SiNW FET biosensor can be further developed for fast identification and further confirmation of a variety of influenza virus strains and other infectious diseases.

Determining the folding and unfolding rate constants of nucleic acids by biosensor. Application to telomere G-quadruplex.

PubMed

Zhao, Yong; Kan, Zhong-yuan; Zeng, Zhi-xiong; Hao, Yu-hua; Chen, Hua; Tan, Zheng

2004-10-20

Nucleic acid molecules may fold into secondary structures, and the formation of such structures is involved in many biological processes and technical applications. The folding and unfolding rate constants define the kinetics of conformation interconversion and the stability of these structures and is important in realizing their functions. We developed a method to determine these kinetic parameters using an optical biosensor based on surface plasmon resonance. The folding and unfolding of a nucleic acid is coupled with a hybridization reaction by immobilization of the target nucleic acid on a sensor chip surface and injection of a complementary probe nucleic acid over the sensor chip surface. By monitoring the time course of duplex formation, both the folding and unfolding rate constants for the target nucleic acid and the association and dissociation rate constants for the target-probe duplex can all be derived from the same measurement. We applied this method to determine the folding and unfolding rate constants of the G-quadruplex of human telomere sequence (TTAGGG)(4) and its association and dissociation rate constants with the complementary strand (CCCTAA)(4). The results show that both the folding and unfolding occur on the time scale of minutes at physiological concentration of K(+). We speculate that this property might be important for telomere elongation. A complete set of the kinetic parameters for both of the structures allows us to study the competition between the formation of the quadruplex and the duplex. Calculations indicate that the formation of both the quadruplex and the duplex is strand concentration-dependent, and the quadruplex can be efficiently formed at low strand concentration. This property may provide the basis for the formation of the quadruplex in vivo in the presence of a complementary strand.

Optical biosensor technologies for molecular diagnostics at the point-of-care

NASA Astrophysics Data System (ADS)

Schotter, Joerg; Schrittwieser, Stefan; Muellner, Paul; Melnik, Eva; Hainberger, Rainer; Koppitsch, Guenther; Schrank, Franz; Soulantika, Katerina; Lentijo-Mozo, Sergio; Pelaz, Beatriz; Parak, Wolfgang; Ludwig, Frank; Dieckhoff, Jan

2015-05-01

Label-free optical schemes for molecular biosensing hold a strong promise for point-of-care applications in medical research and diagnostics. Apart from diagnostic requirements in terms of sensitivity, specificity, and multiplexing capability, also other aspects such as ease of use and manufacturability have to be considered in order to pave the way to a practical implementation. We present integrated optical waveguide as well as magnetic nanoparticle based molecular biosensor concepts that address these aspects. The integrated optical waveguide devices are based on low-loss photonic wires made of silicon nitride deposited by a CMOS compatible plasma-enhanced chemical vapor deposition (PECVD) process that allows for backend integration of waveguides on optoelectronic CMOS chips. The molecular detection principle relies on evanescent wave sensing in the 0.85 μm wavelength regime by means of Mach-Zehnder interferometers, which enables on-chip integration of silicon photodiodes and, thus, the realization of system-on-chip solutions. Our nanoparticle-based approach is based on optical observation of the dynamic response of functionalized magneticcore/ noble-metal-shell nanorods (`nanoprobes') to an externally applied time-varying magnetic field. As target molecules specifically bind to the surface of the nanoprobes, the observed dynamics of the nanoprobes changes, and the concentration of target molecules in the sample solution can be quantified. This approach is suitable for dynamic real-time measurements and only requires minimal sample preparation, thus presenting a highly promising point-of-care diagnostic system. In this paper, we present a prototype of a diagnostic device suitable for highly automated sample analysis by our nanoparticle-based approach.

UV-SPR biosensor for biomolecular interaction studies

NASA Astrophysics Data System (ADS)

Geiss, F. A.; Fossati, S.; Khan, I.; Gisbert Quilis, N.; Knoll, W.; Dostalek, J.

2017-05-01

UV surface plasmon resonance (SPR) for direct in situ detection of protein binding events is reported. A crossed relief aluminum grating was employed for diffraction coupling to surface plasmons as an alternative to more commonly used attenuated total reflection method. Wavelength interrogation of SPR was carried out by using transmission measurements in order to probe odorant-binding protein 14 (OBP14) of the honey bee (Apis mellifera). The native oxide layer on the top of an aluminum grating sensor chip allows for covalent coupling of protein molecules by using regular silane-based linkers. The probing of bound OBP14 protein at UV with confined field of surface plasmons holds potential for further studies of interaction with recently developed artificial fluorescent odorants.

Identification and Affinity-Quantification of ß-Amyloid and α-Synuclein Polypeptides Using On-Line SAW-Biosensor-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Slamnoiu, Stefan; Vlad, Camelia; Stumbaum, Mihaela; Moise, Adrian; Lindner, Kathrin; Engel, Nicole; Vilanova, Mar; Diaz, Mireia; Karreman, Christiaan; Leist, Marcel; Ciossek, Thomas; Hengerer, Bastian; Vilaseca, Marta; Przybylski, Michael

2014-08-01

Bioaffinity analysis using a variety of biosensors has become an established tool for detection and quantification of biomolecular interactions. Biosensors, however, are generally limited by the lack of chemical structure information of affinity-bound ligands. On-line bioaffinity-mass spectrometry using a surface-acoustic wave biosensor (SAW-MS) is a new combination providing the simultaneous affinity detection, quantification, and mass spectrometric structural characterization of ligands. We describe here an on-line SAW-MS combination for direct identification and affinity determination, using a new interface for MS of the affinity-isolated ligand eluate. Key element of the SAW-MS combination is a microfluidic interface that integrates affinity-isolation on a gold chip, in-situ sample concentration, and desalting with a microcolumn for MS of the ligand eluate from the biosensor. Suitable MS- acquisition software has been developed that provides coupling of the SAW-MS interface to a Bruker Daltonics ion trap-MS, FTICR-MS, and Waters Synapt-QTOF- MS systems. Applications are presented for mass spectrometric identifications and affinity (KD) determinations of the neurodegenerative polypeptides, ß-amyloid (Aß), and pathophysiological and physiological synucleins (α- and ß-synucleins), two key polypeptide systems for Alzheimer's disease and Parkinson's disease, respectively. Moreover, first in vivo applications of αSyn polypeptides from brain homogenate show the feasibility of on-line affinity-MS to the direct analysis of biological material. These results demonstrate on-line SAW-bioaffinity-MS as a powerful tool for structural and quantitative analysis of biopolymer interactions.

Flexible plastic, paper and textile lab-on-a chip platforms for electrochemical biosensing.

PubMed

Economou, Anastasios; Kokkinos, Christos; Prodromidis, Mamas

2018-06-26

Flexible biosensors represent an increasingly important and rapidly developing field of research. Flexible materials offer several advantages as supports of biosensing platforms in terms of flexibility, weight, conformability, portability, cost, disposability and scope for integration. On the other hand, electrochemical detection is perfectly suited to flexible biosensing devices. The present paper reviews the field of integrated electrochemical bionsensors fabricated on flexible materials (plastic, paper and textiles) which are used as functional base substrates. The vast majority of electrochemical flexible lab-on-a-chip (LOC) biosensing devices are based on plastic supports in a single or layered configuration. Among these, wearable devices are perhaps the ones that most vividly demonstrate the utility of the concept of flexible biosensors while diagnostic cards represent the state-of-the art in terms of integration and functionality. Another important type of flexible biosensors utilize paper as a functional support material enabling the fabrication of low-cost and disposable paper-based devices operating on the lateral flow, drop-casting or folding (origami) principles. Finally, textile-based biosensors are beginning to emerge enabling real-time measurements in the working environment or in wound care applications. This review is timely due to the significant advances that have taken place over the last few years in the area of LOC biosensors and aims to direct the readers to emerging trends in this field.

Immunodetection of salivary biomarkers by an optical microfluidic biosensor with polyethylenimine-modified polythiophene-C70 organic photodetectors.

PubMed

Dong, Tao; Pires, Nuno Miguel Matos

2017-08-15

This work reports a novel optical microfluidic biosensor with highly sensitive organic photodetectors (OPDs) for absorbance-based detection of salivary protein biomarkers at the point of care. The compact and miniaturized biosensor has comprised OPDs made of polythiophene-C 70 bulk heterojunction for the photoactive layer; whilst a calcium-free cathode interfacial layer, made of linear polyethylenimine, was incorporated to the photodetectors to enhance the low cost. The OPDs realized onto a glass chip were aligned to antibody-functionalized chambers of a poly(methyl methacrylate) microfluidic chip, in where immunogold-silver assays were conducted. The biosensor has detected IL-8, IL-1β and MMP-8 protein in spiked saliva with high detection specificity and short analysis time exhibiting detection limits between 80pgmL -1 and 120pgmL -1 . The result for IL-8 was below the clinical established cut-off of 600pgmL -1 , which revealed the potential of the biosensor to early detection of oral cancer. The detection limit was also comparable to other previously reported immunosensors performed with bulky instrumentation or using inorganic photodetectors. The optical detection sensitivity of the polythiophene-C 70 OPD was enhanced by optimizing the thickness of the photoactive layer and anode interfacial layer prior to the saliva immunoassays. Further, the biosensor was tested with unspiked human saliva samples, and the results of measuring IL-8 and IL-1β were in statistical agreement with those provided by two commercial assays of ELISA. The optical microfluidic biosensor reported hereby offers an attractive and cost-effective tool to diagnostics or screening purposes at the point of care. Copyright © 2017 Elsevier B.V. All rights reserved.

Poly(acrylic acid) brushes pattern as a 3D functional biosensor surface for microchips

NASA Astrophysics Data System (ADS)

Wang, Yan-Mei; Cui, Yi; Cheng, Zhi-Qiang; Song, Lu-Sheng; Wang, Zhi-You; Han, Bao-Hang; Zhu, Jin-Song

2013-02-01

Poly(acrylic acid) (PAA) brushes, a novel three dimensional (3D) precursor layer of biosensor or protein microarrays, possess high protein loading level and low non-specific protein adsorption. In this article, we describe a simple and convenient way to fabricate 3D PAA brushes pattern by microcontact printing (μCP) and characterize it with FT-IR and optical microscopy. The carboxyl groups of PAA brushes can be applied to covalently immobilize protein for immunoassay. Thriving 3D space made by patterning PAA brushes thin film is available to enhance protein immobilization, which is confirmed by measuring model protein interaction between human immunoglobulin G (H-IgG) and goat anti-H-IgG (G-H-IgG) with fluorescence microscopy and surface plasmon resonance imaging (SPRi). As expected, the SPRi signals of H-IgG coating on 3D PAA brushes pattern and further measuring specific binding with G-H-IgG are all larger than that of 3D PAA brushes without pattern and 2D bare gold surface. We further revealed that this surface can be used for high-throughput screening and clinical diagnosis by label-free assaying of Hepatitis-B-Virus surface antibody (HBsAb) with Hepatitis-B-Virus surface antigen (HBsAg) concentration array chip. The linearity range for HBsAb assay is wider than that of conventional ELISA method.

Portable surface plasmon resonance immunosensor for the detection of fluoroquinolone antibiotic residues in milk.

PubMed

Fernández, Fátima; Pinacho, Daniel G; Sánchez-Baeza, Francisco; Marco, M Pilar

2011-05-11

An inexpensive and portable surface plasmon resonance (SPR) sensor, SPReeta Evaluation Kit SPR3, has been used to develop a biosensor for the determination of fluoroquinolone antibiotics (FQs) and to demonstrate its performance analyzing FQ residues in milk samples. The SPReeta three-channel gold chips were activated with a mixed self-assembled monolayer (m-SAM) and functionalized with a FQ haptenized protein. Binding of the antibody produced a concentration-dependent increase of the SPR signal as a result of the change in the refraction index. Similarly, the presence of the FQ produced a dose-dependent decrease of the response, which allowed a good limit of detection (LOD) to be obtained (1.0 ± 0.4 μg L(-1) for enrofloxacin in buffer). The response was reproducible in all three channels, on different injections and days, and also between chips. Milk samples could be analyzed after a simple sample treatment involving fat removal by centrifugation and dilution with water. Under these conditions calibration curves were obtained showing that FQ residues can be analyzed in milk samples with an IC(50) value of 26.4 ± 7.2 μg L(-1) and a LOD of 2.0 ± 0.2 μg L(-1) (for enrofloxacin), far below the European Union regulations for this antibiotic family in this matrix. Finally, the paper also demonstrates that the biosensor is able to selectively detect the presence of FQs in milk samples, even in the presence of other antibiotics. Enrofloxacin, ciprofloxacin, and norfloxacin residues were detected in blind samples supplied by Nestlé Co.

Disposable luciferase-based microfluidic chip for rapid assay of water pollution.

PubMed

Denisov, Ivan; Lukyanenko, Kirill; Yakimov, Anton; Kukhtevich, Igor; Esimbekova, Elena; Belobrov, Peter

2018-06-21

In the present study, we demonstrate the use of a disposable luciferase-based microfluidic bioassay chip for environmental monitoring and methods for fabrication. The designed microfluidic system includes a chamber with immobilized enzymes of bioluminescent bacteria Photobacterium leiognathi and Vibrio fischeri and their substrates, which dissolve after the introduction of the water sample and thus activate bioluminescent reactions. Limits of detection for copper (II) sulfate, 1,3-dihydroxybenzene and 1,4-benzoquinone for the proposed microfluidic biosensor measured 3 μM, 15 mM, and 2 μM respectively, and these values are higher or close to the level of conventional environmental biosensors based on lyophilized bacteria. Approaches for entrapment of enzymes on poly(methyl methacrylate) (PMMA) plates using a gelatin scaffold and solvent bonding of PMMA chip plates under room temperature were suggested. The proposed microfluidic system may be used with some available luminometers and future portable luminescence readers. © 2018 John Wiley & Sons, Ltd.

Advances in the manufacturing, types, and applications of biosensors

NASA Astrophysics Data System (ADS)

Ravindra, Nuggehalli M.; Prodan, Camelia; Fnu, Shanmugamurthy; Padronl, Ivan; Sikha, Sushil K.

2007-12-01

In recent years, there have been significant technological advancements in the manufacturing, types, and applications of biosensors. Applications include clinical and non-clinical diagnostics for home, bio-defense, bio-remediation, environment, agriculture, and the food industry. Biosensors have progressed beyond the detection of biological threats such as anthrax and are finding use in a number of non-biological applications. Emerging biosensor technologies such as lab-on-a-chip have revolutionized the integration approaches for a very flexible, innovative, and user-friendly platform. An overview of the fundamentals, types, applications, and manufacturers, as well as the market trends of biosensors is presented here. Two case studies are discussed: one focused on a characterization technique—patch clamping and dielectric spectroscopy as a biological sensor—and the other about lithium phthalocyanine, a material that is being developed for in-vivo oxymetry.

Detection of norovirus virus-like particles using a surface plasmon resonance-assisted fluoroimmunosensor optimized for quantum dot fluorescent labels.

PubMed

Ashiba, Hiroki; Sugiyama, Yuki; Wang, Xiaomin; Shirato, Haruko; Higo-Moriguchi, Kyoko; Taniguchi, Koki; Ohki, Yoshimichi; Fujimaki, Makoto

2017-07-15

A highly sensitive biosensor to detect norovirus in environment is desired to prevent the spread of infection. In this study, we investigated a design of surface plasmon resonance (SPR)-assisted fluoroimmunosensor to increase its sensitivity and performed detection of norovirus virus-like particles (VLPs). A quantum dot fluorescent dye was employed because of its large Stokes shift. The sensor design was optimized for the CdSe-ZnS-based quantum dots. The optimal design was applied to a simple SPR-assisted fluoroimmunosensor that uses a sensor chip equipped with a V-shaped trench. Excitation efficiency of the quantum dots, degree of electric field enhancement by SPR, and intensity of autofluorescence of a substrate of the sensor chip were theoretically and experimentally evaluated to maximize the signal-to-noise ratio. As the result, an excitation wavelength of 390nm was selected to excite SPR on an Al film of the sensor chip. The sandwich assay of norovirus VLPs was performed using the designed sensor. Minimum detectable concentration of 0.01ng/mL, which corresponds to 100 virus-like particles included in the detection region of the V-trench, was demonstrated. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Sensitive detection of unlabeled oligonucleotides using a paired surface plasma waves biosensor.

PubMed

Li, Ying-Chang; Chiou, Chiuan-Chian; Luo, Ji-Dung; Chen, Wei-Ju; Su, Li-Chen; Chang, Ying-Feng; Chang, Yu-Sun; Lai, Chao-Sung; Lee, Cheng-Chung; Chou, Chien

2012-05-15

Detection of unlabeled oligonucleotides using surface plasmon resonance (SPR) is difficult because of the oligonucleotides' relatively lower molecular weight compared with proteins. In this paper, we describe a method for detecting unlabeled oligonucleotides at low concentration using a paired surface plasma waves biosensor (PSPWB). The biosensor uses a sensor chip with an immobilized probe to detect a target oligonucleotide via sequence-specific hybridization. PSPWB measures the demodulated amplitude of the heterodyne signal in real time. In the meantime, the ratio of the amplitudes between the detected output signal and reference can reduce the excess noise from the laser intensity fluctuation. Also, the common-path propagation of p and s waves cancels the common phase noise induced by temperature variation. Thus, a high signal-to-noise ratio (SNR) of the heterodyne signal is detected. The sequence specificity of oligonucleotide hybridization ensures that the platform is precisely discriminating between target and non-target oligonucleotides. Under optimized experimental conditions, the detected heterodyne signal increases linearly with the logarithm of the concentration of target oligonucleotide over the range 0.5-500 pM. The detection limit is 0.5 pM in this experiment. In addition, the non-target oligonucleotide at concentrations of 10 pM and 10nM generated signals only slightly higher than background, indicating the high selectivity and specificity of this method. Different length of perfectly matched oligonucleotide targets at 10-mer, 15-mer and 20-mer were identified at the concentration of 150 pM. Copyright © 2012 Elsevier B.V. All rights reserved.

A direct determination of AFBs in vinegar by aptamer-based surface plasmon resonance biosensor.

PubMed

Wu, Wenbo; Zhu, Zhiling; Li, Bingjie; Liu, Zhuqing; Jia, Lili; Zuo, Limin; Chen, Long; Zhu, Zhentai; Shan, Guangzhi; Luo, Shi-Zhong

2018-05-01

Aflatoxin (AFB) is one of the most toxic fungal metabolites produced by Aspergillus flavus, which may contaminate food and agricultural products. Herein, an aptamer-based surface plasmon resonance (SPR) biosensor was developed to detect AFBs. The chosen aptamer showed comparable interaction with the two AFBs, namely aflatoxin B1 (AFB1) and aflatoxin B2 (AFB2). Such phenomenon was rarely reported, and might lead to a simultaneous detection of both AFBs. In this study, AFB1 was used to systematically establish the detection method. In the SPR system, streptavidin proteins were immobilized on the surface of a CM5 sensor chip as a cross-linker and biotin-aptamers were captured through streptavidin-biotin interaction. After optimization, the assay showed a dynamic range between 0.09 and 200 ng mL -1 (linear range from 1.5 to 50 ng mL -1 and a LOD of 0.19 ng mL -1 ) of AFB1 in buffer. As expected, the aptasensor showed high specificity towards AFB1 and AFB2, but hardly bound to other toxins with similar structures, including ochratoxin A (OTA), ochratoxin B (OTB), Zeralenone (ZEA) and T-2 toxin (T-2). Determination of AFB1 in vinegar was further performed using the SPR biosensor. Recoveries of AFB1 from spiked samples ranged from 96.3 to 117.8%. The developed SPR assay is a simple, fast and sensitive approach for the detection of residual AFBs in agricultural products and foodstuffs like vinegar. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biosensor discovery of thyroxine transport disrupting chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchesini, Gerardo R.; Meimaridou, Anastasia; Haasnoot, Willem

2008-10-01

Ubiquitous chemicals may interfere with the thyroid system that is essential in the development and physiology of vertebrates. We applied a surface plasmon resonance (SPR) biosensor-based screening method for the fast screening of chemicals with thyroxine (T4) transport disrupting activity. Two inhibition assays using the main thyroid hormone transport proteins, T4 binding globulin (TBG) and transthyretin (TTR), in combination with a T4-coated biosensor chip were optimized and automated for screening chemical libraries. The transport protein-based biosensor assays were rapid, high throughput and bioeffect-related. A library of 62 chemicals including the natural hormones, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and metabolites,more » halogenated bisphenol A (BPA), halogenated phenols, pharmaceuticals, pesticides and other potential environmentally relevant chemicals was tested with the two assays. We discovered ten new active compounds with moderate to high affinity for TBG with the TBG assay. Strikingly, the most potent binding was observed with hydroxylated metabolites of the brominated diphenyl ethers (BDEs) BDE 47, BDE 49 and BDE 99, that are commonly found in human plasma. The TTR assay confirmed the activity of previously identified hydroxylated metabolites of PCBs and PBDEs, halogenated BPA and genistein. These results show that the hydroxylated metabolites of the ubiquitous PBDEs not only target the T4 transport at the TTR level, but also, and to a great extent, at the TBG level where most of the T4 in humans is circulating. The optimized SPR biosensor-based transport protein assay is a suitable method for high throughput screening of large libraries for potential thyroid hormone disrupting compounds.« less

Design methodology and results evaluation of a heating functionality in modular lab-on-chip systems

NASA Astrophysics Data System (ADS)

Streit, Petra; Nestler, Joerg; Shaporin, Alexey; Graunitz, Jenny; Otto, Thomas

2018-06-01

Lab-on-a-chip (LoC) systems offer the opportunity of fast and customized biological analyses executed at the ‘point-of-need’ without expensive lab equipment. Some biological processes need a temperature treatment. Therefore, it is important to ensure a defined and stable temperature distribution in the biosensor area. An integrated heating functionality is realized with discrete resistive heating elements including temperature measurement. The focus of this contribution is a design methodology and evaluation technique of the temperature distribution in the biosensor area with regard to the thermal-electrical behaviour of the heat sources. Furthermore, a sophisticated control of the biosensor temperature is proposed. A finite element (FE) model with one and more integrated heat sources in a polymer-based LoC system is used to investigate the impact of the number and arrangement of heating elements on the temperature distribution around the heating elements and in the biosensor area. Based on this model, various LOC systems are designed and fabricated. Electrical characterization of the heat sources and independent temperature measurements with infrared technique are performed to verify the model parameters and prove the simulation approach. The FE model and the proposed methodology is the foundation for optimization and evaluation of new designs with regard to temperature requirements of the biosensor. Furthermore, a linear dependency of the heater temperature on the electric current is demonstrated in the targeted temperature range of 20 °C to 70 °C enabling the usage of the heating functionality for biological reactions requiring a steady-state temperature up to 70 °C. The correlation between heater and biosensor area temperature is derived for a direct control through the heating current.

Sensitive Detection of Capsaicinoids Using a Surface Plasmon Resonance Sensor with Anti-Homovanillic Acid Polyclonal Antibodies

PubMed Central

Nakamura, Shingo; Yatabe, Rui; Onodera, Takeshi; Toko, Kiyoshi

2013-01-01

Recently, highly functional biosensors have been developed in preparation for possible large-scale terrorist attacks using chemical warfare agents. Practically applicable sensors are required to have various abilities, such as high portability and operability, the capability of performing rapid and continuous measurement, as well as high sensitivity and selectivity. We developed the detection method of capsaicinoids, the main component of some lachrymators, using a surface plasmon resonance (SPR) immunosensor as an on-site detection sensor. Homovanillic acid, which has a vanillyl group similar to capsaicinoids such as capsaicin and dihydrocapsaicin, was bound to Concholepas concholepas hemocyanin (CCH) for use as an immunogen to generate polyclonal antibodies. An indirect competitive assay was carried out to detect capsaicinoids using SPR sensor chips on which different capsaicin analogues were immobilized. For the sensor chip on which 4-hydroxy-3-methoxybenzylamine hydrochloride was immobilized, a detection limit of 150 ppb was achieved. We found that the incubation time was not required and the detection can be completed in five minutes. PMID:25586413

Development of gold nanoparticle-aptamer-based LSPR sensing chips for the rapid detection of Salmonella typhimurium in pork meat.

PubMed

Oh, Seo Yeong; Heo, Nam Su; Shukla, Shruti; Cho, Hye-Jin; Vilian, A T Ezhil; Kim, Jinwoon; Lee, Sang Yup; Han, Young-Kyu; Yoo, Seung Min; Huh, Yun Suk

2017-08-31

A non-labeled, portable plasmonic biosensor-based device was developed to enable the ultra-sensitive and selective detection of Salmonella typhimurium in pork meat samples. Specifically, a plasmonic sensor, using the self-assembly of gold nanoparticles (AuNPs) to achieve a regulated diameter of 20 nm for the AuNP monolayers, was used to conduct high-density deposition on a transparent substrate, which produced longitudinal wavelength extinction shifts via a localized surface plasmon resonance (LSPR) signal. The developed aptamers conjugated to the LSPR sensing chips revealed an ultra-sensitive upper limit of detection (LOD) of approximately 10 4 cfu/mL for S. typhimurium in pure culture under the optimal assay conditions, with a total analysis time of 30-35 min. When the LSPR sensing chips were applied on artificially contaminated pork meat samples, S. typhimurium in the spiked pork meat samples was also detected at an LOD of 1.0 × 10 4 cfu/mL. The developed method could detect S. typhimurium in spiked pork meat samples without a pre-enrichment step. Additionally, the LSPR sensing chips developed against S. typhimurium were not susceptible to any effect of the food matrix or background contaminant microflora. These findings confirmed that the developed gold nanoparticle-aptamer-based LSPR sensing chips could facilitate sensitive detection of S. typhimurium in food samples.

Ultra-Sensitive Lab-on-a-Chip Detection of Sudan I in Food using Plasmonics-Enhanced Diatomaceous Thin Film.

PubMed

Kong, Xianming; Squire, Kenny; Chong, Xinyuan; Wang, Alan X

2017-09-01

Sudan I is a carcinogenic compound containing an azo group that has been illegally utilized as an adulterant in food products to impart a bright red color to foods. In this paper, we develop a facile lab-on-a-chip device for instant, ultra-sensitive detection of Sudan I from real food samples using plasmonics-enhanced diatomaceous thin film, which can simultaneously perform on-chip separation using thin layer chromatography (TLC) and highly specific sensing using surface-enhanced Raman scattering (SERS) spectroscopy. Diatomite is a kind of nature-created photonic crystal biosilica with periodic pores and was used both as the stationary phase of the TLC plate and photonic crystals to enhance the SERS sensitivity. The on-chip chromatography capability of the TLC plate was verified by isolating Sudan I in a mixture solution containing Rhodamine 6G, while SERS sensing was achieved by spraying gold colloidal nanoparticles into the sensing spot. Such plasmonics-enhanced diatomaceous film can effectively detect Sudan I with more than 10 times improvement of the Raman signal intensity than commercial silica gel TLC plates. We applied this lab-on-a-chip device for real food samples and successfully detected Sudan I in chili sauce and chili oil down to 1 ppm, or 0.5 ng/spot. This on-chip TLC-SERS biosensor based on diatomite biosilica can function as a cost-effective, ultra-sensitive, and reliable technology for screening Sudan I and many other illicit ingredients to enhance food safety.

On Chip Protein Pre-Concentration for Enhancing the Sensitivity of Porous Silicon Biosensors.

PubMed

Arshavsky-Graham, Sofia; Massad-Ivanir, Naama; Paratore, Federico; Scheper, Thomas; Bercovici, Moran; Segal, Ester

2017-12-22

Porous silicon (PSi) nanomaterials have been widely studied as label-free optical biosensors for protein detection. However, these biosensors' performance, specifically in terms of their sensitivity (which is typically in the micromolar range), is insufficient for many applications. Herein, we present a proof-of-concept application of the electrokinetic isotachophoresis (ITP) technique for real-time preconcentration of a target protein on a PSi biosensor. With ITP, a highly concentrated target zone is delivered to the sensing area, where the protein target is captured by immobilized aptamers. The detection of the binding events is conducted in a label-free manner by reflective interferometric Fourier transformation spectroscopy (RIFTS). Up to 1000-fold enhancement in local concentration of the protein target and the biosensor's sensitivity are achieved, with a measured limit of detection of 7.5 nM. Furthermore, the assay is successfully performed in complex media, such as bacteria lysate samples, while the selectivity of the biosensor is retained. The presented assay could be further utilized for other protein targets, and to promote the development of clinically useful PSi biosensors.

The Novel Immunobiosensors for Detection of Escherichia coli O157:H7 Using Electrochemical Impedance Spectroscopy.

PubMed

Zhang, Deng; Chen, Songyue; Qin, Lifeng; Li, Rong; Wang, Ping; Li, Yanbin

2005-01-01

Immunobiosensors were developed for detection of Escherichia coli O157:H7 based on the surface immobilization of monoclone antibodies onto indium tin oxide (ITO) electrodes. The immobilization of antibodies onto ITO chips was carried out by silanization. The effects of epoxysilane monolayer, the antibody layer on the electrochemical properties of the electrode, and the combined target bacteria were analyzed through cyclic voltammetry and electrochemical impedance spectroscopy. By using Randles model as the equivalent circuit, the concentration of the target bacteria can be quantitatively analyzed in terms of the change of electron transfer resistance. The biosensor could detect the target bacteria with a detection limit of 4×10³CFU/mL. A linear response was found between 4×10³- 4×10⁶CFU/mL. This biosensor was characterized with high sensitivity, excellent selectivity, short detection time and easy operation It has a promising application in clinical laboratory diagnoses, environmental detection and food safety.

Real-time label-free biosensing with integrated planar waveguide ring resonators

NASA Astrophysics Data System (ADS)

Sohlström, Hans; Gylfason, Kristinn B.; Hill, Daniel

2010-05-01

We review the use of planar integrated optical waveguide ring resonators for label free bio-sensing and present recent results from two European biosensor collaborations: SABIO and InTopSens. Planar waveguide ring resonators are attractive for label-free biosensing due to their small footprint, high Q-factors, and compatibility with on-chip optics and microfluidics. This enables integrated sensor arrays for compact labs-on-chip. One application of label-free sensor arrays is for point-of-care medical diagnostics. Bringing such powerful tools to the single medical practitioner is an important step towards personalized medicine, but requires addressing a number of issues: improving limit of detection, managing the influence of temperature, parallelization of the measurement for higher throughput and on-chip referencing, efficient light-coupling strategies to simplify alignment, and packaging of the optical chip and integration with microfluidics. From the SABIO project we report refractive index measurement and label-free biosensing in an 8-channel slotwaveguide ring resonator sensor array, within a compact cartridge with integrated microfluidics. The sensors show a volume sensing detection limit of 5 x 10-6 RIU and a surface sensing detection limit of 0.9 pg/mm2. From the InTopSens project we report early results on silicon-on-insulator racetrack resonators.

Simultaneous Detection of Escherichia coli O157:H7, Salmonella enteritidis, and Listeria monocytogenes at a Very Low Level Using Simultaneous Enrichment Broth and Multichannel SPR Biosensor.

PubMed

Zhang, Xiaoguang; Tsuji, Sachiko; Kitaoka, Hayato; Kobayashi, Hiroshi; Tamai, Mitsuru; Honjoh, Ken-Ichi; Miyamoto, Takahisa

2017-10-01

Detection of foodborne pathogens at very low levels is still a challenge. A custom-built multichannel surface plasmon resonance (SPR) biosensor and simultaneous enrichment broth (SEB) were used to develop a simultaneous detection method for 3 important foodborne pathogens, Escherichia coli O157:H7 (O157:H7), Salmonella enteritidis, and Listeria monocytogenes, at a very low level. These 3 foodborne pathogens at a very low level (14, 6, and 28 CFU/25 g (mL) for O157:H7, S. enteritidis, and L. monocytogenes, respectively) were inoculated in SEB and incubated at 37 ˚C for 24 h. Sample prepared from the simultaneous enrichment culture was analyzed using the multichannel SPR biosensor and sensor chip immobilized with polyclonal antibodies specific to each of the target pathogens. O157:H7, S. enteritidis, and L. monocytogenes in chicken were detected simultaneously at an inoculum dose of 14, 6, and 28 CFU/25 g, respectively. Our method using a custom-built multichannel SPR biosensor and enrichment in SEB is expected as a rapid and simultaneous detection method for low levels of O157:H7, S. enteritidis, and L. monocytogenes in food. Our method is expected as a rapid and simultaneous detection method for pathogens at very low levels. It has great potential for safety control of food and microbiological detection applications. © 2017 Institute of Food Technologists®.

Hybrid macro-micro fluidics system for a chip-based biosensor

NASA Astrophysics Data System (ADS)

Tamanaha, C. R.; Whitman, L. J.; Colton, R. J.

2002-03-01

We describe the engineering of a hybrid fluidics platform for a chip-based biosensor system that combines high-performance microfluidics components with powerful, yet compact, millimeter-scale pump and valve actuators. The microfluidics system includes channels, valveless diffuser-based pumps, and pinch-valves that are cast into a poly(dimethylsiloxane) (PDMS) membrane and packaged along with the sensor chip into a palm-sized plastic cartridge. The microfluidics are driven by pump and valve actuators contained in an external unit (with a volume ~30 cm3) that interfaces kinematically with the PDMS microelements on the cartridge. The pump actuator is a simple-lever, flexure-hinge displacement amplifier that increases the motion of a piezoelectric stack. The valve actuators are an array of cantilevers operated by shape memory alloy wires. All components can be fabricated without the need for complex lithography or micromachining, and can be used with fluids containing micron-sized particulates. Prototypes have been modeled and tested to ensure the delivery of microliter volumes of fluid and the even dispersion of reagents over the chip sensing elements. With this hybrid approach to the fluidics system, the biochemical assay benefits from the many advantages of microfluidics yet we avoid the complexity and unknown reliability of immature microactuator technologies.

Protein Chips for Detection of Salmonella spp. from Enrichment Culture

PubMed Central

Poltronieri, Palmiro; Cimaglia, Fabio; De Lorenzis, Enrico; Chiesa, Maurizio; Mezzolla, Valeria; Reca, Ida Barbara

2016-01-01

Food pathogens are the cause of foodborne epidemics, therefore there is a need to detect the pathogens in food productions rapidly. A pre-enrichment culture followed by selective agar plating are standard detection methods. Molecular methods such as qPCR have provided a first rapid protocol for detection of pathogens within 24 h of enrichment culture. Biosensors also may provide a rapid tool to individuate a source of Salmonella contamination at early times of pre-enrichment culture. Forty mL of Salmonella spp. enrichment culture were processed by immunoseparation using the Pathatrix, as in AFNOR validated qPCR protocols. The Salmonella biosensor combined with immunoseparation showed a limit of detection of 100 bacteria/40 mL, with a 400 fold increase to previous results. qPCR analysis requires processing of bead-bound bacteria with lysis buffer and DNA clean up, with a limit of detection of 2 cfu/50 μL. Finally, a protein chip was developed and tested in screening and identification of 5 common pathogen species, Salmonella spp., E. coli, S. aureus, Campylobacter spp. and Listeria spp. The protein chip, with high specificity in species identification, is proposed to be integrated into a Lab-on-Chip system, for rapid and reproducible screening of Salmonella spp. and other pathogen species contaminating food productions. PMID:27110786

Integrated optical biosensor for rapid detection of bacteria

NASA Astrophysics Data System (ADS)

Mathesz, Anna; Valkai, Sándor; Újvárosy, Attila; Aekbote, Badri; Sipos, Orsolya; Stercz, Balázs; Kocsis, Béla; Szabó, Dóra; Dér, András

2016-02-01

In medical diagnostics, rapid detection of pathogenic bacteria from body fluids is one of the basic issues. Most state-of-the-art methods require optical labeling, increasing the complexity, duration and cost of the analysis. Therefore, there is a strong need for developing selective sensory devices based on label-free techniques, in order to increase the speed, and reduce the cost of detection. In a recent paper, we have shown that an integrated optical Mach-Zehnder interferometer, a highly sensitive all-optical device made of a cheap photopolymer, can be used as a powerful lab-on-a-chip tool for specific, labelfree detection of proteins. By proper modifications of this technique, our interferometric biosensor was combined with a microfluidic system allowing the rapid and specific detection of bacteria from solutions, having the surface of the sensor functionalized by bacterium-specific antibodies. The experiments proved that the biosensor was able to detect Escherichia coli bacteria at concentrations of 106 cfu/ml within a few minutes, that makes our device an appropriate tool for fast, label-free detection of bacteria from body fluids such as urine or sputum. On the other hand, possible applications of the device may not be restricted to medical microbiology, since bacterial identification is an important task in microbial forensics, criminal investigations, bio-terrorism threats and in environmental studies, as well.

Integrated optical biosensor for rapid detection of bacteria

NASA Astrophysics Data System (ADS)

Mathesz, Anna; Valkai, Sándor; Újvárosy, Attila; Aekbote, Badri; Sipos, Orsolya; Stercz, Balázs; Kocsis, Béla; Szabó, Dóra; Dér, András

2015-12-01

In medical diagnostics, rapid detection of pathogenic bacteria from body fluids is one of the basic issues. Most state-of-the-art methods require optical labeling, increasing the complexity, duration and cost of the analysis. Therefore, there is a strong need for developing selective sensory devices based on label-free techniques, in order to increase the speed, and reduce the cost of detection. In a recent paper, we have shown that an integrated optical Mach-Zehnder interferometer, a highly sensitive all-optical device made of a cheap photopolymer, can be used as a powerful lab-on-a-chip tool for specific, labelfree detection of proteins. By proper modifications of this technique, our interferometric biosensor was combined with a microfluidic system allowing the rapid and specific detection of bacteria from solutions, having the surface of the sensor functionalized by bacterium-specific antibodies. The experiments proved that the biosensor was able to detect Escherichia coli bacteria at concentrations of 106 cfu/ml within a few minutes, that makes our device an appropriate tool for fast, label-free detection of bacteria from body fluids such as urine or sputum. On the other hand, possible applications of the device may not be restricted to medical microbiology, since bacterial identification is an important task in microbial forensics, criminal investigations, bio-terrorism threats and in environmental studies, as well.

New reactive polymer for protein immobilisation on sensor surfaces.

PubMed

Kyprianou, Dimitris; Guerreiro, Antonio R; Chianella, Iva; Piletska, Elena V; Fowler, Steven A; Karim, Kal; Whitcombe, Michael J; Turner, Anthony P F; Piletsky, Sergey A

2009-01-01

Immobilisation of biorecognition elements on transducer surfaces is a key step in the development of biosensors. The immobilisation needs to be fast, cheap and most importantly should not affect the biorecognition activity of the immobilised receptor. A novel protocol for the covalent immobilisation of biomolecules containing primary amines using an inexpensive and simple polymer is presented. This tri-dimensional (3D) network leads to a random immobilisation of antibodies on the polymer and ensures the availability of a high percentage of antibody binding sites. The reactivity of the polymer is based on the reaction between primary amines and thioacetal groups included in the polymer network. These functional groups (thioacetal) do not need any further activation in order to react with proteins, making it attractive for sensor fabrication. The novel polymer also contains thiol derivative groups (disulphide groups or thioethers) that promote self-assembling on a metal transducer surface. For demonstration purposes the polymer was immobilised on Au Biacore chips. The resulting polymer layer was characterised using contact angle meter, atomic force microscopy (AFM) and ellipsometry. A general protocol suitable for the immobilisation of bovine serum albumin (BSA), enzymes and antibodies such as polyclonal anti-microcystin-LR antibody and monoclonal anti-prostate specific antigen (anti-PSA) antibody was then optimised. The affinity characteristics of developed immunosensors were investigated in reaction with microcystin-LR, and PSA. The calculated detection limit for analytes depended on the properties of antibodies. The detection limit for microcystin-LR was 10 ngmL(-1) and for PSA 0.01 ngmL(-1). The non-specific binding of analytes to synthesised polymers was very low. The polymer-coated chips were stored for up to 2 months without any noticeable deterioration in their ability to react with proteins. These findings make this new polymer very promising for the development of low-cost, easy to prepare and sensitive biosensors.

An underlap field-effect transistor for electrical detection of influenza

NASA Astrophysics Data System (ADS)

Lee, Kwang-Won; Choi, Sung-Jin; Ahn, Jae-Hyuk; Moon, Dong-Il; Park, Tae Jung; Lee, Sang Yup; Choi, Yang-Kyu

2010-01-01

An underlap channel-embedded field-effect transistor (FET) is proposed for label-free biomolecule detection. Specifically, silica binding protein fused with avian influenza (AI) surface antigen and avian influenza antibody (anti-AI) were designed as a receptor molecule and a target material, respectively. The drain current was significantly decreased after the binding of negatively charged anti-AI on the underlap channel. A set of control experiments supports that only the biomolecules on the underlap channel effectively modulate the drain current. With the merits of a simple fabrication process, complementary metal-oxide-semiconductor compatibility, and enhanced sensitivity, the underlap FET could be a promising candidate for a chip-based biosensor.

Photonic ring resonance is a versatile platform for performing multiplex immunoassays in real time.

PubMed

Mudumba, Sasi; de Alba, Sophia; Romero, Randy; Cherwien, Carli; Wu, Alice; Wang, Jue; Gleeson, Martin A; Iqbal, Muzammil; Burlingame, Rufus W

2017-09-01

Photonic ring resonance is a property of light where in certain circumstances specific wavelengths are trapped in a ring resonator. Sensors based on silicon photonic ring resonators function by detecting the interaction between light circulating inside the sensor and matter deposited on the sensor surface. Binding of biological material results in a localized change in refractive index on the sensor surface, which affects the circulating optical field extending beyond the sensor boundary. That is, the resonant wavelength will change when the refractive index of the medium around the ring resonator changes. Ring resonators can be fabricated onto small silicon chips, allowing development of a miniature multiplex array of ring based biosensors. This paper describes the properties of such a system when responding to the refractive index changed in a simple and precise way by changing the ionic strength of the surrounding media, and in a more useful way by the binding of macromolecules to the surface above the resonators. Specifically, a capture immunoassay is described that measures the change of resonant wavelength as a patient serum sample with anti-SS-A autoantibodies is flowed over a chip spotted with SS-A antigen and amplified with anti-IgG. The technology has been miniaturized and etched into a 4×6mm silicon chip that can measure 32 different reactions in quadruplicate simultaneously. The variability between 128 rings on a chip as measured by 2M salt assays averaged 0.6% CV. The output of the assays is the average shift per cluster of 4 rings, and the assays averaged 0.5% CV between clusters. The variability between chips averaged 1.8%. Running the same array on multiple instruments showed that after some improvements to the wavelength referencing system, the upper boundary of variation was 3% between 13 different instruments. The immunoassay displayed about 2% higher variability than the salt assays. There are several outstanding features of this system. The amount of antigen used on the chip for each test is around 200 picograms, only a few microliters of sample is necessary, and the assays take <10min. Copyright © 2017 Genalyte Inc. Published by Elsevier B.V. All rights reserved.

Characterizing and modeling protein-surface interactions in lab-on-chip devices

NASA Astrophysics Data System (ADS)

Katira, Parag

Protein adsorption on surfaces determines the response of other biological species present in the surrounding solution. This phenomenon plays a major role in the design of biomedical and biotechnological devices. While specific protein adsorption is essential for device function, non-specific protein adsorption leads to the loss of device function. For example, non-specific protein adsorption on bioimplants triggers foreign body response, in biosensors it leads to reduced signal to noise ratios, and in hybrid bionanodevices it results in the loss of confinement and directionality of molecular shuttles. Novel surface coatings are being developed to reduce or completely prevent the non-specific adsorption of proteins to surfaces. A novel quantification technique for extremely low protein coverage on surfaces has been developed. This technique utilizes measurement of the landing rate of microtubule filaments on kinesin proteins adsorbed on a surface to determine the kinesin density. Ultra-low limits of detection, dynamic range, ease of detection and availability of a ready-made kinesin-microtubule kit makes this technique highly suitable for detecting protein adsorption below the detection limits of standard techniques. Secondly, a random sequential adsorption model is presented for protein adsorption to PEO-coated surfaces. The derived analytical expressions accurately predict the observed experimental results from various research groups, suggesting that PEO chains act as almost perfect steric barriers to protein adsorption. These expressions can be used to predict the performance of a variety of systems towards resisting protein adsorption and can help in the design of better non-fouling surface coatings. Finally, in biosensing systems, target analytes are captured and concentrated on specifically adsorbed proteins for detection. Non-specific adsorption of proteins results in the loss of signal, and an increase in the background. The use of nanoscale transducers as receptors is beneficial from the point of view of signal enhancement, but has a strong mass transport limitation. To overcome this, the use of molecular shuttles has been proposed that can selectively capture analytes and actively transport them to the nanoreceptors. The effect of employing such a two-stage capture process on biosensor sensitivity is theoretically investigated and an optimum design for a kinesin-microtubule-driven hybrid biosensor is proposed.

Applications of commercial biosensors in clinical, food, environmental, and biothreat/biowarfare analyses.

PubMed

Bahadır, Elif Burcu; Sezgintürk, Mustafa Kemal

2015-06-01

The lack of specific, low-cost, rapid, sensitive, and easy detection of biomolecules has resulted in the development of biosensor technology. Innovations in biosensor technology have enabled many biosensors to be commercialized and have enabled biomolecules to be detected onsite. Moreover, the emerging technologies of lab-on-a-chip microdevices and nanosensors offer opportunities for the development of new biosensors with much better performance. Biosensors were first introduced into the laboratory by Clark and Lyons. They developed the first glucose biosensor for laboratory conditions. Then in 1973, a glucose biosensor was commercialized by Yellow Springs Instruments. The commercial biosensors have small size and simple construction and they are ideal for point-of-care biosensing. In addition to glucose, a wide variety of metabolites such as lactate, cholesterol, and creatinine can be detected by using commercial biosensors. Like the glucose biosensors (tests) other commercial tests such as for pregnancy (hCG), Escherichia coli O157, influenza A and B viruses, Helicobacter pylori, human immunodeficiency virus, tuberculosis, and malaria have achieved success. Apart from their use in clinical analysis, commercial tests are also used in environmental (such as biochemical oxygen demand, nitrate, pesticide), food (such as glutamate, glutamine, sucrose, lactose, alcohol, ascorbic acid), and biothreat/biowarfare (Bacillus anthracis, Salmonella, Botulinum toxin) analysis. In this review, commercial biosensors in clinical, environmental, food, and biowarfare analysis are summarized and the commercial biosensors are compared in terms of their important characteristics. This is the first review in which all the commercially available tests are compiled together. Copyright © 2015 Elsevier Inc. All rights reserved.

Improvement of up-converting phosphor technology-based biosensor

NASA Astrophysics Data System (ADS)

Xie, Chengke; Huang, Lihua; Zhang, Youbao; Guo, Xiaoxian; Qu, Jianfeng; Huang, Huijie

2008-12-01

A novel biosensor based on up-converting phosphor technology (UPT) was developed several years ago. It is a kind of optical biosensor using up-converting phosphor (UCP) particles as the biological marker. From then on, some improvements have been made for this UPT-based biosensor. The primary aspects of the improvement lie in the control system. On one hand, the hardware of the control system has been optimized, including replacing two single chip microcomputers (SCM) with only one, the optimal design of the keyboard interface circuit and the liquid crystal module (LCM) control circuit et al.. These result in lower power consumption and higher reliability. On the other hand, a novel signal processing algorithm is proposed in this paper, which can improve the automation and operating simplicity of the UPT-based biosensor. It has proved to have high sensitivity (~ng/ml), high stability and good repeatability (CV<5%), which is better than the former system. It can meet the need of some various applications such as rapid immunoassay, chemical and biological detection and so on.

Impact of SPR biosensor assay configuration on antibody: Neonatal Fc receptor binding data

PubMed Central

Wang, Xiangdan; McKay, Patrick; Dutina, George; Hass, Philip E.; Nijem, Ihsan; Allison, David; Cowan, Kyra J.; Lin, Kevin; Quarmby, Valerie; Yang, Jihong

2017-01-01

ABSTRACT Binding interactions with the neonatal Fc receptor (FcRn) are one determinant of pharmacokinetic properties of recombinant human monoclonal antibody (rhumAb) therapeutics, and a conserved binding motif in the crystallizable fragment (Fc) region of IgG molecules interacts with FcRn. Surface plasmon resonance (SPR) biosensor assays are often used to characterize interactions between FcRn and rhumAb therapeutics. In such assays, generally either the rhumAb (format 1) or the FcRn protein (format 2) is immobilized on a biosensor chip. However, because evidence suggests that, in some cases, the variable domains of a rhumAb may also affect FcRn binding, we evaluated the effect of SPR assay configuration on binding data. We sought to assess FcRn binding properties of 2 rhumAbs (rhumAb1 and rhumAb2) to FcRn proteins using these 2 biosensor assay formats. The two rhumAbs have greater than 99% sequence identity in the Fc domain but differ in their Fab regions. rhumAb2 contains a positively charged patch in the variable domain that is absent in rhumAb1. Our results showed that binding of rhumAb1 to FcRn was independent of biosensor assay configuration, while binding of rhumAb2 to FcRn was highly SPR assay configuration dependent. Further investigations revealed that the format dependency of rhumAb2-FcRn binding is linked to the basic residues that form a positively charged patch in the variable domain of rhumAb2. Our work highlights the importance of analyzing rhumAb-FcRn binding interactions using 2 alternate SPR biosensor assay configurations. This approach may also provide a simple way to identify the potential for non-Fc-driven FcRn binding interactions in otherwise typical IgGs. PMID:28001487

Development of a molecularly imprinted polymer tailored on disposable screen-printed electrodes for dual detection of EGFR and VEGF using nano-liposomal amplification strategy.

PubMed

Johari-Ahar, Mohammad; Karami, Pari; Ghanei, Mostafa; Afkhami, Abbas; Bagheri, Hasan

2018-06-01

This work demonstrates the development of a gold screen-printed electrode (Au-SPE)-based biosensor modified with a molecularly imprinted polymer and amplified using antibody-conjugated nano-liposomes. The developed biosensor was utilized for dual determination of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) as cancer biomarkers. To prepare this biosensor, Au-SPE was modified with 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester) via self-assembly method and then the target proteins (EGFR and VEGF) were covalently attached to the modified SPE. To synthesize the molecularly imprinted polymer, monomers of acrylamide and N,N'-methylenebis(acrylamide) were polymerized around the EGFR and VEGF templates, and to characterize the prepared biosensor, electrochemical impedance spectroscopy was used for analyses of surface changes in the engineered electrodes. To produce reliable electrochemical signals, nano-liposomes which were loaded with Cd(II) and Cu(II) cations and decorated with antibodies specific for EGFR and VEGF were used as an efficient tool for detection of target biomarkers. In the analysis step, potentiometric striping analysis (PSA), as an electrochemical technique, was utilized for sensitive determination of these cations. The limits of detection (LODs) of EGFR and VEGF analyses were found to be 0.01 and 0.005 pg mL -1 with the linear dynamic ranges (LDRs) of 0.05-50000 and 0.01-7000 pg mL -1 , respectively. Moreover, the proposed biosensor was successfully used for sensitive, reproducible, and specific detection of EGFR and VEGF in real samples. Due to the SPE nature of the developed biosensor, we envision that this sensing tool has capability of being integrated with lab-on-a-chip (LOC), microfluidics, and micro total analysis systems. Copyright © 2018 Elsevier B.V. All rights reserved.

CMOS capacitive biosensors for highly sensitive biosensing applications.

PubMed

Chang, An-Yu; Lu, Michael S-C

2013-01-01

Magnetic microbeads are widely used in biotechnology and biomedical research for manipulation and detection of cells and biomolecules. Most lab-on-chip systems capable of performing manipulation and detection require external instruments to perform one of the functions, leading to increased size and cost. This work aims at developing an integrated platform to perform these two functions by implementing electromagnetic microcoils and capacitive biosensors on a CMOS (complementary metal oxide semiconductor) chip. Compared to most magnetic-type sensors, our detection method requires no externally applied magnetic fields and the associated fabrication is less complicated. In our experiment, microbeads coated with streptavidin were driven to the sensors located in the center of microcoils with functionalized anti-streptavidin antibody. Detection of a single microbead was successfully demonstrated using a capacitance-to-frequency readout. The average capacitance changes for the experimental and control groups were -5.3 fF and -0.2 fF, respectively.

Surface stress-based biosensors.

PubMed

Sang, Shengbo; Zhao, Yuan; Zhang, Wendong; Li, Pengwei; Hu, Jie; Li, Gang

2014-01-15

Surface stress-based biosensors, as one kind of label-free biosensors, have attracted lots of attention in the process of information gathering and measurement for the biological, chemical and medical application with the development of technology and society. This kind of biosensors offers many advantages such as short response time (less than milliseconds) and a typical sensitivity at nanogram, picoliter, femtojoule and attomolar level. Furthermore, it simplifies sample preparation and testing procedures. In this work, progress made towards the use of surface stress-based biosensors for achieving better performance is critically reviewed, including our recent achievement, the optimally circular membrane-based biosensors and biosensor array. The further scientific and technological challenges in this field are also summarized. Critical remark and future steps towards the ultimate surface stress-based biosensors are addressed. Copyright © 2013 Elsevier B.V. All rights reserved.

Scalable Low-Cost Fabrication of Disposable Paper Sensors for DNA Detection

PubMed Central

2015-01-01

Controlled integration of features that enhance the analytical performance of a sensor chip is a challenging task in the development of paper sensors. A critical issue in the fabrication of low-cost biosensor chips is the activation of the device surface in a reliable and controllable manner compatible with large-scale production. Here, we report stable, well-adherent, and repeatable site-selective deposition of bioreactive amine functionalities and biorepellant polyethylene glycol-like (PEG) functionalities on paper sensors by aerosol-assisted, atmospheric-pressure, plasma-enhanced chemical vapor deposition. This approach requires only 20 s of deposition time, compared to previous reports on cellulose functionalization, which takes hours. A detailed analysis of the near-edge X-ray absorption fine structure (NEXAFS) and its sensitivity to the local electronic structure of the carbon and nitrogen functionalities. σ*, π*, and Rydberg transitions in C and N K-edges are presented. Application of the plasma-processed paper sensors in DNA detection is also demonstrated. PMID:25423585

Scalable Low-Cost Fabrication of Disposable Paper Sensors for DNA Detection

DOE PAGES

Gandhiraman, Ram P.; Nordlund, Dennis; Jayan, Vivek; ...

2014-11-25

Controlled integration of features that enhance the analytical performance of a sensor chip is a challenging task in the development of paper sensors. A critical issue in the fabrication of low-cost biosensor chips is the activation of the device surface in a reliable and controllable manner compatible with large-scale production. Here, we report stable, well-adherent, and repeatable site-selective deposition of bioreactive amine functionalities and biorepellant polyethylene glycol-like (PEG) functionalities on paper sensors by aerosol-assisted, atmospheric-pressure, plasma-enhanced chemical vapor deposition. This approach requires only 20 s of deposition time, compared to previous reports on cellulose functionalization, which takes hours. We presentmore » a detailed analysis of the near-edge X-ray absorption fine structure (NEXAFS) and its sensitivity to the local electronic structure of the carbon and nitrogen functionalities. σ*, π*, and Rydberg transitions in C and N K-edges. Lastly, application of the plasma-processed paper sensors in DNA detection is also demonstrated.« less

Design of a New Ultracompact Resonant Plasmonic Multi-Analyte Label-Free Biosensing Platform

PubMed Central

De Palo, Maripina; Ciminelli, Caterina

2017-01-01

In this paper, we report on the design of a bio-multisensing platform for the selective label-free detection of protein biomarkers, carried out through a 3D numerical algorithm. The platform includes a number of biosensors, each of them is based on a plasmonic nanocavity, consisting of a periodic metal structure to be deposited on a silicon oxide substrate. Light is strongly confined in a region with extremely small size (=1.57 μm2), to enhance the light-matter interaction. A surface sensitivity Ss = 1.8 nm/nm has been calculated together with a detection limit of 128 pg/mm2. Such performance, together with the extremely small footprint, allow the integration of several devices on a single chip to realize extremely compact lab-on-chip microsystems. In addition, each sensing element of the platform has a good chemical stability that is guaranteed by the selection of gold for its fabrication. PMID:28783075

Interfacial Interaction between Transmembrane Ocular Mucins and Adhesive Polymers and Dendrimers Analyzed by Surface Plasmon Resonance

PubMed Central

Noiray, M.; Briand, E.; Woodward, A. M.; Argüeso, P.; Molina Martínez, I. T.; Herrero-Vanrell, R.; Ponchel, G.

2013-01-01

Purpose Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. Methods The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). Results While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH2(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)≫ CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). Conclusions The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and den-drimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability. PMID:22565639

Protein adsorption/desorption and antibody binding stoichiometry on silicon interferometric biosensors examined with TOF-SIMS

NASA Astrophysics Data System (ADS)

Gajos, Katarzyna; Budkowski, Andrzej; Petrou, Panagiota; Pagkali, Varvara; Awsiuk, Kamil; Rysz, Jakub; Bernasik, Andrzej; Misiakos, Konstantinos; Raptis, Ioannis; Kakabakos, Sotirios

2018-06-01

Time-of-flight secondary ion mass spectrometry has been employed to examine, with biomolecular discrimination, sensing arm areas (20 μm × 600 μm) of integrated onto silicon chips Mach-Zehnder interferometers aiming to optimize their biofunctionalization with regard to indirect immunochemical (competitive) detection of ochratoxin A. Sensing areas are examined after: modification with (3-aminopropyl)triethoxysilane, spotting of OTA-ovalbumin conjugate (probe) from solutions with different concentration, blocking with bovine serum albumin, reaction with OTA-specific mouse monoclonal antibody followed by goat anti-mouse IgG secondary antibody. Component mass loadings of all proteins involved in immunodetection are determined from TOF-SIMS micro-analysis combined with ellipsometry of planar surfaces. These data show that partial desorption of surface-bound probe and blocking protein takes place upon primary immunoreaction to a degree that depends on probe concentration in spotting solution. Taking into account this desorption, apparent binding stoichiometry of both antibodies in immune complexes formed onto chip surface is determined more accurately than the respective evaluation based on real-time sensor response. In addition, mass loadings for probe and secondary antibody is observed to saturate for optimum probe concentrations. Also, principal component analysis of TOF-SIMS data could resolve both immunoreactions and biofunctionalization and discriminate surfaces prepared with optimum probe concentrations from those prepared using suboptimum ones.

Fabrication and Evaluation of a Micro(Bio)Sensor Array Chip for Multiple Parallel Measurements of Important Cell Biomarkers

PubMed Central

Pemberton, Roy M.; Cox, Timothy; Tuffin, Rachel; Drago, Guido A.; Griffiths, John; Pittson, Robin; Johnson, Graham; Xu, Jinsheng; Sage, Ian C.; Davies, Rhodri; Jackson, Simon K.; Kenna, Gerry; Luxton, Richard; Hart, John P.

2014-01-01

This report describes the design and development of an integrated electrochemical cell culture monitoring system, based on enzyme-biosensors and chemical sensors, for monitoring indicators of mammalian cell metabolic status. MEMS technology was used to fabricate a microwell-format silicon platform including a thermometer, onto which chemical sensors (pH, O2) and screen-printed biosensors (glucose, lactate), were grafted/deposited. Microwells were formed over the fabricated sensors to give 5-well sensor strips which were interfaced with a multipotentiostat via a bespoke connector box interface. The operation of each sensor/biosensor type was examined individually, and examples of operating devices in five microwells in parallel, in either potentiometric (pH sensing) or amperometric (glucose biosensing) mode are shown. The performance characteristics of the sensors/biosensors indicate that the system could readily be applied to cell culture/toxicity studies. PMID:25360580

Selective detection of hypertoxic organophosphates pesticides via PDMS composite based acetylcholinesterase-inhibition biosensor.

PubMed

Zhao, Wei; Ge, Pei-Yu; Xu, Jing-Juan; Chen, Hong-Yuan

2009-09-01

We report on a pair of highly sensitive amperometric biosensors for organophosphate pesticides (OPs) based on assembling acetylcholinesterase (AChE) on poly(dimethylsiloxane) (PDMS)-poly(diallydimethylemmonium) (PDDA)/gold nanoparticles (AuNPs) composite film. Two AChE immobilization strategies are proposed based on the composite film with hydrophobic and hydrophilic surface tailored by oxygen plasma. The twin biosensors show interesting different electrochemical performances. The hydrophobic surface based PDMS-PDDAN AuNPs/choline oxidase (ChO)/AChE biosensor (biosensor-1) shows excellent stability and unique selectivity to hypertoxic organophosphate. At optimal conditions, this biosensor-1 could measure 5.0 x 10(-10) g/L paraoxon and 1.0 x 10(-9) g/L parathion. As for the hydrophilic surface based biosensor (biosensor-2), it shows no selectivity but can be commonly used for the detection of most OPs. Based on the structure of AChE, it is assumed that via the hydrophobic interaction between enzyme molecules and hydrophobic surface, the enzyme active sites surrounded by hydrophobic amino acids face toward the surface and get better protection from OPs. This assumption may explain the different performances of the twin biosensors and especially the unique selectivity of biosensor-1 to hypertoxic OPs. Real sample detection was performed and the omethoate residue on Cottomrose Hibiscus leaves was detected with biosensor-1.

Surface plasmon resonance biosensing: Approaches for screening and characterising antibodies for food diagnostics.

PubMed

Yakes, B J; Buijs, J; Elliott, C T; Campbell, K

2016-08-15

Research in biosensing approaches as alternative techniques for food diagnostics for the detection of chemical contaminants and foodborne pathogens has increased over the last twenty years. The key component of such tests is the biorecognition element whereby polyclonal or monoclonal antibodies still dominate the market. Traditionally the screening of sera or cell culture media for the selection of polyclonal or monoclonal candidate antibodies respectively has been performed by enzyme immunoassays. For niche toxin compounds, enzyme immunoassays can be expensive and/or prohibitive methodologies for antibody production due to limitations in toxin supply for conjugate production. Automated, self-regenerating, chip-based biosensors proven in food diagnostics may be utilised as rapid screening tools for antibody candidate selection. This work describes the use of both single channel and multi-channel surface plasmon resonance (SPR) biosensors for the selection and characterisation of antibodies, and their evaluation in shellfish tissue as standard techniques for the detection of domoic acid, as a model toxin compound. The key advantages in the use of these biosensor techniques for screening hybridomas in monoclonal antibody production were the real time observation of molecular interaction and rapid turnaround time in analysis compared to enzyme immunoassays. The multichannel prototype instrument was superior with 96 analyses completed in 2h compared to 12h for the single channel and over 24h for the ELISA immunoassay. Antibodies of high sensitivity, IC50's ranging from 4.8 to 6.9ng/mL for monoclonal and 2.3-6.0ng/mL for polyclonal, for the detection of domoic acid in a 1min analysis time were selected. Although there is a progression for biosensor technology towards low cost, multiplexed portable diagnostics for the food industry, there remains a place for laboratory-based SPR instrumentation for antibody development for food diagnostics as shown herein. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhancing the sensitivity of slow light MZI biosensors through multi-hole defects

NASA Astrophysics Data System (ADS)

Qin, Kun; Zhao, Yiliang; Hu, Shuren; Weiss, Sharon M.

2018-02-01

We demonstrate enhanced detection sensitivity of a slow light Mach-Zehnder interferometer (MZI) sensor by incorporating multi-hole defects (MHDs). Slow light MZI biosensors with a one-dimensional photonic crystal in one arm have been previously shown to improve the performance of traditional MZI sensors based on the increased lightmatter interaction that takes place in the photonic crystal region of the structure. Introducing MHDs in the photonic crystal region increases the available surface area for molecular attachment and further increases the enhanced lightmatter interaction capability of slow light MZIs. The MHDs allow analyte to interact with a greater fraction of the guided wave in the MZI. For a slow light MHD MZI sensor with a 16 μm long sensing arm, a bulk sensitivity of 151,000 rad/RIU-cm is demonstrated experimentally, which is approximately two-fold higher than our previously reported slow light MZI sensors and thirteen-fold higher than traditional MZI biosensors with millimeter length sensing regions. For the label-free detection of nucleic acids, the slow light MZI with MHDs also exhibits a two-fold sensitivity improvement in experiment compared to the slow light MZI without MHDs. Because the detection sensitivity of slow light MHD MZIs scales with the length of the sensing arm, the tradeoff between detection limit and device size can be appropriately mitigated for different applications. All experimental results presented in this work are in good agreement with finite difference-time domain-calculations. Overall, the slow light MZI biosensors with MHDs are a promising platform for highly sensitive and multiplexed lab-on-chip systems.

Sensitive and rapid immunoassay for parathyroid hormone using magnetic particle labels and magnetic actuation.

PubMed

Dittmer, W U; de Kievit, P; Prins, M W J; Vissers, J L M; Mersch, M E C; Martens, M F W C

2008-09-30

A rapid method for the sensitive detection of proteins using actuated magnetic particle labels, which are measured with a giant magneto-resistive (GMR) biosensor, is described. The technique involves a 1-step sandwich immunoassay with no fluid replacement steps. The various assay binding reactions as well as the bound/free separation are entirely controlled by magnetic forces induced by electromagnets above and below the sensor chip. During the assay, particles conjugated with tracer antibodies are actuated through the sample for target capture, and rapidly brought to the sensor surface where they bind to immobilized capture antibodies. Weakly or unbound labels are removed with a magnetic force oriented away from the GMR sensor surface. For the measurement of parathyroid hormone (PTH), a detection limit in the 10 pM range is obtained with a total assay time of 15 min when 300 nm particles are used. The same sensitivity can be achieved in 5 min when 500 nm particles are used. If 500 nm particles are employed in a 15-minute assay, then 0.8 pM of PTH is detectable. The low sample volume, high analytical performance and high speed of the test coupled with the compact GMR biosensor make the system especially suitable for sensitive testing outside of laboratory environments.

Antibody modified gold nano-mushroom arrays for rapid detection of alpha-fetoprotein.

PubMed

Li, Wanbo; Jiang, Xueqin; Xue, Jiancai; Zhou, Zhangkai; Zhou, Jianhua

2015-06-15

Localized surface plasmon resonance (LSPR) combined with immunoassay shows greatly potential in fast detection of tumor markers. In this paper, a highly sensitive LSPR substrate has been fabricated and modified for direct detection of alpha-fetoprotein (AFP). The biosensor was prepared by interference lithography, and modified by covalently immobilizing anti-AFP on the surface of gold nano-mushroom arrays (GNMA). The modification process was investigated by Vis-NIR reflectance spectra and cyclic voltammogram measurements. We revealed the optical properties of the modified GNMA by measuring the Vis-NIR reflectance spectra and simulating its electric intensity field distribution under light illumination. The GNMA substrate was highly sensitive, with a refractive index sensitivity of ~465 nm/RIU. The substrate can be applied to label-free detection of AFP, with the linear range and the limit of detection determined to be 20-200 ng/mL and 24 ng/mL (S/N=3), respectively. We also demonstrated its clinical application by directly detecting AFP in human serum samples. It is expected that our biosensor could be integrated on microfluidic chips for high-throughput detection in portable early diagnosis, post-operative and point-of-care (POC) in clinical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

A Wireless Biomedical Signal Interface System-on-Chip for Body Sensor Networks.

PubMed

Lei Wang; Guang-Zhong Yang; Jin Huang; Jinyong Zhang; Li Yu; Zedong Nie; Cumming, D R S

2010-04-01

Recent years have seen the rapid development of biosensor technology, system-on-chip design, wireless technology. and ubiquitous computing. When assembled into an autonomous body sensor network (BSN), the technologies become powerful tools in well-being monitoring, medical diagnostics, and personal connectivity. In this paper, we describe the first demonstration of a fully customized mixed-signal silicon chip that has most of the attributes required for use in a wearable or implantable BSN. Our intellectual-property blocks include low-power analog sensor interface for temperature and pH, a data multiplexing and conversion module, a digital platform based around an 8-b microcontroller, data encoding for spread-spectrum wireless transmission, and a RF section requiring very few off-chip components. The chip has been fully evaluated and tested by connection to external sensors, and it satisfied typical system requirements.

A comparative analysis of localized and propagating surface plasmon resonance sensors: the binding of concanavalin a to a monosaccharide functionalized self-assembled monolayer.

PubMed

Yonzon, Chanda Ranjit; Jeoung, Eunhee; Zou, Shengli; Schatz, George C; Mrksich, Milan; Van Duyne, Richard P

2004-10-06

A comparative analysis of the properties of two optical biosensor platforms: (1) the propagating surface plasmon resonance (SPR) sensor based on a planar, thin film gold surface and (2) the localized surface plasmon resonance (LSPR) sensor based on surface confined Ag nanoparticles fabricated by nanosphere lithography (NSL) are presented. The binding of Concanavalin A (ConA) to mannose-functionalized self-assembled monolayers (SAMs) was chosen to highlight the similarities and differences between the responses of the real-time angle shift SPR and wavelength shift LSPR biosensors. During the association phase in the real-time binding studies, both SPR and LSPR sensors exhibited qualitatively similar signal vs time curves. However, in the dissociation phase, the SPR sensor showed an approximately 5 times greater loss of signal than the LSPR sensor. A comprehensive set of nonspecific binding studies demonstrated that this signal difference was not the consequence of greater nonspecific binding to the LSPR sensor but rather a systematic function of the Ag nanoparticle's nanoscale structure. Ag nanoparticles with larger aspect ratios showed larger dissociation phase responses than those with smaller aspect ratios. A theoretical analysis based on finite element electrodynamics demonstrates that this results from the characteristic decay length of the electromagnetic fields surrounding Ag nanoparticles being of comparable dimensions to the ConA molecules. Finally, an elementary (2 x 1) multiplexed version of an LSPR carbohydrate sensing chip to probe the simultaneous binding of ConA to mannose and galactose-functionalized SAMs has been demonstrated.

Surface and Electrical Characterization of Ag/AgCl Pseudo-Reference Electrodes Manufactured with Commercially Available PCB Technologies

PubMed Central

Moschou, Despina; Trantidou, Tatiana; Regoutz, Anna; Carta, Daniela; Morgan, Hywel; Prodromakis, Themistoklis

2015-01-01

Lab-on-Chip is a technology that could potentially revolutionize medical Point-of-Care diagnostics. Considerable research effort is focused towards innovating production technologies that will make commercial upscaling financially viable. Printed circuit board manufacturing techniques offer several prospects in this field. Here, we present a novel approach to manufacturing Printed Circuit Board (PCB)-based Ag/AgCl reference electrodes, an essential component of biosensors. Our prototypes were characterized both structurally and electrically. Scanning Electron Microscopy (SEM) and X-Ray Photoelectron Spectroscopy (XPS) were employed to evaluate the electrode surface characteristics. Electrical characterization was performed to determine stability and pH dependency. Finally, we demonstrate utilization along with PCB pH sensors, as a step towards a fully integrated PCB platform, comparing performance with discrete commercial reference electrodes. PMID:26213940

Silicon-on-insulator sensors using integrated resonance-enhanced defect-mediated photodetectors.

PubMed

Fard, Sahba Talebi; Murray, Kyle; Caverley, Michael; Donzella, Valentina; Flueckiger, Jonas; Grist, Samantha M; Huante-Ceron, Edgar; Schmidt, Shon A; Kwok, Ezra; Jaeger, Nicolas A F; Knights, Andrew P; Chrostowski, Lukas

2014-11-17

A resonance-enhanced, defect-mediated, ring resonator photodetector has been implemented as a single unit biosensor on a silicon-on-insulator platform, providing a cost effective means of integrating ring resonator sensors with photodetectors for lab-on-chip applications. This method overcomes the challenge of integrating hybrid photodetectors on the chip. The demonstrated responsivity of the photodetector-sensor was 90 mA/W. Devices were characterized using refractive index modified solutions and showed sensitivities of 30 nm/RIU.

An integrated platform for biomolecule interaction analysis

NASA Astrophysics Data System (ADS)

Jan, Chia-Ming; Tsai, Pei-I.; Chou, Shin-Ting; Lee, Shu-Sheng; Lee, Chih-Kung

2013-02-01

We developed a new metrology platform which can detect real-time changes in both a phase-interrogation mode and intensity mode of a SPR (surface plasmon resonance). We integrated a SPR and ellipsometer to a biosensor chip platform to create a new biomolecular interaction measurement mechanism. We adopted a conductive ITO (indium-tinoxide) film to the bio-sensor platform chip to expand the dynamic range and improve measurement accuracy. The thickness of the conductive film and the suitable voltage constants were found to enhance performance. A circularly polarized ellipsometry configuration was incorporated into the newly developed platform to measure the label-free interactions of recombinant human C-reactive protein (CRP) with immobilized biomolecule target monoclonal human CRP antibody at various concentrations. CRP was chosen as it is a cardiovascular risk biomarker and is an acute phase reactant as well as a specific prognostic indicator for inflammation. We found that the sensitivity of a phaseinterrogation SPR is predominantly dependent on the optimization of the sample incidence angle. The effect of the ITO layer effective index under DC and AC effects as well as an optimal modulation were experimentally performed and discussed. Our experimental results showed that the modulated dynamic range for phase detection was 10E-2 RIU based on a current effect and 10E-4 RIU based on a potential effect of which a 0.55 (°/RIU) measurement was found by angular-interrogation. The performance of our newly developed metrology platform was characterized to have a higher sensitivity and less dynamic range when compared to a traditional full-field measurement system.

A Label-Free Microfluidic Biosensor for Activity Detection of Single Microalgae Cells Based on Chlorophyll Fluorescence

PubMed Central

Wang, Junsheng; Sun, Jinyang; Song, Yongxin; Xu, Yongyi; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

2013-01-01

Detection of living microalgae cells is very important for ballast water treatment and analysis. Chlorophyll fluorescence is an indicator of photosynthetic activity and hence the living status of plant cells. In this paper, we developed a novel microfluidic biosensor system that can quickly and accurately detect the viability of single microalgae cells based on chlorophyll fluorescence. The system is composed of a laser diode as an excitation light source, a photodiode detector, a signal analysis circuit, and a microfluidic chip as a microalgae cell transportation platform. To demonstrate the utility of this system, six different living and dead algae samples (Karenia mikimotoi Hansen, Chlorella vulgaris, Nitzschia closterium, Platymonas subcordiformis, Pyramidomonas delicatula and Dunaliella salina) were tested. The developed biosensor can distinguish clearly between the living microalgae cells and the dead microalgae cells. The smallest microalgae cells that can be detected by using this biosensor are 3 μm ones. Even smaller microalgae cells could be detected by increasing the excitation light power. The developed microfluidic biosensor has great potential for in situ ballast water analysis. PMID:24287532

JPRS Report, Science & Technology Europe

DTIC Science & Technology

1988-06-09

Vico, whose potato chips are known to everyone, the Glucoprocesseur is nevertheless capable of reducing sample analysis times by 75 per- cent—a test...faltering for reasons that are more political than technical, actually already has its biosensors. The Lyonnaise des Eaux company and the Compagnie

Epoxy Chip-in-Carrier Integration and Screen-Printed Metalization for Multichannel Microfluidic Lab-on-CMOS Microsystems.

PubMed

Li, Lin; Yin, Heyu; Mason, Andrew J

2018-04-01

The integration of biosensors, microfluidics, and CMOS instrumentation provides a compact lab-on-CMOS microsystem well suited for high throughput measurement. This paper describes a new epoxy chip-in-carrier integration process and two planar metalization techniques for lab-on-CMOS that enable on-CMOS electrochemical measurement with multichannel microfluidics. Several design approaches with different fabrication steps and materials were experimentally analyzed to identify an ideal process that can achieve desired capability with high yield and low material and tool cost. On-chip electrochemical measurements of the integrated assembly were performed to verify the functionality of the chip-in-carrier packaging and its capability for microfluidic integration. The newly developed CMOS-compatible epoxy chip-in-carrier process paves the way for full implementation of many lab-on-CMOS applications with CMOS ICs as core electronic instruments.

Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations

PubMed Central

Wall, Mark J.

2016-01-01

Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and glutamate. A great deal of experimental and modeling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modeling and experimentally verify our predictions in diffusive environments. NEW & NOTEWORTHY Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue environment and experimentally verify our key predictions. PMID:27927788

Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations.

PubMed

Newton, Adam J H; Wall, Mark J; Richardson, Magnus J E

2017-03-01

Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose, and glutamate. A great deal of experimental and modeling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modeling and experimentally verify our predictions in diffusive environments. NEW & NOTEWORTHY Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue environment and experimentally verify our key predictions. Copyright © 2017 the American Physiological Society.

DNA decorated carbon nanotube sensors on CMOS circuitry for environmental monitoring

NASA Astrophysics Data System (ADS)

Liu, Yu; Chen, Chia-Ling; Agarwal, V.; Li, Xinghui; Sonkusale, S.; Dokmeci, Mehmet R.; Wang, Ming L.

2010-04-01

Single-walled carbon nanotubes (SWNTs) with their large surface area, high aspect ratio are one of the novel materials which have numerous attractive features amenable for high sensitivity sensors. Several nanotube based sensors including, gas, chemical and biosensors have been demonstrated. Moreover, most of these sensors require off chip components to detect the variations in the signals making them complicated and hard to commercialize. Here we present a novel complementary metal oxide semiconductor (CMOS) integrated carbon nanotube sensors for portable high sensitivity chemical sensing applications. Multiple zincation steps have been developed to ascertain proper electrical connectivity between the carbon nanotubes and the foundry made CMOS circuitry. The SWNTs have been integrated onto (CMOS) circuitry as the feedback resistor of a Miller compensated operational amplifier utilizing low temperature Dielectrophoretic (DEP) assembly process which has been tailored to be compatible with the post-CMOS integration at the die level. Building nanotube sensors directly on commercial CMOS circuitry allows single chip solutions eliminating the need for long parasitic lines and numerous wire bonds. The carbon nanotube sensors realized on CMOS circuitry show strong response to various vapors including Dimethyl methylphosphonate and Dinitrotoluene. The remarkable set of attributes of the SWNTs realized on CMOS electronic chips provides an attractive platform for high sensitivity portable nanotube based bio and chemical sensors.

Semiconductor sensor embedded microfluidic chip for protein biomarker detection using a bead-based immunoassay combined with deoxyribonucleic acid strand labeling.

PubMed

Lin, Yen-Heng; Peng, Po-Yu

2015-04-15

Two major issues need to be addressed in applying semiconductor biosensors to detecting proteins in immunoassays. First, the length of the antibody on the sensor surface surpasses the Debye lengths (approximately 1 nm, in normal ionic strength solution), preventing certain specifically bound proteins from being tightly attached to the sensor surface. Therefore, these proteins do not contribute to the sensor's surface potential change. Second, these proteins carry a small charge and can be easily affected by the pH of the surrounding solution. This study proposes a magnetic bead-based immunoassay using a secondary antibody to label negatively charged DNA fragments for signal amplification. An externally imposed magnetic force attaches the analyte tightly to the sensor surface, thereby effectively solving the problem of the analyte protein's distance to the sensor surface surpassing the Debye lengths. In addition, a normal ion intensity buffer can be used without dilution for the proposed method. Experiments revealed that the sensitivity can be improved by using a longer DNA fragment for labeling and smaller magnetic beads as solid support for the antibody. By using a 90 base pair DNA label, the signal was 15 times greater than that without labeling. In addition, by using a 120 nm magnetic bead, a minimum detection limit of 12.5 ng mL(-1) apolipoprotein A1 can be measured. Furthermore, this study integrates a semiconductor sensor with a microfluidic chip. With the help of microvalves and micromixers in the chip, the length of the mixing step for each immunoassay has been reduced from 1h to 20 min, and the sample volume has been reduced from 80 μL to 10 μL. In practice, a protein biomarker in a urinary bladder cancer patient's urine was successfully measured using this technique. This study provides a convenient and effective method to measure protein using a semiconductor sensor. Copyright © 2015 Elsevier B.V. All rights reserved.

Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications.

PubMed

Washburn, Adam L; Bailey, Ryan C

2011-01-21

By leveraging advances in semiconductor microfabrication technologies, chip-integrated optical biosensors are poised to make an impact as scalable and multiplexable bioanalytical measurement tools for lab-on-a-chip applications. In particular, waveguide-based optical sensing technology appears to be exceptionally amenable to chip integration and miniaturization, and, as a result, the recent literature is replete with examples of chip-integrated waveguide sensing platforms developed to address a wide range of contemporary analytical challenges. As an overview of the most recent advances within this dynamic field, this review highlights work from the last 2-3 years in the areas of grating-coupled, interferometric, photonic crystal, and microresonator waveguide sensors. With a focus towards device integration, particular emphasis is placed on demonstrations of biosensing using these technologies within microfluidically controlled environments. In addition, examples of multiplexed detection and sensing within complex matrices--important features for real-world applicability--are given special attention.

Fiber Optic Surface Plasmon Resonance-Based Biosensor Technique: Fabrication, Advancement, and Application.

PubMed

Liang, Gaoling; Luo, Zewei; Liu, Kunping; Wang, Yimin; Dai, Jianxiong; Duan, Yixiang

2016-05-03

Fiber optic-based biosensors with surface plasmon resonance (SPR) technology are advanced label-free optical biosensing methods. They have brought tremendous progress in the sensing of various chemical and biological species. This review summarizes four sensing configurations (prism, grating, waveguide, and fiber optic) with two ways, attenuated total reflection (ATR) and diffraction, to excite the surface plasmons. Meanwhile, the designs of different probes (U-bent, tapered, and other probes) are also described. Finally, four major types of biosensors, immunosensor, DNA biosensor, enzyme biosensor, and living cell biosensor, are discussed in detail for their sensing principles and applications. Future prospects of fiber optic-based SPR sensor technology are discussed.

Study and development of label-free optical biosensors for biomedical applications

NASA Astrophysics Data System (ADS)

Choi, Charles J.

For the majority of assays currently performed, fluorescent or colorimetric chemical labels are commonly attached to the molecules under study so that they may be readily visualized. The methods of using labels to track biomolecular binding events are very sensitive and effective, and are employed as standardized assay protocol across research labs worldwide. However, using labels induces experimental uncertainties due to the effect of the label on molecular conformation, active binding sites, or inability to find an appropriate label that functions equivalently for all molecules in an experiment. Therefore, the ability to perform highly sensitive biochemical detection without the use of fluorescent labels would further simplify assay protocols and would provide quantitative kinetic data, while removing experimental artifacts from fluorescent quenching, shelf-life, and background fluorescence phenomena. In view of the advantages mentioned above, the study and development of optical label-free sensor technologies have been undertaken here. In general, label-free photonic crystal (PC) biosensors and metal nanodome array surface-enhanced Raman scattering (SERS) substrates, both of which are fabricated by nanoreplica molding process, have been used as the method to attack the problem. Chapter 1 shows the work on PC label-free biosensor incorporated microfluidic network for bioassay performance enhancement and kinetic reaction rate constant determination. Chapter 2 describes the work on theoretical and experimental comparison of label-free biosensing in microplate, microfluidic, and spot-based affinity capture assays. Chapter 3 shows the work on integration of PC biosensor with actuate-to-open valve microfluidic chip for pL-volume combinatorial mixing and screening application. In Chapter 4, the development and characterization of SERS nanodome array is shown. Lastly, Chapter 5 describes SERS nanodome sensor incorporated tubing for point-of-care monitoring of intravenous drugs and metabolites.

Optical biosensors.

PubMed

Damborský, Pavel; Švitel, Juraj; Katrlík, Jaroslav

2016-06-30

Optical biosensors represent the most common type of biosensor. Here we provide a brief classification, a description of underlying principles of operation and their bioanalytical applications. The main focus is placed on the most widely used optical biosensors which are surface plasmon resonance (SPR)-based biosensors including SPR imaging and localized SPR. In addition, other optical biosensor systems are described, such as evanescent wave fluorescence and bioluminescent optical fibre biosensors, as well as interferometric, ellipsometric and reflectometric interference spectroscopy and surface-enhanced Raman scattering biosensors. The optical biosensors discussed here allow the sensitive and selective detection of a wide range of analytes including viruses, toxins, drugs, antibodies, tumour biomarkers and tumour cells. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Submicron magnetic core conducting polypyrrole polymer shell: Preparation and characterization.

PubMed

Tenório-Neto, Ernandes Taveira; Baraket, Abdoullatif; Kabbaj, Dounia; Zine, Nadia; Errachid, Abdelhamid; Fessi, Hatem; Kunita, Marcos Hiroiuqui; Elaissari, Abdelhamid

2016-04-01

Magnetic particles are of great interest in various biomedical applications, such as, sample preparation, in vitro biomedical diagnosis, and both in vivo diagnosis and therapy. For in vitro applications and especially in labs-on-a-chip, microfluidics, microsystems, or biosensors, the needed magnetic dispersion should answer various criteria, for instance, submicron size in order to avoid a rapid sedimentation rate, fast separations under an applied magnetic field, and appreciable colloidal stability (stable dispersion under shearing process). Then, the aim of this work was to prepare highly magnetic particles with a magnetic core and conducting polymer shell particles in order to be used not only as a carrier, but also for the in vitro detection step. The prepared magnetic seed dispersions were functionalized using pyrrole and pyrrole-2-carboxylic acid. The obtained core-shell particles were characterized in terms of particle size, size distribution, magnetization properties, FTIR analysis, surface morphology, chemical composition, and finally, the conducting property of those particles were evaluated by cyclic voltammetry. The obtained functional submicron highly magnetic particles are found to be conducting material bearing function carboxylic group on the surface. These promising conducting magnetic particles can be used for both transport and lab-on-a-chip detection. Copyright © 2015. Published by Elsevier B.V.

Analytical applications of aptamers

NASA Astrophysics Data System (ADS)

Tombelli, S.; Minunni, M.; Mascini, M.

2007-05-01

Aptamers are single stranded DNA or RNA ligands which can be selected for different targets starting from a library of molecules containing randomly created sequences. Aptamers have been selected to bind very different targets, from proteins to small organic dyes. Aptamers are proposed as alternatives to antibodies as biorecognition elements in analytical devices with ever increasing frequency. This in order to satisfy the demand for quick, cheap, simple and highly reproducible analytical devices, especially for protein detection in the medical field or for the detection of smaller molecules in environmental and food analysis. In our recent experience, DNA and RNA aptamers, specific for three different proteins (Tat, IgE and thrombin), have been exploited as bio-recognition elements to develop specific biosensors (aptasensors). These recognition elements have been coupled to piezoelectric quartz crystals and surface plasmon resonance (SPR) devices as transducers where the aptamers have been immobilized on the gold surface of the crystals electrodes or on SPR chips, respectively.

Fabrication of microfluidic integrated biosensor

NASA Astrophysics Data System (ADS)

Adam, Tijjani; Dhahi, Th S.; Mohammed, Mohammed; Hashim, U.; Noriman, N. Z.; Dahham, Omar S.

2017-09-01

An event of miniaturizing for sensor systems to carry out biological diagnostics are gaining wade spread acceptance. The system may contain several different sensor units for the detection of specific analyte, the analyte to be detected might be any kind of biological molecules (DNA, mRNA or proteins) or chemical substances. In most cases, the detection is based on receptor-ligand binding like DNA hybridization or antibody-antigen interaction, achieving this on a nanostructure. DNA or protein must be attached to certain locations within the structure. Critical for this is to have a robust binding chemistry to the surface in the microstructure. Here we successfully designed and fabricated microfluidics element for passive fluid delivery into polysilicon Nanowire sensing domain, we further demonstrated a very simple and effective way of integrating the two devices to give full functionalities of laboratory on a single chip. The sensing element was successfully surface modified and tested on real biomedical clinical sample for evaluation and validation.

Grating coupled SPR microarray analysis of proteins and cells in blood from mice with breast cancer.

PubMed

Mendoza, A; Torrisi, D M; Sell, S; Cady, N C; Lawrence, D A

2016-01-21

Biomarker discovery for early disease diagnosis is highly important. Of late, much effort has been made to analyze complex biological fluids in an effort to develop new markers specific for different cancer types. Recent advancements in label-free technologies such as surface plasmon resonance (SPR)-based biosensors have shown promise as a diagnostic tool since there is no need for labeling or separation of cells. Furthermore, SPR can provide rapid, real-time detection of antigens from biological samples since SPR is highly sensitive to changes in surface-associated molecular and cellular interactions. Herein, we report a lab-on-a-chip microarray biosensor that utilizes grating-coupled surface plasmon resonance (GCSPR) and grating-coupled surface plasmon coupled fluorescence (GCSPCF) imaging to detect circulating tumor cells (CTCs) from a mouse model (FVB-MMTV-PyVT). GCSPR and GCSPCF analysis was accomplished by spotting antibodies to surface cell markers, cytokines and stress proteins on a nanofabricated GCSPR microchip and screening blood samples from FVB control mice or FVB-MMTV-PyVT mice with developing mammary carcinomas. A transgenic MMTV-PyVT mouse derived cancer cell line was also analyzed. The analyses indicated that CD24, CD44, CD326, CD133 and CD49b were expressed in both cell lines and in blood from MMTV-PyVT mice. Furthermore, cytokines such as IL-6, IL-10 and TNF-α, along with heat shock proteins HSP60, HSP27, HSc70(HSP73), HSP90 total, HSP70/HSc70, HSP90, HSP70, HSP90 alpha, phosphotyrosine and HSF-1 were overexpressed in MMTV-PyVT mice.

Silicon on-chip bandpass filters for the multiplexing of high sensitivity photonic crystal microcavity biosensors

PubMed Central

Chakravarty, Swapnajit; Yang, Chun-Ju; Wang, Zheng; Tang, Naimei; Fan, Donglei; Chen, Ray T.

2015-01-01

A method for the dense integration of high sensitivity photonic crystal (PC) waveguide based biosensors is proposed and experimentally demonstrated on a silicon platform. By connecting an additional PC waveguide filter to a PC microcavity sensor in series, a transmission passband is created, containing the resonances of the PC microcavity for sensing purpose. With proper engineering of the passband, multiple high sensitivity PC microcavity sensors can be integrated into microarrays and be interrogated simultaneously between a single input and a single output port. The concept was demonstrated with a 2-channel L55 PC biosensor array containing PC waveguide filters. The experiment showed that the sensors on both channels can be monitored simultaneously from a single output spectrum. Less than 3 dB extra loss for the additional PC waveguide filter is observed. PMID:25829549

Trapping of vesicles on patterned surfaces by physisorption for potential biosensing applications.

PubMed

Bera, L K; Ong, Kian Soo; Wong, Zheng Zheng; Fu, Zhikang; Nallani, Madhavan; Shea, Sean O'

2012-01-01

The pre-defined selective positioning of a controlled number of vesicles on a rigid substrate is crucial in many potential applications such as diagnostics, biosensors, lab-on-a chip, microanalyses and reaction chambers. In this paper, the vesicles made up of block copolymer using Poly [-(2-methyloxazoline) -poly- (dimethylsiloxane)-poly- (2-methyloxazoline)] (ABA) with dimensions of 100-200 nm are trapped by physisorption on hydrophilic surfaces. We discuss the protocols established for vesicle trapping. The optimum conditions obtained for physisorption is 15 minutes incubation followed by one cycle of DI water rinse. Trapping of 1-10 vesicles in lobe shape micro-wells fabricated by photo lithography using photoresist on UltraStick(™) slides was demonstrated. To overcome the issue of amalgamation of emitted light from optically sensitive photoresist and fluorescently tagged vesicles, an alternative approach of Si/SiO(2) microwell array coupled with APTES (3-AminoPropylTriEthoxySilane) treated bottom surfaces was developed.

The construction, fouling and enzymatic cleaning of a textile dye surface.

PubMed

Onaizi, Sagheer A; He, Lizhong; Middelberg, Anton P J

2010-11-01

The enzymatic cleaning of a rubisco protein stain bound onto Surface Plasmon Resonance (SPR) biosensor chips having a dye-bound upper layer is investigated. This novel method allowed, for the first time, a detailed kinetic study of rubisco cleanability (defined as fraction of adsorbed protein removed from a surface) from dyed surfaces (mimicking fabrics) at different enzyme concentrations. Analysis of kinetic data using an established mathematical model able to decouple enzyme transfer and reaction processes [Onaizi, He, Middelberg, Chem. Eng. Sci. 64 (2008) 3868] revealed a striking effect of dyeing on enzymatic cleaning performance. Specifically, the absolute rate constants for enzyme transfer to and from a dye-bound rubisco stain were significantly higher than reported previously for un-dyed surfaces. These increased transfer rates resulted in higher surface cleanability. Higher enzyme mobility (i.e., higher enzyme adsorption and desorption rates) at the liquid-dye interface was observed, consistent with previous suggestions that enzyme surface mobility is likely correlated with overall enzyme cleaning performance. Our results show that reaction engineering models of enzymatic action at surfaces may provide insight able to guide the design of better stain-resistant surfaces, and may also guide efforts to improve cleaning formulations. Copyright 2010 Elsevier Inc. All rights reserved.

Nanoporous-Gold-Based Electrode Morphology Libraries for Investigating Structure-Property Relationships in Nucleic Acid Based Electrochemical Biosensors.

PubMed

Matharu, Zimple; Daggumati, Pallavi; Wang, Ling; Dorofeeva, Tatiana S; Li, Zidong; Seker, Erkin

2017-04-19

Nanoporous gold (np-Au) electrode coatings significantly enhance the performance of electrochemical nucleic acid biosensors because of their three-dimensional nanoscale network, high electrical conductivity, facile surface functionalization, and biocompatibility. Contrary to planar electrodes, the np-Au electrodes also exhibit sensitive detection in the presence of common biofouling media due to their porous structure. However, the pore size of the nanomatrix plays a critical role in dictating the extent of biomolecular capture and transport. Small pores perform better in the case of target detection in complex samples by filtering out the large nonspecific proteins. On the other hand, larger pores increase the accessibility of target nucleic acids in the nanoporous structure, enhancing the detection limits of the sensor at the expense of more interference from biofouling molecules. Here, we report a microfabricated np-Au multiple electrode array that displays a range of electrode morphologies on the same chip for identifying feature sizes that reduce the nonspecific adsorption of proteins but facilitate the permeation of target DNA molecules into the pores. We demonstrate the utility of the electrode morphology library in studying DNA functionalization and target detection in complex biological media with a special emphasis on revealing ranges of electrode morphologies that mutually enhance the limit of detection and biofouling resilience. We expect this technique to assist in the development of high-performance biosensors for point-of-care diagnostics and facilitate studies on the electrode structure-property relationships in potential applications ranging from neural electrodes to catalysts.

Hybrid Macro-Micro Fluidics System for a Chip-Based Biosensor

DTIC Science & Technology

2002-02-18

fluids, including elements based on acoustic, centrifugal and electromagnetic forces; electroosmotic and electrophoretic effects; micro- mechanical and... mixed then degassed in a desiccator under vacuum for 30 min. The mixture was poured into the mold and allowed to stand for 5 min to self-level. The PDMS

Quantum confinement effects in lithographic sub-5 nm Silicon nanowire fets and integration of si nanograting fet biosensors

NASA Astrophysics Data System (ADS)

Trivedi, Krutarth B.

In recent years, widespread accessibility to reliable nanofabrication techniques such as high resolution electron beam lithography as well as development of innovative techniques such as nanoimprint lithography and chemically grown nano-materials like carbon nanotubes and graphene have spurred a boom in many fields of research involving nanoscale features and devices. The breadth of fields in which nanoscale features represent a new paradigm is staggering. Scaling down device dimensions to nanoscale enables non-classical quantum behavior and allows for interaction with similarly sized natural materials, like proteins and DNA, as never before, affording an unprecedented level of performance and control and fostering a seemingly boundless array of unique applications. Much of the research effort has been directed toward understanding such interactions to leverage the potential of nanoscale devices to enhance electronic and medical technology. In keeping with the spirit of application based research, my graduate research career has spanned the development of nanoimprint techniques and devices for novel applications, demonstration and study of sub-5 nm Si nanowire FETs exhibiting tangible performance enhancement over conventional MOSFETs, and development of an integrated Si nanograting FET based biosensor and related framework. The following dissertation details my work in fabrication of sub-5 nm Si nanowire FETs and characterization of quantum confinement effects in charge transport of FETs with 2D and 1D channel geometry, fabrication and characterization of schottky contact Si nanograting FET sensors, integration of miniaturized Si nanograting FET biosensors into Chip-in-Strip(c) packaging, development of an automated microfluidic sensing system, and investigation of electrochemical considerations in the Si nanograting FET biosensor gate stack followed by development of a novel patent-pending strategy for a lithographically patterned on-chip gate electrode.

Self-powered microneedle-based biosensors for pain-free high-accuracy measurement of glycaemia in interstitial fluid.

PubMed

Strambini, L M; Longo, A; Scarano, S; Prescimone, T; Palchetti, I; Minunni, M; Giannessi, D; Barillaro, G

2015-04-15

In this work a novel self-powered microneedle-based transdermal biosensor for pain-free high-accuracy real-time measurement of glycaemia in interstitial fluid (ISF) is reported. The proposed transdermal biosensor makes use of an array of silicon-dioxide hollow microneedles that are about one order of magnitude both smaller (borehole down to 4µm) and more densely-packed (up to 1×10(6)needles/cm(2)) than state-of-the-art microneedles used for biosensing so far. This allows self-powered (i.e. pump-free) uptake of ISF to be carried out with high efficacy and reliability in a few seconds (uptake rate up to 1µl/s) by exploiting capillarity in the microneedles. By coupling the microneedles operating under capillary-action with an enzymatic glucose biosensor integrated on the back-side of the needle-chip, glucose measurements are performed with high accuracy (±20% of the actual glucose level for 96% of measures) and reproducibility (coefficient of variation 8.56%) in real-time (30s) over the range 0-630mg/dl, thus significantly improving microneedle-based biosensor performance with respect to the state-of-the-art. Copyright © 2014 Elsevier B.V. All rights reserved.

Microfluidic-integrated biosensors: prospects for point-of-care diagnostics.

PubMed

Kumar, Suveen; Kumar, Saurabh; Ali, Md Azahar; Anand, Pinki; Agrawal, Ved Varun; John, Renu; Maji, Sagar; Malhotra, Bansi D

2013-11-01

There is a growing demand to integrate biosensors with microfluidics to provide miniaturized platforms with many favorable properties, such as reduced sample volume, decreased processing time, low cost analysis and low reagent consumption. These microfluidics-integrated biosensors would also have numerous advantages such as laminar flow, minimal handling of hazardous materials, multiple sample detection in parallel, portability and versatility in design. Microfluidics involves the science and technology of manipulation of fluids at the micro- to nano-liter level. It is predicted that combining biosensors with microfluidic chips will yield enhanced analytical capability, and widen the possibilities for applications in clinical diagnostics. The recent developments in microfluidics have helped researchers working in industries and educational institutes to adopt some of these platforms for point-of-care (POC) diagnostics. This review focuses on the latest advancements in the fields of microfluidic biosensing technologies, and on the challenges and possible solutions for translation of this technology for POC diagnostic applications. We also discuss the fabrication techniques required for developing microfluidic-integrated biosensors, recently reported biomarkers, and the prospects of POC diagnostics in the medical industry. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The heat-transfer method: a versatile low-cost, label-free, fast, and user-friendly readout platform for biosensor applications.

PubMed

van Grinsven, Bart; Eersels, Kasper; Peeters, Marloes; Losada-Pérez, Patricia; Vandenryt, Thijs; Cleij, Thomas J; Wagner, Patrick

2014-08-27

In recent years, biosensors have become increasingly important in various scientific domains including medicine, biology, and pharmacology, resulting in an increased demand for fast and effective readout techniques. In this Spotlight on Applications, we report on the recently developed heat-transfer method (HTM) and illustrate the use of the technique by zooming in on four established bio(mimetic) sensor applications: (i) mutation analysis in DNA sequences, (ii) cancer cell identification through surface-imprinted polymers, (iii) detection of neurotransmitters with molecularly imprinted polymers, and (iv) phase-transition analysis in lipid vesicle layers. The methodology is based on changes in heat-transfer resistance at a functionalized solid-liquid interface. To this extent, the device applies a temperature gradient over this interface and monitors the temperature underneath and above the functionalized chip in time. The heat-transfer resistance can be obtained by dividing this temperature gradient by the power needed to achieve a programmed temperature. The low-cost, fast, label-free and user-friendly nature of the technology in combination with a high degree of specificity, selectivity, and sensitivity makes HTM a promising sensor technology.

Capacitive Biosensors and Molecularly Imprinted Electrodes.

PubMed

Ertürk, Gizem; Mattiasson, Bo

2017-02-17

Capacitive biosensors belong to the group of affinity biosensors that operate by registering direct binding between the sensor surface and the target molecule. This type of biosensors measures the changes in dielectric properties and/or thickness of the dielectric layer at the electrolyte/electrode interface. Capacitive biosensors have so far been successfully used for detection of proteins, nucleotides, heavy metals, saccharides, small organic molecules and microbial cells. In recent years, the microcontact imprinting method has been used to create very sensitive and selective biorecognition cavities on surfaces of capacitive electrodes. This chapter summarizes the principle and different applications of capacitive biosensors with an emphasis on microcontact imprinting method with its recent capacitive biosensor applications.

Towards High Throughput Cell Growth Screening: A New CMOS 8 × 8 Biosensor Array for Life Science Applications.

PubMed

Nabovati, Ghazal; Ghafar-Zadeh, Ebrahim; Letourneau, Antoine; Sawan, Mohamad

2017-04-01

In this paper we present a CMOS capacitive sensor array as a compact and low-cost platform for high-throughput cell growth monitoring. The proposed biosensor, consists of an array of 8 × 8 CMOS fully differential charge-based capacitive measurement sensors. A DC-input Σ∆ modulator is used to convert the sensors' signals to digital values for reading out the biological/chemical data and further signal processing. To compensate the mismatch variations between the current mirror transistors, a calibration circuitry is proposed which removes the output voltage offset with less than 8.2% error. We validate the chip functionality using various organic solvents with different dielectric constants. Moreover, we show the response of the chip to different concentrations of Polystyrene beads that have the same electrical properties as the living cells. The experimental results show that the chip allows the detection of a wide range of Polystyrene beads concentrations from as low as 10 beads/ml to 100 k beads/ml. In addition, we present the experimental results from H1299 (human lung carcinoma) cell line where we show that the chip successfully allows the detection of cell attachment and growth over capacitive electrodes in a 30 h measurement time and the results are in consistency with the standard cell-based assays. The capability of proposed device for label-free and real-time detection of cell growth with very high sensitivity opens up the important opportunity for utilizing the device in rapid screening of living cells.

Application of bioconjugation chemistry on biosensor fabrication for detection of TAR-DNA binding protein 43.

PubMed

Dai, Yifan; Wang, Chunlai; Chiu, Liang-Yuan; Abbasi, Kevin; Tolbert, Blanton S; Sauvé, Geneviève; Yen, Yun; Liu, Chung-Chiun

2018-06-01

A simple-prepare, single-use and cost-effective, in vitro biosensor for the detection of TAR DNA-binding protein 43 (TDP-43), a biomarker of neuro-degenerative disorders, was designed, manufactured and tested. This study reports the first biosensor application for the detection of TDP-43 using a novel biosensor fabrication methodology. Bioconjugation mechanism was applied by conjugating anti-TDP 43 with N-succinimidyl S-acetylthioacetate (SATA) producing a thiol-linked anti-TDP 43, which was used to directly link with gold electrode surface, minimizing the preparation steps for biosensor fabrication and simplifying the biosensor surface. The effectiveness of this bioconjugation mechanism was evaluated and confirmed by FqRRM12 protein, using nuclear magnetic resonance (NMR). The surface coverage of the electrode was analyzed by Time-of-Flight-Secondary Ion Mass Spectrometry (TOF-SIMS). Differential pulse voltammetry (DPV) was acted as the detection transduction mechanism with the use of [Fe(CN) 6 ] 3-/4- redox probe. Human TDP-43 peptide of 0.0005 µg/mL to 2 µg/mL in undiluted human serum was analyzed using this TDP-43 biosensor. Interference study of the TDP-43 biosensor using β-amyloid 42 protein and T-tau protein confirmed the specificity of this TDP-43 biosensor. This bioconjugation chemistry based approach for biosensor fabrication circumvents tedious gold surface modification and functionalization while enabling specific detection of TDP-43 in less than 1 h with a low fabrication cost of a single biosensor less than $3. Copyright © 2018 Elsevier B.V. All rights reserved.

S-Layer Protein-Based Biosensors.

PubMed

Schuster, Bernhard

2018-04-11

The present paper highlights the application of bacterial surface (S-) layer proteins as versatile components for the fabrication of biosensors. One technologically relevant feature of S-layer proteins is their ability to self-assemble on many surfaces and interfaces to form a crystalline two-dimensional (2D) protein lattice. The S-layer lattice on the surface of a biosensor becomes part of the interface architecture linking the bioreceptor to the transducer interface, which may cause signal amplification. The S-layer lattice as ultrathin, highly porous structure with functional groups in a well-defined special distribution and orientation and an overall anti-fouling characteristics can significantly raise the limit in terms of variety and the ease of bioreceptor immobilization, compactness of bioreceptor molecule arrangement, sensitivity, specificity, and detection limit for many types of biosensors. The present paper discusses and summarizes examples for the successful implementation of S-layer lattices on biosensor surfaces in order to give a comprehensive overview on the application potential of these bioinspired S-layer protein-based biosensors.

Silicon on-chip bandpass filters for the multiplexing of high sensitivity photonic crystal microcavity biosensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Hai, E-mail: hai.yan@utexas.edu; Zou, Yi; Yang, Chun-Ju

A method for the dense integration of high sensitivity photonic crystal (PC) waveguide based biosensors is proposed and experimentally demonstrated on a silicon platform. By connecting an additional PC waveguide filter to a PC microcavity sensor in series, a transmission passband is created, containing the resonances of the PC microcavity for sensing purpose. With proper engineering of the passband, multiple high sensitivity PC microcavity sensors can be integrated into microarrays and be interrogated simultaneously between a single input and a single output port. The concept was demonstrated with a 2-channel L55 PC biosensor array containing PC waveguide filters. The experimentmore » showed that the sensors on both channels can be monitored simultaneously from a single output spectrum. Less than 3 dB extra loss for the additional PC waveguide filter is observed.« less

An Oxidase-Based Electrochemical Fluidic Sensor with High-Sensitivity and Low-Interference by On-Chip Oxygen Manipulation

PubMed Central

Radhakrishnan, Nitin; Park, Jongwon; Kim, Chang-Soo

2012-01-01

Utilizing a simple fluidic structure, we demonstrate the improved performance of oxidase-based enzymatic biosensors. Electrolysis of water is utilized to generate bubbles to manipulate the oxygen microenvironment close to the biosensor in a fluidic channel. For the proper enzyme reactions to occur, a simple mechanical procedure of manipulating bubbles was developed to maximize the oxygen level while minimizing the pH change after electrolysis. The sensors show improved sensitivities based on the oxygen dependency of enzyme reaction. In addition, this oxygen-rich operation minimizes the ratio of electrochemical interference signal by ascorbic acid during sensor operation (i.e., amperometric detection of hydrogen peroxide). Although creatinine sensors have been used as the model system in this study, this method is applicable to many other biosensors that can use oxidase enzymes (e.g., glucose, alcohol, phenol, etc.) to implement a viable component for in-line fluidic sensor systems. PMID:23012527

A Real-Time Thermal Self-Elimination Method for Static Mode Operated Freestanding Piezoresistive Microcantilever-Based Biosensors.

PubMed

Ku, Yu-Fu; Huang, Long-Sun; Yen, Yi-Kuang

2018-02-28

Here, we provide a method and apparatus for real-time compensation of the thermal effect of single free-standing piezoresistive microcantilever-based biosensors. The sensor chip contained an on-chip fixed piezoresistor that served as a temperature sensor, and a multilayer microcantilever with an embedded piezoresistor served as a biomolecular sensor. This method employed the calibrated relationship between the resistance and the temperature of piezoresistors to eliminate the thermal effect on the sensor, including the temperature coefficient of resistance (TCR) and bimorph effect. From experimental results, the method was verified to reduce the signal of thermal effect from 25.6 μV/°C to 0.3 μV/°C, which was approximately two orders of magnitude less than that before the processing of the thermal elimination method. Furthermore, the proposed approach and system successfully demonstrated its effective real-time thermal self-elimination on biomolecular detection without any thermostat device to control the environmental temperature. This method realizes the miniaturization of an overall measurement system of the sensor, which can be used to develop portable medical devices and microarray analysis platforms.

All Inkjet-Printed Amperometric Multiplexed Biosensors Based on Nanostructured Conductive Hydrogel Electrodes.

PubMed

Li, Lanlan; Pan, Lijia; Ma, Zhong; Yan, Ke; Cheng, Wen; Shi, Yi; Yu, Guihua

2018-06-13

Multiplexing, one of the main trends in biosensors, aims to detect several analytes simultaneously by integrating miniature sensors on a chip. However, precisely depositing electrode materials and selective enzymes on distinct microelectrode arrays remains an obstacle to massively produced multiplexed sensors. Here, we report on a "drop-on-demand" inkjet printing process to fabricate multiplexed biosensors based on nanostructured conductive hydrogels in which the electrode material and several kinds of enzymes were printed on the electrode arrays one by one by employing a multinozzle inkjet system. The whole inkjet printing process can be finished within three rounds of printing and only one round of alignment. For a page of sensor arrays containing 96 working electrodes, the printing process took merely ∼5 min. The multiplexed assays can detect glucose, lactate, and triglycerides in real time with good selectivity and high sensitivity, and the results in phosphate buffer solutions and calibration serum samples are comparable. The inkjet printing process exhibited advantages of high efficiency and accuracy, which opens substantial possibilities for massive fabrication of integrated multiplexed biosensors for human health monitoring.

Optical biosensor system with integrated microfluidic sample preparation and TIRF based detection

NASA Astrophysics Data System (ADS)

Gilli, Eduard; Scheicher, Sylvia R.; Suppan, Michael; Pichler, Heinz; Rumpler, Markus; Satzinger, Valentin; Palfinger, Christian; Reil, Frank; Hajnsek, Martin; Köstler, Stefan

2013-05-01

There is a steadily growing demand for miniaturized bioanalytical devices allowing for on-site or point-of-care detection of biomolecules or pathogens in applications like diagnostics, food testing, or environmental monitoring. These, so called labs-on-a-chip or micro-total analysis systems (μ-TAS) should ideally enable convenient sample-in - result-out type operation. Therefore, the entire process from sample preparation, metering, reagent incubation, etc. to detection should be performed on a single disposable device (on-chip). In the early days such devices were mainly fabricated using glass or silicon substrates and adapting established fabrication technologies from the electronics and semiconductor industry. More recently, the development focuses on the use of thermoplastic polymers as they allow for low-cost high volume fabrication of disposables. One of the most promising materials for the development of plastic based lab-on-achip systems are cyclic olefin polymers and copolymers (COP/COC) due to their excellent optical properties (high transparency and low autofluorescence) and ease of processing. We present a bioanalytical system for whole blood samples comprising a disposable plastic chip based on TIRF (total internal reflection fluorescence) optical detection. The chips were fabricated by compression moulding of COP and microfluidic channels were structured by hot embossing. These microfluidic structures integrate several sample pretreatment steps. These are the separation of erythrocytes, metering of sample volume using passive valves, and reagent incubation for competitive bioassays. The surface of the following optical detection zone is functionalized with specific capture probes in an array format. The plastic chips comprise dedicated structures for simple and effective coupling of excitation light from low-cost laser diodes. This enables TIRF excitation of fluorescently labeled probes selectively bound to detection spots at the microchannel surface. The fluorescence of these detection arrays is imaged using a simple set-up based on a digital consumer camera. Image processing for spot detection and intensity calculation is accomplished using customized software. Using this combined TIRF excitation and imaging based detection approach allowes for effective suppression of background fluorescence from the sample, multiplexed detection in an array format, as well as internal calibration and background correction.

Optical resonance-enhanced absorption-based near-field immunochip biosensor for allergen detection.

PubMed

Maier, Irene; Morgan, Michael R A; Lindner, Wolfgang; Pittner, Fritz

2008-04-15

An optical immunochip biosensor has been developed as a rapid method for allergen detection in complex food matrixes, and its application evaluated for the detection of the egg white allergens, ovalbumin and ovomucoid. The optical near-field phenomenon underlying the basic principle of the sensor design is called resonance-enhanced absorption (REA), which utilizes gold nanoparticles (Au NPs) as signal transducers in a highly sensitive interferometric setup. Using this approach, a novel, simple, and rapid colorimetric solid-phase immunoassay on a planar chip substrate was realized in direct and sandwich assay formats, with a detection system that does not require any instrumentation for readout. Semiquantitative immunochemical responses are directly visible to the naked eye of the analyst. The biosensor shows concentration-dependent color development by capturing antibody-functionalized Au NPs on allergen-coated chips and has a detection limit of 1 ng/mL. To establish a rapid method, we took advantage of the physicochemical microenvironment of the Au NP-antibody bioconjugate to be bound directly over an interacting poly(styrene-methyl methacrylate) interlayer by an immobilized antigen. In the direct assay format, a coating time with allergen of only 5 min under "soft" nondenaturing conditions was sufficient for accurate reproducibility and sensitivity. In conclusion, the REA-based immunochip sensor is easy to fabricate, is reproducible and selective in its performance, has minimal technical requirements, and will enable high-throughput screening of affinity binding interactions in technological and medical applications.

Handheld Chem/Biosensor Using Extreme Conformational Changes in Designed Binding Proteins to Enhance Surface Plasmon Resonance (SPR)

DTIC Science & Technology

2016-04-01

AFCEC-CX-TY-TR-2016-0007 HANDHELD CHEM/ BIOSENSOR USING EXTREME CONFORMATIONAL CHANGES IN DESIGNED BINDING PROTEINS TO ENHANCE SURFACE PLASMON...Include area code) 03/24/2016 Abstract 08/14/2015--03/31/2016 Handheld chem/ biosensor using extreme conformational changes in designed binding...Baltimore, Maryland on 17-21 April 2016. We propose the development of a highly sensitive handheld chem/ biosensor device using a novel class of engineered

Fast and sensitive detection of foodborne pathogen using electrochemical impedance analysis, urease catalysis and microfluidics.

PubMed

Chen, Qi; Wang, Dan; Cai, Gaozhe; Xiong, Yonghua; Li, Yuntao; Wang, Maohua; Huo, Huiling; Lin, Jianhan

2016-12-15

Early screening of pathogenic bacteria is a key to prevent and control of foodborne diseases. In this study, we developed a fast and sensitive bacteria detection method integrating electrochemical impedance analysis, urease catalysis with microfluidics and using Listeria as model. The Listeria cells, the anti-Listeria monoclonal antibodies modified magnetic nanoparticles (MNPs), and the anti-Listeria polyclonal antibodies and urease modified gold nanoparticles (AuNPs) were incubated in a fluidic separation chip with active mixing to form the MNP-Listeria-AuNP-urease sandwich complexes. The complexes were captured in the separation chip by applying a high gradient magnetic field, and the urea was injected to resuspend the complexes and hydrolyzed under the catalysis of the urease on the complexes into ammonium ions and carbonate ions, which were transported into a microfluidic detection chip with an interdigitated microelectrode for impedance measurement to determine the amount of the Listeria cells. The capture efficiency of the Listeria cells in the separation chip was ∼93% with a shorter time of 30min due to the faster immuno-reaction using the active magnetic mixing. The changes on both impedance magnitude and phase angle were demonstrated to be able to detect the Listeria cells as low as 1.6×10(2)CFU/mL. The detection time was reduced from original ∼2h to current ∼1h. The recoveries of the spiked lettuce samples ranged from 82.1% to 89.6%, indicating the applicability of this proposed biosensor. This microfluidic impedance biosensor has shown the potential for online, automatic and sensitive bacteria separation and detection. Copyright © 2016 Elsevier B.V. All rights reserved.

Directed Evolution to Engineer Monobody for FRET Biosensor Assembly and Imaging at Live-Cell Surface.

PubMed

Limsakul, Praopim; Peng, Qin; Wu, Yiqian; Allen, Molly E; Liang, Jing; Remacle, Albert G; Lopez, Tyler; Ge, Xin; Kay, Brian K; Zhao, Huimin; Strongin, Alex Y; Yang, Xiang-Lei; Lu, Shaoying; Wang, Yingxiao

2018-04-19

Monitoring enzymatic activities at the cell surface is challenging due to the poor efficiency of transport and membrane integration of fluorescence resonance energy transfer (FRET)-based biosensors. Therefore, we developed a hybrid biosensor with separate donor and acceptor that assemble in situ. The directed evolution and sequence-function analysis technologies were integrated to engineer a monobody variant (PEbody) that binds to R-phycoerythrin (R-PE) dye. PEbody was used for visualizing the dynamic formation/separation of intercellular junctions. We further fused PEbody with the enhanced CFP and an enzyme-specific peptide at the extracellular surface to create a hybrid FRET biosensor upon R-PE capture for monitoring membrane-type-1 matrix metalloproteinase (MT1-MMP) activities. This biosensor revealed asymmetric distribution of MT1-MMP activities, which were high and low at loose and stable cell-cell contacts, respectively. Therefore, directed evolution and rational design are promising tools to engineer molecular binders and hybrid FRET biosensors for monitoring molecular regulations at the surface of living cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electrochemical biosensors for biocontaminant detection consisting of carbon nanotubes, platinum nanoparticles, dendrimers, and enzymes.

PubMed

Siriviriyanun, Ampornphan; Imae, Toyoko; Nagatani, Naoki

2013-12-15

The presented approach provides the advanced development of effective, rapid, and versatile electrochemical sensors for a small amount of analytes on potential, cheap, and disposable printed chips. The electrocatalytic activity of this biosensor revealed the feasible detection of hydrogen peroxide at low potential (~0.09 V) and the detection of a biocontaminant inhibitor (organophosphorus pesticide) in a wide range of concentrations. This efficiency comes from the chemical immobilization of catalysts (Pt nanoparticles) and electron transfer-enlarging materials (carbon nanotubes) on an electrode. Especially, dendrimers raise the stable conjugation of enzymes (acetylcholinesterase/choline oxidase/peroxidase) as well as nanoparticles and carbon nanotubes on an electrode. Copyright © 2013 Elsevier Inc. All rights reserved.

A biomolecular detection method based on charge pumping in a nanogap embedded field-effect-transistor biosensor

NASA Astrophysics Data System (ADS)

Kim, Sungho; Ahn, Jae-Hyuk; Park, Tae Jung; Lee, Sang Yup; Choi, Yang-Kyu

2009-06-01

A unique direct electrical detection method of biomolecules, charge pumping, was demonstrated using a nanogap embedded field-effect-transistor (FET). With aid of a charge pumping method, sensitivity can fall below the 1 ng/ml concentration regime in antigen-antibody binding of an avian influenza case. Biomolecules immobilized in the nanogap are mainly responsible for the acute changes of the interface trap density due to modulation of the energy level of the trap. This finding is supported by a numerical simulation. The proposed detection method for biomolecules using a nanogap embedded FET represents a foundation for a chip-based biosensor capable of high sensitivity.

Recent Advances in Exosomal Protein Detection Via Liquid Biopsy Biosensors for Cancer Screening, Diagnosis, and Prognosis.

PubMed

Liu, Chang; Yang, Yunchen; Wu, Yun

2018-03-08

Current cancer diagnostic methods are challenged by low sensitivity, high false positive rate, limited tumor information, uncomfortable or invasive procedures, and high cost. Liquid biopsy that analyzes circulating biomarkers in body fluids represents a promising solution to these challenges. Exosomes are one of the promising cancer biomarkers for liquid biopsy because they are cell-secreted, nano-sized, extracellular vesicles that stably exist in all types of body fluids. Exosomes transfer DNAs, RNAs, proteins, and lipids from parent cells to recipient cells for intercellular communication and play important roles in cancer initiation, progression, and metastasis. Many liquid biopsy biosensors have been developed to offer non- or minimally-invasive, highly sensitive, simple, rapid, and cost-effective cancer diagnostics. This review summarized recent advances of liquid biopsy biosensors with a focus on the detection of exosomal proteins as biomarkers for cancer screening, diagnosis, and prognosis. We reviewed six major types of liquid biopsy biosensors including immunofluorescence biosensor, colorimetric biosensor, surface plasmon resonance (SPR) biosensor, surface-enhanced Raman scattering (SERS) biosensor, electrochemical biosensor, and nuclear magnetic resonance (NMR) biosensor. We shared our perspectives on future improvement of exosome-based liquid biopsy biosensors to accelerate their clinical translation.

A biosensor for cholesterol based on gold nanoparticles-catalyzed luminol electrogenerated chemiluminescence.

PubMed

Zhang, Meihe; Yuan, Ruo; Chai, Yaqin; Chen, Shihong; Zhong, Huaan; Wang, Cun; Cheng, Yinfeng

2012-02-15

A novel cholesterol biosensor was prepared based on gold nanoparticles-catalyzed luminol electrogenerated chemiluminescence (ECL). Firstly, l-cysteine-reduced graphene oxide composites were modified on the surface of a glassy carbon electrode. Then, gold nanoparticles (AuNPs) were self-assembled on it. Subsequently, cholesterol oxidase (ChOx) was adsorbed on the surface of AuNPs to construct a cholesterol biosensor. The stepwise fabrication processes were characterized with cyclic voltammetry and atomic force microscopy. The ECL behaviors of the biosensor were also investigated. It was found that AuNPs not only provided larger surface area for higher ChOx loading but also formed the nano-structured interface on the electrode surface to improve the analytical performance of the ECL biosensor for cholesterol. Besides, based on the efficient catalytic ability of AuNPs to luminol ECL, the response of the biosensor to cholesterol was linear range from 3.3 μM to 1.0 mM with a detection limit of 1.1 μM (S/N=3). In addition, the prepared ECL biosensor exhibited satisfying reproducibility, stability and selectivity. Taking into account the advantages of ECL, we confidently expect that ECL would have potential applications in biotechnology and clinical diagnosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Amperometric biosensor for Salmonella typhimurium detection in milk

USDA-ARS?s Scientific Manuscript database

This paper reports an amperometric biosensor for rapid and sensitive Salmonella Typhimurium detection in milk. The biosensor was assembled from the self-assembled monolayers technique on a gold surface. In this device, polyclonal antibodies were oriented by protein A. The biosensor structure was cha...

Electrical Detection of Cancer Biomarker using Aptamers with Nanogap Break-Junctions

PubMed Central

Ilyas, Azhar; Asghar, Waseem; Allen, Peter B.; Duhon, Holli; Ellington, Andrew D.; Iqbal, Samir M.

2012-01-01

Epidermal Growth Factor Receptor (EGFR) is a cell surface protein overexpressed in cancerous cells. It is known to be the most common oncongene. EGFR concentration also increases in the serum of cancer patients. The detection of small changes in the concentration of EGFR can be critical for early diagnosis, resulting in better treatment and improved survival rate of cancer patients. This article reports an RNA aptamer based approach to selectively capture EGFR protein and an electrical scheme for its detection. Pairs of gold electrodes with nanometer separation were made through confluence of focused ion beam scratching and electromigration. The aptamer was hybridized to a single stranded DNA molecule, which in turn was immobilized on SiO2 surface between the gold nanoelectrodes. The selectivity of the aptamer was demonstrated by using control chips with mutated non–selective aptamer and with no aptamer. Surface functionalization was characterized by optical detection and two orders of magnitude increase in direct current (DC) was measured when selective capture of EGFR occurred. This represents an electronic biosensor for the detection of proteins of interest for medical applications. PMID:22706642

Branched poly(ethyleneimine): a versatile scaffold for patterning polymer brushes by means of remote photocatalytic lithography

NASA Astrophysics Data System (ADS)

Panzarasa, Guido; Dübner, Matthias; Soliveri, Guido; Edler, Matthias; Griesser, Thomas

2017-09-01

Patterning of functional surfaces is one of the cornerstones of nanotechnology as it allows the fabrication of sensors and lab-on-a-chip devices. Here, the patterning of self-assembled monolayers of branched poly(ethyleneimine) (bPEI) on silica was achieved by means of remote photocatalytic lithography. Moreover, when 2-bromoisobutyryl-modified bPEI was used, the resulting pattern could be amplified by grafting polymer brushes by means of surface-initiated atom transfer radical polymerization. In contrast to previous reports for the patterning of bPEI, the present approach can be conducted in minutes instead of hours, reducing the exposure time to UV radiation and enhancing the overall efficiency. Furthermore, our approach is much more user-friendly, allowing a facile fabrication of patterned initiator-modified surfaces and the use of inexpensive instrumentation such as a low-power UV source and a simple photomask. Considering the versatility of bPEI as a scaffold for the development of biosensors, patterning by means of remote photocatalytic lithography will open new opportunities in a broad field of applications.

Biosensing of BCR/ABL fusion gene using an intensity-interrogation surface plasmon resonance imaging system

NASA Astrophysics Data System (ADS)

Wu, Jiangling; Huang, Yu; Bian, Xintong; Li, DanDan; Cheng, Quan; Ding, Shijia

2016-10-01

In this work, a custom-made intensity-interrogation surface plasmon resonance imaging (SPRi) system has been developed to directly detect a specific sequence of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). The variation in the reflected light intensity detected from the sensor chip composed of gold islands array is proportional to the change of refractive index due to the selective hybridization of surface-bound DNA probes with target ssDNA. SPRi measurements were performed with different concentrations of synthetic target DNA sequence. The calibration curve of synthetic target sequence shows a good relationship between the concentration of synthetic target and the change of reflected light intensity. The detection limit of this SPRi measurement could approach 10.29 nM. By comparing SPRi images, the target ssDNA and non-complementary DNA sequence are able to be distinguished. This SPRi system has been applied for assay of BCR/ABL fusion gene extracted from real samples. This nucleic acid-based SPRi biosensor therefore offers an alternative high-effective, high-throughput label-free tool for DNA detection in biomedical research and molecular diagnosis.

Modeling of the Near Field Coupling Between an External Loop and an Implantable Spiral Chip Antennas in Biosensor Systems

NASA Technical Reports Server (NTRS)

Simons, Rainee N.; Miranda, Felix A.

2006-01-01

In this paper, the near field coupling between an external hand-held loop antenna and an implantable miniature (1x1 mm) printed square spiral chip antenna used in bio-MEMS sensors for contact-less powering and RF telemetry is investigated. The loop and the spiral are inductively coupled and effectively form a transformer. The numerical results include the quasi-stationary magnetic field pattern of the implanted antenna, near zone wave impedance as a function of the radial distance and the values of the lumped elements in the equivalent circuit model for the transformer.

A CMOS wireless biomolecular sensing system-on-chip based on polysilicon nanowire technology.

PubMed

Huang, C-W; Huang, Y-J; Yen, P-W; Tsai, H-H; Liao, H-H; Juang, Y-Z; Lu, S-S; Lin, C-T

2013-11-21

As developments of modern societies, an on-field and personalized diagnosis has become important for disease prevention and proper treatment. To address this need, in this work, a polysilicon nanowire (poly-Si NW) based biosensor system-on-chip (bio-SSoC) is designed and fabricated by a 0.35 μm 2-Poly-4-Metal (2P4M) complementary metal-oxide-semiconductor (CMOS) process provided by a commercialized semiconductor foundry. Because of the advantages of CMOS system-on-chip (SoC) technologies, the poly-Si NW biosensor is integrated with a chopper differential-difference amplifier (DDA) based analog-front-end (AFE), a successive approximation analog-to-digital converter (SAR ADC), and a microcontroller to have better sensing capabilities than a traditional Si NW discrete measuring system. In addition, an on-off key (OOK) wireless transceiver is also integrated to form a wireless bio-SSoC technology. This is pioneering work to harness the momentum of CMOS integrated technology into emerging bio-diagnosis technologies. This integrated technology is experimentally examined to have a label-free and low-concentration biomolecular detection for both Hepatitis B Virus DNA (10 fM) and cardiac troponin I protein (3.2 pM). Based on this work, the implemented wireless bio-SSoC has demonstrated a good biomolecular sensing characteristic and a potential for low-cost and mobile applications. As a consequence, this developed technology can be a promising candidate for on-field and personalized applications in biomedical diagnosis.

A High-Performance Application Specific Integrated Circuit for Electrical and Neurochemical Traumatic Brain Injury Monitoring.

PubMed

Pagkalos, Ilias; Rogers, Michelle L; Boutelle, Martyn G; Drakakis, Emmanuel M

2018-05-22

This paper presents the first application specific integrated chip (ASIC) for the monitoring of patients who have suffered a Traumatic Brain Injury (TBI). By monitoring the neurophysiological (ECoG) and neurochemical (glucose, lactate and potassium) signals of the injured human brain tissue, it is possible to detect spreading depolarisations, which have been shown to be associated with poor TBI patient outcome. This paper describes the testing of a new 7.5 mm 2 ASIC fabricated in the commercially available AMS 0.35 μm CMOS technology. The ASIC has been designed to meet the demands of processing the injured brain tissue's ECoG signals, recorded by means of depth or brain surface electrodes, and neurochemical signals, recorded using microdialysis coupled to microfluidics-based electrochemical biosensors. The potentiostats use switchedcapacitor charge integration to record currents with 100 fA resolution, and allow automatic gain changing to track the falling sensitivity of a biosensor. This work supports the idea of a "behind the ear" wireless microplatform modality, which could enable the monitoring of currently non-monitored mobile TBI patients for the onset of secondary brain injury. ©2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Design of surface modifications for nanoscale sensor applications.

PubMed

Reimhult, Erik; Höök, Fredrik

2015-01-14

Nanoscale biosensors provide the possibility to miniaturize optic, acoustic and electric sensors to the dimensions of biomolecules. This enables approaching single-molecule detection and new sensing modalities that probe molecular conformation. Nanoscale sensors are predominantly surface-based and label-free to exploit inherent advantages of physical phenomena allowing high sensitivity without distortive labeling. There are three main criteria to be optimized in the design of surface-based and label-free biosensors: (i) the biomolecules of interest must bind with high affinity and selectively to the sensitive area; (ii) the biomolecules must be efficiently transported from the bulk solution to the sensor; and (iii) the transducer concept must be sufficiently sensitive to detect low coverage of captured biomolecules within reasonable time scales. The majority of literature on nanoscale biosensors deals with the third criterion while implicitly assuming that solutions developed for macroscale biosensors to the first two, equally important, criteria are applicable also to nanoscale sensors. We focus on providing an introduction to and perspectives on the advanced concepts for surface functionalization of biosensors with nanosized sensor elements that have been developed over the past decades (criterion (iii)). We review in detail how patterning of molecular films designed to control interactions of biomolecules with nanoscale biosensor surfaces creates new possibilities as well as new challenges.

Design of Surface Modifications for Nanoscale Sensor Applications

PubMed Central

Reimhult, Erik; Höök, Fredrik

2015-01-01

Nanoscale biosensors provide the possibility to miniaturize optic, acoustic and electric sensors to the dimensions of biomolecules. This enables approaching single-molecule detection and new sensing modalities that probe molecular conformation. Nanoscale sensors are predominantly surface-based and label-free to exploit inherent advantages of physical phenomena allowing high sensitivity without distortive labeling. There are three main criteria to be optimized in the design of surface-based and label-free biosensors: (i) the biomolecules of interest must bind with high affinity and selectively to the sensitive area; (ii) the biomolecules must be efficiently transported from the bulk solution to the sensor; and (iii) the transducer concept must be sufficiently sensitive to detect low coverage of captured biomolecules within reasonable time scales. The majority of literature on nanoscale biosensors deals with the third criterion while implicitly assuming that solutions developed for macroscale biosensors to the first two, equally important, criteria are applicable also to nanoscale sensors. We focus on providing an introduction to and perspectives on the advanced concepts for surface functionalization of biosensors with nanosized sensor elements that have been developed over the past decades (criterion (iii)). We review in detail how patterning of molecular films designed to control interactions of biomolecules with nanoscale biosensor surfaces creates new possibilities as well as new challenges. PMID:25594599

Detection of Salmonella enteritidis Using a Miniature Optical Surface Plasmon Resonance Biosensor

NASA Astrophysics Data System (ADS)

Son, J. R.; Kim, G.; Kothapalli, A.; Morgan, M. T.; Ess, D.

2007-04-01

The frequent outbreaks of foodborne illness demand rapid detection of foodborne pathogens. Unfortunately, conventional methods for pathogen detection and identification are labor-intensive and take days to complete. Biosensors have shown great potential for the rapid detection of foodborne pathogens. Surface plasmon resonance (SPR) sensors have been widely adapted as an analysis tool for the study of various biological binding reactions. SPR biosensors could detect antibody-antigen bindings on the sensor surface by measuring either a resonance angle or refractive index value. In this study, the feasibility of a miniature SPR sensor (Spreeta, TI, USA) for detection of Salmonella enteritidis has been evaluated. Anti-Salmonella antibodies were immobilized on the gold sensor surface by using neutravidin. Salmonella could be detected by the Spreeta biosensor at concentrations down to 105 cfu/ml.

Fabrication and characterization of high-K dielectric integrated silicon nanowire sensor for DNA sensing application (Conference Presentation)

NASA Astrophysics Data System (ADS)

Jayakumar, Ganesh; Legallais, Maxime; Hellström, Per-Erik; Mouis, Mireille; Stambouli, Valérie; Ternon, Céline; Östling, Mikael

2016-09-01

1D silicon nanowires (SiNW) are attractive for charge based DNA sensing applications due to their small size and large surface to volume ratio. An ideal portable biosensor is expected to have repeatable and reliable sensitivity, selectivity, low production cost and small feature size. Instead of using tools such as e-beam that are capital and time intensive, we propose a low cost CMOS self-aligned-double-patterning I-line lithography process to fabricate 60 nm wide SiNW. DNA probes are grafted on a thin dielectric layer that is deposited on top of the SiNW surface. Here we used HfO2 instead of the usual SiO2. Indeed, compared to SiO2, HfO2 has been reported to have higher amount of OH groups on its surface leading to enhanced signal quality. We also report preliminary biosensor characterizations. After HfO2 functionalization and single-stranded DNA probe grafting onto the SiNWs, the sensors were first put in contact with fluorophore labelled complementary DNA targets in order to test the efficiency of DNA hybridization optically. Then, a sequence of hybridization, de-hybridization and re-hybridization steps was followed by Id-Vg measurements in order to measure the electrical response of the sensors to target DNA as well as recycling capability. After each step, SiNW devices exhibited a threshold voltage shift larger than device-to-device dispersion, showing that both complementary DNA hybridization and de-hybridization can be electrically detected. These results are very encouraging as they open new frontiers for heterogeneous integration of liquid interacting array of nano sensors with CMOS circuits to fabricate a complete lab on chip.

Reversible biofunctionalization of surfaces with a switchable mutant of avidin.

PubMed

Pollheimer, Philipp; Taskinen, Barbara; Scherfler, Andreas; Gusenkov, Sergey; Creus, Marc; Wiesauer, Philipp; Zauner, Dominik; Schöfberger, Wolfgang; Schwarzinger, Clemens; Ebner, Andreas; Tampé, Robert; Stutz, Hanno; Hytönen, Vesa P; Gruber, Hermann J

2013-10-16

Label-free biosensors detect binding of prey molecules (″analytes″) to immobile bait molecules on the sensing surface. Numerous methods are available for immobilization of bait molecules. A convenient option is binding of biotinylated bait molecules to streptavidin-functionalized surfaces, or to biotinylated surfaces via biotin-avidin-biotin bridges. The goal of this study was to find a rapid method for reversible immobilization of biotinylated bait molecules on biotinylated sensor chips. The task was to establish a biotin-avidin-biotin bridge which was easily cleaved when desired, yet perfectly stable under a wide range of measurement conditions. The problem was solved with the avidin mutant M96H which contains extra histidine residues at the subunit-subunit interfaces. This mutant was bound to a mixed self-assembled monolayer (SAM) containing biotin residues on 20% of the oligo(ethylene glycol)-terminated SAM components. Various biotinylated bait molecules were bound on top of the immobilized avidin mutant. The biotin-avidin-biotin bridge was stable at pH ≥3, and it was insensitive to sodium dodecyl sulfate (SDS) at neutral pH. Only the combination of citric acid (2.5%, pH 2) and SDS (0.25%) caused instantaneous cleavage of the biotin-avidin-biotin bridge. As a consequence, the biotinylated bait molecules could be immobilized and removed as often as desired, the only limit being the time span for reproducible chip function when kept in buffer (2-3 weeks at 25 °C). As expected, the high isolectric pH (pI) of the avidin mutant caused nonspecific adsorption of proteins. This problem was solved by acetylation of avidin (to pI < 5), or by optimization of SAM formation and passivation with biotin-BSA and BSA.

Multiple biomarkers biosensor with just-in-time functionalization: Application to prostate cancer detection.

PubMed

Parra-Cabrera, C; Samitier, J; Homs-Corbera, A

2016-03-15

We present a novel lab-on-a-chip (LOC) device for the simultaneous detection of multiple biomarkers using simple voltage measurements. The biosensor functionalization is performed in-situ, immediately before its use, facilitating reagents storage and massive devices fabrication. Sensitivity, limit of detection (LOD) and limit of quantification (LOQ) are tunable depending on the in-chip flown sample volumes. As a proof-of-concept, the system has been tested and adjusted to quantify two proteins found in blood that are susceptible to be used combined, as a screening tool, to diagnose prostate cancer (PCa): prostate-specific antigen (PSA) and spondin-2 (SPON2). This combination of biomarkers has been reported to be more specific for PCa diagnostics than the currently accepted but rather controversial PSA indicator. The range of detection for PSA and SPON2 could be adjusted to the clinically relevant range of 1 to 10 ng/ml. The system was tested for specificity to the evaluated biomarkers. This multiplex system can be modified and adapted to detect a larger quantity of biomarkers, or different ones, of relevance to other specific diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensing glucose concentrations at GHz frequencies with a fully embedded Biomicro-electromechanical system (BioMEMS)

NASA Astrophysics Data System (ADS)

Birkholz, M.; Ehwald, K.-E.; Basmer, T.; Kulse, P.; Reich, C.; Drews, J.; Genschow, D.; Haak, U.; Marschmeyer, S.; Matthus, E.; Schulz, K.; Wolansky, D.; Winkler, W.; Guschauski, T.; Ehwald, R.

2013-06-01

The progressive scaling in semiconductor technology allows for advanced miniaturization of intelligent systems like implantable biosensors for low-molecular weight analytes. A most relevant application would be the monitoring of glucose in diabetic patients, since no commercial solution is available yet for the continuous and drift-free monitoring of blood sugar levels. We report on a biosensor chip that operates via the binding competition of glucose and dextran to concanavalin A. The sensor is prepared as a fully embedded micro-electromechanical system and operates at GHz frequencies. Glucose concentrations derive from the assay viscosity as determined by the deflection of a 50 nm TiN actuator beam excited by quasi-electrostatic attraction. The GHz detection scheme does not rely on the resonant oscillation of the actuator and safely operates in fluidic environments. This property favorably combines with additional characteristics—(i) measurement times of less than a second, (ii) usage of biocompatible TiN for bio-milieu exposed parts, and (iii) small volume of less than 1 mm3—to qualify the sensor chip as key component in a continuous glucose monitor for the interstitial tissue.

A Real-Time Thermal Self-Elimination Method for Static Mode Operated Freestanding Piezoresistive Microcantilever-Based Biosensors

PubMed Central

Ku, Yu-Fu; Huang, Long-Sun

2018-01-01

Here, we provide a method and apparatus for real-time compensation of the thermal effect of single free-standing piezoresistive microcantilever-based biosensors. The sensor chip contained an on-chip fixed piezoresistor that served as a temperature sensor, and a multilayer microcantilever with an embedded piezoresistor served as a biomolecular sensor. This method employed the calibrated relationship between the resistance and the temperature of piezoresistors to eliminate the thermal effect on the sensor, including the temperature coefficient of resistance (TCR) and bimorph effect. From experimental results, the method was verified to reduce the signal of thermal effect from 25.6 μV/°C to 0.3 μV/°C, which was approximately two orders of magnitude less than that before the processing of the thermal elimination method. Furthermore, the proposed approach and system successfully demonstrated its effective real-time thermal self-elimination on biomolecular detection without any thermostat device to control the environmental temperature. This method realizes the miniaturization of an overall measurement system of the sensor, which can be used to develop portable medical devices and microarray analysis platforms. PMID:29495574

Slotted Photonic Crystal Sensors

PubMed Central

Scullion, Mark G.; Krauss, Thomas F.; Di Falco, Andrea

2013-01-01

Optical biosensors are increasingly being considered for lab-on-a-chip applications due to their benefits such as small size, biocompatibility, passive behaviour and lack of the need for fluorescent labels. The light guiding mechanisms used by many of them results in poor overlap of the optical field with the target molecules, reducing the maximum sensitivity achievable. This review article presents a new platform for optical biosensors, namely slotted photonic crystals, which provide higher sensitivities due to their ability to confine, spatially and temporally, the optical mode peak within the analyte itself. Loss measurements showed values comparable to standard photonic crystals, confirming their ability to be used in real devices. A novel resonant coupler was designed, simulated, and experimentally tested, and was found to perform better than other solutions within the literature. Combining with cavities, microfluidics and biological functionalization allowed proof-of-principle demonstrations of protein binding to be carried out. Higher sensitivities were observed in smaller structures than possible with most competing devices reported in the literature. This body of work presents slotted photonic crystals as a realistic platform for complete on-chip biosensing; addressing key design, performance and application issues, whilst also opening up exciting new ideas for future study. PMID:23503295

Integrated Optical Mach-Zehnder Interferometer Based on Organic-Inorganic Hybrids for Photonics-on-a-Chip Biosensing Applications.

PubMed

Bastos, Ana R; Vicente, Carlos M S; Oliveira-Silva, Rui; Silva, Nuno J O; Tacão, Marta; Costa, João P da; Lima, Mário; André, Paulo S; Ferreira, Rute A S

2018-03-12

The development of portable low-cost integrated optics-based biosensors for photonics-on-a-chip devices for real-time diagnosis are of great interest, offering significant advantages over current analytical methods. We report the fabrication and characterization of an optical sensor based on a Mach-Zehnder interferometer to monitor the growing concentration of bacteria in a liquid medium. The device pattern was imprinted on transparent self-patternable organic-inorganic di-ureasil hybrid films by direct UV-laser, reducing the complexity and cost production compared with lithographic techniques or three-dimensional (3D) patterning using femtosecond lasers. The sensor performance was evaluated using, as an illustrative example, E. coli cell growth in an aqueous medium. The measured sensitivity (2 × 10 -4 RIU) and limit of detection (LOD = 2 × 10 -4 ) are among the best values known for low-refractive index contrast sensors. Furthermore, the di-ureasil hybrid used to produce this biosensor has additional advantages, such as mechanical flexibility, thermal stability, and low insertion losses due to fiber-device refractive index mismatch (~1.49). Therefore, the proposed sensor constitutes a direct, compact, fast, and cost-effective solution for monitoring the concentration of lived-cells.

Biosensor for metal analysis and speciation

DOEpatents

Aiken, Abigail M.; Peyton, Brent M.; Apel, William A.; Petersen, James N.

2007-01-30

A biosensor for metal analysis and speciation is disclosed. The biosensor comprises an electron carrier immobilized to a surface of an electrode and a layer of an immobilized enzyme adjacent to the electrode. The immobilized enzyme comprises an enzyme having biological activity inhibited by a metal to be detected by the biosensor.

Alpha-fetoprotein detection by using a localized surface plasmon coupled fluorescence fiber-optic biosensor

NASA Astrophysics Data System (ADS)

Chang, Ying-Feng; Chen, Ran-Chou; Li, Ying-Chang; Yu, Chih-Jen; Hsieh, Bao-Yu; Chou, Chien

2007-11-01

Alpha-fetoprotein (AFP) detection by using a localized surface plasmon coupled fluorescence (LSPCF) fiber-optic biosensor is setup and experimentally demonstrated. It is based on gold nanoparticle (GNP) and coupled with localized surface plasmon wave on the surface of GNP. In this experiment, the fluorophores are labeled on anti-AFP which are bound to protein A conjugated GNP. Thus, LSPCF is excited with high efficiency in the near field of localized surface plasmon wave. Therefore, not only the sensitivity of LSPCF biosensor is enhanced but also the specific selectivity of AFP is improved. Experimentally, the ability of real time measurement in the range of AFP concentration from 0.1ng/ml to 100ng/ml was detected. To compare with conventional methods such as enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA), the LSPCF fiber-optic biosensor performs higher or comparable detection sensitivity, respectively.

NIL fabrication of a polymer-based photonic sensor device in P3SENS project

NASA Astrophysics Data System (ADS)

Giannone, Domenico; Dortu, Fabian; Bernier, Damien; Johnson, Nigel P.; Sharp, Graham J.; Hou, Lianping; Khokhar, Ali Z.; Fürjes, Péter; Kurunczi, Sándor; Petrik, Peter; Horvath, Robert; Aalto, Timo; Kolari, Kai; Ylinen, Sami; Haatainen, Tomi; Egger, Holger

2012-06-01

We present the most recent results of EU funded project P3SENS (FP7-ICT-2009.3.8) aimed at the development of a low-cost and medium sensitivity polymer based photonic biosensor for point of care applications in proteomics. The fabrication of the polymer photonic chip (biosensor) using thermal nanoimprint lithography (NIL) is described. This technique offers the potential for very large production at reduced cost. However several technical challenges arise due to the properties of the used materials. We believe that, once the NIL technique has been optimised to the specific materials, it could be even transferred to a kind of roll-to-roll production for manufacturing a very large number of photonic devices at reduced cost.

Development of an alcohol dehydrogenase biosensor for ethanol determination with toluidine blue O covalently attached to a cellulose acetate modified electrode.

PubMed

Alpat, Senol; Telefoncu, Azmi

2010-01-01

In this work, a novel voltammetric ethanol biosensor was constructed using alcohol dehydrogenase (ADH). Firstly, alcohol dehydrogenase was immobilized on the surface of a glassy carbon electrode modified by cellulose acetate (CA) bonded to toluidine blue O (TBO). Secondly, the surface was covered by a glutaraldehyde/bovine serum albumin (BSA) cross-linking procedure to provide a new voltammetric sensor for the ethanol determination. In order to fabricate the biosensor, a new electrode matrix containing insoluble Toluidine Blue O (TBO) was obtained from the process, and enzyme/coenzyme was combined on the biosensor surface. The influence of various experimental conditions was examined for the characterization of the optimum analytical performance. The developed biosensor exhibited sensitive and selective determination of ethanol and showed a linear response between 1 × 10(-5) M and 4 × 10(-4) M ethanol. A detection limit calculated as three times the signal-to-noise ratio was 5.0 × 10(-6) M. At the end of the 20(th) day, the biosensor still retained 50% of its initial activity.

Development of an Alcohol Dehydrogenase Biosensor for Ethanol Determination with Toluidine Blue O Covalently Attached to a Cellulose Acetate Modified Electrode

PubMed Central

Alpat, Şenol; Telefoncu, Azmi

2010-01-01

In this work, a novel voltammetric ethanol biosensor was constructed using alcohol dehydrogenase (ADH). Firstly, alcohol dehydrogenase was immobilized on the surface of a glassy carbon electrode modified by cellulose acetate (CA) bonded to toluidine blue O (TBO). Secondly, the surface was covered by a glutaraldehyde/bovine serum albumin (BSA) cross-linking procedure to provide a new voltammetric sensor for the ethanol determination. In order to fabricate the biosensor, a new electrode matrix containing insoluble Toluidine Blue O (TBO) was obtained from the process, and enzyme/coenzyme was combined on the biosensor surface. The influence of various experimental conditions was examined for the characterization of the optimum analytical performance. The developed biosensor exhibited sensitive and selective determination of ethanol and showed a linear response between 1 × 10−5 M and 4 × 10−4 M ethanol. A detection limit calculated as three times the signal-to-noise ratio was 5.0 × 10−6 M. At the end of the 20th day, the biosensor still retained 50% of its initial activity. PMID:22315566

Evaluation of an affinity-amplified immunoassay of graphene oxide using surface plasmon resonance biosensors

NASA Astrophysics Data System (ADS)

Chiu, Nan-Fu; Huang, Teng-Yi; Kuo, Chun-Chuan

2015-05-01

We describe a fundamental study on the plasmonic properties and advanced biosensing mechanisms of functionalized graphene. We discuss a specific design using modified carboxyl groups, which can modulate surface plasmon (SP) coupling and provide an advantage for their binding to the sensing layer with high-performance affinity in an immunological reaction. The functionalized graphene-based surface plasmon resonance (SPR) biosensors have three advantages: high performance, high sensitivity, and excellent molecular kinetic response. In the future, functionalized graphene sheets will make a unique contribution to photonic and SPR diagnosis devices. We wish to highlight the essential characteristics of functionalized graphene-based SPR biosensors to assist researchers in developing and advancing suitable biosensors for unique applications.

Nanoplasmonic Biosensor Using Localized Surface Plasmon Resonance Spectroscopy for Biochemical Detection.

PubMed

Zhang, Diming; Zhang, Qian; Lu, Yanli; Yao, Yao; Li, Shuang; Liu, Qingjun

2017-01-01

Localized surface plasmon resonance (LSPR) associated with metal nanostructures has developed into a highly useful sensor technique. Optical LSPR spectroscopy of nanostructures often shows sharp absorption and scattering peaks, which can be used to probe several bio-molecular interactions. Here, we report nanoplasmonic biosensors using LSPR on nanocup arrays (nanoCA) to recognize bio-molecular binding for biochemical detection. These sensors can be modified to quantify binding of small molecules to proteins for odorant and explosive detections. Electrochemical LSPR biosensors can also be designed by coupling electrochemistry and LSPR spectroscopy measurements. Multiple sensing information can be obtained and electrochemical LSPR property can be investigated for biosensors. In some applications, the electrochemical LSPR biosensor can be used to quantify immunoreactions and enzymatic activity. The biosensors exhibit better performance than those of conventional optical LSPR measurements. With multi-transducers, the nanoplasmonic biosensor can provide a promising approach for bio-detection in environmental monitoring, healthcare diagnostics, and food quality control.

An integrated paper-based sample-to-answer biosensor for nucleic acid testing at the point of care.

PubMed

Choi, Jane Ru; Hu, Jie; Tang, Ruihua; Gong, Yan; Feng, Shangsheng; Ren, Hui; Wen, Ting; Li, XiuJun; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

2016-02-07

With advances in point-of-care testing (POCT), lateral flow assays (LFAs) have been explored for nucleic acid detection. However, biological samples generally contain complex compositions and low amounts of target nucleic acids, and currently require laborious off-chip nucleic acid extraction and amplification processes (e.g., tube-based extraction and polymerase chain reaction (PCR)) prior to detection. To the best of our knowledge, even though the integration of DNA extraction and amplification into a paper-based biosensor has been reported, a combination of LFA with the aforementioned steps for simple colorimetric readout has not yet been demonstrated. Here, we demonstrate for the first time an integrated paper-based biosensor incorporating nucleic acid extraction, amplification and visual detection or quantification using a smartphone. A handheld battery-powered heating device was specially developed for nucleic acid amplification in POC settings, which is coupled with this simple assay for rapid target detection. The biosensor can successfully detect Escherichia coli (as a model analyte) in spiked drinking water, milk, blood, and spinach with a detection limit of as low as 10-1000 CFU mL(-1), and Streptococcus pneumonia in clinical blood samples, highlighting its potential use in medical diagnostics, food safety analysis and environmental monitoring. As compared to the lengthy conventional assay, which requires more than 5 hours for the entire sample-to-answer process, it takes about 1 hour for our integrated biosensor. The integrated biosensor holds great potential for detection of various target analytes for wide applications in the near future.

Electrochemical and optical biosensors based on nanomaterials and nanostructures: a review.

PubMed

Li, Ming; Li, Rui; Li, Chang Ming; Wu, Nianqiang

2011-06-01

Nanomaterials and nanostructures exhibit unique size-tunable and shape-dependent physicochemical properties that are different from those of bulk materials. Advances of nanomaterials and nanostructures open a new door to develop various novel biosensors. The present work has reviewed the recent progress in electrochemical, surface plasmon resonance (SPR), surface-enhanced Raman scattering (SERS) and fluorescent biosensors based on nanomaterials and nanostructures. An emphasis is put on the research that demonstrates how the performance of biosensors such as the limit of detection, sensitivity and selectivity is improved by the use of nanomaterials and nanostructures.

Nitrogen-Doped Carbon Nanotubes Supported by Macroporous Carbon as an Efficient Enzymatic Biosensing Platform for Glucose.

PubMed

Song, Yonghai; Lu, Xingping; Li, Yi; Guo, Qiaohui; Chen, Shuiliang; Mao, Lanqun; Hou, Haoqing; Wang, Li

2016-01-19

Effective immobilization of enzymes/proteins on an electrode surface is very essential for biosensor development, but it still remains challenging because enzymes/proteins tend to form close-packed structures on the electrode surface. In this work, nitrogen-doped carbon nanotubes (NCNTs) supported by three-dimensional Kenaf Stem-derived porous carbon (3D-KSC) (denoted as 3D-KSC/NCNTs) nanocomposites were constructed as the supporting matrix to load glucose oxidase (GOD) for preparing integrated glucose biosensors. These NCNTs are vertically arrayed on the channel walls of the 3D-KSC via the chemical vapor deposition method, which could noticeably increase the effective surface area, mechanical stability, and active sites (originating from the doped nitrogen) of the nanocomposites. The integrated glucose biosensor exhibits some advantages over the traditional GOD electrodes in terms of the capability to promote the direct electron transfer of GOD, enhance the mechanical stability of the biosensor attributed to the strong interaction between NCNTs and GOD, and enlarge the specific surface area to efficiently load a large number of GODs. The as-prepared biosensor shows a good performance toward both oxygen reduction and glucose biosensing. This study essentially offers a novel approach for the development of biosensors with excellent analytical properties.

Magnetoresistive immunosensor for the detection of Escherichia coli O157:H7 including a microfluidic network.

PubMed

Mujika, M; Arana, S; Castaño, E; Tijero, M; Vilares, R; Ruano-López, J M; Cruz, A; Sainz, L; Berganza, J

2009-01-01

A hand held device has been designed for the immunomagnetic detection and quantification of the pathogen Escherichia coli O157:H7 in food and clinical samples. In this work, a technology to manufacture a Lab on a Chip that integrates a 3D microfluidic network with a microfabricated biosensor has been developed. With this aim, the sensing film optimization, the design of the microfluidic circuitry, the development of the biological protocols involved in the measurements and, finally, the packaging needed to carry out the assays in a safe and straightforward way have been completed. The biosensor is designed to be capable to detect and quantify small magnetic field variations caused by the presence of superparamagnetic beads bound to the antigens previously immobilized on the sensor surface via an antibody-antigen reaction. The giant magnetoresistive multilayer structure implemented as sensing film consists of 20[Cu(5.10nm)/Co(2.47 nm)] with a magnetoresistance of 3.20% at 235Oe and a sensitivity up to 0.06 Omega/Oe between 150Oe and 230Oe. Silicon nitride has been selected as optimum sensor surface coating due to its suitability for antibody immobilization. In order to guide the biological samples towards the sensing area, a microfluidic network made of SU-8 photoresist has been included. Finally, a novel packaging design has been fabricated employing 3D stereolithographic techniques. The microchannels are connected to the outside using standard tubing. Hence, this packaging allows an easy replacement of the used devices.

Scattering-Type Surface-Plasmon-Resonance Biosensors

NASA Technical Reports Server (NTRS)

Wang, Yu; Pain, Bedabrata; Cunningham, Thomas; Seshadri, Suresh

2005-01-01

Biosensors of a proposed type would exploit scattering of light by surface plasmon resonance (SPR). Related prior biosensors exploit absorption of light by SPR. Relative to the prior SPR biosensors, the proposed SPR biosensors would offer greater sensitivity in some cases, enough sensitivity to detect bioparticles having dimensions as small as nanometers. A surface plasmon wave can be described as a light-induced collective oscillation in electron density at the interface between a metal and a dielectric. At SPR, most incident photons are either absorbed or scattered at the metal/dielectric interface and, consequently, reflected light is greatly attenuated. The resonance wavelength and angle of incidence depend upon the permittivities of the metal and dielectric. An SPR sensor of the type most widely used heretofore includes a gold film coated with a ligand a substance that binds analyte molecules. The gold film is thin enough to support evanescent-wave coupling through its thickness. The change in the effective index of refraction at the surface, and thus the change in the SPR response, increases with the number of bound analyte molecules. The device is illuminated at a fixed wavelength, and the intensity of light reflected from the gold surface opposite the ligand-coated surface is measured as a function of the angle of incidence. From these measurements, the angle of minimum reflection intensity is determined

Dual recognition unit strategy improves the specificity of the adenosine triphosphate (ATP) aptamer biosensor for cerebral ATP assay.

PubMed

Yu, Ping; He, Xiulan; Zhang, Li; Mao, Lanqun

2015-01-20

Adenosine triphosphate (ATP) aptamer has been widely used as a recognition unit for biosensor development; however, its relatively poor specificity toward ATP against adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) essentially limits the application of the biosensors in real systems, especially in the complex cerebral system. In this study, for the first time, we demonstrate a dual recognition unit strategy (DRUS) to construct a highly selective and sensitive ATP biosensor by combining the recognition ability of aptamer toward A nucleobase and of polyimidazolium toward phosphate. The biosensors are constructed by first confining the polyimidazolium onto a gold surface by surface-initiated atom transfer radical polymerization (SI-ATRP), and then the aptamer onto electrode surface by electrostatic self-assembly to form dual-recognition-unit-functionalized electrodes. The constructed biosensor based on DRUS not only shows an ultrahigh sensitivity toward ATP with a detection limit down to the subattomole level but also an ultrahigh selectivity toward ATP without interference from ADP and AMP. The constructed biosensor is used for selective and sensitive sensing of the extracellular ATP in the cerebral system by combining in vivo microdialysis and can be used as a promising neurotechnology to probing cerebral ATP concentration.

Device considerations for development of conductance-based biosensors

PubMed Central

Lee, Kangho; Nair, Pradeep R.; Scott, Adina; Alam, Muhammad A.; Janes, David B.

2009-01-01

Design and fabrication of electronic biosensors based on field-effect-transistor (FET) devices require understanding of interactions between semiconductor surfaces and organic biomolecules. From this perspective, we review practical considerations for electronic biosensors with emphasis on molecular passivation effects on FET device characteristics upon immobilization of organic molecules and an electrostatic model for FET-based biosensors. PMID:24753627

Progress of new label-free techniques for biosensors: a review.

PubMed

Sang, Shengbo; Wang, Yajun; Feng, Qiliang; Wei, Ye; Ji, Jianlong; Zhang, Wendong

2016-01-01

The detection techniques used in biosensors can be broadly classified into label-based and label-free. Label-based detection relies on the specific properties of labels for detecting a particular target. In contrast, label-free detection is suitable for the target molecules that are not labeled or the screening of analytes which are not easy to tag. Also, more types of label-free biosensors have emerged with developments in biotechnology. The latest developed techniques in label-free biosensors, such as field-effect transistors-based biosensors including carbon nanotube field-effect transistor biosensors, graphene field-effect transistor biosensors and silicon nanowire field-effect transistor biosensors, magnetoelastic biosensors, optical-based biosensors, surface stress-based biosensors and other type of biosensors based on the nanotechnology are discussed. The sensing principles, configurations, sensing performance, applications, advantages and restriction of different label-free based biosensors are considered and discussed in this review. Most concepts included in this survey could certainly be applied to the development of this kind of biosensor in the future.

Chitosan coated on the layers' glucose oxidase immobilized on cysteamine/Au electrode for use as glucose biosensor.

PubMed

Zhang, Yawen; Li, Yunqiu; Wu, Wenjian; Jiang, Yuren; Hu, Biru

2014-10-15

A glucose biosensor was developed via direct immobilization of glucose oxidase (GOD) by self-assembled cysteamine monolayer on Au electrode surface followed by coating chitosan on the surface of electrode. In this work, chitosan film was coated on the surface of GOD as a protection film to ensure the stability and biocompatibility of the constructed glucose biosensor. The different application ranges of sensors were fabricated by immobilizing varied layers of GOD. The modified surface film was characterized by a scanning electron microscope (SEM) and the fabrication process of the biosensor was confirmed through electrochemical impedance spectroscopy (EIS) of ferrocyanide. The performance of cyclic voltammetry (CV) in the absence and presence of 25 mM glucose and ferrocenemethanol showed a diffusion-controlled electrode process and reflected the different maximum currents between the different GOD layers. With the developed glucose biosensor, the detection limits of the two linear responses are 49.96 μM and 316.8 μM with the sensitivities of 8.91 μA mM(-1)cm(-2) and 2.93 μA mM(-1)cm(-2), respectively. In addition, good stability (up to 30 days) of the developed biosensor was observed. The advantages of this new method for sensors construction was convenient and different width ranges of detection can be obtained by modified varied layers of GOD. The sensor with two layers of enzyme displayed two current linear responses of glucose. The present work provided a simplicity and novelty method for producing biosensors, which may help design enzyme reactors and biosensors in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of a Strategy Based on the Surface Plasmon Resonance Technology for Platelet Compatibility Testing.

PubMed

Wu, Chang-Lin; He, Jian-An; Gu, Da-Yong; Shao, Chao-Peng; Zhu, Yi; Dang, Xin-Tang

2018-01-01

This study was aimed to establish a novel strategy based on the surface plasmon resonance (SPR) technology for platelet compatibility testing. A novel surface matrix was prepared based on poly (OEGMA-co-HEMA) via surface-initiated polymerization as a biosensor surface platform. Type O universal platelets and donor platelets were immobilized on these novel matrices via amine-coupling reaction and worked as a capturing ligand for binding the platelet antibody. Antibodies binding to platelets were monitored in real time by injecting the samples into a microfluidic channel. Clinical serum samples (n = 186) with multiple platelet transfusions were assayed for platelet antibodies using the SPR technology and monoclonal antibody-immobilized platelet antigen (MAIPA) assay. The novel biosensor surface achieved nonfouling background and high immobilization capacity and showed good repeatability and stability after regeneration. The limit of detection of the SPR biosensor for platelet antibody was estimated to be 50 ng/mL. The sensitivity and specificity were 92% and 98.7%. It could detect the platelet antibody directly in serum samples, and the results were similar to MAIPA assay. A novel strategy to facilitate the sensitive and reliable detection of platelet compatibility for developing an SPR-based biosensor was established in this study. The SPR-based biosensor combined with novel surface chemistry is a promising method for platelet compatibility testing.

Biosensors for hepatitis B virus detection.

PubMed

Yao, Chun-Yan; Fu, Wei-Ling

2014-09-21

A biosensor is an analytical device used for the detection of analytes, which combines a biological component with a physicochemical detector. Recently, an increasing number of biosensors have been used in clinical research, for example, the blood glucose biosensor. This review focuses on the current state of biosensor research with respect to efficient, specific and rapid detection of hepatitis B virus (HBV). The biosensors developed based on different techniques, including optical methods (e.g., surface plasmon resonance), acoustic wave technologies (e.g., quartz crystal microbalance), electrochemistry (amperometry, voltammetry and impedance) and novel nanotechnology, are also discussed.

Self-Assembled N-Heterocyclic Carbene-Based Carboxymethylated Dextran Monolayers on Gold as a Tunable Platform for Designing Affinity-Capture Biosensor Surfaces.

PubMed

Li, Zhijun; Munro, Kim; Narouz, Mina R; Lau, Andrew; Hao, Hongxia; Crudden, Cathleen M; Horton, J Hugh

2018-05-30

Sensor surfaces play a predominant role in the development of optical biosensor technologies for the analysis of biomolecular interactions. Thiol-based self-assembled monolayers (SAMs) on gold have been widely used as linker layers for sensor surfaces. However, the degradation of the thiol-gold bond can limit the performance and durability of such surfaces, directly impacting their performance and cost-effectiveness. To this end, a new family of materials based on N-heterocyclic carbenes (NHCs) has emerged as an alternative for surface modification, capable of self-assembling onto a gold surface with higher affinity and superior stability as compared to the thiol-based systems. Here we demonstrate three applications of NHC SAMs supporting a dextran layer as a tunable platform for developing various affinity-capture biosensor surfaces. We describe the development and testing of NHC-based dextran biosensor surfaces modified with each of streptavidin, nitrilotriacetic acid, and recombinant Protein A. These affinity-capture sensor surfaces enable oriented binding of ligands for optimal performance in biomolecular assays. Together, the intrinsic high stability and flexible design of the NHC biosensing platforms show great promise and open up exciting possibilities for future biosensing applications.

Triggered optical biosensor

DOEpatents

Song, Xuedong; Swanson, Basil I.

2001-10-02

An optical biosensor is provided for the detection of a multivalent target biomolecule, the biosensor including a substrate having a bilayer membrane thereon, a recognition molecule situated at the surface, the recognition molecule capable of binding with the multivalent target biomolecule, the recognition molecule further characterized as including a fluorescence label thereon and as being movable at the surface and a device for measuring a fluorescence change in response to binding between the recognition molecule and the multivalent target biomolecule.

Investigation of a Photoelectrochemical Passivated ZnO-Based Glucose Biosensor

PubMed Central

Lee, Ching-Ting; Chiu, Ying-Shuo; Ho, Shu-Ching; Lee, Yao-Jung

2011-01-01

A vapor cooling condensation system was used to deposit high quality intrinsic ZnO thin films and intrinsic ZnO nanorods as the sensing membrane of extended-gate field-effect-transistor (EGFET) glucose biosensors. The sensing sensitivity of the resulting glucose biosensors operated in the linear range was 13.4 μA mM−1 cm−2. To improve the sensing sensitivity of the ZnO-based glucose biosensors, the photoelectrochemical method was utilized to passivate the sidewall surfaces of the ZnO nanorods. The sensing sensitivity of the ZnO-based glucose biosensors with passivated ZnO nanorods was significantly improved to 20.33 μA mM−1 cm−2 under the same measurement conditions. The experimental results verified that the sensing sensitivity improvement was the result of the mitigation of the Fermi level pinning effect caused by the dangling bonds and the surface states induced on the sidewall surface of the ZnO nanorods. PMID:22163867

ZnS nanoparticles electrodeposited onto ITO electrode as a platform for fabrication of enzyme-based biosensors of glucose.

PubMed

Du, Jian; Yu, Xiuping; Wu, Ying; Di, Junwei

2013-05-01

The electrochemical and photoelectrochemical biosensors based on glucose oxidase (GOD) and ZnS nanoparticles modified indium tin oxide (ITO) electrode were investigated. The ZnS nanoparticles were electrodeposited directly on the surface of ITO electrode. The enzyme was immobilized on ZnS/ITO electrode surface by sol-gel method to fabricate glucose biosensor. GOD could electrocatalyze the reduction of dissolved oxygen, which resulted in a great increase of the reduction peak current. The reduction peak current decreased linearly with the addition of glucose, which could be used for glucose detection. Moreover, ZnS nanoparticles deposited on ITO electrode surface showed good photocurrent response under illumination. A photoelectrochemical biosensor for the detection of glucose was also developed by monitoring the decreases in the cathodic peak photocurrent. The results indicated that ZnS nanoparticles deposited on ITO substrate were a good candidate material for the immobilization of enzyme in glucose biosensor construction. Copyright © 2013 Elsevier B.V. All rights reserved.

Live-cell MRI with xenon hyper-CEST biosensors targeted to metabolically labeled cell-surface glycans.

PubMed

Witte, Christopher; Martos, Vera; Rose, Honor May; Reinke, Stefan; Klippel, Stefan; Schröder, Leif; Hackenberger, Christian P R

2015-02-23

The targeting of metabolically labeled glycans with conventional MRI contrast agents has proved elusive. In this work, which further expands the utility of xenon Hyper-CEST biosensors in cell experiments, we present the first successful molecular imaging of such glycans using MRI. Xenon Hyper-CEST biosensors are a novel class of MRI contrast agents with very high sensitivity. We designed a multimodal biosensor for both fluorescent and xenon MRI detection that is targeted to metabolically labeled sialic acid through bioorthogonal chemistry. Through the use of a state of the art live-cell bioreactor, it was demonstrated that xenon MRI biosensors can be used to image cell-surface glycans at nanomolar concentrations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biolayer modeling and optimization for the SPARROW biosensor

NASA Astrophysics Data System (ADS)

Feng, Ke

2007-12-01

Biosensor direct detection of molecular binding events is of significant interest in applications from molecular screening for cancer drug design to bioagent detection for homeland security and defense. The Stacked Planar Affinity Regulated Resonant Optical Waveguide (SPARROW) structure based on coupled waveguides was recently developed to achieve increased sensitivity within a fieldable biosensor device configuration. Under ideal operating conditions, modification of the effective propagation constant of the structure's sensing waveguide through selective attachment of specific targets to probes on the waveguide surface results in a change in the coupling characteristics of the guide over a specifically designed interaction length with the analyte. Monitoring the relative power in each waveguide after interaction enables 'recognition' of those targets which have selectively bound to the surface. However, fabrication tolerances, waveguide interface roughness, biolayer surface roughness and biolayer partial coverage have an effect on biosensor behavior and achievable limit of detection (LOD). In addition to these influences which play a role in device optimization, the influence of the spatially random surface loading of molecular binding events has to be considered, especially for low surface coverage. In this dissertation an analytic model is established for the SPARROW biosensor which accounts for these nonidealities with which the design of the biosensor can be guided and optimized. For the idealized case of uniform waveguide transducer layers and biolayer, both theoretical simulation (analytical expression) and computer simulation (numerical calculation) are completed. For the nonideal case of an inhomogeneous transducer with nonideal waveguide and biolayer surfaces, device output power is affected by such physical influences as surface scattering, coupling length, absorption, and percent coverage of binding events. Using grating and perturbation techniques we explore the influence of imperfect surfaces and random surface loading on scattering loss and coupling length. Results provide a range of achievable limits of detection in the SPARROW device for a given target size, surface loading, and detectable optical power.

Enzyme-linked, aptamer-based, competitive biolayer interferometry biosensor for palytoxin.

PubMed

Gao, Shunxiang; Zheng, Xin; Hu, Bo; Sun, Mingjuan; Wu, Jihong; Jiao, Binghua; Wang, Lianghua

2017-03-15

In this study, we coupled biolayer interferometry (BLI) with competitive binding assay through an enzyme-linked aptamer and developed a real-time, ultra-sensitive, rapid quantitative method for detection of the marine biotoxin palytoxin. Horseradish peroxidase-labeled aptamers were used as biorecognition receptors to competitively bind with palytoxin, which was immobilized on the biosensor surface. The palytoxin: horseradish peroxidase-aptamer complex was then submerged in a 3,3'-diaminobenzidine solution, which resulted in formation of a precipitated polymeric product directly on the biosensor surface and a large change in the optical thickness of the biosensor layer. This change could obviously shift the interference pattern and generate a response profile on the BLI biosensor. The biosensor showed a broad linear range for palytoxin (200-700pg/mL) with a low detection limit (0.04pg/mL). Moreover, the biosensor was applied to the detection of palytoxin in spiked extracts and showed a high degree of selectivity for palytoxin, good reproducibility, and stability. This enzyme-linked, aptamer-based, competitive BLI biosensor offers a promising method for rapid and sensitive detection of palytoxin and other analytes. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterizing Rat PNS Electrophysiological Response to Electrical Stimulation Using in vitro Chip-Based Human Investigational Platform (iCHIP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khani, Joshua; Prescod, Lindsay; Enright, Heather

Ex vivo systems and organ-on-a-chip technology offer an unprecedented approach to modeling the inner workings of the human body. The ultimate goal of LLNL’s in vitro Chip-based Human Investigational Platform (iCHIP) is to integrate multiple organ tissue cultures using microfluidic channels, multi-electrode arrays (MEA), and other biosensors in order to effectively simulate and study the responses and interactions of the major organs to chemical and physical stimulation. In this study, we focused on the peripheral nervous system (PNS) component of the iCHIP system. Specifically we sought to expound on prior research investigating the electrophysiological response of rat dorsal root ganglionmore » cells (rDRGs) to chemical exposures, such as capsaicin. Our aim was to establish a protocol for electrical stimulation using the iCHIP device that would reliably elicit a characteristic response in rDRGs. By varying the parameters for both the stimulation properties – amplitude, phase width, phase shape, and stimulation/ return configuration – and the culture conditions – day in vitro and neural cell types - we were able to make several key observations and uncover a potential convention with a minimal number of devices tested. Future work will seek to establish a standard protocol for human DRGs in the iCHIP which will afford a portable, rapid method for determining the effects of toxins and novel therapeutics on the PNS.« less

Technology modules from micro- and nano-electronics for the life sciences.

PubMed

Birkholz, M; Mai, A; Wenger, C; Meliani, C; Scholz, R

2016-05-01

The capabilities of modern semiconductor manufacturing offer remarkable possibilities to be applied in life science research as well as for its commercialization. In this review, the technology modules available in micro- and nano-electronics are exemplarily presented for the case of 250 and 130 nm technology nodes. Preparation procedures and the different transistor types as available in complementary metal-oxide-silicon devices (CMOS) and BipolarCMOS (BiCMOS) technologies are introduced as key elements of comprehensive chip architectures. Techniques for circuit design and the elements of completely integrated bioelectronics systems are outlined. The possibility for life scientists to make use of these technology modules for their research and development projects via so-called multi-project wafer services is emphasized. Various examples from diverse fields such as (1) immobilization of biomolecules and cells on semiconductor surfaces, (2) biosensors operating by different principles such as affinity viscosimetry, impedance spectroscopy, and dielectrophoresis, (3) complete systems for human body implants and monitors for bioreactors, and (4) the combination of microelectronics with microfluidics either by chip-in-polymer integration as well as Si-based microfluidics are demonstrated from joint developments with partners from biotechnology and medicine. WIREs Nanomed Nanobiotechnol 2016, 8:355-377. doi: 10.1002/wnan.1367 For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

Lithography-free nanofluidic concentrator based on droplets-on-demand system

NASA Astrophysics Data System (ADS)

Yu, Miao; Zhou, Hongbo; Yao, Shuhuai

2013-11-01

Biomarkers are usually low-abundance proteins in biofluids and below detection limit of conventional biosensors. Nanofluidic concentration devices allow efficient biomolecules trapping by utilizing ion concentration polarization near nanochannels. However, once the electric field is turned off, the electrokinetic concentration plug cannot maintain its concentration status and starts to diffuse. In order to maintain the high concentration and extract the concentrated sample for further analysis, a good approach is to encapsulate these plugs into water-in-oil droplets. Here we developed a nanofluidic concentrator based on droplet-on-demand generator to encapsulate concentrated sample in nL droplets. The lithography-free nanochannels were patterned by thermal cracking on the surface of PS Petri-dish. The resulting nanochannel arrays were 30 nm in depth. In combination with microchannels on PDMS, the micro-nano hybrid chip was developed. We used FITC solution to demonstrate that the chip significantly increased the sample concentration for more than 100 folds within 5 minutes. By tuning the pulsed pressure imposed by the solenoid valve connected to the concentration channel, the system can generate a desired volume of droplet with a target sample concentration at a prescribed time. This work was supported by the Research Grants Council of Hong Kong under General Research Fund (Grant No. 621110).

Recent approaches to ameliorate selectivity and sensitivity of enzyme based cholesterol biosensors: a review.

PubMed

Gahlaut, Anjum; Hooda, Vinita; Dhull, Vikas; Hooda, Vikas

2018-05-01

The healthcare area is often reluctant to execute new technology unless they are proven to be safe, constructive and secure. Eventually, an aspiration stands for providing point-of-care testing service to allow a better estimation of the biochemical levels of a patient that entails an insistent remedial action. With increasing mortality rate due to cardiovascular diseases (CVDs) in present scenario, it has become the need of hour to develop more advance methods for their diagnosis, so that it can be determined at sensitive levels and can be prevented from being fatal. Elevated level of cholesterol in blood stream is one of the utmost risk factors which lead to CVDs. Discernible from the vast research in this field, worth of cholesterol biosensors is already recognized and flourished in the clinical analysis of brain and cardiac vascular diseases. It necessitates unremitting progress in the development of biosensing technology towards fabrication, miniaturization and multiplexing ability of cholesterol quantification devices so that they can endow with lab-on-chip-analysis systems to the medical field. Different strategies have been meticulously explored for the engineering of cholesterol biosensors utilizing nanocomposites, conducting polymers, nanotubes and nanoparticles. Foremost, this article reviews the contemporary evolution in cholesterol biosensors, which encompass various strategies for immobilization of enzymes and roles of various matrices and artificial mediators used for the biosensor fabrication. Still there remains an enormous challenge to congregate the demands of performance and yield in a cost effective manner for its application in successful treatments of CVDs.

Nanomaterials towards fabrication of cholesterol biosensors: Key roles and design approaches.

PubMed

Saxena, Urmila; Das, Asim Bikas

2016-01-15

Importance of cholesterol biosensors is already recognized in the clinical diagnosis of cardiac and brain vascular diseases as discernible from the enormous amount of research in this field. Nevertheless, the practical application of a majority of the fabricated cholesterol biosensors is ordinarily limited by their inadequate performance in terms of one or more analytical parameters including stability, sensitivity and detection limit. Nanoscale materials offer distinctive size tunable electronic, catalytic and optical properties which opened new opportunities for designing highly efficient biosensor devices. Incorporation of nanomaterials in biosensing devices has found to improve the electroactive surface, electronic conductivity and biocompatibility of the electrode surfaces which then improves the analytical performance of the biosensors. Here we have reviewed recent advances in nanomaterial-based cholesterol biosensors. Foremost, the diverse roles of nanomaterials in these sensor systems have been discussed. Later, we have exhaustively explored the strategies used for engineering cholesterol biosensors with nanotubes, nanoparticles and nanocomposites. Finally, this review concludes with future outlook signifying some challenges of these nanoengineered cholesterol sensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of aspect ratio and surface defect density on hydrothermally grown ZnO nanorods towards amperometric glucose biosensing applications

NASA Astrophysics Data System (ADS)

Shukla, Mayoorika; Pramila; Dixit, Tejendra; Prakash, Rajiv; Palani, I. A.; Singh, Vipul

2017-11-01

In this work, hydrothermally grown ZnO Nanorods Array (ZNA) has been synthesized over Platinum (Pt) coated glass substrate, for biosensing applications. In-situ addition of strong oxidizing agent viz KMnO4 during hydrothermal growth was found to have profound effect on the physical properties of ZNA. Glucose oxidase (GOx) was later immobilized over ZNA by means of physical adsorption process. Further influence of varying aspect ratio, enzyme loading and surface defects on amperometric glucose biosensor has been analyzed. Significant variation in biosensor performance was observed by varying the amount of KMnO4 addition during the growth. Moreover, investigations revealed that the suppression of surface defects and aspect ratio variation of the ZNA played key role towards the observed improvement in the biosensor performance, thereby significantly affecting the sensitivity and response time of the fabricated biosensor. Among different biosensors fabricated having varied aspect ratio and surface defect density of ZNA, the best electrode resulted into sensitivity and response time to be 18.7 mA cm-2 M-1 and <5 s respectively. The observed results revealed that apart from high aspect ratio nanostructures and the extent of enzyme loading, surface defect density also hold a key towards ZnO nanostructures based bio-sensing applications.

Rapid amplification/detection of nucleic acid targets utilizing a HDA/thin film biosensor.

PubMed

Jenison, Robert; Jaeckel, Heidi; Klonoski, Joshua; Latorra, David; Wiens, Jacinta

2014-08-07

Thin film biosensors exploit a flat, optically coated silicon-based surface whereupon formation of nucleic acid hybrids are enzymatically transduced in a molecular thin film that can be detected by the unaided human eye under white light. While the limit of sensitivity for detection of nucleic acid targets is at sub-attomole levels (60 000 copies) many clinical specimens containing bacterial pathogens have much lower levels of analyte present. Herein, we describe a platform, termed HDA/thin film biosensor, which performs helicase-dependant nucleic acid amplification on a thin film biosensor surface to improve the limit of sensitivity to 10 copies of the mecA gene present in methicillin-resistant strains of Staphylococcus. As double-stranded DNA is unwound by helicase it was either bound by solution-phase DNA primers to be copied by DNA polymerase or hybridized to surface immobilized probe on the thin film biosensor surface to be detected. Herein, we show that amplification reactions on the thin film biosensor are equivalent to in standard thin wall tubes, with detection at the limit of sensitivity of the assay occurring after 30 minutes of incubation time. Further we validate the approach by detecting the presence of the mecA gene in methicillin-resistant Staphylococcus aureus (MRSA) from positive blood culture aliquots with high specificity (signal/noise ratio of 105).

Development and applications of 3-dimensional integration nanotechnologies.

PubMed

Kim, Areum; Choi, Eunmi; Son, Hyungbin; Pyo, Sung Gyu

2014-02-01

Unlike conventional two-dimensional (2D) planar structures, signal or power is supplied through through-silicon via (TSV) in three-dimensional (3D) integration technology to replace wires for binding the chip/wafer. TSVs have becomes an essential technology, as they satisfy Moore's law. This 3D integration technology enables system and sensor functions at a nanoscale via the implementation of a highly integrated nano-semiconductor as well as the fabrication of a single chip with multiple functions. Thus, this technology is considered to be a new area of development for the systemization of the nano-bio area. In this review paper, the basic technology required for such 3D integration is described and methods to measure the bonding strength in order to measure the void occurring during bonding are introduced. Currently, CMOS image sensors and memory chips associated with nanotechnology are being realized on the basis of 3D integration technology. In this paper, we intend to describe the applications of high-performance nano-biosensor technology currently under development and the direction of development of a high performance lab-on-a-chip (LOC).

Non-invasive, in vitro analysis of islet insulin production enabled by an optical porous silicon biosensor.

PubMed

Chhasatia, Rinku; Sweetman, Martin J; Harding, Frances J; Waibel, Michaela; Kay, Tom; Thomas, Helen; Loudovaris, Thomas; Voelcker, Nicolas H

2017-05-15

A label-free porous silicon (pSi) based, optical biosensor, using both an antibody and aptamer bioreceptor motif has been developed for the detection of insulin. Two parallel biosensors were designed and optimised independently, based on each bioreceptor. Both bioreceptors were covalently attached to a thermally hydrosilylated pSi surface though amide coupling, with unreacted surface area rendered stable and low fouling by incorporation of PEG moieties. The insulin detection ability of each biosensor was determined using interferometric reflectance spectroscopy, using a range of different media both with and without serum. Sensing performance was compared in terms of response value, response time and limit of detection (LOD) for each platform. In order to demonstrate the capability of the best performing biosensor to detect insulin from real samples, an in vitro investigation with the aptamer-modified surface was performed. This biosensor was exposed to buffer conditioned by glucose-stimulated human islets, with the result showing a positive response and a high degree of selectivity towards insulin capture. The obtained results correlated well with the ELISA used in the clinic for assaying glucose-stimulated insulin release from donor islets. We anticipate that this type of sensor can be applied as a rapid point-of-use biosensor to assess the quality of donor islets in terms of their insulin production efficiency, prior to transplantation. Copyright © 2017 Elsevier B.V. All rights reserved.

An InN/InGaN Quantum Dot Electrochemical Biosensor for Clinical Diagnosis

PubMed Central

Alvi, Naveed ul Hassan; Gómez, Victor J.; Rodriguez, Paul E.D. Soto; Kumar, Praveen; Zaman, Saima; Willander, Magnus; Nötzel, Richard

2013-01-01

Low-dimensional InN/InGaN quantum dots (QDs) are demonstrated for realizing highly sensitive and efficient potentiometric biosensors owing to their unique electronic properties. The InN QDs are biochemically functionalized. The fabricated biosensor exhibits high sensitivity of 97 mV/decade with fast output response within two seconds for the detection of cholesterol in the logarithmic concentration range of 1 × 10−6 M to 1 × 10−3 M. The selectivity and reusability of the biosensor are excellent and it shows negligible response to common interferents such as uric acid and ascorbic acid. We also compare the biosensing properties of the InN QDs with those of an InN thin film having the same surface properties, i.e., high density of surface donor states, but different morphology and electronic properties. The sensitivity of the InN QDs-based biosensor is twice that of the InN thin film-based biosensor, the EMF is three times larger, and the response time is five times shorter. A bare InGaN layer does not produce a stable response. Hence, the superior biosensing properties of the InN QDs are governed by their unique surface properties together with the zero-dimensional electronic properties. Altogether, the InN QDs-based biosensor reveals great potential for clinical diagnosis applications. PMID:24132228

Highly sensitive surface-scanning detector for the direct bacterial detection using magnetoelastic (ME) biosensors

NASA Astrophysics Data System (ADS)

Liu, Yuzhe; Horikawa, Shin; Chen, I.-Hsuan; Du, Songtao; Wikle, Howard C.; Suh, Sang-Jin; Chin, Bryan A.

2017-05-01

This paper demonstrates a highly sensitive surface-scanning detector used for magnetoelastic (ME) biosensors for the detection of Salmonella on the surface of a polyethylene (PE) food preparation surface. The design and fabrication methods of the new planar spiral coil are introduced. Different concentrations of Salmonella were measured on the surface of a PE board. The efficacy of Salmonella capture and detection is discussed.

Integrated Optical Mach-Zehnder Interferometer Based on Organic-Inorganic Hybrids for Photonics-on-a-Chip Biosensing Applications

PubMed Central

Oliveira-Silva, Rui; Silva, Nuno J. O.; André, Paulo S.; Ferreira, Rute A. S.

2018-01-01

The development of portable low-cost integrated optics-based biosensors for photonics-on-a-chip devices for real-time diagnosis are of great interest, offering significant advantages over current analytical methods. We report the fabrication and characterization of an optical sensor based on a Mach-Zehnder interferometer to monitor the growing concentration of bacteria in a liquid medium. The device pattern was imprinted on transparent self-patternable organic-inorganic di-ureasil hybrid films by direct UV-laser, reducing the complexity and cost production compared with lithographic techniques or three-dimensional (3D) patterning using femtosecond lasers. The sensor performance was evaluated using, as an illustrative example, E. coli cell growth in an aqueous medium. The measured sensitivity (2 × 10−4 RIU) and limit of detection (LOD = 2 × 10−4) are among the best values known for low-refractive index contrast sensors. Furthermore, the di-ureasil hybrid used to produce this biosensor has additional advantages, such as mechanical flexibility, thermal stability, and low insertion losses due to fiber-device refractive index mismatch (~1.49). Therefore, the proposed sensor constitutes a direct, compact, fast, and cost-effective solution for monitoring the concentration of lived-cells. PMID:29534514

Synthesis and assessment of peptide-nanocellulosic biosensors

USDA-ARS?s Scientific Manuscript database

Nanocellulose is an ideal transducer surface for biosensors: it provides a high surface area, easily derivatized with bioactive molecules, and abrogates binding of proteins present in biological fluids where analytes and clinical biomarkers are of interest. Here an example of approaches to biosenso...

A novel C-shaped, gold nanoparticle coated, embedded polymer waveguide for localized surface plasmon resonance based detection.

PubMed

Prabhakar, Amit; Mukherji, Soumyo

2010-12-21

In this study, a novel embedded optical waveguide based sensor which utilizes localized surface plasmon resonance of gold nanoparticles coated on a C-shaped polymer waveguide is being reported. The sensor, as designed, can be used as an analysis chip for detection of minor variations in the refractive index of its microenvironment, which makes it suitable for wide scale use as an affinity biosensor. The C-shaped waveguide coupled with microfluidic channel was fabricated by single step patterning of SU8 on an oxidized silicon wafer. The absorbance due to the localized surface plasmon resonance (LSPR) of SU8 waveguide bound gold nano particle (GNP) was found to be linear with refractive index changes between 1.33 and 1.37. A GNP coated C-bent waveguide of 200 μ width with a bend radius of 1 mm gave rise to a sensitivity of ~5 ΔA/RIU at 530 nm as compared to the ~2.5 ΔA/RIU (refractive index units) of the same dimension bare C-bend SU8 waveguide. The resolution of the sensor probe was ~2 × 10(-4) RIU.

The Application of Whole Cell-Based Biosensors for Use in Environmental Analysis and in Medical Diagnostics

PubMed Central

Gui, Qingyuan; Lawson, Tom; Shan, Suyan; Yan, Lu; Liu, Yong

2017-01-01

Various whole cell-based biosensors have been reported in the literature for the last 20 years and these reports have shown great potential for their use in the areas of pollution detection in environmental and in biomedical diagnostics. Unlike other reviews of this growing field, this mini-review argues that: (1) the selection of reporter genes and their regulatory proteins are directly linked to the performance of celllular biosensors; (2) broad enhancements in microelectronics and information technologies have also led to improvements in the performance of these sensors; (3) their future potential is most apparent in their use in the areas of medical diagnostics and in environmental monitoring; and (4) currently the most promising work is focused on the better integration of cellular sensors with nano and micro scaled integrated chips. With better integration it may become practical to see these cells used as (5) real-time portable devices for diagnostics at the bedside and for remote environmental toxin detection and this in situ application will make the technology commonplace and thus as unremarkable as other ubiquitous technologies. PMID:28703749

NFC-enabled, tattoo-like stretchable biosensor manufactured by "cut-and-paste" method.

PubMed

Hyoyoung Jeong; Taewoo Ha; Kuang, Irene; Linxiao Shen; Zhaohe Dai; Nan Sun; Nanshu Lu

2017-07-01

The wearables industry is lacking in devices that have the ability to provide valuable biometrics data in a soft, wireless and disposable system. Such a system should be high performance, multifunctional, but battery-free and low cost. Near field communication (NFC) is a wireless communication protocol built in many smartphones nowadays that can read data from battery-free passive tags. As a result, NFC-enabled wearable biosensors have been reported, but they are either unstretchable or have to be manufactured by labor- and time-intensive photolithography and transfer-printing processes. Using a dry and freeform "cut-and-paste" method, we have built a wireless and low-cost stretchable biosensor that integrates temperature sensor, light source/sensor, NFC chip, and antenna. It is battery-free and can be laminated on any part of human skin like a temporary transfer tattoo. The sensor can fully follow the stretching and compression of skin without mechanical failure or delamination. Thus, it is imperceptible to wear and can perform high-fidelity sensing. Potential applications include, but are not limited to, skin thermography and photometry.

Microcavity surface plasmon resonance bio-sensors

NASA Astrophysics Data System (ADS)

Mosavian, Nazanin

This work discusses a miniature surface plasmon biosensor which uses a dielectric sub- micron diameter core with gold spherical shell. The shell has a subwavelength nanoaperture believed to excite stationary plasmon resonances at the biosensor's surface. The sub-micron cavity enhances the measurement sensitivity of molecules binding to the sensor surface. We used visible-range optical spectroscopy to study the wavelength shift as bio-molecules absorbed-desorbed at the shell surface. We also used Scanning Electron Microscopy (SEM) and Focused Ion Beam (FIB) ablation to study the characteristics of microcavity surface plasmon resonance sensor (MSPRS) and the inner structure formed with metal deposition and its spectrum. We found that resonances at 580 nm and 670 nm responded to bound test agents and that Surface Plasmon Resonance (SPR) sensor intensity could be used to differentiate between D-glucose and L-glucose. The responsiveness of the system depended upon the mechanical integrity of the metallic surface coating.

Redesigning of Microbial Cell Surface and Its Application to Whole-Cell Biocatalysis and Biosensors.

PubMed

Han, Lei; Zhao, Yukun; Cui, Shan; Liang, Bo

2018-06-01

Microbial cell surface display technology can redesign cell surfaces with functional proteins and peptides to endow cells some unique features. Foreign peptides or proteins are transported out of cells and immobilized on cell surface by fusing with anchoring proteins, which is an effective solution to avoid substance transfer limitation, enzyme purification, and enzyme instability. As the most frequently used prokaryotic and eukaryotic protein surface display system, bacterial and yeast surface display systems have been widely applied in vaccine, biocatalysis, biosensor, bioadsorption, and polypeptide library screening. In this review of bacterial and yeast surface display systems, different cell surface display mechanisms and their applications in biocatalysis as well as biosensors are described with their strengths and shortcomings. In addition to single enzyme display systems, multi-enzyme co-display systems are presented here. Finally, future developments based on our and other previous reports are discussed.

Piezoelectric biosensor with a ladder polymer substrate coating

DOEpatents

Renschler, Clifford L.; White, Christine A.; Carter, Robert M.

1998-01-01

A piezoelectric biosensor substrate useful for immobilizing biomolecules in an oriented manner on the surface of a piezoelectric sensor has a ladder polymer of polyacrylonitrile. To make the substrate, a solution of an organic polymer, preferably polyacrylonitrile, is applied to the surface of a piezoelectric sensor. The organic polymer is modifying by heating the polymer in a controlled fashion in air such that a ladder polymer is produced which, in turn, forms the attachment point for the biomolecules comprising the piezoelectric biosensor.

Piezoelectric biosensor with a ladder polymer substrate coating

DOEpatents

Renschler, C.L.; White, C.A.; Carter, R.M.

1998-09-29

A piezoelectric biosensor substrate useful for immobilizing biomolecules in an oriented manner on the surface of a piezoelectric sensor has a ladder polymer of polyacrylonitrile. To make the substrate, a solution of an organic polymer, preferably polyacrylonitrile, is applied to the surface of a piezoelectric sensor. The organic polymer is modifying by heating the polymer in a controlled fashion in air such that a ladder polymer is produced which, in turn, forms the attachment point for the biomolecules comprising the piezoelectric biosensor. 3 figs.

Overview of Piezoelectric Biosensors, Immunosensors and DNA Sensors and Their Applications.

PubMed

Pohanka, Miroslav

2018-03-19

Piezoelectric biosensors are a group of analytical devices working on a principle of affinity interaction recording. A piezoelectric platform or piezoelectric crystal is a sensor part working on the principle of oscillations change due to a mass bound on the piezoelectric crystal surface. In this review, biosensors having their surface modified with an antibody or antigen, with a molecularly imprinted polymer, with genetic information like single stranded DNA, and biosensors with bound receptors of organic of biochemical origin, are presented and discussed. The mentioned recognition parts are frequently combined with use of nanoparticles and applications in this way are also introduced. An overview of the current literature is given and the methods presented are commented upon.

Theory and Applications of Surface Plasmon Resonance, Resonant Mirror, Resonant Waveguide Grating, and Dual Polarization Interferometry Biosensors

PubMed Central

Daghestani, Hikmat N.; Day, Billy W.

2010-01-01

Biosensors have been used extensively in the scientific community for several purposes, most notably to determine association and dissociation kinetics, protein-ligand, protein-protein, or nucleic acid hybridization interactions. A number of different types of biosensors are available in the field, each with real or perceived benefits over the others. This review discusses the basic theory and operational arrangements of four commercially available types of optical biosensors: surface plasmon resonance, resonant mirror, resonance waveguide grating, and dual polarization interferometry. The different applications these techniques offer are discussed from experiments and results reported in recently published literature. Additionally, recent advancements or modifications to the current techniques are also discussed. PMID:22163431

Thickness dependence of polydopamine thin films on detection sensitivity of surface plasmon-enhanced fluorescence biosensors

NASA Astrophysics Data System (ADS)

Toma, Mana; Tawa, Keiko

2018-03-01

A bioinspired polydopamine (PDA) coating is a good candidate for the rapid and cheap chemical modification of biosensor surfaces. Herein, we report the effect of PDA thickness on the detection sensitivity of a fluorescence biosensor utilizing surface plasmon-enhanced fluorescence. The thickness of PDA films was tuned by the incubation time of the dopamine solution and varied from 1 to 17 nm. The detection sensitivity was evaluated as the limit of detection (LOD) of a fluorescently labelled target analyte by a model immunoassay. The LOD was determined to be 1.6 pM for the thickest PDA film and was improved to 1.0 pM by reducing the thickness to the range from 1 to 5 nm, corresponding to the incubation time of 10 to 60 min. The experimental results indicate that the PDA coating is suitable for the surface functionalization of biosensors in mass production as it does not require precise control of the incubation time.

Enhancement in sensitivity of graphene-based zinc oxide assisted bimetallic surface plasmon resonance (SPR) biosensor

NASA Astrophysics Data System (ADS)

Kumar, Rajeev; Kushwaha, Angad S.; Srivastava, Monika; Mishra, H.; Srivastava, S. K.

2018-03-01

In the present communication, a highly sensitive surface plasmon resonance (SPR) biosensor with Kretschmann configuration having alternate layers, prism/zinc oxide/silver/gold/graphene/biomolecules (ss-DNA) is presented. The optimization of the proposed configuration has been accomplished by keeping the constant thickness of zinc oxide (32 nm), silver (32 nm), graphene (0.34 nm) layer and biomolecules (100 nm) for different values of gold layer thickness (1, 3 and 5 nm). The sensitivity of the proposed SPR biosensor has been demonstrated for a number of design parameters such as gold layer thickness, number of graphene layer, refractive index of biomolecules and the thickness of biomolecules layer. SPR biosensor with optimized geometry has greater sensitivity (66 deg/RIU) than the conventional (52 deg/RIU) as well as other graphene-based (53.2 deg/RIU) SPR biosensor. The effect of zinc oxide layer thickness on the sensitivity of SPR biosensor has also been analysed. From the analysis, it is found that the sensitivity increases significantly by increasing the thickness of zinc oxide layer. It means zinc oxide intermediate layer plays an important role to improve the sensitivity of the biosensor. The sensitivity of SPR biosensor also increases by increasing the number of graphene layer (upto nine layer).

Microfluidic biosensor for β-Hydroxybutyrate (βHBA) determination of subclinical ketosis diagnosis.

PubMed

Weng, Xuan; Zhao, Wenting; Neethirajan, Suresh; Duffield, Todd

2015-02-12

Determination of β-hydroxybutyrate (βHBA) is a gold standard for diagnosis of Subclinical Ketosis (SCK), a common disease in dairy cows that causes significant economic loss. Early detection of SCK can help reduce the risk of the disease progressing into clinical stage, thus minimizing economic losses on dairy cattle. Conventional laboratory methods are time consuming and labor-intensive, requiring expensive and bulky equipment. Development of portable and robust devices for rapid on-site SCK diagnosis is an effective way to prevent and control ketosis and can significantly aid in the management of dairy animal health. Microfluidic technology provides a rapid, cost-effective way to develop handheld devices for on-farm detection of sub-clinical ketosis. In this study, a highly sensitive microfluidics-based biosensor for on-site SCK diagnosis has been developed. A rapid, low-cost microfluidic biosensor with high sensitivity and specificity was developed for SCK diagnosis. Determination of βHBA was employed as the indicator in the diagnosis of SCK. On-chip detection using miniaturized and cost-effective optical sensor can be finished in 1 minute with a detection limit of 0.05 mM concentration. Developed microfluidic biosensor was successfully tested with the serum samples from dairy cows affected by SCK. The results of the developed biosensor agreed well with two other laboratory methods. The biosensor was characterized by high sensitivity and specificity towards βHBA with a detection limit of 0.05 mM. The developed microfluidic biosensor provides a promising prototype for a cost-effective handheld meter for on-site SCK diagnosis. By using microfluidic method, the detection time is significantly decreased compared to other laboratory methods. Here, we demonstrate a field-deployable device to precisely identify and measure subclinical ketosis by specific labeling and quantification of β-hydroxybutyate in cow blood samples. A real-time on-site detection system will maximize convenience for the farmers.

Direct correlation between potentiometric and impedance biosensing of antibody-antigen interactions using an integrated system

NASA Astrophysics Data System (ADS)

Tsai, Meng-Yen; Creedon, Niamh; Brightbill, Eleanor; Pavlidis, Spyridon; Brown, Billyde; Gray, Darren W.; Shields, Niall; Sayers, Ríona; Mooney, Mark H.; O'Riordan, Alan; Vogel, Eric M.

2017-08-01

A fully integrated system that combines extended gate field-effect transistor (EGFET)-based potentiometric biosensors and electrochemical impedance spectroscopy (EIS)-based biosensors has been demonstrated. This integrated configuration enables the sequential measurement of the same immunological binding event on the same sensing surface and consequently sheds light on the fundamental origins of sensing signals produced by FET and EIS biosensors, as well as the correlation between the two. Detection of both the bovine serum albumin (BSA)/anti-BSA model system in buffer solution and bovine parainfluenza antibodies in complex blood plasma samples was demonstrated using the integrated biosensors. Comparison of the EGFET and EIS sensor responses reveals similar dynamic ranges, while equivalent circuit modeling of the EIS response shows that the commonly reported total impedance change (ΔZtotal) is dominated by the change in charge transfer resistance (Rct) rather than surface capacitance (Csurface). Using electrochemical kinetics and the Butler-Volmer equation, we unveil that the surface potential and charge transfer resistance, measured by potentiometric and impedance biosensors, respectively, are, in fact, intrinsically linked. This observation suggests that there is no significant gain in using the FET/EIS integrated system and leads to the demonstration that low-cost EGFET biosensors are sufficient as a detection tool to resolve the charge information of biomolecules for practical sensing applications.

Passivated aluminum nanohole arrays for label-free biosensing applications.

PubMed

Canalejas-Tejero, Víctor; Herranz, Sonia; Bellingham, Alyssa; Moreno-Bondi, María Cruz; Barrios, Carlos Angulo

2014-01-22

We report the fabrication and performance of a surface plasmon resonance aluminum nanohole array refractometric biosensor. An aluminum surface passivation treatment based on oxygen plasma is developed in order to circumvent the undesired effects of oxidation and corrosion usually found in aluminum-based biosensors. Immersion tests in deionized water and device simulations are used to evaluate the effectiveness of the passivation process. A label-free bioassay based on biotin analysis through biotin-functionalized dextran-lipase conjugates immobilized on the biosensor-passivated surface in aqueous media is performed as a proof of concept to demonstrate the suitability of these nanostructured aluminum films for biosensing.

Construction of titanium dioxide nanorod/graphite microfiber hybrid electrodes for a high performance electrochemical glucose biosensor

NASA Astrophysics Data System (ADS)

Zhang, Jian; Yu, Xin; Guo, Weibo; Qiu, Jichuan; Mou, Xiaoning; Li, Aixue; Liu, Hong

2016-04-01

The demand for a highly sensitive and selective glucose biosensor which can be used for implantable or on-time monitoring is constantly increasing. In this work, TiO2 nanorods were synthesized in situ on the surface of graphite microfibers to yield TiO2 nanorod/graphite microfiber hybrid electrodes. The TiO2 nanorods not only retain the high activity of the immobilized glucose molecule, but also promote the direct electron transfer process on the electrode surface. As a working electrode in an electrochemical glucose biosensor in a flowing system, the microfiber hybrid electrodes exhibit high sensitivity, selectivity and stability. Due to its simplicity, low cost, high stability, and unique morphology, the TiO2 nanorod/graphite microfiber hybrid electrode is expected to be an excellent candidate for an implantable biosensor or for in situ flow monitoring.The demand for a highly sensitive and selective glucose biosensor which can be used for implantable or on-time monitoring is constantly increasing. In this work, TiO2 nanorods were synthesized in situ on the surface of graphite microfibers to yield TiO2 nanorod/graphite microfiber hybrid electrodes. The TiO2 nanorods not only retain the high activity of the immobilized glucose molecule, but also promote the direct electron transfer process on the electrode surface. As a working electrode in an electrochemical glucose biosensor in a flowing system, the microfiber hybrid electrodes exhibit high sensitivity, selectivity and stability. Due to its simplicity, low cost, high stability, and unique morphology, the TiO2 nanorod/graphite microfiber hybrid electrode is expected to be an excellent candidate for an implantable biosensor or for in situ flow monitoring. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01360k

Thin Hydrogel Films for Optical Biosensor Applications

PubMed Central

Mateescu, Anca; Wang, Yi; Dostalek, Jakub; Jonas, Ulrich

2012-01-01

Hydrogel materials consisting of water-swollen polymer networks exhibit a large number of specific properties highly attractive for a variety of optical biosensor applications. This properties profile embraces the aqueous swelling medium as the basis of biocompatibility, non-fouling behavior, and being not cell toxic, while providing high optical quality and transparency. The present review focuses on some of the most interesting aspects of surface-attached hydrogel films as active binding matrices in optical biosensors based on surface plasmon resonance and optical waveguide mode spectroscopy. In particular, the chemical nature, specific properties, and applications of such hydrogel surface architectures for highly sensitive affinity biosensors based on evanescent wave optics are discussed. The specific class of responsive hydrogel systems, which can change their physical state in response to externally applied stimuli, have found large interest as sophisticated materials that provide a complex behavior to hydrogel-based sensing devices. PMID:24957962

MineLoC: A Rapid Production of Lab-on-a-Chip Biosensors Using 3D Printer and the Sandbox Game, Minecraft.

PubMed

Kim, Kyukwang; Kim, Hyeongkeun; Kim, Seunggyu; Jeon, Jessie S

2018-06-10

Here, MineLoC is described as a pipeline developed to generate 3D printable models of master templates for Lab-on-a-Chip (LoC) by using a popular multi-player sandbox game “Minecraft”. The user can draw a simple diagram describing the channels and chambers of the Lab-on-a-Chip devices with pre-registered color codes which indicate the height of the generated structure. MineLoC converts the diagram into large chunks of blocks (equal sized cube units composing every object in the game) in the game world. The user and co-workers can simultaneously access the game and edit, modify, or review, which is a feature not generally supported by conventional design software. Once the review is complete, the resultant structure can be exported into a stereolithography (STL) file which can be used in additive manufacturing. Then, the Lab-on-a-Chip device can be fabricated by the standard protocol to produce a Lab-on-a-Chip. The simple polydimethylsiloxane (PDMS) device for the bacterial growth measurement used in the previous research was copied by the proposed method. The error calculation by a 3D model comparison showed an accuracy of 86%. It is anticipated that this work will facilitate more use of 3D printer-based Lab-on-a-Chip fabrication, which greatly lowers the entry barrier in the field of Lab-on-a-Chip research.

Mediatorless Impedance Studies with Titanium Dioxide Conjugated Gold Nanoparticles for Hydrogen Peroxide Detection

PubMed Central

Abdul Halim, Nur Hamidah; Lee, Yook Heng; Marugan, Radha Swathe Priya Malon; Hashim, Uda

2017-01-01

An impedimetric-based biosensor constructed using gold nanoparticles (AuNP) entrapped within titanium dioxide (TiO2) particles for hydrogen peroxide (H2O2) detection is the main feature of this research. The matrix of the biosensor employed the surface of TiO2, which was previously modified with an amine terminal group using 3-Aminopropyltriethoxysilane (APTS) at a low temperature to create a ready to immobilise surface for the biosensor application. Hemoglobin (Hb), which exhibits peroxidase-like activity, was used as the bioreceptor in the biosensor to detect H2O2 in solution. The analysis was carried out using an alternative impedance method, in which the biosensor exhibited a wide linear range response between 1 × 10−4 M and 1.5 × 10−2 M and a limit of detection (LOD) of 1 × 10−5 M without a redox mediator. PMID:28927005

Application of a Nanostructured Enzymatic Biosensor Based on Fullerene and Gold Nanoparticles to Polyphenol Detection.

PubMed

Tortolini, Cristina; Sanzò, Gabriella; Antiochia, Riccarda; Mazzei, Franco; Favero, Gabriele

2017-01-01

Electrochemical biosensors provide an attractive means of analyzing the content of a biological sample due to the direct conversion of a biological event to an electronic signal. The signal transduction and the general performance of electrochemical biosensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale. The most common surface modification techniques, the various electrochemical transduction mechanisms, and the choice of the recognition receptor molecules all influence the ultimate sensitivity of the sensor. We show herein a novel electrochemical biosensing platform based on the coupling of two different nanostructured materials (gold nanoparticles and fullerenols) displaying interesting electrochemical features. The use of these nanomaterials improved the electrochemical performance of the proposed biosensor.An application of the nanostructured enzyme-based biosensor has been developed for evaluating the detection of polyphenols either in buffer solution or in real wine samples.

Easy-to-Fabricate and High-Sensitivity LSPR Type Specific Protein Detection Sensor Using AAO Nano-Pore Size Control

PubMed Central

Kim, Sae-Wan; Lee, Jae-Sung; Lee, Sang-Won; Kang, Byoung-Ho; Kwon, Jin-Beom; Kim, Ok-Sik; Kim, Ju-Seong; Kim, Eung-Soo; Kwon, Dae-Hyuk; Kang, Shin-Won

2017-01-01

In this study, we developed a pore size/pore area-controlled optical biosensor-based anodic aluminum oxide (AAO) nanostructure. As the pore size of AAO increases, the unit cell of AAO increases, which also increases the non-pore area to which the antibody binds. The increase in the number of antibodies immobilized on the surface of the AAO enables effective detection of trace amounts of antigen, because increased antigen-antibody bonding results in a larger surface refractive index change. High sensitivity was thus achieved through amplification of the interference wave of two vertically-incident reflected waves through the localized surface plasmon resonance phenomenon. The sensitivity of the fabricated sensor was evaluated by measuring the change in wavelength with the change in the refractive index of the device surface, and sensitivity was increased with increasing pore-size and non-pore area. The sensitivity of the fabricated sensor was improved and up to 11.8 ag/mL serum amyloid A1 antigen was detected. In addition, the selectivity of the fabricated sensor was confirmed through a reaction with a heterogeneous substance, C-reactive protein antigen. By using hard anodization during fabrication of the AAO, the fabrication time of the device was reduced and the AAO chip was fabricated quickly and easily. PMID:28406469

Nano/biosensors based on large-area graphene

NASA Astrophysics Data System (ADS)

Ducos, Pedro Jose

Two dimensional materials have properties that make them ideal for applications in chemical and biomolecular sensing. Their high surface/volume ratio implies that all atoms are exposed to the environment, in contrast to three dimensional materials with most atoms shielded from interactions inside the bulk. Graphene additionally has an extremely high carrier mobility, even at ambient temperature and pressure, which makes it ideal as a transduction device. The work presented in this thesis describes large-scale fabrication of Graphene Field Effect Transistors (GFETs), their physical and chemical characterization, and their application as biomolecular sensors. Initially, work was focused on developing an easily scalable fabrication process. A large-area graphene growth, transfer and photolithography process was developed that allowed the scaling of production of devices from a few devices per single transfer in a chip, to over a thousand devices per transfer in a full wafer of fabrication. Two approaches to biomolecules sensing were then investigated, through nanoparticles and through chemical linkers. Gold and platinum Nanoparticles were used as intermediary agents to immobilize a biomolecule. First, gold nanoparticles were monodispersed and functionalized with thiolated probe DNA to yield DNA biosensors with a detection limit of 1 nM and high specificity against noncomplementary DNA. Second, devices are modified with platinum nanoparticles and functionalized with thiolated genetically engineered scFv HER3 antibodies to realize a HER3 biosensor. Sensors retain the high affinity from the scFv fragment and show a detection limit of 300 pM. We then show covalent and non-covalent chemical linkers between graphene and antibodies. The chemical linker 1-pyrenebutanoic acid succinimidyl ester (pyrene) stacks to the graphene by Van der Waals interaction, being a completely non-covalent interaction. The linker 4-Azide-2,3,5,6-tetrafluorobenzoic acid, succinimidyl ester (azide) is a photoactivated perfluorophenyl azide that covalently binds to graphene. A comparison is shown for genetically engineered scFv HER3 antibodies and show a low detection limit of 10 nM and 100 pM for the pyrene and azide, respectively. Finally, we use the azide linker to demonstrate a large-scale fabrication of a multiplexed array for Lyme disease. Simultaneous detection of a mixture of two target proteins of the Lyme disease bacterium (Borrelia burgdorferi), this is done by separating the antibodies corresponding to each target in the mixture to different regions of the chip. We show we can differentiate concentrations of the two targets.

Facile synthesis of tetragonal columnar-shaped TiO2 nanorods for the construction of sensitive electrochemical glucose biosensor.

PubMed

Yang, Zhanjun; Tang, Yan; Li, Juan; Zhang, Yongcai; Hu, Xiaoya

2014-04-15

A tetragonal columnar-shaped TiO2 (TCS-TiO2) nanorods are synthesized via a facile route for the immobilization of glucose oxidase (GOx). A novel electrochemical glucose biosensor is constructed based on the direct electrochemistry of GOx at TCS-TiO2 modified glassy carbon electrode. The fabricated biosensor is characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, electrochemical impedance spectra and cyclic voltammetry. The immobilized enzyme molecules on TCS-TiO2 nanorods retain its native structure and bioactivity and show a surface controlled, quasi-reversible and fast electron transfer process. The TCS-TiO2 nanorods have large surface area and provide a favorable microenvironment for enhancing the electron transfer between enzyme and electrode surface. The constructed glucose biosensor shows wide linear range from 5.0×10(-6) to 1.32×10(-3) M with a high sensitivity of 23.2 mA M(-1) cm(-2). The detection limit is calculated to be 2.0×10(-6) M at signal-to-noise of 3. The proposed glucose biosensor also exhibits excellent selectivity, good reproducibility, and acceptable operational stability. Furthermore, the biosensor can be successfully applied in the detection of glucose in serum sample at the applied potential of -0.50 V. The TCS-TiO2 nanorods provide an efficient and promising platform for the immobilization of proteins and development of excellent biosensors. © 2013 Published by Elsevier B.V.

A modular microfluidic architecture for integrated biochemical analysis.

PubMed

Shaikh, Kashan A; Ryu, Kee Suk; Goluch, Edgar D; Nam, Jwa-Min; Liu, Juewen; Thaxton, C Shad; Chiesl, Thomas N; Barron, Annelise E; Lu, Yi; Mirkin, Chad A; Liu, Chang

2005-07-12

Microfluidic laboratory-on-a-chip (LOC) systems based on a modular architecture are presented. The architecture is conceptualized on two levels: a single-chip level and a multiple-chip module (MCM) system level. At the individual chip level, a multilayer approach segregates components belonging to two fundamental categories: passive fluidic components (channels and reaction chambers) and active electromechanical control structures (sensors and actuators). This distinction is explicitly made to simplify the development process and minimize cost. Components belonging to these two categories are built separately on different physical layers and can communicate fluidically via cross-layer interconnects. The chip that hosts the electromechanical control structures is called the microfluidic breadboard (FBB). A single LOC module is constructed by attaching a chip comprised of a custom arrangement of fluid routing channels and reactors (passive chip) to the FBB. Many different LOC functions can be achieved by using different passive chips on an FBB with a standard resource configuration. Multiple modules can be interconnected to form a larger LOC system (MCM level). We demonstrated the utility of this architecture by developing systems for two separate biochemical applications: one for detection of protein markers of cancer and another for detection of metal ions. In the first case, free prostate-specific antigen was detected at 500 aM concentration by using a nanoparticle-based bio-bar-code protocol on a parallel MCM system. In the second case, we used a DNAzyme-based biosensor to identify the presence of Pb(2+) (lead) at a sensitivity of 500 nM in <1 nl of solution.

An amorphous silicon photodiode microfluidic chip to detect nanomolar quantities of HIV-1 virion infectivity factor.

PubMed

Vistas, Cláudia R; Soares, Sandra S; Rodrigues, Rogério M M; Chu, Virginia; Conde, João P; Ferreira, Guilherme N M

2014-08-07

A hydrogenated amorphous silicon (a-Si:H) photosensor was explored for the quantitative detection of a HIV-1 virion infectivity factor (Vif) at a detection limit in the single nanomolar range. The a-Si:H photosensor was coupled with a microfluidic channel that was functionalized with a recombinant single chain variable fragment antibody. The biosensor selectively recognizes HIV-1 Vif from human cell extracts.

Development of a Biosensor Nanofluidic Platform for Integration with Terahertz Spectroscopic System

DTIC Science & Technology

2014-06-27

space. The instrumentation for fabrication of micro/nano-fluidic chips including a Laser-Cutting System, a Sputtering system, a Spin Coating ...polyester (PET) substrate, as PET is more chemically and thermally resistant, and can be readily obtained in a variety of thicknesses down to 12.5 um...to create the array pattern on the silver coated PET substrate. Copper was then electrodeposited to a thickness of 5 um around the photoresist

A novel lab-on-chip platform with integrated solid phase PCR and Supercritical Angle Fluorescence (SAF) microlens array for highly sensitive and multiplexed pathogen detection.

PubMed

Hung, Tran Quang; Chin, Wai Hoe; Sun, Yi; Wolff, Anders; Bang, Dang Duong

2017-04-15

Solid-phase PCR (SP-PCR) has become increasingly popular for molecular diagnosis and there have been a few attempts to incorporate SP-PCR into lab-on-a-chip (LOC) devices. However, their applicability for on-line diagnosis is hindered by the lack of sensitive and portable on-chip optical detection technology. In this paper, we addressed this challenge by combining the SP-PCR with super critical angle fluorescence (SAF) microlens array embedded in a microchip. We fabricated miniaturized SAF microlens array as part of a microfluidic chamber in thermoplastic material and performed multiplexed SP-PCR directly on top of the SAF microlens array. Attribute to the high fluorescence collection efficiency of the SAF microlens array, the SP-PCR assay on the LOC platform demonstrated a high sensitivity of 1.6 copies/µL, comparable to off-chip detection using conventional laser scanner. The combination of SP-PCR and SAF microlens array allows for on-chip highly sensitive and multiplexed pathogen detection with low-cost and compact optical components. The LOC platform would be widely used as a high-throughput biosensor to analyze food, clinical and environmental samples. Copyright © 2016 Elsevier B.V. All rights reserved.

The Extended Core Coax: A novel nanoarchitecture for lab-on-a-chip electrochemical diagnostics

NASA Astrophysics Data System (ADS)

Valera, Amy E.; D'Imperio, Luke; Burns, Michael J.; Naughton, Michael J.; Chiles, Thomas C.

We report a novel nanoarchitecture, the Extended Core Coax (ECC) that has applicability for the detection of biomarkers in lab-on-a-chip diagnostic devices. ECC is capable of providing accessible, highly sensitive, and specific disease diagnosis at point-of-care. The architecture represents a vertically oriented nanocoax comprised of a gold inner metal core that extends 200nm above a chrome outer metal shield, separated by a dielectric annulus. Each ECC chip contains 7 discrete sensing arrays, 0.49 mm2 in size, containing 35,000 nanoscale coaxes wired in parallel. Previous non-extended nanocoaxial architectures have demonstrated a limit of detection (LOD) of 2 ng/mL of cholera toxin using an off-chip setup. This sensitivity compares favorably to the standard optical ELISA used in clinical settings. The ECC matches this LOD, and additionally offers the benefit of specific and reliable biofunctionalization on the extended gold core. Thus, the ECC is an attractive candidate for development as a full lab-on-a-chip biosensor for detection of infectious disease biomarkers, such as cholera toxin, through tethering of biomarker recognition proteins, such as antibodies, directly on the device. Support from the National Institutes of Health (National Cancer Institute award No. CA137681 and National Institute of Allergy and Infectious Diseases award No. AI100216).

Measurement of salivary cortisol by a chemiluminescent organic-based immunosensor.

PubMed

Pires, N M M; Dong, T

2014-01-01

A highly sensitive chemiluminescent immunoassay (CLIA) using a sensitive organic photodetector was developed to detect human cortisol, an important biomarker for stress-related diseases. The developed CLIA was performed onto gold-coated glass chips, on which anti-cortisol antibodies were immobilised and chemiluminescent horseradish peroxidase-luminol-peroxide reactions were generated. Using cortisol-spiked artificial saliva samples, the CLIA biosensor showed a linear range of detection between 0.1 ng/mL and 175 ng/mL and a detection limit of 80 pg/mL. The sensor response was highly specific to cortisol and did not vary significantly between assays. The results indicate the potential clinical application of the CLIA sensor. Furthermore, the simple layered structure of the organic photodetector may encourage the realisation of integrated optical biosensors for point-of-use measurement of salivary cortisol levels.

Portable microsystem integrates multifunctional dielectrophoresis manipulations and a surface stress biosensor to detect red blood cells for hemolytic anemia.

PubMed

Sang, Shengbo; Feng, Qiliang; Jian, Aoqun; Li, Huiming; Ji, Jianlong; Duan, Qianqian; Zhang, Wendong; Wang, Tao

2016-09-20

Hemolytic anemia intensity has been suggested as a vital factor for the growth of certain clinical complications of sickle cell disease. However, there is no effective and rapid diagnostic method. As a powerful platform for bio-particles testing, biosensors integrated with microfluidics offer great potential for a new generation of portable point of care systems. In this paper, we describe a novel portable microsystem consisting of a multifunctional dielectrophoresis manipulations (MDM) device and a surface stress biosensor to separate and detect red blood cells (RBCs) for diagnosis of hemolytic anemia. The peripheral circuit to power the interdigitated electrode array of the MDM device and the surface stress biosensor test platform were integrated into a portable signal system. The MDM includes a preparing region, a focusing region, and a sorting region. Simulation and experimental results show the RBCs trajectories when they are subjected to the positive DEP force, allowing the successful sorting of living/dead RBCs. Separated RBCs are then transported to the biosensor and the capacitance values resulting from the variation of surface stress were measured. The diagnosis of hemolytic anemia can be realized by detecting RBCs and the portable microsystem provides the assessment to the hemolytic anemia patient.

Detection of benzimidazole carbamates and amino metabolites in liver by surface plasmon resonance-biosensor

USDA-ARS?s Scientific Manuscript database

Two surface plasmon resonance (SPR) biosensor screening assays were developed and validated to detect 11 benzimidazole carbamate (BZT) and four amino-benzimidazole veterinary drug residues in liver tissue. The assays used polyclonal antibodies, raised in sheep, to detect BZTs and amino-benzimidazole...

Development of a multilayered polymeric DNA biosensor using radio frequency technology with gold and magnetic nanoparticles.

PubMed

Yang, Cheng-Hao; Kuo, Long-Sheng; Chen, Ping-Hei; Yang, Chii-Rong; Tsai, Zuo-Min

2012-01-15

This study utilized the radio frequency (RF) technology to develop a multilayered polymeric DNA sensor with the help of gold and magnetic nanoparticles. The flexible polymeric materials, poly (p-xylylene) (Parylene) and polyethylene naphtholate (PEN), were used as substrates to replace the conventional rigid substrates such as glass and silicon wafers. The multilayered polymeric RF biosensor, including the two polymer layers and two copper transmission structure layers, was developed to reduce the total sensor size and further enhance the sensitivity of the biochip in the RF DNA detection. Thioglycolic acid (TGA) was used on the surface of the proposed biochip to form a thiolate-modified sensing surface for DNA hybridization. Gold nanoparticles (AuNPs) and magnetic nanoparticles (MNPs) were used to immobilize on the surface of the biosensor to enhance overall detection sensitivity. In addition to gold nanoparticles, the magnetic nanoparticles has been demonstrated the applicability for RF DNA detection. The performance of the proposed biosensor was evaluated by the shift of the center frequency of the RF biosensor because the electromagnetic characteristic of the biosensors can be altered by the immobilized multilayer nanoparticles on the biosensor. The experimental results show that the detection limit of the DNA concentration can reach as low as 10 pM, and the largest shift of the center frequency with triple-layer AuNPs and MNPs can approach 0.9 and 0.7 GHz, respectively. Such the achievement implies that the developed biosensor can offer an alternative inexpensive, disposable, and highly sensitive option for application in biomedicine diagnostic systems because the price and size of each biochip can be effectively reduced by using fully polymeric materials and multilayer-detecting structures. Copyright © 2011 Elsevier B.V. All rights reserved.

Potentiometric glucose biosensor based on core-shell Fe3O4-enzyme-polypyrrole nanoparticles.

PubMed

Yang, Zhengpeng; Zhang, Chunjing; Zhang, Jianxin; Bai, Wanbei

2014-01-15

Core-shell Fe3O4-enzyme-polypyrrole (Ppy) nanoparticles with excellent magnetism and conductivity were successfully prepared via the surface modification and enzyme self-encapsulation within Ppy. A novel potentiometric glucose biosensor has been constructed by effectively attaching the proposed Fe3O4-enzyme-Ppy nanoparticles to the surface of the magnetic glassy carbon electrode (MGCE). The optimum biosensing conditions could be provided with polymerization time of pyrrole for 6h and 0.42 mg immobilization amount of Fe3O4-enzyme-Ppy nanoparticles on MGCE. The performance of the developed glucose biosensor was evaluated and the results indicated that a sensitive glucose biosensor could be fabricated. The obtained glucose biosensor presents shorter response time (6 s), wider linear range (0.5 μM to 34 mM), lower limit of detection (LOD, 0.3 μM), high-selectivity monitoring of glucose and good stability (with about 98.1% of the initial response signal retained after 20 days). The analytical application of the glucose biosensor confirms the feasibility of glucose detection in serum sample. © 2013 Elsevier B.V. All rights reserved.

Mechanistic Challenges and Advantages of Biosensor Miniaturization into the Nanoscale.

PubMed

Soleymani, Leyla; Li, Feng

2017-04-28

Over the past few decades, there has been tremendous interest in developing biosensing systems that combine high sensitivity and specificity with rapid sample-to-answer times, portability, low-cost operation, and ease-of-use. Miniaturizing the biosensor dimensions into the nanoscale has been identified as a strategy for addressing the functional requirements of point-of-care and wearable biosensors. However, it is important to consider that decreasing the critical dimensions of biosensing elements impacts the two most important performance metrics of biosensors: limit-of-detection and response time. Miniaturization into the nanoscale enhances signal-to-noise-ratio by increasing the signal density (signal/geometric surface area) and reducing background signals. However, there is a trade-off between the enhanced signal transduction efficiency and the longer time it takes to collect target analytes on sensor surfaces due to the increase in mass transport times. By carefully considering the signal transduction mechanisms and reaction-transport kinetics governing different classes of biosensors, it is possible to develop structure-level and device-level strategies for leveraging miniaturization toward creating biosensors that combine low limit-of-detection with rapid response times.

On the origin of enhanced sensitivity in nanoscale FET-based biosensors

PubMed Central

Shoorideh, Kaveh; Chui, Chi On

2014-01-01

Electrostatic counter ion screening is a phenomenon that is detrimental to the sensitivity of charge detection in electrolytic environments, such as in field-effect transistor-based biosensors. Using simple analytical arguments, we show that electrostatic screening is weaker in the vicinity of concave curved surfaces, and stronger in the vicinity of convex surfaces. We use this insight to show, using numerical simulations, that the enhanced sensitivity observed in nanoscale biosensors is due to binding of biomolecules in concave corners where screening is reduced. We show that the traditional argument, that increased surface area-to-volume ratio for nanoscale sensors is responsible for their increased sensitivity, is incorrect. PMID:24706861

Electronic Biosensors Based on III-Nitride Semiconductors.

PubMed

Kirste, Ronny; Rohrbaugh, Nathaniel; Bryan, Isaac; Bryan, Zachary; Collazo, Ramon; Ivanisevic, Albena

2015-01-01

We review recent advances of AlGaN/GaN high-electron-mobility transistor (HEMT)-based electronic biosensors. We discuss properties and fabrication of III-nitride-based biosensors. Because of their superior biocompatibility and aqueous stability, GaN-based devices are ready to be implemented as next-generation biosensors. We review surface properties, cleaning, and passivation as well as different pathways toward functionalization, and critically analyze III-nitride-based biosensors demonstrated in the literature, including those detecting DNA, bacteria, cancer antibodies, and toxins. We also discuss the high potential of these biosensors for monitoring living cardiac, fibroblast, and nerve cells. Finally, we report on current developments of covalent chemical functionalization of III-nitride devices. Our review concludes with a short outlook on future challenges and projected implementation directions of GaN-based HEMT biosensors.

Platinum nanoparticles functionalized nitrogen doped graphene platform for sensitive electrochemical glucose biosensing.

PubMed

Yang, Zhanjun; Cao, Yue; Li, Juan; Jian, Zhiqin; Zhang, Yongcai; Hu, Xiaoya

2015-04-29

In this work, we reported an efficient platinum nanoparticles functionalized nitrogen doped graphene (PtNPs@NG) nanocomposite for devising novel electrochemical glucose biosensor for the first time. The fabricated PtNPs@NG and biosensor were characterized using transmission electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, static water contact angle, UV-vis spectroscopy, electrochemical impedance spectra and cyclic voltammetry, respectively. PtNPs@NG showed large surface area and excellent biocompatibility, and enhanced the direct electron transfer between enzyme molecules and electrode surface. The glucose oxidase (GOx) immobilized on PtNPs@NG nanocomposite retained its bioactivity, and exhibited a surface controlled, quasi-reversible and fast electron transfer process. The constructed glucose biosensor showed wide linear range from 0.005 to 1.1mM with high sensitivity of 20.31 mA M(-1) cm(-2). The detection limit was calculated to be 0.002 mM at signal-to-noise of 3, which showed 20-fold decrease in comparison with single NG-based electrochemical biosensor for glucose. The proposed glucose biosensor also demonstrated excellent selectivity, good reproducibility, acceptable stability, and could be successfully applied in the detection of glucose in serum samples at the applied potential of -0.33 V. This research provided a promising biosensing platform for the development of excellent electrochemical biosensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Using a surface plasmon resonance biosensor for rapid detection of salmonella typhimurium in chicken carcass

USDA-ARS?s Scientific Manuscript database

Chicken is one of the most popular meat products in the world. Salmonella Typhimurium is a common foodborne pathogens associated with the processing of poultry. An optical Surface Plasmon Resonance (SPR) biosensor was sensitive to the presence of Salmonella Typhimurium in chicken carcass. The Spr...

Laser induced forward transfer technique for the immobilization of biomaterials in biosensors applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Papazoglou, Symeon; Chatzipetrou, Marianeza; Massaouti, Maria; Zergioti, Ioanna

2017-02-01

Laser Induced Forward Transfer (LIFT) is a direct write technique, able to create micropatterns of biomaterials on sensing devices. In this conference we will present a new approach using LIFT for the printing and direct immobilization of biomaterials on a great variety of surfaces, for bio-sensor applications. The basic requirement for the fabrication of a biosensor is to stabilize a biomaterial that brings the physicochemical changes in close proximity to a transducer. In this direction, several immobilization methods such as covalent binding and crosslinking have been implemented. The presence of the additional functionalization steps in the biosensors fabrication, is among the main disadvantages of chemical immobilization methods. Our approach employs the LIFT technique for the direct immobilization of biomaterials, either by physical adsorption or by covalent bonding of the biomaterials. The physical adsorption of the biomaterials, occurs on hydrophobic or super-hydrophobic surfaces, due to the transition of the wetting properties of the surfaces upon the impact of the biomaterials with high velocity. The unique characteristic of LIFT technique to create high speed liquid jets, leads to the penetration of the biomaterial in the micro/nano roughness of the surface, resulting in their direct immobilization, without the need of any chemical functionalization layers. Moreover, we will also present the direct immobilization of biomaterials on Screen Printed Electrodes, for enzymatic biosensors, with a limit of detection (LOD) for catechol at 150 nM, and protein biosensors, used for the detection of herbicides, with an LOD of 8-10 nM.

A novel mast cell co-culture microfluidic chip for the electrochemical evaluation of food allergen.

PubMed

Jiang, Hui; Jiang, Donglei; Zhu, Pei; Pi, Fuwei; Ji, Jian; Sun, Chao; Sun, Jiadi; Sun, Xiulan

2016-09-15

In this study a novel cell-to-cell electrochemical microfluidic chip was developed for qualitative and quantitative analysis of food allergen. Microfluidic cell culture, food allergen-induced cell morphological changes, and cell metabolism measurements were performed simultaneously using the aforementioned device. RBL-2H3 mast cells and ANA-1 macrophages have been used within a cell co-culture model to observe their allergic response when they are introduced to the antigen stimulus. Two cell cultivation microfluidic channels are located in the microfluidic chip, which is fabricated with four groups of gold electrodes, with an additional "capillary". In order to detect the allergic response, the cells were stimulated with dinitrophenylated bovine serum albumin (DNP-BSA) without anti-DNP IgE incubation. When exocytosis occurs, the cell-secreted inflammatory cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) and cell impedance changes were detected using cell-based electrochemical assay. Results indicate that the real-time cell allergic response are accurately monitored by this electrochemical microfluidic chip, which provides a general example of rapidly prototyped low-cost biosensor technology for applications in both food allergen detection and investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

Anisotropic multi-spot DBR porous silicon chip for the detection of human immunoglobin G.

PubMed

Cho, Bomin; Um, Sungyong; Sohn, Honglae

2014-07-01

Asymmetric porous silicon multilayer (APSM)-based optical biosensor was developed to specify human Immunoglobin G (Ig G). APSM chip was generated by an electrochemical etching of silicon wafer using an asymmetric electrode configuration in aqueous ethanolic HF solution and constituted with nine arrayed porous silicon multilayer. APSM prepared from anisotropic etching conditions displayed a sharp reflection resonance in the reflectivity spectrum. Each spot displayed single reflection resonance at different wavelengths as a function of the lateral distance from the Pt counter electrode. The sensor system was consisted of the 3 x 3 spot array of APSM modified with protein A. The system was probed with an aqueous human Ig G. Molecular binding and specificity was monitored as a shift in wavelength of reflection resonance.

Cell chips as new tools for cell biology--results, perspectives and opportunities.

PubMed

Primiceri, Elisabetta; Chiriacò, Maria Serena; Rinaldi, Ross; Maruccio, Giuseppe

2013-10-07

Cell culture technologies were initially developed as research tools for studying cell functions, but nowadays they are essential for the biotechnology industry, with rapidly expanding applications requiring more and more advancements with respect to traditional tools. Miniaturization and integration of sensors and microfluidic components with cell culture techniques open the way to the development of cellomics as a new field of research targeting innovative analytic platforms for high-throughput studies. This approach enables advanced cell studies under controllable conditions by providing inexpensive, easy-to-operate devices. Thanks to their numerous advantages cell-chips have become a hotspot in biosensors and bioelectronics fields and have been applied to very different fields. In this review exemplary applications will be discussed, for cell counting and detection, cytotoxicity assays, migration assays and stem cell studies.

Plasmonic biosensors.

PubMed

Hill, Ryan T

2015-01-01

The unique optical properties of plasmon resonant nanostructures enable exploration of nanoscale environments using relatively simple optical characterization techniques. For this reason, the field of plasmonics continues to garner the attention of the biosensing community. Biosensors based on propagating surface plasmon resonances (SPRs) in films are the most well-recognized plasmonic biosensors, but there is great potential for the new, developing technologies to surpass the robustness and popularity of film-based SPR sensing. This review surveys the current plasmonic biosensor landscape with emphasis on the basic operating principles of each plasmonic sensing technique and the practical considerations when developing a sensing platform with the various techniques. The 'gold standard' film SPR technique is reviewed briefly, but special emphasis is devoted to the up-and-coming localized surface plasmon resonance and plasmonically coupled sensor technology. © 2014 Wiley Periodicals, Inc.

Guided-Wave Optical Biosensors

PubMed Central

Passaro, Vittorio M. N.; Dell'Olio, Francesco; Casamassima, Biagio; De Leonardis, Francesco

2007-01-01

Guided-wave optical biosensors are reviewed in this paper. Advantages related to optical technologies are presented and integrated architectures are investigated in detail. Main classes of bio receptors and the most attractive optical transduction mechanisms are discussed. The possibility to use Mach-Zehnder and Young interferometers, microdisk and microring resonators, surface plasmon resonance, hollow and antiresonant waveguides, and Bragg gratings to realize very sensitive and selective, ultra-compact and fast biosensors is discussed. Finally, CMOS-compatible technologies are proved to be the most attractive for fabrication of guided-wave photonic biosensors.

Nanomaterials-based enzyme electrochemical biosensors operating through inhibition for biosensing applications.

PubMed

Kurbanoglu, Sevinc; Ozkan, Sibel A; Merkoçi, Arben

2017-03-15

In recent years great progress has been made in applying nanomaterials to design novel biosensors. Use of nanomaterials offers to biosensing platforms exceptional optical, electronic and magnetic properties. Nanomaterials can increase the surface of the transducing area of the sensors that in turn bring an increase in catalytic behaviors. They have large surface-to-volume ratio, controlled morphology and structure that also favor miniaturization, an interesting advantage when the sample volume is a critical issue. Biosensors have great potential for achieving detect-to-protect devices: devices that can be used in detections of pollutants and other treating compounds/analytes (drugs) protecting citizens' life. After a long term focused scientific and financial efforts/supports biosensors are expected now to fulfill their promise such as being able to perform sampling and analysis of complex samples with interest for clinical or environment fields. Among all types of biosensors, enzymatic biosensors, the most explored biosensing devices, have an interesting property, the inherent inhibition phenomena given the enzyme-substrate complex formation. The exploration of such phenomena is making remarkably important their application as research and applied tools in diagnostics. Different inhibition biosensor systems based on nanomaterials modification has been proposed and applied. The role of nanomaterials in inhibition-based biosensors for the analyses of different groups of drugs as well as contaminants such as pesticides, phenolic compounds and others, are discussed in this review. This deep analysis of inhibition-based biosensors that employ nanomaterials will serve researchers as a guideline for further improvements and approaching of these devices to real sample applications so as to reach society needs and such biosensor market demands. Copyright © 2016 Elsevier B.V. All rights reserved.

Near field detector for integrated surface plasmon resonance biosensor applications.

PubMed

Bora, Mihail; Celebi, Kemal; Zuniga, Jorge; Watson, Colin; Milaninia, Kaveh M; Baldo, Marc A

2009-01-05

Integrated surface plasmon resonance biosensors promise to enable compact and portable biosensing at high sensitivities. To replace the far field detector traditionally used to detect surface plasmons we integrate a near field detector below a functionalized gold film. The evanescent field of a surface plasmon at the aqueous-gold interface is converted into photocurrent by a thin film organic heterojunction diode. We demonstrate that use of the near field detector is equivalent to the traditional far field measurement of reflectivity. The sensor is stable and reversible in an aqueous environment for periods of 6 hrs. For specific binding of neutravidin, the detection limit is 4 microg/cm(2). The sensitivity can be improved by reducing surface roughness of the gold layers and optimization of the device design. From simulations, we predict a maximum sensitivity that is two times lower than a comparable conventional SPR biosensor.

Photonic crystal fiber-based plasmonic biosensor with external sensing approach

NASA Astrophysics Data System (ADS)

Rifat, Ahmmed A.; Hasan, Md. Rabiul; Ahmed, Rajib; Butt, Haider

2018-01-01

We propose a simple photonic crystal fiber (PCF) biosensor based on the surface plasmon resonance effect. The sensing properties are characterized using the finite element method. Chemically stable gold material is deposited on the outer surface of the PCF to realize the practical sensing approach. The performance of the modeled biosensor is investigated in terms of wavelength sensitivity, amplitude sensitivity, sensor resolution, and linearity of the resonant wavelength with the variation of structural parameters. In the sensing range of 1.33 to 1.37, maximum sensitivities of 4000 nm/RIU and 478 are achieved with the high sensor resolutions of 2.5×10-5 and 2.1×10-5 RIU using wavelength and amplitude interrogation methods, respectively. The designed biosensor will reduce fabrication complexity due to its simple and realistic hexagonal lattice structure. It is anticipated that the proposed biosensor may find possible applications for unknown biological and biochemical analyte detections with a high degree of accuracy.

Immune biosensors based on the SPR and TIRE: efficiency of their application for bacteria determination

NASA Astrophysics Data System (ADS)

Starodub, N. F.; Ogorodniichuk, J.; Lebedeva, T.; Shpylovyy, P.

2013-11-01

In this work we have designed high-specific biosensors for Salmonella typhimurium detection based on the surface plasmon resonance (SPR) and total internal reflection ellipsometry (TIRE). It has been demonstrated high selectivity and sensitivity of analysis. As a registering part for our experiments the Spreeta (USA) and "Plasmonotest" (Ukraine) with flowing cell have been applied among of SPR device. Previous researches confirmed an efficiency of SPR biosensors using for detecting of specific antigen-antibody interactions therefore this type of reactions with some previous preparations of surface binding layer was used as reactive part. It has been defined that in case with Spreeta sensitivity was on the level 103 - 107 cells/ml. Another biosensor based on the SPR has shown the sensitivity within 101 - 106 cells/ml. Maximal sensitivity was on the level of several cells in 10 ml (up to the fact that less than 5 cells) which has been obtained using the biosensor based on TIRE.

Detection of egg yolk antibodies reflecting Salmonella enteritidis infections using a surface plasmon resonance biosensor.

PubMed

Thomas, Ekelijn; Bouma, Annemarie; van Eerden, Ellen; Landman, Wil J M; van Knapen, Frans; Stegeman, Arjan; Bergwerff, Aldert A

2006-08-31

A surface plasmon resonance (SPR) biosensor assay was developed on the basis of a lipopolysaccharide antigen of Salmonella enterica serovar enteritidis (S. enterica serovar enteritidis) to detect egg yolk antibodies against S. enterica serovar enteritidis. This biosensor assay was compared to two commercial ELISA kits based on LPS antigen and flagellar antigen. A number of 163 egg yolk and combined egg white and yolk samples from chickens experimentally infected with S. enterica serovar enteritidis and 90 egg yolk and combined egg white and yolk samples from uninfected chickens were analyzed. Receiver operating characteristic analysis of the data calculated a diagnostic sensitivity of 82% and a diagnostic specificity of 100%. The within-day coefficient of variation of a positive internal-control egg yolk was 1%. The SPR biosensor assay was able to detect antibodies in a significantly higher percentage of known positive samples than the commercial ELISA's. The anticipated use of the SPR biosensor assay is to determine the S. enterica serovar enteritidis serostatus of non-vaccinated layer hens.

Portable evanescent wave fiber biosensor for highly sensitive detection of Shigella

NASA Astrophysics Data System (ADS)

Xiao, Rui; Rong, Zhen; Long, Feng; Liu, Qiqi

2014-11-01

A portable evanescent wave fiber biosensor was developed to achieve the rapid and highly sensitive detection of Shigella. In this study, a DNA probe was covalently immobilized onto fiber-optic biosensors that can hybridize with a fluorescently labeled complementary DNA. The sensitivity of detection for synthesized oligonucleotides can reach 10-10 M. The surface of the sensor can be regenerated with 0.5% sodium dodecyl sulfate solution (pH 1.9) for over 30 times without significant deterioration of performance. The total analysis time for a single sample, including the time for measurement and surface regeneration, was less than 6 min. We employed real-time polymerase chain reaction (PCR) and compared the results of both methods to investigate the actual Shigella DNA detection capability of the fiber-optic biosensor. The fiber-optic biosensor could detect as low as 102 colony-forming unit/mL Shigella. This finding was comparable with that by real-time PCR, which suggests that this method is a potential alternative to existing detection methods.

Biosensor of endotoxin and sepsis

NASA Astrophysics Data System (ADS)

Shao, Yang; Wang, Xiang; Wu, Xi; Gao, Wei; He, Qing-hua; Cai, Shaoxi

2001-09-01

To investigate the relation between biosensor of endotoxin and endotoxin of plasma in sepsis. Method: biosensor of endotoxin was designed with technology of quartz crystal microbalance bioaffinity sensor ligand of endotoxin were immobilized by protein A conjugate. When a sample soliton of plasma containing endotoxin 0.01, 0.03, 0.06, 0.1, 0.5, 1.0Eu, treated with perchloric acid and injected into slot of quartz crystal surface respectively, the ligand was released from the surface of quartz crystal to form a more stable complex with endotoxin in solution. The endotoxin concentration corresponded to the weight change on the crystal surface, and caused change of frequency that occurred when desorbed. The result was biosensor of endotoxin might detect endotoxin of plasma in sepsis, measurements range between 0.05Eu and 0.5Eu in the stop flow mode, measurement range between 0.1Eu and 1Eu in the flow mode. The sensor of endotoxin could detect the endotoxin of plasm rapidly, and use for detection sepsis in clinically.

Development of conductometric biosensor array for simultaneous determination of maltose, lactose, sucrose and glucose.

PubMed

Soldatkin, O O; Peshkova, V M; Saiapina, O Y; Kucherenko, I S; Dudchenko, O Y; Melnyk, V G; Vasylenko, O D; Semenycheva, L M; Soldatkin, A P; Dzyadevych, S V

2013-10-15

The aim of this work was to develop an array of biosensors for simultaneous determination of four carbohydrates in solution. Several enzyme systems selective to lactose, maltose, sucrose and glucose were immobilised on the surface of four conductometric transducers and served as bio-recognition elements of the biosensor array. Direct enzyme analysis carried out by the developed biosensors was highly sensitive to the corresponding substrates. The analysis lasted 2 min. The dynamic range of substrate determination extended from 0.001 mM to 1.0-3.0mM, and strongly depended on the enzyme system used. An effect of the solution pH, ionic strength and buffer capacity on the biosensors responses was investigated; the conditions of simultaneous operation of all biosensors were optimised. The data on cross-impact of the substrates of all biosensors were obtained; the biosensor selectivity towards possible interfering carbohydrates was tested. The developed biosensor array showed good signal reproducibility and storage stability. The biosensor array is suited for simultaneous, quick, simple, and selective determination of maltose, lactose, sucrose and glucose. © 2013 Elsevier B.V. All rights reserved.

Microfluidics Integrated Biosensors: A Leading Technology towards Lab-on-a-Chip and Sensing Applications

PubMed Central

Luka, George; Ahmadi, Ali; Najjaran, Homayoun; Alocilja, Evangelyn; DeRosa, Maria; Wolthers, Kirsten; Malki, Ahmed; Aziz, Hassan; Althani, Asmaa; Hoorfar, Mina

2015-01-01

A biosensor can be defined as a compact analytical device or unit incorporating a biological or biologically derived sensitive recognition element immobilized on a physicochemical transducer to measure one or more analytes. Microfluidic systems, on the other hand, provide throughput processing, enhance transport for controlling the flow conditions, increase the mixing rate of different reagents, reduce sample and reagents volume (down to nanoliter), increase sensitivity of detection, and utilize the same platform for both sample preparation and detection. In view of these advantages, the integration of microfluidic and biosensor technologies provides the ability to merge chemical and biological components into a single platform and offers new opportunities for future biosensing applications including portability, disposability, real-time detection, unprecedented accuracies, and simultaneous analysis of different analytes in a single device. This review aims at representing advances and achievements in the field of microfluidic-based biosensing. The review also presents examples extracted from the literature to demonstrate the advantages of merging microfluidic and biosensing technologies and illustrate the versatility that such integration promises in the future biosensing for emerging areas of biological engineering, biomedical studies, point-of-care diagnostics, environmental monitoring, and precision agriculture. PMID:26633409

The Highly Robust Electrical Interconnects and Ultrasensitive Biosensors Based on Embedded Carbon Nanotube Arrays

NASA Technical Reports Server (NTRS)

Li, Jun; Cassell, Alan; Koehne, Jessica; Chen, Hua; Ng, Hou Tee; Ye, Qi; Stevens, Ramsey; Han, Jie; Meyyappan, M.

2003-01-01

We report on our recent breakthroughs in two different applications using well-aligned carbon nanotube (CNT) arrays on Si chips, including (1) a novel processing solution for highly robust electrical interconnects in integrated circuit manufacturing, and (2) the development of ultrasensitive electrochemical DNA sensors. Both of them rely on the invention of a bottom-up fabrication scheme which includes six steps, including: (a) lithographic patterning, (b) depositing bottom conducting contacts, (c) depositing metal catalysts, (d) CNT growth by plasma enhanced chemical vapor deposition (PECVD), (e) dielectric gap-filling, and (f) chemical mechanical polishing (CMP). Such processes produce a stable planarized surface with only the open end of CNTs exposed, whch can be further processed or modified for different applications. By depositing patterned top contacts, the CNT can serve as vertical interconnects between the two conducting layers. This method is fundamentally different fiom current damascene processes and avoids problems associated with etching and filling of high aspect ratio holes at nanoscales. In addition, multiwalled CNTs (MWCNTs) are highly robust and can carry a current density of 10(exp 9) A/square centimeters without degradation. It has great potential to help extending the current Si technology. The embedded MWCNT array without the top contact layer can be also used as a nanoelectrode array in electrochemical biosensors. The cell time-constant and sensitivity can be dramatically improved. By functionalizing the tube ends with specific oligonucleotide probes, specific DNA targets can be detected with electrochemical methods down to subattomoles.

[Preparation of poly(methyl acrylate) microfluidic chips surface-modified by hyperbranched polyamide ester and their application in the separation of biomolecules].

PubMed

Liu, Bing; Lin, Donge; Xu, Lin; Lei, Yanhui; Bo, Qianglong; Shou, Chongqi

2012-05-01

The surface of poly (methyl acrylate) (PMMA) microfluidic chips were modified using hyperbranched polyamide ester via chemical bonding. The contact angles of the modified chips were measured. The surface morphology was observed by scanning electron microscope (SEM) and stereo microscope. The results showed that the surface of the modified chips was coated by a dense, uniform, continuous, hydrophilic layer of hyperbranched polyamide ester. The hydrophilic of the chip surface was markedly improved. The contact angle of the chips modified decreased from 89.9 degrees to 29.5 degrees. The electro osmotic flow (EOF) in the modified microchannel was lower than that in the unmodified microchannel. Adenosine and L-lysine were detected and separated via the modified PMMA microfluidic chips. Compared with unmodified chips, the modified chips successfully separated the two biomolecules. The detection peaks were clear and sharp. The separation efficiencies of adenosine and L-lysine were 8.44 x 10(4) plates/m and 9.82 x 10(4) plates/m respectively, and the resolutions (Rs) was 5.31. The column efficiencies and resolutions of the modified chips were much higher than those of the unmodified chips. It was also observed that the modified chips possessed good reproducibility of migration time. This research may provide a new and effective method to improve the hydrophilicity of the PMMA surface and the application of PMMA microfluidic chips in the determination of trace biomolecules.

Electrically-receptive and thermally-responsive paper-based sensor chip for rapid detection of bacterial cells.

PubMed

Khan, Muhammad S; Misra, Santosh K; Dighe, Ketan; Wang, Zhen; Schwartz-Duval, Aaron S; Sar, Dinabandhu; Pan, Dipanjan

2018-07-01

Although significant technological advancements have been made in the development of analytical biosensor chips for detecting bacterial strains (E. coli, S. Mutans and B. Subtilis), critical requirements i.e. limit of detection (LOD), fast time of response, ultra-sensitivity with high reproducibility and good shelf-life with robust sensing capability have yet to be met within a single sensor chip. In order to achieve these criteria, we present an electrically-receptive thermally-responsive (ER-TR) sensor chip comprised of simple filter paper used as substrate coated with composite of poly(N-isopropylacrylamide) polymer (PNIPAm) - graphene nanoplatelet (GR) followed by evaporation of Au electrodes for capturing both Gram-positive (S. mutans and B. subtilis) and Gram-negative (E. coli) bacterial cells in real-time. Autoclave water, tap water, lake water and milk samples were tested with ER-TR chip with and without bacterial strains at varying concentration range 10 1 -10 5 cells/mL. The sensor was integrated with in-house built printed circuit board (PCB) to transmit/receive electrical signals. The interaction of E. coli, S. mutans and B. subtilis cells with fibers of PNIPAm-GR resulted in a change of electrical resistance and the readout was monitored wirelessly in real-time using MATLAB algorithm. Finally, prepared ER-TR chip exhibited the reproducibility of 85-97% with shelf-life of up to four weeks after testing with lake water sample. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunomagnetic separation for MEMS-based biosensor of waterborne pathogens detection

NASA Astrophysics Data System (ADS)

Guo, Jianjiang; Zhang, Rongbiao

2017-07-01

Rapid isolation and detection of special pathogens present in environmental drinking water is critical for water quality monitoring. Numerical analysis and experimental investigations on immunomagnetic capture and isolation of waterborne pathogens with magnetic nanoparticles (MNPs) in microfluidic channel are performed. A finite-element COMSOL-based model is established to demonstrate the novel method of on-chip capturing pathogens using MNPs together with periodic pulse magnetic field. Simulation results determine the optimum magnetic pole current and switching frequency for magnetic separation. With the magnetic isolation experiment platform built up, as a pathogen example of Escherichia coli O157:H7, the performance of the method is experimentally verified. Both numerical and experimental results are found to agree reasonably well. Results of these investigations show that the capture efficiency of the immunomagnetic separation method is more than 92%, which could be encouraging for the design and optimization of MEMS-based biosensor of waterborne pathogen detection.

Surface desensitization of polarimetric waveguide interferometers

NASA Astrophysics Data System (ADS)

Worth, Colin

Non-specific binding of small molecules to the surface of waveguide biosensors presents a major obstacle to surface-sensing techniques that attempt to detect very low concentrations (<1 g/mm2) of large (500 nm to 3 mum) biological objects. Interferometric waveguide biosensors use the interaction of an evanescent light field outside of the guiding layer with a biological sample to detect a particular type of cell or bacteria at some distance from the sensor surface. In such experiments, binding of small proteins close to the surface can be a significant source of noise. It is possible to significantly improve the signal-to-noise ratio by varying the properties of the biosensor, in order to reduce or eliminate the biosensor's response to a thin protein layer at the waveguide surface, without significantly reducing the response to larger target particles. In many biosensing applications, specifically bound particles, such as bacteria, are much larger than non-specifically bound particles such as proteins. In addition, due to laminar flow conditions at the sensor surface, the latter smaller particles tend to accumulate on the sensor surface. By varying the waveguide parameters, it is possible to vary the sensitivity of the detector response as a function of sample distance from the detector, by changing the properties of the TE0 and TM0 guided modes. This results in a signal reduction of more than 85%, for thin (30 nm or less) layers adjacent to the waveguide surface.

An amperometric hydrogen peroxide biosensor based on Co3O4 nanoparticles and multiwalled carbon nanotube modified glassy carbon electrode

NASA Astrophysics Data System (ADS)

Kaçar, Ceren; Dalkiran, Berna; Erden, Pınar Esra; Kiliç, Esma

2014-08-01

In this work a new type of hydrogen peroxide biosensor was fabricated based on the immobilization of horseradish peroxidase (HRP) by cross-linking on a glassy carbon electrode (GCE) modified with Co3O4 nanoparticles, multiwall carbon nanotubes (MWCNTs) and gelatin. The introduction of MWCNTs and Co3O4 nanoparticles not only enhanced the surface area of the modified electrode for enzyme immobilization but also facilitated the electron transfer rate, resulting in a high sensitivity of the biosensor. The fabrication process of the sensing surface was characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Amperometric detection of hydrogen peroxide was investigated by holding the modified electrode at -0.30 V (vs. Ag/AgCl). The biosensor showed optimum response within 5 s at pH 7.0. The optimized biosensor showed linear response range of 7.4 × 10-7-1.9 × 10-5 M with a detection limit of 7.4 × 10-7. The applicability of the purposed biosensor was tested by detecting hydrogen peroxide in disinfector samples. The average recovery was calculated as 100.78 ± 0.89.

An efficient biosensor made of an electromagnetic trap and a magneto-resistive sensor.

PubMed

Li, Fuquan; Kosel, Jürgen

2014-09-15

Magneto-resistive biosensors have been found to be useful because of their high sensitivity, low cost, small size, and direct electrical output. They use super-paramagnetic beads to label a biological target and detect it via sensing the stray field. In this paper, we report a new setup for magnetic biosensors, replacing the conventional "sandwich" concept with an electromagnetic trap. We demonstrate the capability of the biosensor in the detection of E. coli. The trap is formed by a current-carrying microwire that attracts the magnetic beads into a sensing space on top of a tunnel magneto-resistive sensor. The sensor signal depends on the number of beads in the sensing space, which depends on the size of the beads. This enables the detection of biological targets, because such targets increase the volume of the beads. Experiments were carried out with a 6 µm wide microwire, which attracted the magnetic beads from a distance of 60 μm, when a current of 30 mA was applied. A sensing space of 30 µm in length and 6 µm in width was defined by the magnetic sensor. The results showed that individual E. coli bacterium inside the sensing space could be detected using super-paramagnetic beads that are 2.8 µm in diameter. The electromagnetic trap setup greatly simplifies the device and reduces the detection process to two steps: (i) mixing the bacteria with magnetic beads and (ii) applying the sample solution to the sensor for measurement, which can be accomplished within about 30 min with a sample volume in the µl range. This setup also ensures that the biosensor can be cleaned easily and re-used immediately. The presented setup is readily integrated on chips via standard microfabrication techniques. Copyright © 2014 Elsevier B.V. All rights reserved.

Dual-mode acoustic wave biosensors microarrays

NASA Astrophysics Data System (ADS)

Auner, Gregory W.; Shreve, Gina; Ying, Hao; Newaz, Golam; Hughes, Chantelle; Xu, Jianzeng

2003-04-01

We have develop highly sensitive and selective acoustic wave biosensor arrays with signal analysis systems to provide a fingerprint for the real-time identification and quantification of a wide array of bacterial pathogens and environmental health hazards. We have developed an unique highly sensitive dual mode acoustic wave platform prototype that, when combined with phage based selective detection elements, form a durable bacteria sensor. Arrays of these new real-time biosensors are integrated to form a biosensor array on a chip. This research and development program optimizes advanced piezoelectric aluminum nitride wide bandgap semiconductors, novel micromachining processes, advanced device structures, selective phage displays development and immobilization techniques, and system integration and signal analysis technology to develop the biosensor arrays. The dual sensor platform can be programmed to sense in a gas, vapor or liquid environment by switching between acoustic wave resonate modes. Such a dual mode sensor has tremendous implications for applications involving monitoring of pathogenic microorganisms in the clinical setting due to their ability to detect airborne pathogens. This provides a number of applications including hospital settings such as intensive care or other in-patient wards for the reduction of nosocomial infections and maintenance of sterile environments in surgical suites. Monitoring for airborn pathogen transmission in public transportation areas such as airplanes may be useful for implementation of strategies for redution of airborn transmission routes. The ability to use the same sensor in the liquid sensing mode is important for tracing the source of airborn pathogens to local liquid sources. Sensing of pathogens in saliva will be useful for sensing oral pathogens and support of decision-making strategies regarding prevention of transmission and support of treatment strategies.

Simulation and fabrication of a new novel 3D injectable biosensor for high throughput genomics and proteomics in a lab-on-a-chip device.

PubMed

Esfandyarpour, Rahim; Esfandyarpour, Hesaam; Harris, James S; Davis, Ronald W

2013-11-22

Biosensors are used for the detection of biochemical molecules such as proteins and nucleic acids. Traditional techniques, such as enzyme-linked immuno-sorbent assay (ELISA), are sensitive but require several hours to yield a result and usually require the attachment of a fluorophore molecule to the target molecule. Micromachined biosensors that employ electrical detection are now being developed. Here we describe one such device, which is ultrasensitive, real-time, label free and localized. It is called the nanoneedle biosensor and shows promise to overcome some of the current limitations of biosensors. The key element of this device is a 10 nm wide annular gap at the end of the needle, which is the sensitive part of the sensor. The total diameter of the sensor is about 100 nm. Any change in the population of molecules in this gap results in a change of impedance across the gap. Single molecule detection should be possible because the sensory part of the sensor is in the range of bio-molecules of interest. To increase throughput we can flow the solution containing the target molecules over an array of such structures, each with its own integrated read-out circuitry to allow 'real-time' detection (i.e. several minutes) of label free molecules without sacrificing sensitivity. To fabricate the arrays we used electron beam lithography together with associated pattern transfer techniques. Preliminary measurements on individual needle structures in water are consistent with the design. Since the proposed sensor has a rigid nano-structure, this technology, once fully developed, could ultimately be used to directly monitor protein quantities within a single living cell, an application that would have significant utility for drug screening and studying various intracellular signaling pathways.

Simulation and fabrication of a new novel 3D injectable biosensor for high throughput genomics and proteomics in a lab-on-a-chip device

NASA Astrophysics Data System (ADS)

Esfandyarpour, Rahim; Esfandyarpour, Hesaam; Harris, James S.; Davis, Ronald W.

2013-11-01

Biosensors are used for the detection of biochemical molecules such as proteins and nucleic acids. Traditional techniques, such as enzyme-linked immuno-sorbent assay (ELISA), are sensitive but require several hours to yield a result and usually require the attachment of a fluorophore molecule to the target molecule. Micromachined biosensors that employ electrical detection are now being developed. Here we describe one such device, which is ultrasensitive, real-time, label free and localized. It is called the nanoneedle biosensor and shows promise to overcome some of the current limitations of biosensors. The key element of this device is a 10 nm wide annular gap at the end of the needle, which is the sensitive part of the sensor. The total diameter of the sensor is about 100 nm. Any change in the population of molecules in this gap results in a change of impedance across the gap. Single molecule detection should be possible because the sensory part of the sensor is in the range of bio-molecules of interest. To increase throughput we can flow the solution containing the target molecules over an array of such structures, each with its own integrated read-out circuitry to allow ‘real-time’ detection (i.e. several minutes) of label free molecules without sacrificing sensitivity. To fabricate the arrays we used electron beam lithography together with associated pattern transfer techniques. Preliminary measurements on individual needle structures in water are consistent with the design. Since the proposed sensor has a rigid nano-structure, this technology, once fully developed, could ultimately be used to directly monitor protein quantities within a single living cell, an application that would have significant utility for drug screening and studying various intracellular signaling pathways.

Characterization of immobilization methods of antiviral antibodies in serum for electrochemical biosensors

NASA Astrophysics Data System (ADS)

Huy, Tran Quang; Hanh, Nguyen Thi Hong; Van Chung, Pham; Anh, Dang Duc; Nga, Phan Thi; Tuan, Mai Anh

2011-06-01

In this paper, we describes different methods to immobilize Japanese encephalitis virus (JEV) antibodies in human serum onto the interdigitated surface of a microelectrode sensor for optimizing electrochemical detection: (1) direct covalent binding to the silanized surface, (2) binding to the silanized surface via a cross-linker of glutaraldehyde (GA), (3) binding to glutaraldehyde/silanized surface via goat anti-human IgG polyclonal antibody and (4) binding to glutaraldehyde/silanized surface via protein A (PrA). Field emission scanning electron microscopy, Fourier transform infrared spectrometry, and fluorescence microscopy are used to verify the characteristics of antibodies on the interdigitated surface after the serum antibodies immobilization. The analyzed results indicate that the use of protein A is an effective choice for immobilization and orientation of antibodies in serum for electrochemical biosensors. This study provides an advantageous immobilization method of serum containing antiviral antibodies to develop electrochemical biosensors for preliminary screening of viruses in clinical samples from outbreaks.

Modified surface of titanium dioxide nanoparticles-based biosensor for DNA detection

NASA Astrophysics Data System (ADS)

Nadzirah, Sh.; Hashim, U.; Rusop, M.

2018-05-01

A new technique was used to develop a simple and selective picoammeter DNA biosensor for identification of E. coli O157:H7. This biosensor was fabricated from titanium dioxide nanoparticles that was synthesized by sol-gel method and spin-coated on silicon dioxide substrate via spinner. 3-Aminopropyl triethoxy silane (APTES) was used to modify the surface of TiO2. Simple surface modification approach has been applied; which is single dropping of APTES onto the TiO2 nanoparticles surface. Carboxyl modified probe DNA has been bind onto the surface of APTES/TiO2 without any amplifier element. Electrical signal has been used as the indicator to differentiate each step (surface modification of TiO2 and probe DNA immobilization). The I-V measurements indicate extremely low current (pico-ampere) flow through the device which is 2.8138E-10 A for pure TiO2 nanoparticles, 2.8124E-10 A after APTES modification and 3.5949E-10 A after probe DNA immobilization.

Detection of copper ions in drinking water using the competitive adsorption of proteins.

PubMed

Wang, Ran; Wang, Wei; Ren, Hao; Chae, Junseok

2014-07-15

Heavy metal ions, i.e., Cu(2+), are harmful to the environment and our health. In order to detect them, and circumvent or alleviate the weaknesses of existing detecting technologies, we contrive a unique Surface Plasmon Resonance (SPR) biosensor combined with competitive adsorption of proteins, termed the Vroman effect. This approach adopts native proteins (albumin) as bio-receptors that interact with Cu(2+) to be denatured. Denaturation disrupts the conformation of albumin so that it weakens its affinity to adsorb on the sensing surface. Through the competitive adsorption between the denatured albumins and the native ones, the displacement occurs adjacent to the sensing surface, and this process is real-time monitored by SPR, a surface-sensitive label-free biosensor. The affinities of native albumin is significantly higher than that of denatured albumin, demonstrated by measured KD of native and denatured albumin to gold surafce, 5.8±0.2×10(-5) M and 5.4±0.1×10(-4) M, respectively. Using our biosensor, Cu(2+) with concentration down to 0.1mg/L is detected in PBS, tap water, deionized water, and bottled water. The SPR biosensor is characterized for 5 different heavy metal ions, Cu(2+), Fe(3+), Mn(2+), Pb(2+), and Hg(2+), most common heavy metal ions found in tap water. At the maximum contaminant level (MCL) suggested by the United States Environmental Protection Agency (EPA), the SPR biosensor produces 13.5±0.4, 1.5±0.4, 0, 0, and 0 mDeg, respectively, suggesting the biosensor may be used to detect Cu(2+) in tap water samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Electrochemical sensors and biosensors based on less aggregated graphene.

PubMed

Bo, Xiangjie; Zhou, Ming; Guo, Liping

2017-03-15

As a novel single-atom-thick sheet of sp 2 hybridized carbon atoms, graphene (GR) has attracted extensive attention in recent years because of its unique and remarkable properties, such as excellent electrical conductivity, large theoretical specific surface area, and strong mechanical strength. However, due to the π-π interaction, GR sheets are inclined to stack together, which may seriously degrade the performance of GR with the unique single-atom layer. In recent years, an increasing number of GR-based electrochemical sensors and biosensors are reported, which may reflect that GR has been considered as a kind of hot and promising electrode material for electrochemical sensor and biosensor construction. However, the active sites on GR surface induced by the irreversible GR aggregations would be deeply secluded inside the stacked GR sheets and therefore are not available for the electrocatalysis. So the alleviation or the minimization of the aggregation level for GR sheets would facilitate the exposure of active sites on GR and effectively upgrade the performance of GR-based electrochemical sensors and biosensors. Less aggregated GR with low aggregation and high dispersed structure can be used in improving the electrochemical activity of GR-based electrochemical sensors or biosensors. In this review, we summarize recent advances and new progress for the development of electrochemical sensors based on less aggregated GR. To achieve such goal, many strategies (such as the intercalation of carbon materials, surface modification, and structural engineering) have been applied to alleviate the aggregation level of GR in order to enhance the performance of GR-based electrochemical sensors and biosensors. Finally, the challenges associated with less aggregated GR-based electrochemical sensors and biosensors as well as related future research directions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Bacterial communities in commercial aircraft high-efficiency particulate air (HEPA) filters assessed by PhyloChip analysis.

PubMed

Korves, T M; Piceno, Y M; Tom, L M; Desantis, T Z; Jones, B W; Andersen, G L; Hwang, G M

2013-02-01

Air travel can rapidly transport infectious diseases globally. To facilitate the design of biosensors for infectious organisms in commercial aircraft, we characterized bacterial diversity in aircraft air. Samples from 61 aircraft high-efficiency particulate air (HEPA) filters were analyzed with a custom microarray of 16S rRNA gene sequences (PhyloChip), representing bacterial lineages. A total of 606 subfamilies from 41 phyla were detected. The most abundant bacterial subfamilies included bacteria associated with humans, especially skin, gastrointestinal and respiratory tracts, and with water and soil habitats. Operational taxonomic units that contain important human pathogens as well as their close, more benign relatives were detected. When compared to 43 samples of urban outdoor air, aircraft samples differed in composition, with higher relative abundance of Firmicutes and Gammaproteobacteria lineages in aircraft samples, and higher relative abundance of Actinobacteria and Betaproteobacteria lineages in outdoor air samples. In addition, aircraft and outdoor air samples differed in the incidence of taxa containing human pathogens. Overall, these results demonstrate that HEPA filter samples can be used to deeply characterize bacterial diversity in aircraft air and suggest that the presence of close relatives of certain pathogens must be taken into account in probe design for aircraft biosensors. A biosensor that could be deployed in commercial aircraft would be required to function at an extremely low false alarm rate, making an understanding of microbial background important. This study reveals a diverse bacterial background present on aircraft, including bacteria closely related to pathogens of public health concern. Furthermore, this aircraft background is different from outdoor air, suggesting different probes may be needed to detect airborne contaminants to achieve minimal false alarm rates. This study also indicates that aircraft HEPA filters could be used with other molecular techniques to further characterize background bacteria and in investigations in the wake of a disease outbreak. © 2012 John Wiley & Sons A/S.

Detection of prostate specific antigen (PSA) in human saliva using an ultra-sensitive nanocomposite of graphene nanoplatelets with diblock-co-polymers and Au electrodes.

PubMed

Khan, M S; Dighe, K; Wang, Z; Srivastava, I; Daza, E; Schwartz-Dual, A S; Ghannam, J; Misra, S K; Pan, D

2018-02-26

Prostate-specific antigen (PSA) is a commonly used biomarker for the detection of prostate cancer (PCa) and there are numerous data available for its invasive detection in the serum and whole blood. In this work, an electrochemical sensing method was devised to detect traces of PSA in human saliva using a hybrid nanocomposite of graphene nanoplatelets with diblock co-polymers and Au electrodes (GRP-PS 67 -b-PAA 27 -Au). The pure graphitic composition on filter paper provides significantly high electrical and thermal conductivity while PS 67 -b-PAA 27 makes an amphiphilic bridge between GRP units. The sensor utilizes the binding of an anti-PSA antibody with an antigen-PSA to act as a resistor in a circuit providing an impedance change that in turn allows for the detection and quantification of PSA in saliva samples. A miniaturized electrical impedance analyzer was interfaced with a sensor chip and the data were recorded in real-time using a Bluetooth-enabled module. This fully integrated and optimized sensing device exhibited a wide PSA range of detection from 0.1 pg mL -1 to 100 ng mL -1 (R 2 = 0.963) with a lower limit of detection of 40 fg mL -1 . The performance of the biosensor chip was validated with an enzyme-linked immunosorbent assay technique with a regression coefficient as high as 0.940. The advantages of the newly developed saliva-PSA electrical biosensor over previously reported serum-PSA electrochemical biosensors include a faster response time (3-5 min) to achieve a stable electrical signal for PSA detection, high selectivity, improved sensitivity, no additional requirement of a redox electrolyte for electron exchange and excellent shelf life. The presented sensor is aimed for clinical commercialization to detect PSA in human saliva.

Carbon Nanofiber Electrode Array for Neurochemical Monitoring

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.

2017-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report using vertically aligned CNF as neurotransmitter recording electrodes for application in a smart deep brain stimulation (DBS) device. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

A label-free optical biosensor for serotyping "unknown" influenza viruses

NASA Astrophysics Data System (ADS)

Zhang, Hanyuan; Henry Dunand, Carole; Wilson, Patrick; Miller, Benjamin L.

2016-05-01

The ability to accurately classify influenza viruses is critical to understanding patterns of infection, vaccine efficacy, and to the process of developing new vaccines. Unfortunately, this task is hampered both by the virus' ability to undergo antigenic drift and shift (rendering it a "previously unknown" strain), and by technological limitations. In an effort to overcome these challenges, we have developed a label-free human monoclonal antibody array for flu serology, using a pattern recognition approach to assign virus serotype. The array is built on the Arrayed Imaging Reflectometry (AIR) platform. AIR relies on the creation of a near-perfect antireflective condition on the surface of a silicon chip. When this antireflective condition is perturbed because of binding to an antibody spot (or other immobilized probe molecule), binding may be sensitively and quantitatively detected as an increase in reflected light. We describe fabrication and characterization of the array, and preliminary testing with isolated influenza hemagglutinin. We anticipate that this approach may be extended to other viruses by expansion of the array.

Amperometric Choline Biosensor Fabricated through Electrostatic Assembly of Bienzyme/Polyelectrolyte Hybrid Layers on Carbon Nanotubes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jun; Liu, Guodong; Lin, Yuehe

2006-03-01

We report a flow injection amperometric choline biosensors based on the electrostatic assembly of an enzyme of choline oxidase (ChO) and a bi-enzyme of ChO and horseradish peroxidase (HRP) onto multi-wall carbon nanotubes (MWCNT) modified glassy carbon (GC) electrodes. These choline biosensors were fabricated by immobilization of enzymes on the negatively charged MWCNT surface through alternatively assembling a cationic polydiallydiimethylammonium chloride (PDDA) layer and an enzyme layer. Using this layer-by-layer assembling approach, bioactive nanocomposite film of a PDDA/ChO/PDDA/HRP/PDDA/CNT (ChO/HRP/CNT) and a PDDA/ChO/PDDA/ CNT (ChO/ CNT) were fabricated on GC surface, respectively. Owning to the electrocatalytic effect of carbon nanotubes, themore » measurement of faradic responses resulting from enzymatic reactions has been realized at low potential with acceptable sensitivity. It is found the ChO/HRP/CNT biosensor is more sensitive than the ChO/CNT one. Experimental parameters affecting the sensitivity of biosensors, e.g. applied potential, flow rate, etc. were optimized and potential interference was examined. The response time for this choline biosensor is fast (less than a few seconds). The linear range of detection for the choline biosensor is from 5 x 10-5 to 5 x 10-3 M and the detection limit is determined to be about 1.0 x 10-5 M.« less

A novel nano-photonics biosensor concept for rapid molecular diagnostics

NASA Astrophysics Data System (ADS)

Klunder, Dion J. W.; van Herpen, Maarten M. J. W.; Kolesnychenko, Aleksey; Hornix, Eefje; Kahya, Nicoletta; de Boer, Ruth; Stapert, Henk

2008-04-01

We present a novel nano-photonics biosensor concept that offers an ultra-high surface specificity and excellent suppression of background signals due to the sample fluid on top of the biosensor. In our contribution, we will briefly discuss the operation principle and fabrication of the biosensor, followed by a more detailed discussion on the experimentally determined performance parameters. Recent results on detection of fluorescently labeled molecules in a highly fluorescent background will be shown, and we will give an outlook on real-time detection of bio-molecules such as proteins and nucleic acids.

Impedimetric investigation of dual electrical properties of reduced graphene-oxide-based biosensors in the detection of dopamine.

PubMed

Shu-Ping Lin; Jhong-Yi Ciou; Tung-Yen Lai; Tsung-Wu Lin

2017-07-01

Because of the properties of high charge mobility, large detection area and chemical stability of graphene, it has been applied in many biomedical applications. Graphene oxide (GO) with abundant oxygenated functional groups is easily to form an aqueous suspension by sonication. Here, the exposed areas on the patterned-circuit silicon-based chips were first modified by (3-aminopropyl) trimethoxysilane (APTMS) for later chemically immobilized GO. After that, solution-based reduction process using hydrazine was used to gain reduced GO (RGO)-based biosensors. ESCA survey spectra showed oxygen-containing functional groups of GO decreased from 47% to 5.7%, 4.1%, 3.8%, and 3.6% under varied reduction times of 30 min, 40 min, 50 min, and 60 min, respectively. D/G intensity ratio (I D /I G ) in Raman spectra showed 1.03 after 60-min reduction process. The 60-min reduction process was further used in the electrical sensing experiments. Since different deposited layers of graphene were obtained in our experimental processes, 60-min-RGO-based biosensors have been found that those immobilized RGO possessed semiconductive property as the layers are less than 11. By contrary, when the layers were above 11, the immobilized RGO would resemble metallic material. In addition, the impedimetric analyses indicated obvious signal responses above 86 kHz and showed a concentration-dependent trend in dopamine sensing in physiological phosphate buffered saline (PBS) using 60-min-RGO-based biosensors which were feature of semiconductor.

Highly stable porous silicon-carbon composites as label-free optical biosensors.

PubMed

Tsang, Chun Kwan; Kelly, Timothy L; Sailor, Michael J; Li, Yang Yang

2012-12-21

A stable, label-free optical biosensor based on a porous silicon-carbon (pSi-C) composite is demonstrated. The material is prepared by electrochemical anodization of crystalline Si in an HF-containing electrolyte to generate a porous Si template, followed by infiltration of poly(furfuryl) alcohol (PFA) and subsequent carbonization to generate the pSi-C composite as an optically smooth thin film. The pSi-C sensor is significantly more stable toward aqueous buffer solutions (pH 7.4 or 12) compared to thermally oxidized (in air, 800 °C), hydrosilylated (with undecylenic acid), or hydrocarbonized (with acetylene, 700 °C) porous Si samples prepared and tested under similar conditions. Aqueous stability of the pSi-C sensor is comparable to related optical biosensors based on porous TiO(2) or porous Al(2)O(3). Label-free optical interferometric biosensing with the pSi-C composite is demonstrated by detection of rabbit IgG on a protein-A-modified chip and confirmed with control experiments using chicken IgG (which shows no affinity for protein A). The pSi-C sensor binds significantly more of the protein A capture probe than porous TiO(2) or porous Al(2)O(3), and the sensitivity of the protein-A-modified pSi-C sensor to rabbit IgG is found to be ~2× greater than label-free optical biosensors constructed from these other two materials.

Contact pin-printing of albumin-fungicide conjugate for silicon nitride-based sensors biofunctionalization: Multi-technique surface analysis for optimum immunoassay performance

NASA Astrophysics Data System (ADS)

Gajos, Katarzyna; Budkowski, Andrzej; Tsialla, Zoi; Petrou, Panagiota; Awsiuk, Kamil; Dąbczyński, Paweł; Bernasik, Andrzej; Rysz, Jakub; Misiakos, Konstantinos; Raptis, Ioannis; Kakabakos, Sotirios

2017-07-01

Mass fabrication of integrated biosensors on silicon chips is facilitated by contact pin-printing, applied for biofunctionalization of individual Si3N4-based transducers at wafer-scale. To optimize the biofunctionalization for immunochemical (competitive) detection of fungicide thiabendazole (TBZ), Si3N4 surfaces are modified with (3-aminopropyl)triethoxysilane and examined after: immobilization of BSA-TBZ conjugate (probe) from solutions with different concentration, blocking with bovine serum albumin (BSA), and immunoreaction with a mouse monoclonal antibody against TBZ. Nanostructure, surface density, probe composition and coverage uniformity of protein layers are evaluated with Atomic Force Microscopy, Spectroscopic Ellipsometry, Time-of-Flight Secondary Ion Mass Spectrometry and X-ray Photoelectron Spectroscopy. Contact pin-printing of overlapping probe spots is compared with hand spotted areas. Contact pin-printing resulted in two-fold increase of immobilized probe surface density as compared to hand spotting. Regarding BSA-TBZ immobilization, an incomplete monolayer develops into a bilayer as the concentration of BSA-TBZ molecules in the printing solution increases from 25 to 100 μg/mL. Upon blocking, however, a complete protein monolayer is formed for all the BSA-TBZ concentrations used. Free surface sites are filled with BSA for low surface coverage with BSA-TBZ, whereas loosely bound BSA-TBZ molecules are removed from the BSA-TBZ bilayer. As a consequence immunoreaction efficiency increases with the printing probe concentration.

A highly sensitive SPRi biosensing strategy for simultaneous detection of multiplex miRNAs based on strand displacement amplification and AuNP signal enhancement.

PubMed

Wei, Xiaotong; Duan, Xiaolei; Zhou, Xiaoyan; Wu, Jiangling; Xu, Hongbing; Min, Xun; Ding, Shijia

2018-06-07

Herein, a dual channel surface plasmon resonance imaging (SPRi) biosensor has been developed for the simultaneous and highly sensitive detection of multiplex miRNAs based on strand displacement amplification (SDA) and DNA-functionalized AuNP signal enhancement. In the presence of target miRNAs (miR-21 or miR-192), the miRNAs could specifically hybridize with the corresponding hairpin probes (H) and initiate the SDA, resulting in massive triggers. Subsequently, the two parts of the released triggers could hybridize with capture probes (CP) and DNA-functionalized AuNPs, assembling DNA sandwiches with great mass on the chip surface. A significantly amplified SPR signal readout was achieved. This established biosensing method was capable of simultaneously detecting multiplex miRNAs with a limit of detection down to 0.15 pM for miR-21 and 0.22 pM for miR-192. This method exhibited good specificity and acceptable reproducibility. Moreover, the developed method was applied to the determination of target miRNAs in a complex matrix. Thus, this developed SPRi biosensing method may present a potential alternative tool for miRNA detection in biomedical research and clinical diagnosis.

Design and integration of a generic disposable array-compatible sensor housing into an integrated disposable indirect microfluidic flow injection analysis system.

PubMed

Rapp, Bastian E; Schickling, Benjamin; Prokop, Jürgen; Piotter, Volker; Rapp, Michael; Länge, Kerstin

2011-10-01

We describe an integration strategy for arbitrary sensors intended to be used as biosensors in biomedical or bioanalytical applications. For such devices ease of handling (by a potential end user) as well as strict disposable usage are of importance. Firstly we describe a generic array compatible polymer sensor housing with an effective sample volume of 1.55 μl. This housing leaves the sensitive surface of the sensor accessible for the application of biosensing layers even after the embedding. In a second step we show how this sensor housing can be used in combination with a passive disposable microfluidic chip to set up arbitrary 8-fold sensor arrays and how such a system can be complemented with an indirect microfluidic flow injection analysis (FIA) system. This system is designed in a way that it strictly separates between disposable and reusable components- by introducing tetradecane as an intermediate liquid. This results in a sensor system compatible with the demands of most biomedical applications. Comparative measurements between a classical macroscopic FIA system and this integrated indirect microfluidic system are presented. We use a surface acoustic wave (SAW) sensor as an exemplary detector in this work.

Fabrication and Characterization of a Stabilized Thin Film Ag/AgCl Reference Electrode Modified with Self-Assembled Monolayer of Alkane Thiol Chains for Rapid Biosensing Applications.

PubMed

Rahman, Tanzilur; Ichiki, Takanori

2017-10-13

The fabrication of miniaturized electrical biosensing devices can enable the rapid on-chip detection of biomarkers such as miRNA molecules, which is highly important in early-stage cancer detection. The challenge in realizing such devices remains in the miniaturization of the reference electrodes, which is an integral part of electrical detection. Here, we report on a novel thin film Ag/AgCl reference electrode (RE) that has been fabricated on top of a Au-sputtered glass surface, which was coated with a self-assembled monolayer (SAM) of 6-mercepto-1-hexanol (MCH). The electrode showed very little measurement deviation (-1.5 mv) from a commercial Ag/AgCl reference electrode and exhibited a potential drift of only ± 0.2 mV/h. In addition, the integration of this SAM-modified microfabricated thin film RE enabled the rapid detection (<30 min) of miRNA (let-7a). The electrode can be integrated seamlessly into a microfluidic device, allowing the highly stable and fast measurement of surface potential and is expected to be very useful for the development of miniature electrical biosensors.

Nanoplatforms for Detection, Remediation and Protection Against Chem-Bio Warfare

NASA Astrophysics Data System (ADS)

Denkbaş, E. B.; Bayram, C.; Kavaz, D.; Çirak, T.; Demirbilek, M.

Chemical and biological substances have been used as warfare agents by terrorists by varying degree of sophistication. It is critical that these agents be detected in real-time with high level of sensitively, specificity, and accuracy. Many different types of techniques and systems have been developed to detect these agents. But there are some limitations in these conventional techniques and systems. Limitations include the collection, handling and sampling procedures, detection limits, sample transfer, expensive equipment, personnel training, and detection materials. Due to the unique properties such as quantum effect, very high surface/volume ratio, enhanced surface reactivity, conductivity, electrical and magnetic properties of the nanomaterials offer great opportunity to develop very fast, sensitive, accurate and cost effective detection techniques and systems to detect chemical and biological (chem.-bio) warfare agents. Furthermore, surface modification of the materials is very easy and effective way to get functional or smart surfaces to be used as nano-biosensor platform. In that respect many different types of nanomaterials have been developed and used for the detection, remediation and protection, such as gold and silver nanoparticles, quantum dots, Nano chips and arrays, fluorescent polymeric and magnetic nanoparticles, fiber optic and cantilever based nanobiosensors, nanofibrillar nanostructures etc. This study summarizes preparation and characterization of nanotechnology based approaches for the detection of and remediation and protection against chem.-bio warfare agents.

Rapid culture-independent microbial analysis aboard the international space station (ISS) stage two: quantifying three microbial biomarkers.

PubMed

Morris, Heather C; Damon, Michael; Maule, Jake; Monaco, Lisa A; Wainwright, Norm

2012-09-01

Abstract A portable, rapid, microbial detection unit, the Lab-On-a-Chip Application Development Portable Test System (LOCAD-PTS), was launched to the International Space Station (ISS) as a technology demonstration unit in December 2006. Results from the first series of experiments designed to detect Gram-negative bacteria on ISS surfaces by quantifying a single microbial biomarker lipopolysaccharide (LPS) were reported in a previous article. Herein, we report additional technology demonstration experiments expanding the on-orbit capabilities of the LOCAD-PTS to detecting three different microbial biomarkers on ISS surfaces. Six different astronauts on more than 20 occasions participated in these experiments, which were designed to test the new beta-glucan (fungal cell wall molecule) and lipoteichoic acid (LTA; Gram-positive bacterial cell wall component) cartridges individually and in tandem with the existing Limulus Amebocyte Lysate (LAL; Gram-negative bacterial LPS detection) cartridges. Additionally, we conducted the sampling side by side with the standard culture-based detection method currently used on the ISS. Therefore, we present data on the distribution of three microbial biomarkers collected from various surfaces in every module present on the ISS at the time of sampling. In accordance with our previous experiments, we determined that spacecraft surfaces known to be frequently in contact with crew members demonstrated higher values of all three microbial molecules. Key Words: Planetary protection-Spaceflight-Microbiology-Biosensor. Astrobiology 12, 830-840.

An enzyme-free and label-free surface plasmon resonance biosensor for ultrasensitive detection of fusion gene based on DNA self-assembly hydrogel with streptavidin encapsulation.

PubMed

Guo, Bin; Wen, Bo; Cheng, Wei; Zhou, Xiaoyan; Duan, Xiaolei; Zhao, Min; Xia, Qianfeng; Ding, Shijia

2018-07-30

In this research, an enzyme-free and label-free surface plasmon resonance (SPR) biosensing strategy has been developed for ultrasensitive detection of fusion gene based on the heterogeneous target-triggered DNA self-assembly aptamer-based hydrogel with streptavidin (SA) encapsulation. In the presence of target, the capture probes (Cp) immobilized on the chip surface can capture the PML/RARα, forming a Cp-PML/RARα duplex. After that, the aptamer-based network hydrogel nanostructure is formed on the gold surface via target-triggered self-assembly of X shaped polymers. Subsequently, the SA can be encapsulated into hydrogel by the specific binding of SA aptamer, forming the complex with super molecular weight. Thus, the developed strategy achieves dramatic enhancement of the SPR signal. Using PML/RARα "S" subtype as model analyte, the developed biosensing method can detect target down to 45.22 fM with a wide linear range from 100 fM to 10 nM. Moreover, the high efficiency biosensing method shows excellent practical ability to identify the clinical PCR products of PML/RARα. Thus, this proposed strategy presents a powerful platform for ultrasensitive detection of fusion gene and early diagnosis and monitoring of disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Bioorthogonal in Situ Hydrogels Based on Polyether Polyols for New Biosensor Materials with High Sensitivity.

PubMed

Herrmann, Anna; Kaufmann, Lena; Dey, Pradip; Haag, Rainer; Schedler, Uwe

2018-04-04

Both noncovalent and covalent encapsulations of active biomolecules, for example, proteins and oligonucleotides, for a new biosensor matrix in an in situ bioorthogonal hydrogel formation via a strain-promoted azide-alkyne cycloaddition reaction were investigated. Unspecific interaction between the gel and the biomolecules as well as protein denaturation was prevented by the bioorthogonal gel components, which ensure a uniform aqueous environment in the hydrogel network. No leaching of the active biomolecules was observed. Additionally, a much higher and also adjustable loading of biomolecules in the hydrogel matrix was achieved compared to conventional biosensor surfaces, where the sensor molecules are immobilized on monolayers (2D surfaces) or brushlike structures (3D surfaces). Spotting experiments of the hydrogel confirm the possibility to use this new surface for microarray-based multiplex applications which require very high signal-to-noise ratios.

Immobilization Techniques in the Fabrication of Nanomaterial-Based Electrochemical Biosensors: A Review

PubMed Central

Putzbach, William; Ronkainen, Niina J.

2013-01-01

The evolution of 1st to 3rd generation electrochemical biosensors reflects a simplification and enhancement of the transduction pathway. However, in recent years, modification of the transducer with nanomaterials has become increasingly studied and imparts many advantages. The sensitivity and overall performance of enzymatic biosensors has improved tremendously as a result of incorporating nanomaterials in their fabrication. Given the unique and favorable qualities of gold nanoparticles, graphene and carbon nanotubes as applied to electrochemical biosensors, a consolidated survey of the different methods of nanomaterial immobilization on transducer surfaces and enzyme immobilization on these species is beneficial and timely. This review encompasses modification of enzymatic biosensors with gold nanoparticles, carbon nanotubes, and graphene. PMID:23580051

Immobilization techniques in the fabrication of nanomaterial-based electrochemical biosensors: a review.

PubMed

Putzbach, William; Ronkainen, Niina J

2013-04-11

The evolution of 1st to 3rd generation electrochemical biosensors reflects a simplification and enhancement of the transduction pathway. However, in recent years, modification of the transducer with nanomaterials has become increasingly studied and imparts many advantages. The sensitivity and overall performance of enzymatic biosensors has improved tremendously as a result of incorporating nanomaterials in their fabrication. Given the unique and favorable qualities of gold nanoparticles, graphene and carbon nanotubes as applied to electrochemical biosensors, a consolidated survey of the different methods of nanomaterial immobilization on transducer surfaces and enzyme immobilization on these species is beneficial and timely. This review encompasses modification of enzymatic biosensors with gold nanoparticles, carbon nanotubes, and graphene.

Aryl Diazonium Chemistry for the Surface Functionalization of Glassy Biosensors.

PubMed

Zheng, Wei; van den Hurk, Remko; Cao, Yong; Du, Rongbing; Sun, Xuejun; Wang, Yiyu; McDermott, Mark T; Evoy, Stephane

2016-03-14

Nanostring resonator and fiber-optics-based biosensors are of interest as they offer high sensitivity, real-time measurements and the ability to integrate with electronics. However, these devices are somewhat impaired by issues related to surface modification. Both nanostring resonators and photonic sensors employ glassy materials, which are incompatible with electrochemistry. A surface chemistry approach providing strong and stable adhesion to glassy surfaces is thus required. In this work, a diazonium salt induced aryl film grafting process is employed to modify a novel SiCN glassy material. Sandwich rabbit IgG binding assays are performed on the diazonium treated SiCN surfaces. Fluorescently labelled anti-rabbit IgG and anti-rabbit IgG conjugated gold nanoparticles were used as markers to demonstrate the absorption of anti-rabbit IgG and therefore verify the successful grafting of the aryl film. The results of the experiments support the effectiveness of diazonium chemistry for the surface functionalization of SiCN surfaces. This method is applicable to other types of glassy materials and potentially can be expanded to various nanomechanical and optical biosensors.

Aryl Diazonium Chemistry for the Surface Functionalization of Glassy Biosensors

PubMed Central

Zheng, Wei; van den Hurk, Remko; Cao, Yong; Du, Rongbing; Sun, Xuejun; Wang, Yiyu; McDermott, Mark T.; Evoy, Stephane

2016-01-01

Nanostring resonator and fiber-optics-based biosensors are of interest as they offer high sensitivity, real-time measurements and the ability to integrate with electronics. However, these devices are somewhat impaired by issues related to surface modification. Both nanostring resonators and photonic sensors employ glassy materials, which are incompatible with electrochemistry. A surface chemistry approach providing strong and stable adhesion to glassy surfaces is thus required. In this work, a diazonium salt induced aryl film grafting process is employed to modify a novel SiCN glassy material. Sandwich rabbit IgG binding assays are performed on the diazonium treated SiCN surfaces. Fluorescently labelled anti-rabbit IgG and anti-rabbit IgG conjugated gold nanoparticles were used as markers to demonstrate the absorption of anti-rabbit IgG and therefore verify the successful grafting of the aryl film. The results of the experiments support the effectiveness of diazonium chemistry for the surface functionalization of SiCN surfaces. This method is applicable to other types of glassy materials and potentially can be expanded to various nanomechanical and optical biosensors. PMID:26985910

A large response range reflectometric urea biosensor made from silica-gel nanoparticles.

PubMed

Alqasaimeh, Muawia; Heng, Lee Yook; Ahmad, Musa; Raj, A S Santhana; Ling, Tan Ling

2014-07-22

A new silica-gel nanospheres (SiO2NPs) composition was formulated, followed by biochemical surface functionalization to examine its potential in urea biosensor development. The SiO2NPs were basically synthesized based on sol-gel chemistry using a modified Stober method. The SiO2NPs surfaces were modified with amine (-NH2) functional groups for urease immobilization in the presence of glutaric acid (GA) cross-linker. The chromoionophore pH-sensitive dye ETH 5294 was physically adsorbed on the functionalized SiO2NPs as pH transducer. The immobilized urease determined urea concentration reflectometrically based on the colour change of the immobilized chromoionophore as a result of the enzymatic hydrolysis of urea. The pH changes on the biosensor due to the catalytic enzyme reaction of immobilized urease were found to correlate with the urea concentrations over a linear response range of 50-500 mM (R2 = 0.96) with a detection limit of 10 mM urea. The biosensor response time was 9 min with reproducibility of less than 10% relative standard deviation (RSD). This optical urea biosensor did not show interferences by Na+, K+, Mg2+ and NH4+ ions. The biosensor performance has been validated using urine samples in comparison with a non-enzymatic method based on the use of p-dimethylaminobenzaldehyde (DMAB) reagent and demonstrated a good correlation between the two different methods (R2 = 0.996 and regression slope of 1.0307). The SiO2NPs-based reflectometric urea biosensor showed improved dynamic linear response range when compared to other nanoparticle-based optical urea biosensors.

Nanosized zeolites as a perspective material for conductometric biosensors creation

NASA Astrophysics Data System (ADS)

Kucherenko, Ivan; Soldatkin, Oleksandr; Kasap, Berna Ozansoy; Kirdeciler, Salih Kaan; Kurc, Burcu Akata; Jaffrezic-Renault, Nicole; Soldatkin, Alexei; Lagarde, Florence; Dzyadevych, Sergei

2015-05-01

In this work, the method of enzyme adsorption on different zeolites and mesoporous silica spheres (MSS) was investigated for the creation of conductometric biosensors. The conductometric transducers consisted of gold interdigitated electrodes were placed on the ceramic support. The transducers were modified with zeolites and MSS, and then the enzymes were adsorbed on the transducer surface. Different methods of zeolite attachment to the transducer surface were used; drop coating with heating to 200°C turned out to be the best one. Nanozeolites beta and L, zeolite L, MSS, and silicalite-1 (80 to 450 nm) were tested as the adsorbents for enzyme urease. The biosensors with all tested particles except zeolite L had good analytical characteristics. Silicalite-1 (450 nm) was also used for adsorption of glucose oxidase, acetylcholinesterase, and butyrylcholinesterase. The glucose and acetylcholine biosensors were successfully created, whereas butyrylcholinesterase was not adsorbed on silicalite-1. The enzyme adsorption on zeolites and MSS is simple, quick, well reproducible, does not require use of toxic compounds, and therefore can be recommended for the development of biosensors when these advantages are especially important.

Fiber optic-based biosensor

NASA Technical Reports Server (NTRS)

Ligler, Frances S.

1991-01-01

The NRL fiber optic biosensor is a device which measures the formation of a fluorescent complex at the surface of an optical fiber. Antibodies and DNA binding proteins provide the mechanism for recognizing an analyze and immobilizing a fluorescent complex on the fiber surface. The fiber optic biosensor is fast, sensitive, and permits analysis of hazardous materials remote from the instrumentation. The fiber optic biosensor is described in terms of the device configuration, chemistry for protein immobilization, and assay development. A lab version is being used for assay development and performance characterization while a portable device is under development. Antibodies coated on the fiber are stable for up to two years of storage prior to use. The fiber optic biosensor was used to measure concentration of toxins in the parts per billion (ng/ml) range in under a minute. Immunoassays for small molecules and whole bacteria are under development. Assays using DNA probes as the detection element can also be used with the fiber optic sensor, which is currently being developed to detect biological warfare agents, explosives, pathogens, and toxic materials which pollute the environment.

Study of zeolite influence on analytical characteristics of urea biosensor based on ion-selective field-effect transistors

PubMed Central

2014-01-01

A possibility of the creation of potentiometric biosensor by adsorption of enzyme urease on zeolite was investigated. Several variants of zeolites (nano beta, calcinated nano beta, silicalite, and nano L) were chosen for experiments. The surface of pH-sensitive field-effect transistors was modified with particles of zeolites, and then the enzyme was adsorbed. As a control, we used the method of enzyme immobilization in glutaraldehyde vapour (without zeolites). It was shown that all used zeolites can serve as adsorbents (with different effectiveness). The biosensors obtained by urease adsorption on zeolites were characterized by good analytical parameters (signal reproducibility, linear range, detection limit and the minimal drift factor of a baseline). In this work, it was shown that modification of the surface of pH-sensitive field-effect transistors with zeolites can improve some characteristics of biosensors. PMID:24636423

Fabrication and characterization of SPR chips with the modified bovine serum albumin

NASA Astrophysics Data System (ADS)

Chen, Xing; Zhang, Lu-lu; Cui, Da-fu

2016-03-01

A facile surface plasmon resonance (SPR) chip is developed for small molecule determination and analysis. The SPR chip was prepared based on a self assembling principle, in which the modified bovine serum albumin (BSA) was directly self-assembled onto the bare gold surface. The surface morphology of the chip with the modified BSA was investigated by atomic force microscopy (AFM) and its optical properties were characterized. The surface binding capacity of the bare facile SPR chip with a uniform morphology is 8 times of that of the bare control SPR chip. Based on the experiments of immune reaction between cortisol antibody and cortisol derivative, the sensitivity of the facile SPR chip with the modified BSA is much higher than that of the control SPR chip with the un-modified BSA. The facile SPR chip has been successfully used to detect small molecules. The lowest detection limit is 5 ng/mL with a linear range of 5—100 ng/mL for cortisol analysis. The novel facile SPR chip can also be applied to detect other small molecules.

3D DNA origami as programmable anchoring points for bioreceptors in fiber optic surface plasmon resonance biosensing.

PubMed

Daems, Devin; Pfeifer, Wolfgang; Rutten, Iene; Sacca, Barbara; Spasic, Dragana; Lammertyn, Jeroen

2018-06-27

Many challenges in biosensing originate from the fact that the all-important nano-architecture of the biosensor's surface, including precise density and orientation of bioreceptors, is not entirely comprehended. Here we introduced a 3D DNA origami as bioreceptor carrier to functionalize the fiber optic surface plasmon resonance (FO-SPR) sensor with nanoscale precision. Starting from a 24-helix bundle, two distinct DNA origami structures were designed to position thrombin-specific aptamers with different density and distance (27 and 113 nm) from the FO-SPR surface. The origami-based biosensors proved to be not only capable of reproducible, label-free thrombin detection, but revealed also valuable innovative features: (1) a significantly better performance in the absence of backfilling, known as essential in biosensing field, suggesting improved bioreceptor orientation and accessibility and (2) a wider linear range compared to previously reported thrombin biosensors. We envisage that our method will be beneficial both for scientists and clinicians looking for new surface (bio)chemistry and improved diagnostics.

A size selective porous silicon grating-coupled Bloch surface and sub-surface wave biosensor.

PubMed

Rodriguez, Gilberto A; Ryckman, Judson D; Jiao, Yang; Weiss, Sharon M

2014-03-15

A porous silicon (PSi) grating-coupled Bloch surface and sub-surface wave (BSW/BSSW) biosensor is demonstrated to size selectively detect the presence of both large and small molecules. The BSW is used to sense large immobilized analytes at the surface of the structure while the BSSW that is confined inside but near the top of the structure is used to sensitively detect small molecules. Functionality of the BSW and BSSW modes is theoretically described by dispersion relations, field confinements, and simulated refractive index shifts within the structure. The theoretical results are experimentally verified by detecting two different small chemical molecules and one large 40 base DNA oligonucleotide. The PSi-BSW/BSSW structure is benchmarked against current porous silicon technology and is shown to have a 6-fold higher sensitivity in detecting large molecules and a 33% improvement in detecting small molecules. This is the first report of a grating-coupled BSW biosensor and the first report of a BSSW propagating mode. © 2013 Published by Elsevier B.V.

An imaging surface plasmon resonance biosensor assay for the detection of T-2 toxin and masked T-2 toxin-3-glucoside in wheat

USDA-ARS?s Scientific Manuscript database

A sensitive, rapid, and reproducible imaging surface plasmon resonance (iSPR) biosensor assay was developed to detect T-2 toxin and T-2 toxin-3-glucoside (T2-G) in wheat. In this competitive assay, an amplification strategy was used after conjugating a secondary antibody (Ab2) with gold nanoparticle...

Evolvable Smartphone-Based Platforms for Point-of-Care In-Vitro Diagnostics Applications.

PubMed

Patou, François; AlZahra'a Alatraktchi, Fatima; Kjægaard, Claus; Dimaki, Maria; Madsen, Jan; Svendsen, Winnie E

2016-09-03

The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market. For instance, the increasing level of complexity of instrumented lab-on-chip devices, coupled to the sporadic nature of point-of-care testing, threatens the viability of a business model mainly relying on disposable/consumable lab-on-chips. We argued recently that system evolvability, defined as the design characteristic that facilitates more manageable transitions between system generations via the modification of an inherited design, can help remedy these limitations. In this paper, we discuss how platform-based design can constitute a formal entry point to the design and implementation of evolvable smart device/lab-on-chip systems. We present both a hardware/software design framework and the implementation details of a platform prototype enabling at this stage the interfacing of several lab-on-chip variants relying on current- or impedance-based biosensors. Our findings suggest that several change-enabling mechanisms implemented in the higher abstraction software layers of the system can promote evolvability, together with the design of change-absorbing hardware/software interfaces. Our platform architecture is based on a mobile software application programming interface coupled to a modular hardware accessory. It allows the specification of lab-on-chip operation and post-analytic functions at the mobile software layer. We demonstrate its potential by operating a simple lab-on-chip to carry out the detection of dopamine using various electroanalytical methods.

Evolvable Smartphone-Based Platforms for Point-of-Care In-Vitro Diagnostics Applications

PubMed Central

Patou, François; AlZahra’a Alatraktchi, Fatima; Kjægaard, Claus; Dimaki, Maria; Madsen, Jan; Svendsen, Winnie E.

2016-01-01

The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market. For instance, the increasing level of complexity of instrumented lab-on-chip devices, coupled to the sporadic nature of point-of-care testing, threatens the viability of a business model mainly relying on disposable/consumable lab-on-chips. We argued recently that system evolvability, defined as the design characteristic that facilitates more manageable transitions between system generations via the modification of an inherited design, can help remedy these limitations. In this paper, we discuss how platform-based design can constitute a formal entry point to the design and implementation of evolvable smart device/lab-on-chip systems. We present both a hardware/software design framework and the implementation details of a platform prototype enabling at this stage the interfacing of several lab-on-chip variants relying on current- or impedance-based biosensors. Our findings suggest that several change-enabling mechanisms implemented in the higher abstraction software layers of the system can promote evolvability, together with the design of change-absorbing hardware/software interfaces. Our platform architecture is based on a mobile software application programming interface coupled to a modular hardware accessory. It allows the specification of lab-on-chip operation and post-analytic functions at the mobile software layer. We demonstrate its potential by operating a simple lab-on-chip to carry out the detection of dopamine using various electroanalytical methods. PMID:27598208

Substrate specificity and interferences of a direct-electron-transfer-based glucose biosensor.

PubMed

Felice, Alfons K G; Sygmund, Christoph; Harreither, Wolfgang; Kittl, Roman; Gorton, Lo; Ludwig, Roland

2013-05-01

Electrochemical sensors for glucose monitoring employ different signal transduction strategies for electron transfer from the biorecognition element to the electrode surface. We present a biosensor that employs direct electron transfer and evaluate its response to various interfering substances known to affect glucose biosensors. The enzyme cellobiose dehydrogenase (CDH) was adsorbed on the surface of a carbon working electrode and covalently bound by cross linking. The response of CDH-modified electrodes to glucose and possible interfering compounds was measured by flow-injection analysis, linear sweep, and chronoamperometry. Chronoamperometry showed initial swelling/wetting of the electrode. After stabilization, the signal was stable and a sensitivity of 0.21 µA mM-1 cm-2 was obtained. To investigate the influence of the interfering substances on the biorecognition element, the simplest possible sensor architecture was used. The biosensor showed little (<5% signal deviation) or no response to various reported electroactive or otherwise interfering substances. Direct electron transfer from the biorecognition element to the electrode is a new principle applied to glucose biosensors, which can be operated at a low polarization potential of -100 mV versus silver/silver chloride. The reduction of interferences by electrochemically active substances is an attractive feature of this promising technology for the development of continuous glucose biosensors. © 2013 Diabetes Technology Society.

A novel approach for the fabrication of a flexible glucose biosensor: The combination of vertically aligned CNTs and a conjugated polymer.

PubMed

Gokoglan, Tugba Ceren; Soylemez, Saniye; Kesik, Melis; Dogru, Itir Bakis; Turel, Onur; Yuksel, Recep; Unalan, Husnu Emrah; Toppare, Levent

2017-04-01

A novel flexible glucose biosensor using vertically aligned carbon nanotubes (VACNT) and a conjugated polymer (CP) was fabricated. A scaffold based on VACNT grown on aluminum foil (VACNT-Al foil) with poly (9,9-di-(2-ethylhexyl)-fluorenyl-2,7-diyl)-end capped with 2,5-diphenyl-1,2,4-oxadiazole (PFLO) was used as the immobilization matrix for the glucose biosensor. Glucose oxidase (GOx) was immobilized on a modified indium tin oxide (ITO) coated polyethylene terephthalate (PET) electrode surface. The biosensor response at a potential of -0.7V versus Ag wire was followed by the decrease in oxygen level as a result of enzymatic reaction. The biosensor exhibited a linear range between 0.02mM and 0.5mM glucose and kinetic parameters (K M app , I max , limit of detection (LOD) and sensitivity) were estimated as 0.193mM, 8.170μA, 7.035×10 -3 mM and 65.816μA/mMcm 2 , respectively. Scanning electron microscopy (SEM) was used for surface characterization. The constructed biosensor was applied to determine the glucose content in several beverages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design and development of a microfluidic platform for use with colorimetric gold nanoprobe assays

NASA Astrophysics Data System (ADS)

Bernacka-Wojcik, Iwona

Due to the importance and wide applications of the DNA analysis, there is a need to make genetic analysis more available and more affordable. As such, the aim of this PhD thesis is to optimize a colorimetric DNA biosensor based on gold nanoprobes developed in CEMOP by reducing its price and the needed volume of solution without compromising the device sensitivity and reliability, towards the point of care use. Firstly, the price of the biosensor was decreased by replacing the silicon photodetector by a low cost, solution processed TiO2 photodetector. To further reduce the photodetector price, a novel fabrication method was developed: a cost-effective inkjet printing technology that enabled to increase TiO2 surface area. Secondly, the DNA biosensor was optimized by means of microfluidics that offer advantages of miniaturization, much lower sample/reagents consumption, enhanced system performance and functionality by integrating different components. In the developed microfluidic platform, the optical path length was extended by detecting along the channel and the light was transmitted by optical fibres enabling to guide the light very close to the analysed solution. Microfluidic chip of high aspect ratio ( 13), smooth and nearly vertical sidewalls was fabricated in PDMS using a SU-8 mould for patterning. The platform coupled to the gold nanoprobe assay enabled detection of Mycobacterium tuberculosis using 3 mul on DNA solution, i.e. 20 times less than in the previous state-of-the-art. Subsequently, the bio-microfluidic platform was optimized in terms of cost, electrical signal processing and sensitivity to colour variation, yielding 160% improvement of colorimetric AuNPs analysis. Planar microlenses were incorporated to converge light into the sample and then to the output fibre core increasing 6 times the signal-to-losses ratio. The optimized platform enabled detection of single nucleotide polymorphism related with obesity risk (FTO) using target DNA concentration below the limit of detection of the conventionally used microplate reader (i.e. 15 ng/mul) with 10 times lower solution volume (3 mul). The combination of the unique optical properties of gold nanoprobes with microfluidic platform resulted in sensitive and accurate sensor for single nucleotide polymorphism detection operating using small volumes of solutions and without the need for substrate functionalization or sophisticated instrumentation. Simultaneously, to enable on chip reagents mixing, a PDMS micromixer was developed and optimized for the highest efficiency, low pressure drop and short mixing length. The optimized device shows 80% of mixing efficiency at Re = 0.1 in 2.5 mm long mixer with the pressure drop of 6 Pa, satisfying requirements for the application in the microfluidic platform for DNA analysis.

Method for detection of a few pathogenic bacteria and determination of live versus dead cells

NASA Astrophysics Data System (ADS)

Horikawa, Shin; Chen, I.-Hsuan; Du, Songtao; Liu, Yuzhe; Wikle, Howard C.; Suh, Sang-Jin; Barbaree, James M.; Chin, Bryan A.

2016-05-01

This paper presents a method for detection of a few pathogenic bacteria and determination of live versus dead cells. The method combines wireless phage-coated magnetoelastic (ME) biosensors and a surface-scanning dectector, enabling real-time monitoring of the growth of specific bacteria in a nutrient broth. The ME biosensor used in this investigation is composed of a strip-shaped ME resonator upon which an engineered bacteriophage is coated to capture a pathogen of interest. E2 phage with high binding affinity for Salmonella Typhimurium was used as a model study. The specificity of E2 phage has been reported to be 1 in 105 background bacteria. The phage-coated ME biosensors were first exposed to a low-concentration Salmonella suspension to capture roughly 300 cells on the sensor surface. When the growth of Salmonella in the broth occurs, the mass of the biosensor increases, which results in a decrease in the biosensor's resonant frequency. Monitoring of this mass- induced resonant frequency change allows for real-time detection of the presence of Salmonella. Detection of a few bacteria is also possible by growing them to a sufficient number. The surface-scanning detector was used to measure resonant frequency changes of 25 biosensors sequentially in an automated manner as a function of time. This methodology offers direct, real-time detection, quantification, and viability determination of specific bacteria. The rate of the sensor's resonant frequency change was found to be largely dependent on the number of initially bound cells and the efficiency of cell growth.

Nanostructured enzymatic biosensor based on fullerene and gold nanoparticles: preparation, characterization and analytical applications.

PubMed

Lanzellotto, C; Favero, G; Antonelli, M L; Tortolini, C; Cannistraro, S; Coppari, E; Mazzei, F

2014-05-15

In this work a novel electrochemical biosensing platform based on the coupling of two different nanostructured materials (gold nanoparticles and fullerenols) displaying interesting electrochemical features, has been developed and characterized. Gold nanoparticles (AuNPs) exhibit attractive electrocatalytic behavior stimulating in the last years, several sensing applications; on the other hand, fullerene and its derivatives are a very promising family of electroactive compounds although they have not yet been fully employed in biosensing. The methodology proposed in this work was finalized to the setup of a laccase biosensor based on a multilayer material consisting in AuNPs, fullerenols and Trametes versicolor Laccase (TvL) assembled layer by layer onto a gold (Au) electrode surface. The influence of different modification step procedures on the electroanalytical performance of biosensors has been evaluated. Cyclic voltammetry, chronoamperometry, surface plasmon resonance (SPR) and scanning tunneling microscopy (STM) were used to characterize the modification of surface and to investigate the bioelectrocatalytic biosensor response. This biosensor showed fast amperometric response to gallic acid, which is usually considered a standard for polyphenols analysis of wines, with a linear range 0.03-0.30 mmol L(-1) (r(2)=0.9998), with a LOD of 0.006 mmol L(-1) or expressed as polyphenol index 5.0-50 mg L(-1) and LOD 1.1 mg L(-1). A tentative application of the developed nanostructured enzyme-based biosensor was performed evaluating the detection of polyphenols either in buffer solution or in real wine samples. Copyright © 2013 Elsevier B.V. All rights reserved.

A novel DNA nanosensor based on CdSe/ZnS quantum dots and synthesized Fe3O4 magnetic nanoparticles.

PubMed

Hushiarian, Roozbeh; Yusof, Nor Azah; Abdullah, Abdul Halim; Ahmad, Shahrul Ainliah Alang; Dutse, Sabo Wada

2014-04-09

Although nanoparticle-enhanced biosensors have been extensively researched, few studies have systematically characterized the roles of nanoparticles in enhancing biosensor functionality. This paper describes a successful new method in which DNA binds directly to iron oxide nanoparticles for use in an optical biosensor. A wide variety of nanoparticles with different properties have found broad application in biosensors because their small physical size presents unique chemical, physical, and electronic properties that are different from those of bulk materials. Of all nanoparticles, magnetic nanoparticles are proving to be a versatile tool, an excellent case in point being in DNA bioassays, where magnetic nanoparticles are often used for optimization of the hybridization and separation of target DNA. A critical step in the successful construction of a DNA biosensor is the efficient attachment of biomolecules to the surface of magnetic nanoparticles. To date, most methods of synthesizing these nanoparticles have led to the formation of hydrophobic particles that require additional surface modifications. As a result, the surface to volume ratio decreases and nonspecific bindings may occur so that the sensitivity and efficiency of the device deteriorates. A new method of large-scale synthesis of iron oxide (Fe3O4) nanoparticles which results in the magnetite particles being in aqueous phase, was employed in this study. Small modifications were applied to design an optical DNA nanosensor based on sandwich hybridization. Characterization of the synthesized particles was carried out using a variety of techniques and CdSe/ZnS core-shell quantum dots were used as the reporter markers in a spectrofluorophotometer. We showed conclusively that DNA binds to the surface of ironoxide nanoparticles without further surface modifications and that these magnetic nanoparticles can be efficiently utilized as biomolecule carriers in biosensing devices.

Self-assembly of glucose oxidase on reduced graphene oxide-magnetic nanoparticles nanocomposite-based direct electrochemistry for reagentless glucose biosensor.

PubMed

Pakapongpan, Saithip; Poo-Arporn, Rungtiva P

2017-07-01

A novel approach of the immobilization of a highly selective and stable glucose biosensor based on direct electrochemistry was fabricated by a self-assembly of glucose oxidase (GOD) on reduced graphene oxide (RGO) covalently conjugated to magnetic nanoparticles (Fe 3 O 4 NPs) modified on a magnetic screen-printed electrode (MSPE). The RGO-Fe 3 O 4 nanocomposite has remarkable enhancement in large surface areas, is favorable environment for enzyme immobilization, facilitates electron transfer between enzymes and electrode surfaces and possesses superparamagnetism property. The morphology and electrochemical properties of RGO-Fe 3 O 4 /GOD were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, cyclic voltammetry (CV) and amperometry. The modified electrode was a fast, direct electron transfer with an apparent electron transfer rate constant (k s ) of 13.78s -1 . The proposed biosensor showed fast amperometric response (3s) to glucose with a wide linear range from 0.05 to 1mM, a low detection limit of 0.1μM at a signal to noise ratio of 3 (S/N=3) and good sensitivity (5.9μA/mM). The resulting biosensor has high stability, good reproducibility, excellent selectivity and successfully applied detection potential at -0.45V. This mediatorless glucose sensing used the advantages of covalent bonding and self-assembly as a new approach for immobilizing enzymes without any binder. It would be worth noting that it opens a new avenue for fabricating excellent electrochemical biosensors. This is a new approach that reporting the immobilization of glucose oxidase on reduced graphene oxide (RGO) covalently conjugated to magnetic nanoparticles (Fe 3 O 4 NPs) by electrostatic interaction and modified screen printed electrode. We propose the reagentless with fabrication method without binder and adhesive agents for immobilized enzyme. Fe 3 O 4 NPs increasing surface area to enhance the immobilization and prevent the leaching of enzymes at electrode surfaces by magnetic stickers which is improve the stability of the biosensor. Based on this synthesis technique, it is a good new strategy and simple used to fabrication of third-generation glucose biosensor and this nanocomposite could be used as a platform for disposable biosensor and biofuel cell applications. Copyright © 2017 Elsevier B.V. All rights reserved.

The Impact Of Surface Shape Of Chip-Breaker On Machined Surface

NASA Astrophysics Data System (ADS)

Šajgalík, Michal; Czán, Andrej; Martinček, Juraj; Varga, Daniel; Hemžský, Pavel; Pitela, David

2015-12-01

Machined surface is one of the most used indicators of workpiece quality. But machined surface is influenced by several factors such as cutting parameters, cutting material, shape of cutting tool or cutting insert, micro-structure of machined material and other known as technological parameters. By improving of these parameters, we can improve machined surface. In the machining, there is important to identify the characteristics of main product of these processes - workpiece, but also the byproduct - the chip. Size and shape of chip has impact on lifetime of cutting tools and its inappropriate form can influence the machine functionality and lifetime, too. This article deals with elimination of long chip created when machining of shaft in automotive industry and with impact of shape of chip-breaker on shape of chip in various cutting conditions based on production requirements.

A nano-patterned self assembled monolayer (SAM) rutile titania cancer chip for rapid, low cost, highly sensitive, direct cancer analysis in MALDI-MS.

PubMed

Manikandan, M; Gopal, Judy; Hasan, Nazim; Wu, Hui-Fen

2014-12-01

We developed a cancer chip by nano-patterning a highly sensitive SAM titanium surface capable of capturing and sensing concentrations as low as 10 cancer cells/mL from the environment by Matrix Assisted Laser Desorption and Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). The current approach evades any form of pretreatment and sample preparation processes; it is time saving and does not require the (expensive) conventional MALDI target plate. The home made aluminium (Al) target holder cost, on which we loaded the cancer chips for MALDI-TOF MS analysis, is about 60 USD. While the conventional stainless steel MALDI target plate is more than 700 USD. The SAM surface was an effective platform leading to on-chip direct MALDI-MS detection of cancer cells. We compared the functionality of this chip with the unmodified titanium surfaces and thermally oxidized (TO) titanium surfaces. The lowest detectable concentration of the TO chip was 10(3) cells/mL, while the lowest detectable concentration of the control or unmodified titanium chips was 10(6) cells/mL. Compared to the control surface, the SAM cancer chip showed 100,000 times of enhanced sensitivity and compared with the TO chip, 1000 times of increased sensitivity. The high sensitivity of the SAM surfaces is attributed to the presence of the rutile SAM, surface roughness and surface wettability as confirmed by AFM, XRD, contact angle microscope and FE-SEM. This study opens a new avenue for the potent application of the SAM cancer chip for direct cancer diagnosis by MALDI-TOF MS in the near future. Copyright © 2014. Published by Elsevier B.V.

Evaluation of Louisiana's maintenance chip seal and micro-surfacing program.

DOT National Transportation Integrated Search

2002-07-01

This report focuses valuation of Louisiana DOTD's chip seal and micro-surfacing treatments. The report discusses the performance in terms of Pavement Condition Index (PCI) of 40 chip seal and 24 micro-surface projects after approximately 52 months of...

Precise and selective sensing of DNA-DNA hybridization by graphene/Si-nanowires diode-type biosensors.

PubMed

Kim, Jungkil; Park, Shin-Young; Kim, Sung; Lee, Dae Hun; Kim, Ju Hwan; Kim, Jong Min; Kang, Hee; Han, Joong-Soo; Park, Jun Woo; Lee, Hosun; Choi, Suk-Ho

2016-08-18

Single-Si-nanowire (NW)-based DNA sensors have been recently developed, but their sensitivity is very limited because of high noise signals, originating from small source-drain current of the single Si NW. Here, we demonstrate that chemical-vapor-deposition-grown large-scale graphene/surface-modified vertical-Si-NW-arrays junctions can be utilized as diode-type biosensors for highly-sensitive and -selective detection of specific oligonucleotides. For this, a twenty-seven-base-long synthetic oligonucleotide, which is a fragment of human DENND2D promoter sequence, is first decorated as a probe on the surface of vertical Si-NW arrays, and then the complementary oligonucleotide is hybridized to the probe. This hybridization gives rise to a doping effect on the surface of Si NWs, resulting in the increase of the current in the biosensor. The current of the biosensor increases from 19 to 120% as the concentration of the target DNA varies from 0.1 to 500 nM. In contrast, such biosensing does not come into play by the use of the oligonucleotide with incompatible or mismatched sequences. Similar results are observed from photoluminescence microscopic images and spectra. The biosensors show very-uniform current changes with standard deviations ranging ~1 to ~10% by ten-times endurance tests. These results are very promising for their applications in accurate, selective, and stable biosensing.

Adhesion kinetics of human primary monocytes, dendritic cells, and macrophages: Dynamic cell adhesion measurements with a label-free optical biosensor and their comparison with end-point assays.

PubMed

Orgovan, Norbert; Ungai-Salánki, Rita; Lukácsi, Szilvia; Sándor, Noémi; Bajtay, Zsuzsa; Erdei, Anna; Szabó, Bálint; Horvath, Robert

2016-09-01

Monocytes, dendritic cells (DCs), and macrophages (MFs) are closely related immune cells that differ in their main functions. These specific functions are, to a considerable degree, determined by the differences in the adhesion behavior of the cells. To study the inherently and essentially dynamic aspects of the adhesion of monocytes, DCs, and MFs, dynamic cell adhesion assays were performed with a high-throughput label-free optical biosensor [Epic BenchTop (BT)] on surfaces coated with either fibrinogen (Fgn) or the biomimetic copolymer PLL-g-PEG-RGD. Cell adhesion profiles typically reached their maximum at ∼60 min after cell seeding, which was followed by a monotonic signal decrease, indicating gradually weakening cell adhesion. According to the biosensor response, cell types could be ordered by increasing adherence as monocytes, MFs, and DCs. Notably, all three cell types induced a larger biosensor signal on Fgn than on PLL-g-PEG-RGD. To interpret this result, the molecular layers were characterized by further exploiting the potentials of the biosensor: by measuring the adsorption signal induced during the surface coating procedure, the authors could estimate the surface density of adsorbed molecules and, thus, the number of binding sites potentially presented for the adhesion receptors. Surfaces coated with PLL-g-PEG-RGD presented less RGD sites, but was less efficient in promoting cell spreading than those coated with Fgn; hence, other binding sites in Fgn played a more decisive role in determining cell adherence. To support the cell adhesion data obtained with the biosensor, cell adherence on Fgn-coated surfaces 30-60 min after cell seeding was measured with three complementary techniques, i.e., with (1) a fluorescence-based classical adherence assay, (2) a shear flow chamber applying hydrodynamic shear stress to wash cells away, and (3) an automated micropipette using vacuum-generated fluid flow to lift cells up. These techniques confirmed the results obtained with the high-temporal-resolution Epic BT, but could only provide end-point data. In contrast, complex, nonmonotonic cell adhesion kinetics measured by the high-throughput optical biosensor is expected to open a window on the hidden background of the immune cell-extracellular matrix interactions.

Surface Generated Acoustic Wave Biosensors for the Detection of Pathogens: A Review

PubMed Central

Rocha-Gaso, María-Isabel; March-Iborra, Carmen; Montoya-Baides, Ángel; Arnau-Vives, Antonio

2009-01-01

This review presents a deep insight into the Surface Generated Acoustic Wave (SGAW) technology for biosensing applications, based on more than 40 years of technological and scientific developments. In the last 20 years, SGAWs have been attracting the attention of the biochemical scientific community, due to the fact that some of these devices - Shear Horizontal Surface Acoustic Wave (SH-SAW), Surface Transverse Wave (STW), Love Wave (LW), Flexural Plate Wave (FPW), Shear Horizontal Acoustic Plate Mode (SH-APM) and Layered Guided Acoustic Plate Mode (LG-APM) - have demonstrated a high sensitivity in the detection of biorelevant molecules in liquid media. In addition, complementary efforts to improve the sensing films have been done during these years. All these developments have been made with the aim of achieving, in a future, a highly sensitive, low cost, small size, multi-channel, portable, reliable and commercially established SGAW biosensor. A setup with these features could significantly contribute to future developments in the health, food and environmental industries. The second purpose of this work is to describe the state-of-the-art of SGAW biosensors for the detection of pathogens, being this topic an issue of extremely importance for the human health. Finally, the review discuses the commercial availability, trends and future challenges of the SGAW biosensors for such applications. PMID:22346725

Highly sensitive photoelectrochemical biosensor for kinase activity detection and inhibition based on the surface defect recognition and multiple signal amplification of metal-organic frameworks.

PubMed

Wang, Zonghua; Yan, Zhiyong; Wang, Feng; Cai, Jibao; Guo, Lei; Su, Jiakun; Liu, Yang

2017-11-15

A turn-on photoelectrochemical (PEC) biosensor based on the surface defect recognition and multiple signal amplification of metal-organic frameworks (MOFs) was proposed for highly sensitive protein kinase activity analysis and inhibitor evaluation. In this strategy, based on the phosphorylation reaction in the presence of protein kinase A (PKA), the Zr-based metal-organic frameworks (UiO-66) accommodated with [Ru(bpy) 3 ] 2+ photoactive dyes in the pores were linked to the phosphorylated kemptide modified TiO 2 /ITO electrode through the chelation between the Zr 4+ defects on the surface of UiO-66 and the phosphate groups in kemptide. Under visible light irradiation, the excited electrons from [Ru(bpy) 3 ] 2+ adsorbed in the pores of UiO-66 injected into the TiO 2 conduction band to generate photocurrent, which could be utilized for protein kinase activities detection. The large surface area and high porosities of UiO-66 facilitated a large number of [Ru(bpy) 3 ] 2+ that increased the photocurrent significantly, and afforded a highly sensitive PEC analysis of kinase activity. The detection limit of the as-proposed PEC biosensor was 0.0049UmL -1 (S/N!=!3). The biosensor was also applied for quantitative kinase inhibitor evaluation and PKA activities detection in MCF-7 cell lysates. The developed visible-light PEC biosensor provides a simple detection procedure and a cost-effective manner for PKA activity assays, and shows great potential in clinical diagnosis and drug discoveries. Copyright © 2017 Elsevier B.V. All rights reserved.

Immuno-biosensor for Detection of CD20-Positive Cells Using Surface Plasmon Resonance.

PubMed

Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili; Fathi, Farzaneh; Ezzati Nazhad Dolatabadi, Jafar

2017-06-01

Purpose: Surface plasmon resonance (SPR) sensing confers a real-time assessment of molecular interactions between biomolecules and their ligands. This approach is highly sensitive and reproducible and could be employed to confirm the successful binding of drugs to cell surface targets. The specific affinity of monoclonal antibodies (MAb) for their target antigens is being utilized for development of immuno-sensors and therapeutic agents. CD20 is a surface protein of B lymphocytes which has been widely employed for immuno-targeting of B-cell related disorders. In the present study, binding ability of an anti-CD20 MAb to surface antigens of intact target cells was investigated by SPR technique. Methods: Two distinct strategies were used for immobilization of the anti-CD20 MAb onto gold (Au) chips. MUA (11-mercaptoundecanoic acid) and Staphylococcus aureus protein A (SpA) were the two systems used for this purpose. A suspension of CD20-positive Raji cells was injected in the analyte phase and the resulting interactions were analyzed and compared to those of MOLT-4 cell line as CD20-negative control. Results: Efficient binding of anti-CD20 MAb to the surface antigens of Raji cell line was confirmed by both immobilizing methods, whereas this MAb had not a noticeable affinity to the MOLT-4 cells. Conclusion: According to the outcomes, the investigated MAb had acceptable affinity and specificity to the target antigens on the cell surface and could be utilized for immuno-detection of CD20-positive intact cells by SPR method.

Immuno-biosensor for Detection of CD20-Positive Cells Using Surface Plasmon Resonance

PubMed Central

Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili; Fathi, Farzaneh; Ezzati Nazhad Dolatabadi, Jafar

2017-01-01

Purpose: Surface plasmon resonance (SPR) sensing confers a real-time assessment of molecular interactions between biomolecules and their ligands. This approach is highly sensitive and reproducible and could be employed to confirm the successful binding of drugs to cell surface targets. The specific affinity of monoclonal antibodies (MAb) for their target antigens is being utilized for development of immuno-sensors and therapeutic agents. CD20 is a surface protein of B lymphocytes which has been widely employed for immuno-targeting of B-cell related disorders. In the present study, binding ability of an anti-CD20 MAb to surface antigens of intact target cells was investigated by SPR technique. Methods: Two distinct strategies were used for immobilization of the anti-CD20 MAb onto gold (Au) chips. MUA (11-mercaptoundecanoic acid) and Staphylococcus aureus protein A (SpA) were the two systems used for this purpose. A suspension of CD20-positive Raji cells was injected in the analyte phase and the resulting interactions were analyzed and compared to those of MOLT-4 cell line as CD20-negative control. Results: Efficient binding of anti-CD20 MAb to the surface antigens of Raji cell line was confirmed by both immobilizing methods, whereas this MAb had not a noticeable affinity to the MOLT-4 cells. Conclusion: According to the outcomes, the investigated MAb had acceptable affinity and specificity to the target antigens on the cell surface and could be utilized for immuno-detection of CD20-positive intact cells by SPR method. PMID:28761820

Computational modeling of mediator oxidation by oxygen in an amperometric glucose biosensor.

PubMed

Simelevičius, Dainius; Petrauskas, Karolis; Baronas, Romas; Razumienė, Julija

2014-02-07

In this paper, an amperometric glucose biosensor is modeled numerically. The model is based on non-stationary reaction-diffusion type equations. The model consists of four layers. An enzyme layer lies directly on a working electrode surface. The enzyme layer is attached to an electrode by a polyvinyl alcohol (PVA) coated terylene membrane. This membrane is modeled as a PVA layer and a terylene layer, which have different diffusivities. The fourth layer of the model is the diffusion layer, which is modeled using the Nernst approach. The system of partial differential equations is solved numerically using the finite difference technique. The operation of the biosensor was analyzed computationally with special emphasis on the biosensor response sensitivity to oxygen when the experiment was carried out in aerobic conditions. Particularly, numerical experiments show that the overall biosensor response sensitivity to oxygen is insignificant. The simulation results qualitatively explain and confirm the experimentally observed biosensor behavior.

Computational Modeling of Mediator Oxidation by Oxygen in an Amperometric Glucose Biosensor

PubMed Central

Šimelevičius, Dainius; Petrauskas, Karolis; Baronas, Romas; Julija, Razumienė

2014-01-01

In this paper, an amperometric glucose biosensor is modeled numerically. The model is based on non-stationary reaction-diffusion type equations. The model consists of four layers. An enzyme layer lies directly on a working electrode surface. The enzyme layer is attached to an electrode by a polyvinyl alcohol (PVA) coated terylene membrane. This membrane is modeled as a PVA layer and a terylene layer, which have different diffusivities. The fourth layer of the model is the diffusion layer, which is modeled using the Nernst approach. The system of partial differential equations is solved numerically using the finite difference technique. The operation of the biosensor was analyzed computationally with special emphasis on the biosensor response sensitivity to oxygen when the experiment was carried out in aerobic conditions. Particularly, numerical experiments show that the overall biosensor response sensitivity to oxygen is insignificant. The simulation results qualitatively explain and confirm the experimentally observed biosensor behavior. PMID:24514882

Biosensoric potential of microbial fuel cells.

PubMed

Schneider, György; Kovács, Tamás; Rákhely, Gábor; Czeller, Miklós

2016-08-01

Recent progress in microbial fuel cell (MFC) technology has highlighted the potential of these devices to be used as biosensors. The advantages of MFC-based biosensors are that they are phenotypic and can function in either assay- or flow-through formats. These features make them appropriate for contiguous on-line monitoring in laboratories and for in-field applications. The selectivity of an MFC biosensor depends on the applied microorganisms in the anodic compartment where electron transfer (ET) between the artificial surface (anode) and bacterium occurs. This process strongly determines the internal resistance of the sensoric system and thus influences signal outcome and response time. Despite their beneficial characteristics, the number of MFC-based biosensoric applications has been limited until now. The aim of this mini-review is to turn attention to the biosensoric potential of MFCs by summarizing ET mechanisms on which recently established and future sensoric devices are based.

Electrochemical biosensing of galactose based on carbon materials: graphene versus multi-walled carbon nanotubes.

PubMed

Dalkıran, Berna; Erden, Pınar Esra; Kılıç, Esma

2016-06-01

In this study, two enzyme electrodes based on graphene (GR), Co3O4 nanoparticles and chitosan (CS) or multi-walled carbon nanotubes (MWCNTs), Co3O4 nanoparticles, and CS, were fabricated as novel biosensing platforms for galactose determination, and their performances were compared. Galactose oxidase (GaOx) was immobilized onto the electrode surfaces by crosslinking with glutaraldehyde. Optimum working conditions of the biosensors were investigated and the analytical performance of the biosensors was compared with respect to detection limit, linearity, repeatability, and stability. The MWCNTs-based galactose biosensor provided about 1.6-fold higher sensitivity than its graphene counterpart. Moreover, the linear working range and detection limit of the MWCNTs-based galactose biosensor was superior to the graphene-modified biosensor. The successful application of the purposed biosensors for galactose biosensing in human serum samples was also investigated.

Label-free detection of glycoproteins by the lectin biosensor down to attomolar level using gold nanoparticles

PubMed Central

Bertok, Tomas; Sediva, Alena; Katrlik, Jaroslav; Gemeiner, Pavol; Mikula, Milan; Nosko, Martin; Tkac, Jan

2016-01-01

We present here an ultrasensitive electrochemical biosensor based on a lectin biorecognition capable to detect concentrations of glycoproteins down to attomolar (aM) level by investigation of changes in the charge transfer resistance (Rct) using electrochemical impedance spectroscopy (EIS). On polycrystalline gold modified by an aminoalkanethiol linker layer, gold nanoparticles were attached. A Sambucus nigra agglutinin was covalently immobilised on a mixed self-assembled monolayer formed on gold nanoparticles and finally, the biosensor surface was blocked by poly(vinylalcohol). The lectin biosensor was applied for detection of sialic acid containing glycoproteins fetuin and asialofetuin. Building of a biosensing interface was carefully characterised by a broad range of techniques such as electrochemistry, EIS, atomic force microscopy, scanning electron microscopy and surface plasmon resonance with the best performance of the biosensor achieved by application of HS-(CH2)11-NH2 linker and gold nanoparticles with a diameter of 20 nm. The lectin biosensor responded to an addition of fetuin (8.7% of sialic acid) with sensitivity of (338 ± 11) Ω decade-1 and to asialofetuin (≤ 0.5% of sialic acid) with sensitivity of (109 ± 10) Ω decade-1 with a blank experiment with oxidised asialofetuin (without recognisable sialic acid) revealing sensitivity of detection of (79 ± 13) Ω decade-1. These results suggest the lectin biosensor responded to changes in the glycan amount in a quantitative way with a successful validation by a lectin microarray. Such a biosensor device has a great potential to be employed in early biomedical diagnostics of diseases such as arthritis or cancer, which are connected to aberrant glycosylation of protein biomarkers in biological fluids. PMID:23601864

A Large Response Range Reflectometric Urea Biosensor Made from Silica-Gel Nanoparticles

PubMed Central

Alqasaimeh, Muawia; Heng, Lee Yook; Ahmad, Musa; Raj, A.S. Santhana; Ling, Tan Ling

2014-01-01

A new silica-gel nanospheres (SiO2NPs) composition was formulated, followed by biochemical surface functionalization to examine its potential in urea biosensor development. The SiO2NPs were basically synthesized based on sol–gel chemistry using a modified Stober method. The SiO2NPs surfaces were modified with amine (-NH2) functional groups for urease immobilization in the presence of glutaric acid (GA) cross-linker. The chromoionophore pH-sensitive dye ETH 5294 was physically adsorbed on the functionalized SiO2NPs as pH transducer. The immobilized urease determined urea concentration reflectometrically based on the colour change of the immobilized chromoionophore as a result of the enzymatic hydrolysis of urea. The pH changes on the biosensor due to the catalytic enzyme reaction of immobilized urease were found to correlate with the urea concentrations over a linear response range of 50–500 mM (R2 = 0.96) with a detection limit of 10 mM urea. The biosensor response time was 9 min with reproducibility of less than 10% relative standard deviation (RSD). This optical urea biosensor did not show interferences by Na+, K+, Mg2+ and NH4+ ions. The biosensor performance has been validated using urine samples in comparison with a non-enzymatic method based on the use of p-dimethylaminobenzaldehyde (DMAB) reagent and demonstrated a good correlation between the two different methods (R2 = 0.996 and regression slope of 1.0307). The SiO2NPs-based reflectometric urea biosensor showed improved dynamic linear response range when compared to other nanoparticle-based optical urea biosensors. PMID:25054632

Hybrid electro-optical nanosystem for neurons investigation

NASA Astrophysics Data System (ADS)

Miu, Mihaela; Kleps, Irina; Craciunoiu, Florea; Simion, Monica; Bragaru, Adina; Ignat, Teodora

2010-11-01

The scope of this paper is development of a new laboratory-on-a-chip (LOC) device for biomedical studies consisting of a microfluidic system coupled to microelectronic/optical transducers with nanometric features, commonly called biosensors. The proposed device is a hybrid system with sensing element on silicon (Si) chip and microfluidic system on polydimethylsiloxane (PDMS) substrates, taking into accounts their particular advantages. Different types of nanoelectrode arrays, positioned in the reactor, have been investigated as sensitive elements for electrical detection and the recording of neuron extracellular electric activity has been monitorized in parallel with whole-cell patch-clamp membrane current. Moreover, using an additional porosification process the sensing element became efficient for optical detection also. The preliminary test results demonstrate the functionality of the proposed design and also the fabrication technology, the devices bringing advantages in terms enhancement of sensitivity in both optoelectronic detection schemes.

A Bioanalytical Chemistry Experiment for Undergraduate Students: Biosensors Based on Metal Nanoparticles

ERIC Educational Resources Information Center

Niagi, John; Warner, John; Andreesco, Silvana

2007-01-01

The study describes the development of new biosensors based on metal nanoparticles because of its high surface area and large binding ability. The adopted procedure is extremely simple and versatile and can be used in various applications of electrochemistry.

A Versatile Method for Functionalizing Surfaces with Bioactive Glycans

PubMed Central

Cheng, Fang; Shang, Jing; Ratner, Daniel M.

2011-01-01

Microarrays and biosensors owe their functionality to our ability to display surface-bound biomolecules with retained biological function. Versatile, stable, and facile methods for the immobilization of bioactive compounds on surfaces have expanded the application of high-throughput ‘omics’-scale screening of molecular interactions by non-expert laboratories. Herein, we demonstrate the potential of simplified chemistries to fabricate a glycan microarray, utilizing divinyl sulfone (DVS)-modified surfaces for the covalent immobilization of natural and chemically derived carbohydrates, as well as glycoproteins. The bioactivity of the captured glycans was quantitatively examined by surface plasmon resonance imaging (SPRi). Composition and spectroscopic evidence of carbohydrate species on the DVS-modified surface were obtained by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), respectively. The site-selective immobilization of glycans based on relative nucleophilicity (reducing sugar vs. amine- and sulfhydryl-derived saccharides) and anomeric configuration was also examined. Our results demonstrate straightforward and reproducible conjugation of a variety of functional biomolecules onto a vinyl sulfone-modified biosensor surface. The simplicity of this method will have a significant impact on glycomics research, as it expands the ability of non-synthetic laboratories to rapidly construct functional glycan microarrays and quantitative biosensors. PMID:21142056

A novel surface plasmon resonance biosensor based on the PDA-AgNPs-PDA-Au film sensing platform for horse IgG detection

NASA Astrophysics Data System (ADS)

Wang, Ning; Zhang, Di; Deng, Xinyu; Sun, Ying; Wang, Xinghua; Ma, Pinyi; Song, Daqian

2018-02-01

Herein we report a novel polydopamine-silver nanoparticle-polydopamine-gold (PDA-AgNPs-PDA-Au) film based surface plasmon resonance (SPR) biosensor for horse IgG detection. The PDA-AgNPs-PDA-Au film sensing platform was built on Au-film via layer-by-layer self-assembly. Ag ion was reduced in situ to AgNPs in presence of PDA. The top PDA layer can prevent AgNPs from being oxidized and connect with antibody via Schiff alkali reaction directly. The morphology and thickness of the modified gold film were characterized using scanning electron microscope and Talystep. Experimental results show that the PDA-AgNPs-PDA-Au film sensing platform is stable, regenerative and sensitive for horse IgG detection. The detection limit of horse IgG obtained with the present biosensor is 0.625 μg mL- 1, which is 2-fold and 4-fold lower than that obtained with biosensor based on PDA modified Au film and conventional biosensor based on MPA, respectively. Furthermore, when challenged to real serum samples, our sensor exhibited excellent specificity to horse IgG, suggesting its potential for industrial application.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawal, Abdulazeez T., E-mail: abdul.lawal@yahoo.com

Graphical abstract: Carbon nanotubes. - Highlights: • This review discusses synthesis and applications of carbon nanotubes sensors. • The review summarizes contributions of carbon nanotube to electrochemical biosensor. • Good electrical conductivity makes carbon nanotubes a good material for biosensors. • Carbon nanotubes promotes electron transfer that aids biosensing of biomolecules. - Abstract: This review summarizes the most recent contributions in the fabrication of carbon nanotubes-based electrochemical biosensors in recent years. It discusses the synthesis and application of carbon nanotubes to the assembly of carbon nanotube-based electrochemical sensors, its analytical performance and future expectations. An increasing number of reviews andmore » publications involving carbon nanotubes sensors have been reported ever since the first design of carbon nanotube electrochemical biosensors. The large surface area and good electrical conductivity of carbon nanotubes allow them to act as “electron wire” between the redox center of an enzyme or protein and an electrode's surface, which make them very excellent material for the design of electrochemical biosensors. Carbon nanotubes promote the different rapid electron transfers that facilitate accurate and selective detection of cytochrome-c, β-nicotinamide adenine dinucleotide, hemoglobin and biomolecules, such as glucose, cholesterol, ascorbic acid, uric acid, dopamine pesticides, metals ions and hydrogen peroxide.« less

Highly sensitive nano-porous lattice biosensor based on localized surface plasmon resonance and interference.

PubMed

Yeom, Se-Hyuk; Kim, Ok-Geun; Kang, Byoung-Ho; Kim, Kyu-Jin; Yuan, Heng; Kwon, Dae-Hyuk; Kim, Hak-Rin; Kang, Shin-Won

2011-11-07

We propose a design for a highly sensitive biosensor based on nanostructured anodized aluminum oxide (AAO) substrates. A gold-deposited AAO substrate exhibits both optical interference and localized surface plasmon resonance (LSPR). In our sensor, application of these disparate optical properties overcomes problems of limited sensitivity, selectivity, and dynamic range seen in similar biosensors. We fabricated uniform periodic nanopore lattice AAO templates by two-step anodizing and assessed their suitability for application in biosensors by characterizing the change in optical response on addition of biomolecules to the AAO template. To determine the suitability of such structures for biosensing applications, we immobilized a layer of C-reactive protein (CRP) antibody on a gold coating atop an AAO template. We then applied a CRP antigen (Ag) atop the immobilized antibody (Ab) layer. The shift in reflectance is interpreted as being caused by the change in refractive index with membrane thickness. Our results confirm that our proposed AAO-based biosensor is highly selective toward detection of CRP antigen, and can measure a change in CRP antigen concentration of 1 fg/ml. This method can provide a simple, fast, and sensitive analysis for protein detection in real-time.

An enzyme-chromogenic surface plasmon resonance biosensor probe for hydrogen peroxide determination using a modified Trinder's reagent.

PubMed

Nakamura, Hideaki; Mogi, Yotaro; Akimoto, Takuo; Naemura, Kiyoshi; Kato, Teru; Yano, Kazuyoshi; Karube, Isao

2008-11-15

An absorption-based surface plasmon resonance (SPR(Abs)) biosensor probe has been developed for simple and reproducible measurements of hydrogen peroxide using a modified Trinder's reagent (a chromogenic reagent). The reagent enabled the determination of the hydrogen peroxide concentration by the development of deep color dyes (lambda(max)=630 nm) through the oxidative coupling reaction with N-ethyl-N-(2-hydroxy-3-sulfopropyl)-3,5-dimethylaniline sodium salt monohydrate (MAOS; C(13)H(20)NNaO(4)S.H(2)O) and 4-aminoantipyrine (4-AA) in the presence of hydrogen peroxide and horseradish peroxidase (HRP). In the present study, urea as an adduct of hydrogen peroxide for color development could be omitted from the measurement solution. The measurement solution containing 5mM hydrogen peroxide was deeply colored at a high absorbance value calculated as 46.7cm(-1) and was directly applied to the SPR(Abs) biosensing without dilution. The measurement was simply performed by dropping the measurement solution onto the surface of the SPR sensor probe, and the SPR(Abs) biosensor response to hydrogen peroxide was obtained as a reflectivity change in the SPR spectrum. After investigation of the pH profiles in the SPR(Abs) biosensor probe, a linear calibration curve was obtained between 1.0 and 50mM hydrogen peroxide (r=0.991, six points, average of relative standard deviation; 0.152%, n=3) with a detection limit of 0.5mM. To examine the applicability of this SPR(Abs) biosensor probe, 20mM glucose detection using glucose oxidase was also confirmed without influence of the refractive index in the measurement solution. Thus, the SPR(Abs) biosensor probe employing the modified Trinder's reagent demonstrated applicability to other analyte biosensing tools.

A Disposable Organophosphorus Pesticides Enzyme Biosensor Based on Magnetic Composite Nano-Particles Modified Screen Printed Carbon Electrode

PubMed Central

Gan, Ning; Yang, Xin; Xie, Donghua; Wu, Yuanzhao; Wen, Weigang

2010-01-01

A disposable organophosphorus pesticides (OPs) enzyme biosensor based on magnetic composite nanoparticle-modified screen printed carbon electrodes (SPCE) has been developed. Firstly, an acetylcholinesterase (AChE)-coated Fe3O4/Au (GMP) magnetic nanoparticulate (GMP-AChE) was synthesized. Then, GMP-AChE was absorbed on the surface of a SPCE modified by carbon nanotubes (CNTs)/nano-ZrO2/prussian blue (PB)/Nafion (Nf) composite membrane by an external magnetic field. Thus, the biosensor (SPCE│CNTs/ZrO2/PB/Nf│GMP-AChE) for OPs was fabricated. The surface of the biosensor was characterized by scanning electron micrography (SEM) and X-ray fluorescence spectrometery (XRFS) and its electrochemical properties were studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The degree of inhibition (A%) of the AChE by OPs was determined by measuring the reduction current of the PB generated by the AChE-catalyzed hydrolysis of acetylthiocholine (ATCh). In pH = 7.5 KNO3 solution, the A was related linearly to the concentration of dimethoate in the range from 1.0 × 10−3–10 ng·mL−1 with a detection limit of 5.6 × 10−4 ng·mL−1. The recovery rates in Chinese cabbage exhibited a range of 88%–105%. The results were consistent with the standard gas chromatography (GC) method. Compared with other enzyme biosensors the proposed biosensor exhibited high sensitivity, good selectivity with disposable, low consumption of sample. In particular its surface can be easily renewed by removal of the magnet. The convenient, fast and sensitive voltammetric measurement opens new opportunities for OPs analysis. PMID:22315558

The Vital Function of Fe3O4@Au nanocomposites for Hydrolase Biosensor Design and Its Application in Detection of Methyl Parathion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Yuting; Zhang, Weiying; Lin, Yuehe

A nanocomposite of gold nanoparticles (AuNPs) decorating a magnetic Fe3O4 core was synthesized using cysteamine (SH–NH2) as linker, and characterized by TEM, XPS, UV and electrochemistry. Then a hydrolase biosensor, based on self-assembly of methyl parathion hydrolase (MPH) on the Fe3O4@Au nanocomposite, was developed for sensitive and selective detection of the organophosphorus pesticide (OP) methyl parathion. The magnetic nanocomposite provides an easy way to construct the enzyme biosensor by simply exerting an external magnetic field, and also provides a simple way to renew the electrode surface by removing the magnet. Unlike inhibition-based enzyme biosensors, the hydrolase is not poisoned bymore » OPs and thus is reusable for continuous measurement. AuNPs not only provide a large surface area, high loading efficiency and fast electron transfer, but also stabilize the enzyme through electrostatic interactions. The MPH biosensor shows rapid response and high selectivity for detection of methyl parathion, with a linear range from 0.5 to 1000 ng/mL and a detection limit of 0.1 ng/mL. It also shows acceptable reproducibility and stability. The simplicity and ease of operation of the proposed method has great potential for on-site detection of P–S containing pesticides and provides a promising strategy to construct a robust biosensor.« less

Miniaturised enzymatic conductometric biosensor with Nafion membrane for the direct determination of formaldehyde in water samples.

PubMed

Nguyen-Boisse, Thanh-Thuy; Saulnier, Joëlle; Jaffrezic-Renault, Nicole; Lagarde, Florence

2014-02-01

A new conductometric enzyme-based biosensor was developed for the determination of formaldehyde (FA) in aqueous solutions. The biosensor was prepared by cross-linking formaldehyde dehydrogenase from Pseudomonas putida with bovine serum albumin in saturated glutaraldehyde vapours (GA) at the surface of interdigitated gold microelectrodes. Nicotinamide adenine dinucleotide cofactor (NAD(+)) was added in solution at each measurement to maintain enzyme activity. Addition of a Nafion layer over the enzyme modified electrode resulted in a significant increase of biosensor signal due to enhanced accumulation of protons generated by enzymatic reaction at the electrode surface. Different parameters affecting enzyme activity or playing a role in ionic transfer through the Nafion membrane were optimised. In optimal conditions (0.045 mg enzyme, 30 min exposure to GA, 0.3 μL of a 1% (v/v) Nafion solution deposit, measurement in 5 mM phosphate buffer pH 7 containing 20 μM NAD(+)), the biosensor signal was linear up to 10 mM FA, and the detection limit was 18 μM. Relative standard deviations calculated from five consecutive replicates of FA solutions were lower than 5% in the 1-10 mM range. The biosensor was successfully applied to the determination of FA in spiked water samples (tap water and Rhone river water), with recoveries in the 95-110% range.

Nano-machining of biosensor electrodes through gold nanoparticles deposition produced by femtosecond laser ablation

NASA Astrophysics Data System (ADS)

Della Ventura, B.; Funari, R.; Anoop, K. K.; Amoruso, S.; Ausanio, G.; Gesuele, F.; Velotta, R.; Altucci, C.

2015-06-01

We report an application of femtosecond laser ablation to improve the sensitivity of biosensors based on a quartz crystal microbalance device. The nanoparticles produced by irradiating a gold target with 527-nm, 300-fs laser pulses, in high vacuum, are directly deposited on the quartz crystal microbalance electrode. Different gold electrodes are fabricated by varying the deposition time, thus addressing how the nanoparticles surface coverage influences the sensor response. The modified biosensor is tested by weighting immobilized IgG antibody from goat and its analyte (IgG from mouse), and the results are compared with a standard electrode. A substantial increase of biosensor sensitivity is achieved, thus demonstrating that femtosecond laser ablation and deposition is a viable physical method to improve the biosensor sensitivity by means of nanostructured electrodes.

Illuminating Cell Biology

NASA Technical Reports Server (NTRS)

2002-01-01

NASA's Ames Research Center awarded Ciencia, Inc., a Small Business Innovation Research contract to develop the Cell Fluorescence Analysis System (CFAS) to address the size, mass, and power constraints of using fluorescence spectroscopy in the International Space Station's Life Science Research Facility. The system will play an important role in studying biological specimen's long-term adaptation to microgravity. Commercial applications for the technology include diverse markets such as food safety, in situ environmental monitoring, online process analysis, genomics and DNA chips, and non-invasive diagnostics. Ciencia has already sold the system to the private sector for biosensor applications.

Label-free electrical detection using carbon nanotube-based biosensors.

PubMed

Maehashi, Kenzo; Matsumoto, Kazuhiko

2009-01-01

Label-free detections of biomolecules have attracted great attention in a lot of life science fields such as genomics, clinical diagnosis and practical pharmacy. In this article, we reviewed amperometric and potentiometric biosensors based on carbon nanotubes (CNTs). In amperometric detections, CNT-modified electrodes were used as working electrodes to significantly enhance electroactive surface area. In contrast, the potentiometric biosensors were based on aptamer-modified CNT field-effect transistors (CNTFETs). Since aptamers are artificial oligonucleotides and thus are smaller than the Debye length, proteins can be detected with high sensitivity. In this review, we discussed on the technology, characteristics and developments for commercialization in label-free CNT-based biosensors.

A biosensor based on graphite epoxy composite electrode for aspartame and ethanol detection.

PubMed

Kirgöz, Ulkü Anik; Odaci, Dilek; Timur, Suna; Merkoçi, Arben; Alegret, Salvador; Beşün, Nurgün; Telefoncu, Azmi

2006-06-16

A gelatin membrane with carboxyl esterase and alcohol oxidase was subsequently integrated onto the surface of a graphite epoxy composite electrode (GECE). The developed biosensors showed linearity in the range of 2.5-400 microM for aspartame and 2.5-25 microM for ethanol with response times of 170 and 70s for each analyte, respectively. The resulting bienzyme biosensor was used for aspartame detection in diet coke samples and ethanol detection in beer and wine samples. From the obtained results, it can be concluded that the developed biosensor is a selective, practical and economic tool for aspartame and ethanol detection in real samples.

Development and surface characterization of a glucose biosensor based on a nanocolumnar ZnO film

NASA Astrophysics Data System (ADS)

Rodrigues, A.; Castegnaro, M. V.; Arguello, J.; Alves, M. C. M.; Morais, J.

2017-04-01

Highly oriented nanostructured ZnO films were grown on the surface of stainless steel plates (ZnO/SS) by chemical bath deposition (CBD). The films consisted of vertically aligned ZnO nanocolumns, ∼1 μm long and ∼80 nm wide, as observed by SEM (scanning electron microscopy) and FIB (focused ion beam). XRD (X-ray diffraction) confirmed the c-axis preferred orientation of the ZnO columns, which were functionalized with the glucose oxidase (GOx) enzyme into a biosensor of glucose. The electrochemical response studied by CV (cyclic voltammetry) proved that the biosensor was capable of detecting glucose from 1.5 up to 16 mM concentration range. XPS (X-ray photoelectron spectroscopy) analysis, excited with synchrotron radiation, probed the atom specific chemical environment at the electrode's surface and shed some light on the nature of the ZnO-GOx interaction.

One-chip biosensor for simultaneous disease marker/calibration substance measurement in human urine by electrochemical surface plasmon resonance method.

PubMed

Nakamoto, Kohei; Kurita, Ryoji; Niwa, Osamu

2010-12-15

We have developed a miniaturized electrochemical surface plasmon resonance biosensor for measuring two biomolecules that have very different molecular sizes, one is transferrin (MW=75 kDa) as a disease marker protein, the other is creatinine (MW=113) as a calibration marker for the accurate measurement of human urinary samples. The sensor has a PDMS based microchannel that is 2 mm wide and 20 μm deep. Two gold films were integrated in the microchannel; one was modified with anti-transferrin antibody for immuno-reaction, and the other was modified with osmium-poly-vinylpyridine wired horseradish peroxidase (Os-gel-HRP). We further immobilized a tri-enzyme layer of creatininase, creatinase and sarcosine oxidase in order to measure creatinine by converting it to hydrogen peroxide in the upstream channel. We measured the transferrin concentration from the refractive index change involved in an immuno-complex formation, and we were simultaneously able to measure creatinine by employing the refractive index change in the Os-gel-HRP caused by oxidation with the hydrogen peroxide produced from creatinine by the tri-enzyme. The effects of ascorbic acid and uric acid in urine samples were sufficiently eliminated by adding ascorbate oxidase and uricase to the urine samples during sampling. We were able to measure two analyte concentrations within 15 min by one simple injection of 50 μL of diluted human urine into our sensor. The detectable transferrin and creatinine ranges were 20 ng/mL to 10 μg/mL, and 10 μM to 10 mM, respectively, which are sufficient levels for clinical tests. Finally, we compared the results obtained using our sensor with those obtained with a conventional immunoassay and the Jaffe method. We obtained a similar trend that can reduce the fluctuation in the urinary transferrin concentration from three different samples by calibrating the creatinine concentration. Copyright © 2010 Elsevier B.V. All rights reserved.

Biosensors Fabricated through Electrostatic Assembly of Enzymes/Polyelectrolyte Hybrid Layers on Carbon Nanotubes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yuehe; Liu, Guodong; Wang, Jun

2006-06-01

Carbon nanotubes (CNTs) have emerged as new class of nanomaterials that is receiving considerable interest because of their unique structure, mechanical, and electronic properties. One promising application of CNTs is to fabricate highly sensitive chemo/biosensors.1-4 For construction of these CNT-based sensors, the CNTs first have to be modified with some molecules specific to the interests. Generally, covalent binding, affinity, and electrostatic interaction have been utilized for the modification of CNTs. Among them, the electrostatic method is attractive due to its simplicity and high efficiency. In present work, we have developed highly sensitively amperometric biosensors for glucose, choline, organophosphate pesticide (OPP)more » and nerve agents (NAs) based on electrostatically assembling enzymes on the surface of CNTs. All these biosensors were fabricated by immobilization of enzymes on the negatively charged CNTs surface through alternately assembling a cationic poly(diallydimethylammonium chloride) (PDDA) layer and an enzyme layer. Using this layer-by-layer (LBL) technique, a bioactive nanocomposite film was fabricated on the electrode surface. Owing to the electrocatalytic effect of CNTs, an amplified electrochemical signal was achieved, which leads to low detections limits for glucose, choline, and OPP and NAs.« less

Design trade-off between spatial resolution and power consumption in CMOS biosensor circuit based on millimeter-wave LC oscillator array

NASA Astrophysics Data System (ADS)

Matsunaga, Maya; Kobayashi, Atsuki; Nakazato, Kazuo; Niitsu, Kiichi

2018-03-01

In this paper, we describe a trade-off between spatial resolution and power consumption in an LC oscillator-based CMOS biosensor, which can detect biomolecules by observing the resonance frequency shift due to changes in the complex permittivity of the biomolecules. The optimal operating frequency and improvement in the image resolution of the sensor output require a reduction in the size of the inductor. However, it is necessary to increase the transconductance of the cross-coupling transistor to achieve the oscillation condition, although the power consumption increases. We confirmed the trade-off between the spatial resolution and the power consumption of this sensor using SPICE simulation. A test chip was fabricated using a 65 nm CMOS process, and the transition in the peak frequency and the power consumption were measured. When the outer diameter of the inductor was 46 µm, the power consumption was 31.2 mW, which matched well with the simulation results.

An enzymatic biosensor based on three-dimensional ZnO nanotetrapods spatial net modified AlGaAs/GaAs high electron mobility transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Yu; Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania 18015; Zhang, Xiaohui

2014-11-24

We designed and constructed three dimensional (3D) zinc oxide Nanotetrapods (T-ZnOs) modified AlGaAs/GaAs high electron mobility transistors (HEMTs) for enzymatic uric acid (UA) detection. The chemical vapor deposition synthesized T-ZnOs was distributed on the gate areas of HEMTs in order to immobilize uricase and improve the sensitivity of the HEMTs. Combining with the high efficiency of enzyme immobilization by T-ZnOs and high sensitivity from HEMT, the as-constructed uricase/T-ZnOs/HEMTs biosensor showed fast response towards UA at ∼1 s, wide linear range from 0.2 nM to 0.2 mM and the low detect limit at 0.2 nM. The results point out an avenue to design electronic devicemore » as miniaturized lab-on-chip device for high sensitive and specific in biomedical and clinical diagnosis applications.« less

Miniature Wireless BioSensor for Remote Endoscopic Monitoring

NASA Astrophysics Data System (ADS)

Nemiroski, Alex; Brown, Keith; Issadore, David; Westervelt, Robert; Thompson, Chris; Obstein, Keith; Laine, Michael

2009-03-01

We have built a miniature wireless biosensor with fluorescence detection capability that explores the miniaturization limit for a self-powered sensor device assembled from the latest off-the-shelf technology. The device is intended as a remote medical sensor to be inserted endoscopically and remainin a patient's gastrointestinal tract for a period of weeks, recording and transmitting data as necessary. A sensing network may be formed by using multiple such devices within the patient, routing information to an external receiver that communicates through existing mobilephone networks to relay data remotely. By using a monolithic IC chip with integrated processor, memory, and 2.4 GHz radio,combined with a photonic sensor and miniature battery, we have developed a fully functional computing device in a form factorcompliantwith insertion through the narrowest endoscopic channels (less than 3mm x 3mm x 20mm). We envision similar devices with various types of sensors to be used in many different areas of the human body.

A portable array biosensor for food safety

NASA Astrophysics Data System (ADS)

Golden, Joel P.; Ngundi, Miriam M.; Shriver-Lake, Lisa C.; Taitt, Chris R.; Ligler, Frances S.

2004-11-01

An array biosensor developed for simultaneous analysis of multiple samples has been utilized to develop assays for toxins and pathogens in a variety of foods. The biochemical component of the multi-analyte biosensor consists of a patterned array of biological recognition elements immobilized on the surface of a planar waveguide. A fluorescence assay is performed on the patterned surface, yielding an array of fluorescent spots, the locations of which are used to identify what analyte is present. Signal transduction is accomplished by means of a diode laser for fluorescence excitation, optical filters and a CCD camera for image capture. A laptop computer controls the miniaturized fluidics system and image capture. Results for four mycotoxin competition assays in buffer and food samples are presented.

Directed-Assembly of Carbon Nanotubes on Soft Substrates for Flexible Biosensor Array

NASA Astrophysics Data System (ADS)

Lee, Hyoung Woo; Koh, Juntae; Lee, Byung Yang; Kim, Tae Hyun; Lee, Joohyung; Hong, Seunghun; Yi, Mihye; Jhon, Young Min

2009-03-01

We developed a method to selectively assemble and align carbon nanotubes (CNTs) on soft substrates for flexible biosensors. In this strategy, thin oxide layer was deposited on soft substrates via low temperature plasma enhanced chemical vapor deposition, and linker-free assembly process was applied onto the oxide surface where the assembly of carbon nanotubes was guided by methyl-terminated molecular patterns on the oxide surface. The electrical characterization of the fabricated CNT devices exhibited typical p-type gating effect and 1/f noise behavior. The bare oxide regions near CNTs were functionalized with glutamate oxidase to fabricate selective biosensors to detect two forms of glutamate substances existing in different situations: L-glutamic acid, a neuro-transmitting material, and monosodium glutamate, a food additive.

Expanding Cancer Detection Using Molecular Imprinting for a Novel Point-of-Care Diagnostic Device

NASA Astrophysics Data System (ADS)

Yu, Yingjie; Rafailovich, Miriam; Wang, Yantian; Kang, Yeona; Zhang, Lingxi; Rigas, Basil; Division of Gastroenterology, School of Medicine Team

2013-03-01

We propose the use of a potentiometric biosensor that incorporates the efficient and specific molecular imprinting (MI) method with a self-assembled monolayer (SAM). We first tested the biosensor using carcinoembryonic antigen, CEA, a biomarker associated with pancreatic cancer. No change in detection efficiency was observed, indicating that the sensor is able to discriminate for the template analyte even in concentrated solution of similar substances. In addition, we use biosensor to discriminate normal fibrinogen and damaged fibrinogen, which is critical for the detection of bleeding disorder. Computer simulations of the protein structure were performed in order to estimate the changes in morphology and determine the sensitivity of the biosensor to conformational changes in the proteins. We found that even small changes in PH can generate rotation of the surface functional groups. Yet, the results show that only when the detection and imprinting conditions are similar, robust signals occurs. Hence we concluded that both morphology and surface chemistry play a role in the recognition.

Highly Sensitive and Reusable Membraneless Field-Effect Transistor (FET)-Type Tungsten Diselenide (WSe2) Biosensors.

PubMed

Lee, Hae Won; Kang, Dong-Ho; Cho, Jeong Ho; Lee, Sungjoo; Jun, Dong-Hwan; Park, Jin-Hong

2018-05-30

In recent years when the demand for high-performance biosensors has been aroused, a field-effect transistor (FET)-type biosensor (BioFET) has attracted great interest because of its high sensitivity, label-free detection, fast detection speed, and miniaturization. However, the insulating membrane in the conventional BioFET, which is essential in preventing the surface dangling bonds of typical semiconductors from nonspecific bindings, has limited the sensitivity of biosensors. Here, we present a highly sensitive and reusable membraneless BioFET based on a defect-free van der Waals material, tungsten diselenide (WSe 2 ). We intentionally generated a few surface defects that serve as extra binding sites for the bioreceptor immobilization through weak oxygen plasma treatment, consequently magnifying the sensitivity values to 2.87 × 10 5 A/A for 10 mM glucose. The WSe 2 BioFET also maintained its high sensitivity even after several cycles of rinsing and glucose application were repeated.

Simulation of Graphene Field-Effect Transistor Biosensors for Bacterial Detection.

PubMed

Wu, Guangfu; Meyyappan, Meyya; Lai, King Wai Chiu

2018-05-25

Foodborne illness is correlated with the existence of infectious pathogens such as bacteria in food and drinking water. Probe-modified graphene field effect transistors (G-FETs) have been shown to be suitable for Escherichia coli ( E. coli ) detection. Here, the G-FETs for bacterial detection are modeled and simulated with COMSOL Multiphysics to understand the operation of the biosensors. The motion of E. coli cells in electrolyte and the surface charge of graphene induced by E. coli are systematically investigated. The comparison between the simulation and experimental data proves the sensing probe size to be a key parameter affecting the surface charge of graphene induced by bacteria. Finally, the relationship among the change in source-drain current (∆ I ds ), graphene-bacteria distance and bacterial concentration is established. The shorter graphene-bacteria distance and higher bacterial concentration give rise to better sensing performance (larger ∆ I ds ) of the G-FETs biosensors. The simulation here could serve as a guideline for the design and optimization of G-FET biosensors for various applications.

An ultra-sensitive Au nanoparticles functionalized DNA biosensor for electrochemical sensing of mercury ions.

PubMed

Zhang, Yanyan; Zhang, Cong; Ma, Rui; Du, Xin; Dong, Wenhao; Chen, Yuan; Chen, Qiang

2017-06-01

The present work describes an effective strategy to fabricate a highly sensitive and selective DNA-biosensor for the determination of mercury ions (Hg 2+ ). The DNA 1 was modified onto the surface of Au electrode by the interaction between sulfydryl group and Au electrode. DNA probe is complementary with DNA 1. In the presence of Hg 2+ , the electrochemical signal increases owing to that Hg 2+ -mediated thymine bases induce the conformation of DNA probe to change from line to hairpin and less DNA probes adsorb into DNA 1. Taking advantage of its reduction property, methylene blue is considered as the signal indicating molecule. For improving the sensitivity of the biosensor, Au nanoparticles (Au NPs) modified reporter DNA 3 is used to adsorb DNA 1. Electrochemical behaviors of the biosensor were evaluated by electrochemical impedance spectroscopy and cyclic voltammetry. Several important parameters which could affect the property of the biosensor were studied and optimized. Under the optimal conditions, the biosensor exhibits wide linear range, high sensitivity and low detection limit. Besides, it displays superior selectivity and excellent stability. The biosensor was also applied for water sample detection with satisfactory result. The novel strategy of fabricating biosensor provides a potential platform for fabricating a variety of metal ions biosensors. Copyright © 2017 Elsevier B.V. All rights reserved.

Chip PCR. I. Surface passivation of microfabricated silicon-glass chips for PCR.

PubMed Central

Shoffner, M A; Cheng, J; Hvichia, G E; Kricka, L J; Wilding, P

1996-01-01

The microreaction volumes of PCR chips (a microfabricated silicon chip bonded to a piece of flat glass to form a PCR reaction chamber) create a relatively high surface to volume ratio that increases the significance of the surface chemistry in the polymerase chain reaction (PCR). We investigated several surface passivations in an attempt to identify 'PCR friendly' surfaces and used those surfaces to obtain amplifications comparable with those obtained in conventional PCR amplification systems using polyethylene tubes. Surface passivations by a silanization procedure followed by a coating of a selected protein or polynucleotide and the deposition of a nitride or oxide layer onto the silicon surface were investigated. Native silicon was found to be an inhibitor of PCR and amplification in an untreated PCR chip (i.e. native slicon) had a high failure rate. A silicon nitride (Si(3)N(4) reaction surface also resulted in consistent inhibition of PCR. Passivating the PCR chip using a silanizing agent followed by a polymer treatment resulted in good amplification. However, amplification yields were inconsistent and were not always comparable with PCR in a conventional tube. An oxidized silicon (SiO(2) surface gave consistent amplifications comparable with reactions performed in a conventional PCR tube. PMID:8628665

Deposition of functionalized polymer layers in surface plasmon resonance immunosensors by in-situ polymerization in the evanescent wave field.

PubMed

Chegel, Vladimir; Whitcombe, Michael J; Turner, Nicholas W; Piletsky, Sergey A

2009-01-01

Traditionally, the integration of sensing gel layers in surface plasmon resonance (SPR) is achieved via "bulk" methods, such as precipitation, spin-coating or in-situ polymerization onto the total surface of the sensor chip, combined with covalent attachment of the antibody or receptor to the gel surface. This is wasteful in terms of materials as the sensing only occurs at the point of resonance interrogated by the laser. By isolating the sensing materials (antibodies, enzymes, aptamers, polymers, MIPs, etc.) to this exact spot a more efficient use of these recognition elements will be achieved. Here we present a method for the in-situ formation of polymers, using the energy of the evanescent wave field on the surface of an SPR device, specifically localized at the point of interrogation. Using the photo-initiator couple of methylene blue (sensitizing dye) and sodium p-toluenesulfinate (reducing agent) we polymerized a mixture of N,N-methylene-bis-acrylamide and methacrylic acid in water at the focal point of SPR. No polymerization was seen in solution or at any other sites on the sensor surface. Varying parameters such as monomer concentration and exposure time allowed precise control over the polymer thickness (from 20-200 nm). Standard coupling with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide was used for the immobilization of protein G which was used to bind IgG in a typical biosensor format. This model system demonstrated the characteristic performance for this type of immunosensor, validating our deposition method.

An acetylcholinesterase biosensor based on graphene-gold nanocomposite and calcined layered double hydroxide.

PubMed

Zhai, Chen; Guo, Yemin; Sun, Xia; Zheng, Yuhe; Wang, Xiangyou

2014-05-10

In this study, a novel acetylcholinesterase-based biosensor was fabricated. Acetylcholinesterase (AChE) was immobilized onto a glassy carbon electrode (GCE) with the aid of Cu-Mg-Al calcined layered double hydroxide (CLDH). CLDH can provide a bigger effective surface area for AChE loading, which could improve the precision and stability of AChE biosensor. However, the poor electroconductibility of CLDHs could lead to the low sensitivity of AChE biosensor. In order to effectively compensate the disadvantages of CLDHs, graphene-gold nanocomposites were used for improving the electron transfer rate. Thus, the graphene-gold nanocomposite (GN-AuNPs) was firstly modified onto the GCE, and then the prepared CLDH-AChE composite was immobilized onto the modified GCE to construct a sensitive AChE biosensor for pesticides detection. Relevant parameters were studied in detail and optimized, including the pH of the acetylthiocholine chloride (ATCl) solution, the amount of AChE immobilized on the biosensor and the inhibition time governing the analytical performance of the biosensor. The biosensor detected chlorpyrifos at concentrations ranging from 0.05 to 150μg/L. The detection limit for chlorpyrifos was 0.05μg/L. Copyright © 2014 Elsevier Inc. All rights reserved.

Recent advances in transition-metal dichalcogenides based electrochemical biosensors: A review.

PubMed

Wang, Yi-Han; Huang, Ke-Jing; Wu, Xu

2017-11-15

Layered transition metal dichalcogenides (TMDCs) comprise a category of two-dimensional (2D) materials that offer exciting properties, including large surface area, metallic and semi-conducting electrical capabilities, and intercalatable morphologies. Biosensors employ biological molecules to recognize the target and utilize output elements which can translate the biorecognition event into electrical, optical or mass-sensitive signals to determine the quantities of the target. TMDCs nanomaterials have been widely applied in various electrochemical biosensors with high sensitivity and selectivity. The marriage of TMDCs and electrochemical biosensors has created many productive sensing strategies for applications in the areas of clinical diagnosis, environmental monitoring and food safety. In recent years, an increasing number of TMDCs-based electrochemical biosensors are reported, suggesting TMDCs offers new possibilities of improving the performance of electrochemical biosensors. This review summarizes recent advances in electrochemical biosensors based on TMDCs for detection of various inorganic and organic analytes in the last five years, including glucose, proteins, DNA, heavy metal, etc. In addition, we also point out the challenges and future perspectives related to the material design and development of TMDCs-based electrochemical biosensors. Copyright © 2017 Elsevier B.V. All rights reserved.

High-performance glucose biosensor based on chitosan-glucose oxidase immobilized polypyrrole/Nafion/functionalized multi-walled carbon nanotubes bio-nanohybrid film.

PubMed

Shrestha, Bishnu Kumar; Ahmad, Rafiq; Mousa, Hamouda M; Kim, In-Gi; Kim, Jeong In; Neupane, Madhav Prasad; Park, Chan Hee; Kim, Cheol Sang

2016-11-15

A highly electroactive bio-nanohybrid film of polypyrrole (PPy)-Nafion (Nf)-functionalized multi-walled carbon nanotubes (fMWCNTs) nanocomposite was prepared on the glassy carbon electrode (GCE) by a facile one-step electrochemical polymerization technique followed by chitosan-glucose oxidase (CH-GOx) immobilization on its surface to achieve a high-performance glucose biosensor. The as-fabricated nanohybrid composite provides high surface area for GOx immobilization and thus enhances the enzyme-loading efficiency. The structural characterization revealed that the PPy-Nf-fMWCNTs nanocomposite films were uniformly formed on GCE and after GOx immobilization, the surface porosities of the film were decreased due to enzyme encapsulation inside the bio-nanohybrid composite materials. The electrochemical behavior of the fabricated biosensor was investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and amperometry measurements. The results indicated an excellent catalytic property of bio-nanohybrid film for glucose detection with improved sensitivity of 2860.3μAmM(-1)cm(-2), the linear range up to 4.7mM (R(2)=0.9992), and a low detection limit of 5μM under a signal/noise (S/N) ratio of 3. Furthermore, the resulting biosensor presented reliable selectivity, better long-term stability, good repeatability, reproducibility, and acceptable measurement of glucose concentration in real serum samples. Thus, this fabricated biosensor provides an efficient and highly sensitive platform for glucose sensing and can open up new avenues for clinical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparative study of in-flow and micro-patterning biofunctionalization protocols for nanophotonic silicon-based biosensors.

PubMed

González-Guerrero, Ana Belén; Alvarez, Mar; García Castaño, Andrés; Domínguez, Carlos; Lechuga, Laura M

2013-03-01

Reliable immobilization of bioreceptors over any sensor surface is the most crucial step for achieving high performance, selective and sensitive biosensor devices able to analyze human samples without the need of previous processing. With this aim, we have implemented an optimized scheme to covalently biofunctionalize the sensor area of a novel nanophotonic interferometric biosensor. The proposed method is based on the ex-situ silanization of the silicon nitride transducer surface by the use of a carboxyl water soluble silane, the carboxyethylsilanetriol sodium salt (CTES). The use of an organosilane stable in water entails advantages in comparison with usual trialkoxysilanes such as avoiding the generation of organic waste and leading to the assembly of compact monolayers due to the high dielectric constant of water. Additionally, cross-linking is prevented when the conditions (e.g. immersion time, concentration of silane) are optimized. This covalent strategy is followed by the bioreceptor linkage on the sensor area surface using two different approaches: an in-flow patterning and a microcontact printing using a biodeposition system. The performance of the different bioreceptor layers assembled is compared by the real-time and label-free immunosensing of the proteins BSA/mAb BSA, employed as a model molecular pair. Although the results demonstrated that both strategies provide the biosensor with a stable biological interface, the performance of the bioreceptor layer assembled by microcontact printing slightly improves the biosensing capabilities of the photonic biosensor. Copyright © 2012 Elsevier Inc. All rights reserved.

An ultrasensitive hollow-silica-based biosensor for pathogenic Escherichia coli DNA detection.

PubMed

Ariffin, Eda Yuhana; Lee, Yook Heng; Futra, Dedi; Tan, Ling Ling; Karim, Nurul Huda Abd; Ibrahim, Nik Nuraznida Nik; Ahmad, Asmat

2018-03-01

A novel electrochemical DNA biosensor for ultrasensitive and selective quantitation of Escherichia coli DNA based on aminated hollow silica spheres (HSiSs) has been successfully developed. The HSiSs were synthesized with facile sonication and heating techniques. The HSiSs have an inner and an outer surface for DNA immobilization sites after they have been functionalized with 3-aminopropyltriethoxysilane. From field emission scanning electron microscopy images, the presence of pores was confirmed in the functionalized HSiSs. Furthermore, Brunauer-Emmett-Teller (BET) analysis indicated that the HSiSs have four times more surface area than silica spheres that have no pores. These aminated HSiSs were deposited onto a screen-printed carbon paste electrode containing a layer of gold nanoparticles (AuNPs) to form a AuNP/HSiS hybrid sensor membrane matrix. Aminated DNA probes were grafted onto the AuNP/HSiS-modified screen-printed electrode via imine covalent bonds with use of glutaraldehyde cross-linker. The DNA hybridization reaction was studied by differential pulse voltammetry using an anthraquinone redox intercalator as the electroactive DNA hybridization label. The DNA biosensor demonstrated a linear response over a wide target sequence concentration range of 1.0×10 -12 -1.0×10 -2 μM, with a low detection limit of 8.17×10 -14 μM (R 2 = 0.99). The improved performance of the DNA biosensor appeared to be due to the hollow structure and rough surface morphology of the hollow silica particles, which greatly increased the total binding surface area for high DNA loading capacity. The HSiSs also facilitated molecule diffusion through the silica hollow structure, and substantially improved the overall DNA hybridization assay. Graphical abstract Step-by-step DNA biosensor fabrication based on aminated hollow silica spheres.

Food pathogen detection using Ag nanorod-based surface plasmon resonance sensor

USDA-ARS?s Scientific Manuscript database

Food safety is world-wide issue for protecting public health. Many researchers have been working on development of biosensors for pathogenic bacteria detection. However, current biosensing methods and techniques do not meet the requirement of demanding as a biosensor in terms of sensitivity, speci...

Development of L-lactate dehydrogenase biosensor based on porous silicon resonant microcavities as fluorescence enhancers.

PubMed

Jenie, S N Aisyiyah; Prieto-Simon, Beatriz; Voelcker, Nicolas H

2015-12-15

The up-regulation of L-lactate dehydrogenase (LDH), an intracellular enzyme present in most of all body tissues, is indicative of several pathological conditions and cellular death. Herein, we demonstrate LDH detection using porous silicon (pSi) microcavities as a luminescence-enhancing optical biosensing platform. Non-fluorescent resazurin was covalently attached onto the pSi surface via thermal hydrocarbonisation, thermal hydrosylilation and acylation. Each surface modification step was confirmed by means of FTIR and the optical shifts of the resonance wavelength of the microcavity. Thermal hydrocarbonisation also afforded excellent surface stability, ensuring that the resazurin was not reduced on the pSi surface. Using a pSi microcavity biosensor, the fluorescence signal upon detection of LDH was amplified by 10 and 5-fold compared to that of a single layer and a detuned microcavity, respectively, giving a limit of detection of 0.08 U/ml. The biosensor showed a linear response between 0.16 and 6.5 U/ml, covering the concentration range of LDH in normal as well as damaged tissues. The biosensor was selective for LDH and did not produce a signal upon incubation with another NAD-dependant enzyme L-glutamic dehydrogenase. The use of the pSi microcavity as a sensing platform reduced reagent usage by 30% and analysis time threefold compared to the standard LDH assay in solution. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel interdigitated capacitor based biosensor for detection of cardiovascular risk marker.

PubMed

Quershi, Anjum; Gurbuz, Yasar; Kang, Weng P; Davidson, Jimmy L

2009-12-15

C-reactive protein (CRP) is a potential biomarker whose elevated levels in humans determine cardiovascular disease risk and inflammation. In this study, we have developed a novel capacitive biosensor for detection of CRP-antigen using capacitor with interdigitated gold (GID) electrodes on nanocrystalline diamond (NCD) surface. The NCD surface served as a dielectric layer between the gold electrodes. GID-surface was functionalized by antibodies and the immobilization was confirmed by Fourier transform spectroscopy (FT-IR) and contact angle measurements. The CRP-antigen detection was performed by capacitive/dielectric-constant measurements. The relaxation time and polarizability constants were estimated using Cole-Cole model. Our results showed that the relaxation time constant (tau) of only CRP-antibody was within 10(-16)-10(-13)s, which was increased to 10(-11)s after the incubation with CRP-antigen, suggesting that the CRP-antigen was captured by the antibodies on GID-surface. In addition, polarizability constant (m) of CRP was also increased upon incubation with increasing concentration of CRP-antigen. Our results showed that the response of GID-NCD-based capacitive biosensor for CRP-antigen was dependent on both concentration (25-800ng/ml) as well as frequency (50-350MHz). Furthermore, using optimized conditions, the GID-NCD based capacitive biosensor developed in this study can potentially be used for detection of elevated levels of protein risk markers in suspected subjects for early diagnosis of disease.

Amperometric L-glutamate biosensor based on bacterial cell-surface displayed glutamate dehydrogenase.

PubMed

Liang, Bo; Zhang, Shu; Lang, Qiaolin; Song, Jianxia; Han, Lihui; Liu, Aihua

2015-07-16

A novel L-glutamate biosensor was fabricated using bacteria surface-displayed glutamate dehydrogenase (Gldh-bacteria). Here the cofactor NADP(+)-specific dependent Gldh was expressed on the surface of Escherichia coli using N-terminal region of ice nucleation protein (INP) as the anchoring motif. The cell fractionation assay and SDS-PAGE analysis indicated that the majority of INP-Gldh fusion proteins were located on the surface of cells. The biosensor was fabricated by successively casting polyethyleneimine (PEI)-dispersed multi-walled carbon nanotubes (MWNTs), Gldh-bacteria and Nafion onto the glassy carbon electrode (Nafion/Gldh-bacteria/PEI-MWNTs/GCE). The MWNTs could not only significantly lower the oxidation overpotential towards NAPDH, which was the product of NADP(+) involving in the oxidation of glutamate by Gldh, but also enhanced the current response. Under the optimized experimental conditions, the current-time curve of the Nafion/Gldh-bacteria/PEI-MWNTs/GCE was performed at +0.52 V (vs. SCE) by amperometry varying glutamate concentration. The current response was linear with glutamate concentration in two ranges (10 μM-1 mM and 2-10 mM). The low limit of detection was estimated to be 2 μM glutamate (S/N=3). Moreover, the proposed biosensor is stable, specific, reproducible and simple, which can be applied to real samples detection. Copyright © 2015 Elsevier B.V. All rights reserved.

A smartphone controlled handheld microfluidic liquid handling system.

PubMed

Li, Baichen; Li, Lin; Guan, Allan; Dong, Quan; Ruan, Kangcheng; Hu, Ronggui; Li, Zhenyu

2014-10-21

Microfluidics and lab-on-a-chip technologies have made it possible to manipulate small volume liquids with unprecedented resolution, automation and integration. However, most current microfluidic systems still rely on bulky off-chip infrastructures such as compressed pressure sources, syringe pumps and computers to achieve complex liquid manipulation functions. Here, we present a handheld automated microfluidic liquid handling system controlled by a smartphone, which is enabled by combining elastomeric on-chip valves and a compact pneumatic system. As a demonstration, we show that the system can automatically perform all the liquid handling steps of a bead-based HIV1 p24 sandwich immunoassay on a multi-layer PDMS chip without any human intervention. The footprint of the system is 6 × 10.5 × 16.5 cm, and the total weight is 829 g including battery. Powered by a 12.8 V 1500 mAh Li battery, the system consumed 2.2 W on average during the immunoassay and lasted for 8.7 h. This handheld microfluidic liquid handling platform is generally applicable to many biochemical and cell-based assays requiring complex liquid manipulation and sample preparation steps such as FISH, PCR, flow cytometry and nucleic acid sequencing. In particular, the integration of this technology with read-out biosensors may help enable the realization of the long-sought Tricorder-like handheld in vitro diagnostic (IVD) systems.

Nanophotonic lab-on-a-chip platforms including novel bimodal interferometers, microfluidics and grating couplers.

PubMed

Duval, Daphné; González-Guerrero, Ana Belén; Dante, Stefania; Osmond, Johann; Monge, Rosa; Fernández, Luis J; Zinoviev, Kirill E; Domínguez, Carlos; Lechuga, Laura M

2012-05-08

One of the main limitations for achieving truly lab-on-a-chip (LOC) devices for point-of-care diagnosis is the incorporation of the "on-chip" detection. Indeed, most of the state-of-the-art LOC devices usually require complex read-out instrumentation, losing the main advantages of portability and simplicity. In this context, we present our last advances towards the achievement of a portable and label-free LOC platform with highly sensitive "on-chip" detection by using nanophotonic biosensors. Bimodal waveguide interferometers fabricated by standard silicon processes have been integrated with sub-micronic grating couplers for efficient light in-coupling, showing a phase resolution of 6.6 × 10(-4)× 2π rad and a limit of detection of 3.3 × 10(-7) refractive index unit (RIU) in bulk. A 3D network of SU-8 polymer microfluidics monolithically assembled at the wafer-level was included, ensuring perfect sealing and compact packaging. To overcome some of the drawbacks inherent to interferometric read-outs, a novel all-optical wavelength modulation system has been implemented, providing a linear response and a direct read-out of the phase variation. Sensitivity, specificity and reproducibility of the wavelength modulated BiMW sensor has been demonstrated through the label-free immunodetection of the human hormone hTSH at picomolar level using a reliable biofunctionalization process.

Construction of uric acid biosensor based on biomimetic titanate nanotubes.

PubMed

Tao, Haisheng; Wang, Xuebin; Wang, Xizhang; Hu, Yemin; Ma, Yanwen; Lu, Yinong; Hu, Zheng

2010-02-01

A uric acid biosensor has been fabricated through the immobilization of uricase on glassy carbon electrode modified by biomimetic titanate nanotubes of high specific surface area synthesized by hydrothermal decomposition. The so-constructed biosensor presents a high affinity to uric acid with a small apparent Michaelis-Menten constant of only 0.66 mM. The biosensor exhibits fairly good electrochemical properties such as the high sensitivity of 184.3 microAcm(-2)mM(-1), the fast response of less than 2 s, as well as the wide linear range from 1 microM to 5 mM. These performances indicate that titanate nanotubes could provide a favorable microenvironment for uricase immobilization, stabilize its biological activity, and function as an efficient electron conducting tunnel to facilitate the electron transfer. This suggests an important potential of titanate nanotubes in uric acid biosensors.

Smartphone-based point-of-care testing of salivary α-amylase for personal psychological measurement.

PubMed

Zhang, Lin; Yang, Wentao; Yang, Yuankui; Liu, Hong; Gu, Zhongze

2015-11-07

Here we report a smartphone-based potentiometric biosensor for point-of-care testing of salivary α-amylase (sAA), which is one of the most sensitive indices of autonomic nervous system activity, and therefore a promising non-invasive biomarker for mental health. The biosensing system includes a smartphone having a sAA-detection App, a potentiometric reader and a sensing chip with preloaded reagents. The saliva sample wicks into the reaction zone on the sensing chip so that the sAA reacts with the preloaded reagents, resulting in conversion of an electron mediator Fe(CN)6(3-) to Fe(CN)6(4-). The sensing chip is then pressed by fingers to push the reaction mixture into the detection zone for the potentiometric measurement. The potential measured by the smartphone-powered potentiometric reader is sent to the smartphone App via the USB port, and converted into sAA concentration based on a calibration curve. Using our method, sAA in real human sample is quantitatively analyzed within 5 min. The results are in good agreement with that obtained using a reference method, and correlated to psychological states of the subjects.

Chemistry integrated circuit: chemical system on a complementary metal oxide semiconductor integrated circuit.

PubMed

Nakazato, Kazuo

2014-03-28

By integrating chemical reactions on a large-scale integration (LSI) chip, new types of device can be created. For biomedical applications, monolithically integrated sensor arrays for potentiometric, amperometric and impedimetric sensing of biomolecules have been developed. The potentiometric sensor array detects pH and redox reaction as a statistical distribution of fluctuations in time and space. For the amperometric sensor array, a microelectrode structure for measuring multiple currents at high speed has been proposed. The impedimetric sensor array is designed to measure impedance up to 10 MHz. The multimodal sensor array will enable synthetic analysis and make it possible to standardize biosensor chips. Another approach is to create new functional devices by integrating molecular systems with LSI chips, for example image sensors that incorporate biological materials with a sensor array. The quantum yield of the photoelectric conversion of photosynthesis is 100%, which is extremely difficult to achieve by artificial means. In a recently developed process, a molecular wire is plugged directly into a biological photosynthetic system to efficiently conduct electrons to a gold electrode. A single photon can be detected at room temperature using such a system combined with a molecular single-electron transistor.

Flexible Molybdenum Electrodes towards Designing Affinity Based Protein Biosensors.

PubMed

Kamakoti, Vikramshankar; Panneer Selvam, Anjan; Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Prasad, Shalini

2016-07-18

Molybdenum electrode based flexible biosensor on porous polyamide substrates has been fabricated and tested for its functionality as a protein affinity based biosensor. The biosensor performance was evaluated using a key cardiac biomarker; cardiac Troponin-I (cTnI). Molybdenum is a transition metal and demonstrates electrochemical behavior upon interaction with an electrolyte. We have leveraged this property of molybdenum for designing an affinity based biosensor using electrochemical impedance spectroscopy. We have evaluated the feasibility of detection of cTnI in phosphate-buffered saline (PBS) and human serum (HS) by measuring impedance changes over a frequency window from 100 mHz to 1 MHz. Increasing changes to the measured impedance was correlated to the increased dose of cTnI molecules binding to the cTnI antibody functionalized molybdenum surface. We achieved cTnI detection limit of 10 pg/mL in PBS and 1 ng/mL in HS medium. The use of flexible substrates for designing the biosensor demonstrates promise for integration with a large-scale batch manufacturing process.

[Amperometric biosensor for lactate analysis in wines and grape must during fermentation].

PubMed

Shkotova, L V; Horiushkina, T B; Slast'ia, E A; Soldatkin, O P; Tranh-Minh, S; Chovelon, J M; Dziadevych, S V

2005-01-01

The amperometric biosensor based on lactate oxidase for determination of lactate has been developed, and two methods of immobilization of lactate oxidase on the surface of industrial screen-printed platinum electrodes SensLab were compared. A sensor with immobilized in the Resydrol polymer lactate oxidase by the method of physical adsorption is characterized of narrow dynamic range and greater response value in comparison with a biosensor based on immobilised in poly(3,4-ethylenedioxythiophene) lactate oxidase by the method of electrochemical polymerization. Operational stability of the biosensor developed was studied and it was shown, that the immobilization method does not influence their stability. The analysis of the lactate in wine and during wine fermentation has been conducted. High correlation of the data obtained by means of amperometric lactate biosensor and a standard method of an ionic chromatography has been shown. The developed biosensor could be applied in the food industry for the control and optimization of the wine fermentation process, and quality control of wine.

Quality assessment of SPR sensor chips; case study on L1 chips.

PubMed

Olaru, Andreea; Gheorghiu, Mihaela; David, Sorin; Polonschii, Cristina; Gheorghiu, Eugen

2013-07-15

Surface quality of the Surface Plasmon Resonance (SPR) chips is a major limiting issue in most SPR analyses, even more for supported lipid membranes experiments, where both the organization of the lipid matrix and the subsequent incorporation of the target molecule depend on the surface quality. A novel quantitative method to characterize the quality of SPR sensors chips is described for L1 chips subject to formation of lipid films, injection of membrane disrupting compounds, followed by appropriate regeneration procedures. The method consists in analysis of the SPR reflectivity curves for several standard solutions (e.g. PBS, HEPES or deionized water). This analysis reveals the decline of sensor surface as a function of the number of experimental cycles (consisting in biosensing assay and regeneration step) and enables active control of surface regeneration for enhanced reproducibility. We demonstrate that quantitative evaluation of the changes in reflectivity curves (shape of the SPR dip) and of the slope of the calibration curve provides a rapid and effective procedure for surface quality assessment. Whereas the method was tested on L1 SPR sensors chips, we stress on its amenability to assess the quality of other types of SPR chips, as well. Copyright © 2013 Elsevier B.V. All rights reserved.

A low-cost photonic biosensor built on a polymer platform

NASA Astrophysics Data System (ADS)

Wang, Linghua; Kodeck, Valérie; Van Vlierberghe, Sandra; Ren, Jun; Teng, Jie; Han, Xiuyou; Jian, Xigao; Baets, Roel; Morthier, Geert; Zhao, Mingshan

2011-12-01

Planar integrated optical biosensors are becoming more and more important as they facilitate label-free and real time monitoring biosensing with high sensitivity. In this paper, the systematic research on one kind of optical biosensor, based on a resonant principle in a polymer ring resonator, will be presented. Reduced footprint and high sensitivity are advantages of this kind of biosensor. Rather than expensive CMOS fabrication, the device with high performance is fabricated through a simple UV based soft imprint technique utilizing self-developed low loss polymer material. The measurement results for the bulk sensing of a NaCl solution and the surface sensing of a minimal amount of avidin molecules in a buffered solution will be presented.

Molecularly imprinted hydroxyapatite thin film for bilirubin recognition.

PubMed

Yang, Zhengpeng; Zhang, Chunjing

2011-11-15

A novel piezoelectric sensor has been developed for bilirubin (BR) detection, based on the modification of molecularly imprinted hydroxyapatite (HAP) film onto a quartz crystal by molecular imprinting and surface sol-gel technique. The performance of the developed BR biosensor was evaluated and the results indicated that a sensitive BR biosensor could be fabricated. The obtained BR biosensor presents high-selectivity monitoring of BR, better reproducibility, shorter response time (37 min), wider linear range (0.05-80μM) and lower detection limit (0.01μM). The analytical application of the BR biosensor confirms the feasibility of BR detection in serum sample. Copyright © 2011 Elsevier B.V. All rights reserved.

A novel amperometric biosensor based on banana peel (Musa cavendish) tissue homogenate for determination of phenolic compounds.

PubMed

Ozcan, Hakki Mevlut; Sagiroglu, Ayten

2010-08-01

In this study the biosensor was constructed by immobilizing tissue homogenate of banana peel onto a glassy carbon electrode surface. Effects of immobilization materials amounts, effects of pH, buffer concentration and temperature on biosensor response were studied. In addition, the detection ranges of 13 phenolic compounds were obtained with the help of the calibration graphs. Storage stability, repeatability of the biosensor, inhibitory effect and sample applications were also investigated. A typical calibration curve for the sensor revealed a linear range of 10-80 microM catechol. In reproducibility studies, variation coefficient and standard deviation were calculated as 2.69%, 1.44 x 10(-3) microM, respectively.

Bi nanowire-based thermal biosensor for the detection of salivary cortisol using the Thomson effect

NASA Astrophysics Data System (ADS)

Lee, Seunghyun; Hyun Lee, Jung; Kim, MinGin; Kim, Jeongmin; Song, Min-Jung; Jung, Hyo-Il; Lee, Wooyoung

2013-09-01

We present a study of a thermal biosensor based on bismuth nanowire that is fabricated for the detection of the human stress hormone cortisol using the Thomson effect. The Bi nanowire was grown using the On-Film Formation of Nanowires (OFF-ON) method. The thermal device was fabricated using photolithography, and the sensing area was modified with immobilized anti-cortisol antibodies conjugated with protein G for the detection of cortisol. The voltages were measured with two probe tips during surface modification to investigate the biochemical reactions in the fabricated thermal biosensor. The Bi nanowire-based thermal biosensor exhibited low detection limit and good selectivity for the detection of cortisol.

Carbon Nanofiber Nanoelectrodes for Biosensing Applications

NASA Technical Reports Server (NTRS)

Koehne, Jessica Erin

2014-01-01

A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. Here, we report two studies using vertically aligned CNF nanoelectrodes for biomedical applications. CNF arrays are investigated as neural stimulation and neurotransmitter recording electrodes for application in deep brain stimulation (DBS). Polypyrrole coated CNF nanoelectrodes have shown great promise as stimulating electrodes due to their large surface area, low impedance, biocompatibility and capacity for highly localized stimulation. CNFs embedded in SiO2 have been used as sensing electrodes for neurotransmitter detection. Our approach combines a multiplexed CNF electrode chip, developed at NASA Ames Research Center, with the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS) system, developed at the Mayo Clinic. Preliminary results indicate that the CNF nanoelectrode arrays are easily integrated with WINCS for neurotransmitter detection in a multiplexed array format. In the future, combining CNF based stimulating and recording electrodes with WINCS may lay the foundation for an implantable smart therapeutic system that utilizes neurochemical feedback control while likely resulting in increased DBS application in various neuropsychiatric disorders. In total, our goal is to take advantage of the nanostructure of CNF arrays for biosensing studies requiring ultrahigh sensitivity, high-degree of miniaturization, and selective biofunctionalization.

Resonant nanopillars as label-free optical biosensors

NASA Astrophysics Data System (ADS)

López-Hernandez, Ana; Casquel, Rafael; Holgado, Miguel; Cornago, Iñaki; Fernández, Fátima; Ciaurriz, Paula; Sanza, Francisco J.; Santamaría, Beatriz; Maigler, Maria V.; Laguna, María. Fe

2018-02-01

In recent works it has been demonstrated the suitability of using resonant nanopillars (R-NPs) as biochemical. In this work it has been shown the capability of the R-NPs to behave as label-free multiplexed biological sensors. Each R-NP is formed by silicon oxide (SiO2) and silicon nitride (Si3N4) Bragg reflectors and a central cavity of SiO2, and they are grouped into eight arrays called BICELLs, which are distributed on a single chip of quartz substrate for multiplexing measurements. For the biological sensing assessment it was developed an immunoassay on the eight single BICELLs. The biofunctionalization process was performed by a silanization protocol based on 3-aminopropyltrymethoxysilane (APTMS) and glutaradheyde (GA) as a linker between APTMS and the IgG which acted as biorreceptor for the anti-IgG recognition. In this work, there were compared two forms of immobilization: on one hand by incubating the R-NPs under static drop of 50 μg/mL and on the second hand by introducing the sensing chip in a flow cell with a continuous flow of the same concentration of IgG. The eight arrays of R-NPs or BICELLs were independently optically interrogated by a bundle of fiber connected to a spectrometer. The multiplexing analysis showed reproducibility among the BICELLs, suggesting the potentially of using R-NPs for multiplexed biosensors. Performance in the immobilization process apparently does not have a signification effect. However the election of one method or another should be a commitment between time and resources.

All-carbon suspended nanowire sensors as a rapid highly-sensitive label-free chemiresistive biosensing platform.

PubMed

Thiha, Aung; Ibrahim, Fatimah; Muniandy, Shalini; Dinshaw, Ignatius Julian; Teh, Swe Jyan; Thong, Kwai Lin; Leo, Bey Fen; Madou, Marc

2018-06-01

Nanowire sensors offer great potential as highly sensitive electrochemical and electronic biosensors because of their small size, high aspect ratios, and electronic properties. Nevertheless, the available methods to fabricate carbon nanowires in a controlled manner remain limited to expensive techniques. This paper presents a simple fabrication technique for sub-100 nm suspended carbon nanowire sensors by integrating electrospinning and photolithography techniques. Carbon Microelectromechanical Systems (C-MEMS) fabrication techniques allow fabrication of high aspect ratio carbon structures by patterning photoresist polymers into desired shapes and subsequent carbonization of resultant structures by pyrolysis. In our sensor platform, suspended nanowires were deposited by electrospinning while photolithography was used to fabricate support structures. We have achieved suspended carbon nanowires with sub-100 nm diameters in this study. The sensor platform was then integrated with a microfluidic chip to form a lab-on-chip device for label-free chemiresistive biosensing. We have investigated this nanoelectronics label-free biosensor's performance towards bacterial sensing by functionalization with Salmonella-specific aptamer probes. The device was tested with varying concentrations of Salmonella Typhimurium to evaluate sensitivity and various other bacteria to investigate specificity. The results showed that the sensor is highly specific and sensitive in detection of Salmonella with a detection limit of 10 CFU mL -1 . Moreover, this proposed chemiresistive assay has a reduced turnaround time of 5 min and sample volume requirement of 5 µL which are much less than reported in the literature. Copyright © 2018 Elsevier B.V. All rights reserved.

Label-free capacitive biosensor for sensitive detection of multiple biomarkers using gold interdigitated capacitor arrays.

PubMed

Qureshi, Anjum; Niazi, Javed H; Kallempudi, Saravan; Gurbuz, Yasar

2010-06-15

In this study, a highly sensitive and label-free multianalyte capacitive immunosensor was developed based on gold interdigitated electrodes (GID) capacitor arrays to detect a panel of disease biomarkers. C-reactive protein (CRP), TNFalpha, and IL6 have strong and consistent relationships between markers of inflammation and future cardiovascular risk (CVR) events. Early detection of a panel of biomarkers for a disease could enable accurate prediction of a disease risk. The detection of protein biomarkers was based on relative change in capacitive/dielectric properties. Two different lab-on-a-chip formats were employed for multiple biomarker detection on GID-capacitors. In format I, capacitor arrays were immobilized with pure forms of anti-CRP, -TNFalpha, and -IL6 antibodies in which each capacitor array contained a different immobilized antibody. Here, the CRP and IL6 were detected in the range 25 pg/ml to 25 ng/ml and 25 pg/ml to 1 ng/ml for TNFalpha in format I. Sensitive detection was achieved with chips co-immobilized (diluted) with equimolar mixtures of anti-CRP, -IL6, and -TNFalpha antibodies (format II) in which all capacitors in an array were identical and tested for biomarkers with sequential incubation. The resulting response to CRP, IL6, and TNFalpha in format II for all biomarkers was found to be within 25 pg/ml to 25 ng/ml range. The capacitive biosensor for panels of inflammation and CVR markers show significant clinical value and provide great potential for detection of biomarker panel in suspected subjects for early diagnosis. Copyright 2010 Elsevier B.V. All rights reserved.

Laser-assisted patterning of double-sided adhesive tapes for optofluidic chip integration

NASA Astrophysics Data System (ADS)

Zamora, Vanessa; Janeczka, Christian; Arndt-Staufenbiel, Norbert; Havlik, George; Queisser, Marco; Schröder, Henning

2018-02-01

Portable high-sensitivity biosensors exhibit a growing demand in healthcare, food industry and environmental monitoring sectors. Optical biosensors based on photonic integration platforms are attractive candidates due to their high sensitivity, compactness and multiplexing capabilities. However, they need a low-cost and reliable integration with the microfluidic system. Laser-micropatterned double-sided biocompatible adhesive tapes are promising bonding layers for hybrid integration of an optofluidic biochip. As a part of the EU-PHOCNOSIS project, double-sided adhesive tapes have been proposed to integrate the polymer microfluidic system with the optical integrated waveguide sensor chip. Here the adhesive tape should be patterned in a micrometer scale in order to create an interaction between the sample that flows through the polymer microchannel and the photonic sensing microstructure. Three laser-assisted structuring methods are investigated to transfer microchannel patterns to the adhesive tape. The test structure design consists of a single channel with 400 μm wide, 30 mm length and two circular receivers with 3 mm radius. The best structuring results are found by using the picosecond UV laser where smooth and straight channel cross-sections are obtained. Such patterned tapes are used to bond blank polymer substrates to blank silicon substrates. As a proof of concept, the hybrid integration is tested using colored DI-water. Structuring tests related to the reduction of channel widths are also considered in this work. The use of this technique enables a simple and rapid manufacturing of narrow channels (50-60 μm in width) in adhesive tapes, achieving a cheap and stable integration of the optofluidic biochip.

H2O2 sensing using HRP modified catalyst-free ZnO nanorods synthesized by RF sputtering

NASA Astrophysics Data System (ADS)

Srivastava, Amit; Kumar, Naresh; Singh, Priti; Singh, Sunil Kumar

2017-06-01

Catalyst-free ( 00 l) oriented ZnO nanorods (NRs) -based biosensor for the H2O2 sensing has been reported. The (002) oriented ZnO NRs as confirmed by X-ray diffraction were successfully grown on indium tin oxide (ITO) coated glass substrate by radio frequency (RF) sputtering technique without using any catalyst. Horseradish peroxidase (HRP) enzyme was immobilized on ZnO NRs by physical adsorption technique to prepare the biosensor. In this HRP/ZnO NR/ITO bioelectrode, nafion solution was added to form a tight membrane on surface. The prepared bioelectrode has been used for biosensing measurements by electrochemical analyzer. The electrochemical studies reveal that the prepared HRP/ZnO NR/ITO biosensor is highly sensitive to the detection of H2O2 over a linear range of 0.250-10 μM. The ZnO NR-based biosensor showed lower value of detection limit (0.125 μM) and higher sensitivity (13.40 µA/µM cm2) towards H2O2. The observed value of higher sensitivity attributed to larger surface area of ZnO nanostructure for effective loading of HRP besides its high electron communication capability. In addition, the biosensor also shows lower value of enzyme's kinetic parameter (Michaelis-Menten constant, K m) of 0.262 μM which indicates enhanced enzyme affinity of HRP to H2O2. The reported biosensor may be useful for various applications in biosensing, clinical, food, and beverage industry.

Current trends in nanobiosensor technology

PubMed Central

Wu, Diana; Langer, Robert S

2014-01-01

The development of tools and processes used to fabricate, measure, and image nanoscale objects has lead to a wide range of work devoted to producing sensors that interact with extremely small numbers (or an extremely small concentration) of analyte molecules. These advances are particularly exciting in the context of biosensing, where the demands for low concentration detection and high specificity are great. Nanoscale biosensors, or nanobiosensors, provide researchers with an unprecedented level of sensitivity, often to the single molecule level. The use of biomolecule-functionalized surfaces can dramatically boost the specificity of the detection system, but can also yield reproducibility problems and increased complexity. Several nanobiosensor architectures based on mechanical devices, optical resonators, functionalized nanoparticles, nanowires, nanotubes, and nanofibers have been demonstrated in the lab. As nanobiosensor technology becomes more refined and reliable, it is likely it will eventually make its way from the lab to the clinic, where future lab-on-a-chip devices incorporating an array of nanobiosensors could be used for rapid screening of a wide variety of analytes at low cost using small samples of patient material. PMID:21391305

Graphene-Based Materials for Biosensors: A Review

PubMed Central

Suvarnaphaet, Phitsini; Pechprasarn, Suejit

2017-01-01

The advantages conferred by the physical, optical and electrochemical properties of graphene-based nanomaterials have contributed to the current variety of ultrasensitive and selective biosensor devices. In this review, we present the points of view on the intrinsic properties of graphene and its surface engineering concerned with the transduction mechanisms in biosensing applications. We explain practical synthesis techniques along with prospective properties of the graphene-based materials, which include the pristine graphene and functionalized graphene (i.e., graphene oxide (GO), reduced graphene oxide (RGO) and graphene quantum dot (GQD). The biosensing mechanisms based on the utilization of the charge interactions with biomolecules and/or nanoparticle interactions and sensing platforms are also discussed, and the importance of surface functionalization in recent up-to-date biosensors for biological and medical applications. PMID:28934118

Directed assembly of carbon nanotubes on soft substrates for use as a flexible biosensor array.

PubMed

Koh, Juntae; Yi, Mihye; Yang Lee, Byung; Kim, Tae Hyun; Lee, Joohyung; Jhon, Young Min; Hong, Seunghun

2008-12-17

We have developed a method to selectively assemble and align carbon nanotubes (CNTs) on soft substrates for use as flexible biosensors. In this strategy, a thin oxide layer was deposited on soft substrates via low temperature plasma enhanced chemical vapor deposition, and a linker-free assembly process was applied on the oxide surface where the assembly of carbon nanotubes was guided by methyl-terminated molecular patterns on the oxide surface. The electrical characterization of the fabricated CNT devices exhibited a typical p-type gating effect and 1/f noise behavior. The bare oxide regions near CNTs were functionalized with glutamate oxidase to fabricate selective biosensors to detect two forms of glutamate substances existing in different situations: L-glutamic acid, a neurotransmitting material, and monosodium glutamate, a food additive.

Bio-sensing applications of cerium oxide nanoparticles: Advantages and disadvantages.

PubMed

Charbgoo, Fahimeh; Ramezani, Mohammad; Darroudi, Majid

2017-10-15

Cerium oxide nanoparticles (CNPs) contain several properties such as catalytic activity, fluorescent quencher and electrochemical, high surface area, and oxygen transfer ability, which have attracted considerable attention in developing high-sensitive biosensors. CNPs can be used as a whole sensor or a part of recognition or transducer element. However, reports have shown that applying these nanoparticles in sensor design could remarkably enhance detection sensitivity. CNP's outstanding properties in biosensors which go from high catalytic activity and surface area to oxygen transfer and fluorescent quenching capabilities are also highlighted. Herein, we discuss the advantages and disadvantages of CNPs-based biosensors that function through various detection modes including colorimetric, electrochemistry, and chemoluminescent regarding the detection of small organic chemicals, metal ions and biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Label-free detection of biomolecules with Ta2O5-based field effect devices

NASA Astrophysics Data System (ADS)

Branquinho, Rita Maria Mourao Salazar

Field-effect-based devices (FEDs) are becoming a basic structural element in a new generation of micro biosensors. Their numerous advantages such as small size, labelfree response and versatility, together with the possibility of on-chip integration of biosensor arrays with a future prospect of low-cost mass production, make their development highly desirable. The present thesis focuses on the study and optimization of tantalum pentoxide (Ta2O5) deposited by rf magnetron sputtering at room temperature, and their application as sensitive layer in biosensors based on field effect devices (BioFEDs). As such, the influence of several deposition parameters and post-processing annealing temperature and surface plasma treatment on the film¡¦s properties was investigated. Electrolyte-insulator-semiconductor (EIS) field-effect-based sensors comprising the optimized Ta2O5 sensitive layer were applied to the development of BioFEDs. Enzyme functionalized sensors (EnFEDs) were produced for penicillin detection. These sensors were also applied to the label free detection of DNA and the monitoring of its amplification via polymerase chain reaction (PCR), real time PCR (RT-PCR) and loop mediated isothermal amplification (LAMP). Ion sensitive field effect transistors (ISFETs) based on semiconductor oxides comprising the optimized Ta2O5 sensitive layer were also fabricated. EIS sensors comprising Ta2O5 films produced with optimized conditions demonstrated near Nernstian pH sensitivity, 58+/-0.3 mV/pH. These sensors were successfully applied to the label-free detection of penicillin and DNA. Penicillinase functionalized sensors showed a 29+/-7 mV/mM sensitivity towards penicillin detection up to 4 mM penicillin concentration. DNA detection was achieved with 30 mV/mugM sensitivity and DNA amplification monitoring with these sensors showed comparable results to those obtained with standard fluorescence based methods. Semiconductor oxides-based ISFETs with Ta2O5 sensitive layer were also produced. Finally, the high quality and sensitivity demonstrated by Ta2O5 thin films produced at low temperature by rf magnetron sputtering allows for their application as sensitive layer in field effect sensors.

Protein-Modified-Paramagnetic-Particles as a Tool for Detection of Silver(I) Ions

NASA Astrophysics Data System (ADS)

Kizek, R.; Krizkova, S.; Adam, V.; Huska, D.; Hubalek, J.; Trnkova, L.

2009-04-01

In a number of published articles the toxic effect of silver(I) ions on aquatic organisms is described. Silver(I) ions in aquatic environment are stable in a wide range of pH. Under alkali pH AgOH and Ag(OH)2- can be formed. However, in water environment there are many compounds to interact with silver(I) ions. The most important ones are chloride anions, which forms insoluble precipitate with silver(I) ions (AgCl). The insoluble silver containing compounds do not pose any threat to aquatic organisms. Toxicity of silver ions is probably caused by their very good affinity to nucleic acids and also proteins. The binding into active enzyme site leads to the expressive enzyme reaction inhibition. Silver(I) ions are into living environment introduced thanks to anthropogenic activities. They easily contaminate atmosphere as well as aquatic environment or soils. Several authors described using of carbon electrode as working electrode for determination of silver. Recently, we have suggested heavy metal biosensor based on interaction of metal ions with low molecular mass protein called metallothionein (MT), which was adsorbed on the surface of hanging mercury drop electrode (HMDE). The biosensor was successfully used for detection of cadmium(II) and zinc(II) ions, cisplatin, cisplatin-DNA adducts and palladium(II) ions. Due to the convincing results with MT as biological component we report on suggesting of heavy metal biosensor based on immobilization of metallothionein (MT) on the surface of carbon paste electrode (CPE) via MT-antibodies. Primarily we studied of basic electrochemical behaviour of MT at surface of carbon paste electrode by using of square wave voltammetry (SWV). Detection limit (3 S/N) for MT was evaluated as 0.1 μg/ml. After that we have evaluated the electroactivity of MT at surface of SWV, we aimed our attention on the way of capturing of MT on the surface of CPE. We choose antibody against MT obtained from chicken eggs for these purposes. Antibodies incorporated mixed with carbon paste were stable. Even after 14 days we did not determine change in the peak height higher than 5 %. Further linkage of MT with polyclonal chicken antibodies incorporated in carbon paste electrode was determined by SWV. Two signals were observed in voltammograms, cysMT corresponding to -SH moieties of MT and Wa corresponding to tryptophan residues of chicken antibodies. We optimized time of interaction (300 s) and concentration of MT (125 µg/ml) to suggest silver(I) ions biosensor. Biosensor (MT-antibody-modified CPE) prepared under the optimized conditions was utilized for silver(I) ions detection. The detection limit (3 S/N) for silver(I) ions were estimated as 100 nM. The proposed biosensor was tested by detection of silver(I) ions spiked in various water samples (from very pure distilled water to rainwater). Recoveries varied from 74 to 104 %. MT, low molecular mass proteins rich cysteine, play important role in the processes of heavy metals ions metabolism. Due to their unique physico-chemical properties they are able to bind heavy metals with high affinity. We used this feature to suggest simple biosensor based on immobilization of MT on the surface of carbon paste electrode via chicken antibodies against MT. The suggested biosensor was further successfully employed to detect silver(I) ions. The main advantage of the biosensor is that it can be easily miniaturized, whereas carbon nanostructures with immobilized MT should be used as working electrodes. Acknowledgements Financial support from INCHEMBIOL MSMT 0021622412 and GA CR 526/07/0674 is highly acknowledged.

Three dimensional, multi-chip module

DOEpatents

Bernhardt, A.F.; Petersen, R.W.

1993-08-31

A plurality of multi-chip modules are stacked and bonded around the perimeter by sold-bump bonds to adjacent modules on, for instance, three sides of the perimeter. The fourth side can be used for coolant distribution, for more interconnect structures, or other features, depending on particular design considerations of the chip set. The multi-chip modules comprise a circuit board, having a planarized interconnect structure formed on a first major surface, and integrated circuit chips bonded to the planarized interconnect surface. Around the periphery of each circuit board, long, narrow dummy chips'' are bonded to the finished circuit board to form a perimeter wall. The wall is higher than any of the chips on the circuit board, so that the flat back surface of the board above will only touch the perimeter wall. Module-to-module interconnect is laser-patterned on the sides of the boards and over the perimeter wall in the same way and at the same time that chip to board interconnect may be laser-patterned.

Three dimensional, multi-chip module

DOEpatents

Bernhardt, Anthony F.; Petersen, Robert W.

1993-01-01

A plurality of multi-chip modules are stacked and bonded around the perimeter by sold-bump bonds to adjacent modules on, for instance, three sides of the perimeter. The fourth side can be used for coolant distribution, for more interconnect structures, or other features, depending on particular design considerations of the chip set. The multi-chip modules comprise a circuit board, having a planarized interconnect structure formed on a first major surface, and integrated circuit chips bonded to the planarized interconnect surface. Around the periphery of each circuit board, long, narrow "dummy chips" are bonded to the finished circuit board to form a perimeter wall. The wall is higher than any of the chips on the circuit board, so that the flat back surface of the board above will only touch the perimeter wall. Module-to-module interconnect is laser-patterned o the sides of the boards and over the perimeter wall in the same way and at the same time that chip to board interconnect may be laser-patterned.

Graphene-based biosensors.

PubMed

Szunerits, Sabine; Boukherroub, Rabah

2018-06-06

Reliable data obtained from analysis of DNA, proteins, bacteria and other disease-related molecules or organisms in biological samples have become a fundamental and crucial part of human health diagnostics and therapy. The development of non-invasive tests that are rapid, sensitive, specific and simple would allow patient discomfort to be prevented, delays in diagnosis to be avoided and the status of a disease to be followed up. Bioanalysis is thus a progressive discipline for which the future holds many exciting opportunities. The use of biosensors for the early diagnosis of diseases has become widely accepted as a point-of-care diagnosis with appropriate specificity in a short time. To allow a reliable diagnosis of a disease at an early stage, highly sensitive biosensors are required as the corresponding biomarkers are generally expressed at very low concentrations. In the past 50 years, various biosensors have been researched and developed encompassing a wide range of applications. This contrasts the limited number of commercially available biosensors. When it comes to sensing of biomarkers with the required picomolar (pM) sensitivity for real-time sensing of biological samples, only a handful of sensing systems have been proposed, and these are often rather complex and costly. Lately, graphene-based materials have been considered as superior over other nanomaterials for the development of sensitive biosensors. The advantages of graphene-based sensor interfaces are numerous, including enhanced surface loading of the desired ligand due to the high surface-to-volume ratio, excellent conductivity and a small band gap that is beneficial for sensitive electrical and electrochemical read-outs, as well as tunable optical properties for optical read-outs such as fluorescence and plasmonics. In this paper, we review the advances made in recent years on graphene-based biosensors in the field of medical diagnosis.

Carbohydrate-based electrochemical biosensor for detection of a cancer biomarker in human plasma.

PubMed

Devillers, Marion; Ahmad, Lama; Korri-Youssoufi, Hafsa; Salmon, Laurent

2017-10-15

Autocrine motility factor (AMF) is a tumor-secreted cytokine that stimulates tumor cell motility in vitro and metastasis in vivo. AMF could be detected in serum or urine of cancer patients with worse prognosis. Reported as a cancer biomarker, AMF secretion into body fluids might be closely related to metastases formation. In this study, a sensitive and specific carbohydrate-based electrochemical biosensor was designed for the detection and quantification of a protein model of AMF, namely phosphoglucose isomerase from rabbit muscle (RmPGI). Indeed, RmPGI displays high homology with AMF and has been shown to have AMF activity. The biosensor was constructed by covalent binding of the enzyme substrate d-fructose 6-phosphate (F6P). Immobilization was achieved on a gold surface electrode following a bottom-up approach through an aminated surface obtained by electrochemical patterning of ethylene diamine and terminal amine polyethylene glycol chain to prevent non-specific interactions. Carbohydrate-protein interactions were quantified in a range of 10 fM to 100nM. Complex formation was analyzed through monitoring of the redox couple Fe 2+ /Fe 3+ by electrochemical impedance spectroscopy and square wave voltammetry. The F6P-biosensor demonstrates a detection limit of 6.6 fM and high selectivity when compared to other non-specific glycolytic proteins such as d-glucose-6-phosphate dehydrogenase. Detection of protein in spiked plasma was demonstrated and accuracy of 95% is obtained compared to result obtained in PBS (phosphate buffered saline). F6P-biosensor is a very promising proof of concept required for the design of a carbohydrate-based electrochemical biosensor using the enzyme substrate as bioreceptor. Such biosensor could be generalized to detect other protein biomarkers of interest. Copyright © 2017 Elsevier B.V. All rights reserved.

Amperometric biosensor system for simultaneous determination of adenosine-5'-triphosphate and glucose.

PubMed

Kucherenko, Ivan S; Didukh, Daria Yu; Soldatkin, Oleksandr O; Soldatkin, Alexei P

2014-06-03

The majority of biosensors for adenosine-5'-triphosphate (ATP) determination are based on cascades of enzymatic reactions; therefore, they are sensitive to glucose or glycerol (depending on the enzymatic system) as well as to ATP. The presence of unknown concentrations of these substances in the sample greatly complicates the determination of ATP. To overcome this disadvantage of known biosensors, we developed a biosensor system consisting of two biosensors: the first one is based on glucose oxidase and is intended for measuring glucose concentration, and the second one is based on glucose oxidase and hexokinase and is sensitive toward both glucose and ATP. Using glucose concentration measured by the first biosensor, we can analyze the total response to glucose and ATP obtained by the second biosensor. Platinum disc electrodes were used as amperometric transducers. The polyphenilenediamine membrane was deposited onto the surface of platinum electrodes to avoid the response to electroactive substances. The effect of glucose concentration on biosensor determination of ATP was studied. The reproducibility of biosensor responses to glucose and ATP during a day was tested (relative standard deviation, RSD, of responses to glucose was 3-6% and to ATP was 8-12%) as well as storage stability of the biosensors (no decrease of glucose responses and 43% drop of ATP responses during 50 days). The measurements of ATP and glucose in pharmaceutical vials (including mixtures of ATP and glucose) were carried out. It was shown that the developed biosensor system can be used for simultaneous analysis of glucose and ATP concentrations in water solutions.

Two-dimensional Layered MoS2 Biosensors Enable Highly Sensitive Detection of Biomolecules

NASA Astrophysics Data System (ADS)

Lee, Joonhyung; Dak, Piyush; Lee, Yeonsung; Park, Heekyeong; Choi, Woong; Alam, Muhammad A.; Kim, Sunkook

2014-12-01

We present a MoS2 biosensor to electrically detect prostate specific antigen (PSA) in a highly sensitive and label-free manner. Unlike previous MoS2-FET-based biosensors, the device configuration of our biosensors does not require a dielectric layer such as HfO2 due to the hydrophobicity of MoS2. Such an oxide-free operation improves sensitivity and simplifies sensor design. For a quantitative and selective detection of PSA antigen, anti-PSA antibody was immobilized on the sensor surface. Then, introduction of PSA antigen, into the anti-PSA immobilized sensor surface resulted in a lable-free immunoassary format. Measured off-state current of the device showed a significant decrease as the applied PSA concentration was increased. The minimum detectable concentration of PSA is 1 pg/mL, which is several orders of magnitude below the clinical cut-off level of ~4 ng/mL. In addition, we also provide a systematic theoretical analysis of the sensor platform - including the charge state of protein at the specific pH level, and self-consistent channel transport. Taken together, the experimental demonstration and the theoretical framework provide a comprehensive description of the performance potential of dielectric-free MoS2-based biosensor technology.

Performance oriented guidance for Mississippi chip seals - volume I.

DOT National Transportation Integrated Search

2013-12-01

A five year laboratory study was conducted to investigate near surface properties of flexible pavements in relation to : how they are affected by bituminous surface treatments. Chip seals and scrub seals (a specialized type of chip seal) : were the f...

Wideband Fully-Programmable Dual-Mode CMOS Analogue Front-End for Electrical Impedance Spectroscopy

PubMed Central

Valente, Virgilio; Demosthenous, Andreas

2016-01-01

This paper presents a multi-channel dual-mode CMOS analogue front-end (AFE) for electrochemical and bioimpedance analysis. Current-mode and voltage-mode readouts, integrated on the same chip, can provide an adaptable platform to correlate single-cell biosensor studies with large-scale tissue or organ analysis for real-time cancer detection, imaging and characterization. The chip, implemented in a 180-nm CMOS technology, combines two current-readout (CR) channels and four voltage-readout (VR) channels suitable for both bipolar and tetrapolar electrical impedance spectroscopy (EIS) analysis. Each VR channel occupies an area of 0.48 mm2, is capable of an operational bandwidth of 8 MHz and a linear gain in the range between −6 dB and 42 dB. The gain of the CR channel can be set to 10 kΩ, 50 kΩ or 100 kΩ and is capable of 80-dB dynamic range, with a very linear response for input currents between 10 nA and 100 μA. Each CR channel occupies an area of 0.21 mm2. The chip consumes between 530 μA and 690 μA per channel and operates from a 1.8-V supply. The chip was used to measure the impedance of capacitive interdigitated electrodes in saline solution. Measurements show close matching with results obtained using a commercial impedance analyser. The chip will be part of a fully flexible and configurable fully-integrated dual-mode EIS system for impedance sensors and bioimpedance analysis. PMID:27463721

Nanotechnology-Based Surface Plasmon Resonance Affinity Biosensors for In Vitro Diagnostics

PubMed Central

Antiochia, Riccarda; Bollella, Paolo; Favero, Gabriele

2016-01-01

In the last decades, in vitro diagnostic devices (IVDDs) became a very important tool in medicine for an early and correct diagnosis, a proper screening of targeted population, and also assessing the efficiency of a specific therapy. In this review, the most recent developments regarding different configurations of surface plasmon resonance affinity biosensors modified by using several nanostructured materials for in vitro diagnostics are critically discussed. Both assembly and performances of the IVDDs tested in biological samples are reported and compared. PMID:27594884

Recent development of nano-materials used in DNA biosensors.

PubMed

Xu, Kai; Huang, Junran; Ye, Zunzhong; Ying, Yibin; Li, Yanbin

2009-01-01

As knowledge of the structure and function of nucleic acid molecules has increased, sequence-specific DNA detection has gained increased importance. DNA biosensors based on nucleic acid hybridization have been actively developed because of their specificity, speed, portability, and low cost. Recently, there has been considerable interest in using nano-materials for DNA biosensors. Because of their high surface-to-volume ratios and excellent biological compatibilities, nano-materials could be used to increase the amount of DNA immobilization; moreover, DNA bound to nano-materials can maintain its biological activity. Alternatively, signal amplification by labeling a targeted analyte with nano-materials has also been reported for DNA biosensors in many papers. This review summarizes the applications of various nano-materials for DNA biosensors during past five years. We found that nano-materials of small sizes were advantageous as substrates for DNA attachment or as labels for signal amplification; and use of two or more types of nano-materials in the biosensors could improve their overall quality and to overcome the deficiencies of the individual nano-components. Most current DNA biosensors require the use of polymerase chain reaction (PCR) in their protocols. However, further development of nano-materials with smaller size and/or with improved biological and chemical properties would substantially enhance the accuracy, selectivity and sensitivity of DNA biosensors. Thus, DNA biosensors without PCR amplification may become a reality in the foreseeable future.

Recent Development of Nano-Materials Used in DNA Biosensors

PubMed Central

Xu, Kai; Huang, Junran; Ye, Zunzhong; Ying, Yibin; Li, Yanbin

2009-01-01

As knowledge of the structure and function of nucleic acid molecules has increased, sequence-specific DNA detection has gained increased importance. DNA biosensors based on nucleic acid hybridization have been actively developed because of their specificity, speed, portability, and low cost. Recently, there has been considerable interest in using nano-materials for DNA biosensors. Because of their high surface-to-volume ratios and excellent biological compatibilities, nano-materials could be used to increase the amount of DNA immobilization; moreover, DNA bound to nano-materials can maintain its biological activity. Alternatively, signal amplification by labeling a targeted analyte with nano-materials has also been reported for DNA biosensors in many papers. This review summarizes the applications of various nano-materials for DNA biosensors during past five years. We found that nano-materials of small sizes were advantageous as substrates for DNA attachment or as labels for signal amplification; and use of two or more types of nano-materials in the biosensors could improve their overall quality and to overcome the deficiencies of the individual nano-components. Most current DNA biosensors require the use of polymerase chain reaction (PCR) in their protocols. However, further development of nano-materials with smaller size and/or with improved biological and chemical properties would substantially enhance the accuracy, selectivity and sensitivity of DNA biosensors. Thus, DNA biosensors without PCR amplification may become a reality in the foreseeable future. PMID:22346713

Fabrication and characterization of a chemically oxidized-nanostructured porous silicon based biosensor implementing orienting protein A.

PubMed

Naveas, Nelson; Hernandez-Montelongo, Jacobo; Pulido, Ruth; Torres-Costa, Vicente; Villanueva-Guerrero, Raúl; Predestinación García Ruiz, Josefa; Manso-Silván, Miguel

2014-03-01

Nanostructured porous silicon (PSi) elicits as a very attractive material for future biosensing systems due to its high surface area, biocompatibility and well-established fabrication methods. In order to engineer its performance as a biosensor transducer platform, the density of immunoglobulins properly immobilized and oriented onto the surface needs to be optimized. In this work we fabricated and characterized a novel biosensing system focusing on the improvement of the biofunctionalization cascade. The system consists on a chemically oxidized PSi platform derivatized with 3-aminopropyltriethoxysilane (APTS) that is coupled to Staphylococcus protein A (SpA). The chemical oxidation has previously demonstrated to enhance the biofunctionalization process and here "by implementing SpA" a molecularly oriented immunosensor is achieved. The biosensor system is characterized in terms of its chemical composition, wettability and optical reflectance. Finally, this system is successfully exploited to develop a biosensor for detecting asymmetric dimethylarginine (ADMA), an endogenous molecule involved in cardiovascular diseases. Therefore, this work is relevant from the point of view of design and optimization of the biomolecular immobilization cascade on PSi surfaces with the added value of contribution to the development of new assays for detecting ADMA with a view on prevention of cardiovascular diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

Multienzyme decorated polysaccharide amplified electrogenerated chemiluminescence biosensor for cytosensing and cell surface carbohydrate profiling.

PubMed

Zhang, Ling; Wang, Yangzhong; Tian, Qianqian; Liu, Yang; Li, Jinghong

2017-03-15

A novel ECL biosensor for cytosensing and cell surface carbohydrate expression evaluation was developed, by the integration of the peptide modified interface for highly specific carbohydrate recognition and sodium alginate loaded glucose oxidase as the signal probe with high signal amplification efficiency. A cysteine-terminated peptide self-assembled on the electrode through Au-S bond to construct a functional interface for cell capture, with decent biocompatibility and high affinity for the human breast cancer cell MCF-7. Concanavalin A lectin modified gold nanoparticles specifically recognized the cell surface carbohydrates and were absorbed on the electrode, followed by the immobilization of multiple glucose oxidase conjugated sodium alginate, which could remarkably increase the sensitivity of the biosensor with enhanced catalysis. The as-proposed ECL cytosensor was successfully applied for the detection of the MCF-7 tumor cells, whose glycans on the cell membranes are over-expressed. A low detection limit of 150cellsmL -1 was obtained, with a wide dynamic linear range from 5.0×10 2 to 5.0×10 5 cellsmL -1 . Due to the excellent sensitivity, stability and biocompatibility, the ECL biosensor would be promising in reliable diagnostics of glycan relevant biomarkers for cancer and other diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Facile construction of a highly sensitive DNA biosensor by in-situ assembly of electro-active tags on hairpin-structured probe fragment

PubMed Central

Wang, Qingxiang; Gao, Feng; Ni, Jiancong; Liao, Xiaolei; Zhang, Xuan; Lin, Zhenyu

2016-01-01

An ultrasensitive DNA biosensor has been developed through in-situ labeling of electroactive melamine-Cu2+ complex (Mel-Cu2+) on the end of hairpin-like probe using gold nanoparticles (AuNPs) as the signal amplification platform. The 3′-thiolated hairpin-like probe was first immobilized to the gold electrode surface by the Au-S bond. The AuNPs were then tethered on the free 5′-end of the immobilized probe via the special affinity between Au and the modified -NH2. Followed by, the Mel and Cu2+ were assembled on the AuNPs surface through Au-N bond and Cu2+-N bond, respectively. Due to the surface area and electrocatalytic effects of the AuNPs, the loading amount and electron transfer kinetic of the Mel-Cu2+ were enhanced greatly, resulting in significantly enhanced electrochemical response of the developed biosensor. Compared with the synthesis process of conventional electroactive probe DNA accomplished by homogeneous method, the method presented in this work is more reagent- and time-saving. The proposed biosensor showed high selectivity, wide linear range and low detection limit. This novel strategy could also be extended to the other bioanalysis platforms such as immunosensors and aptasensors. PMID:26931160

Surface Plasmon Resonance Investigations of Bioselective Element Based on the Recombinant Protein A for Immunoglobulin Detection

NASA Astrophysics Data System (ADS)

Bakhmachuk, A.; Gorbatiuk, O.; Rachkov, A.; Dons'koi, B.; Khristosenko, R.; Ushenin, I.; Peshkova, V.; Soldatkin, A.

2017-02-01

The developed surface plasmon resonance (SPR) biosensor based on the recombinant Staphylococcal protein A with an additional cysteine residue (SPA-Cys) used as a biorecognition component showed a good selectivity and sensitivity for the immunoglobulin detection. The developed biosensor with SPA-Cys-based bioselective element can also be used as a first step of immunosensor creation. The successful immobilization of SPA-Cys on the nanolayer gold sensor surface of the SPR spectrometer was performed. The efficiency of blocking nonspecific sorption sites on the sensor surface with milk proteins, gelatin, BSA, and HSA was studied, and a rather high efficiency of using gelatin was confirmed. The SPR biosensor selectively interacted with IgG and did not interact with the control proteins. The linear dependence of the sensor response on the IgG concentration in the range from 2 to 10 μg/ml was shown. Using the calibration curve, the IgG concentration was measured in the model samples. The determined concentrations are in good agreement ( r 2 = 0.97) with the given concentration of IgG.

PEP-on-DEP: A competitive peptide-based disposable electrochemical aptasensor for renin diagnostics.

PubMed

Biyani, Manish; Kawai, Keiko; Kitamura, Koichiro; Chikae, Miyuki; Biyani, Madhu; Ushijima, Hiromi; Tamiya, Eiichi; Yoneda, Takashi; Takamura, Yuzuru

2016-10-15

Antibody-based immunosensors are relatively less accessible to a wide variety of unreachable targets, such as low-molecular-weight biomarkers that represent a rich untapped source of disease-specific diagnostic information. Here, we present a peptide aptamer-based electrochemical sensor technology called 'PEP-on-DEP' to detect less accessible target molecules, such as renin, and to improve the quality of life. Peptide-based aptamers represent a relatively smart class of affinity binders and show great promise in biosensor development. Renin is involved in the regulation of arterial blood pressure and is an emerging biomarker protein for predicting cardiovascular risk and prognosis. To our knowledge, no studies have described aptamer molecules that can be used as new potent probes for renin. Here, we describe a portable electrochemical biosensor platform based on the newly identified peptide aptamer molecules for renin. We constructed a randomized octapeptide library pool with diversified sequences and selected renin specific peptide aptamers using cDNA display technology. We identified a few peptide aptamer sequences with a KD in the µM binding affinity range for renin. Next, we grafted the selected peptide aptamers onto gold nanoparticles and detected renin in a one-step competitive assay using our originally developed DEP (Disposable Electrochemical Printed) chip and a USB powered portable potentiostat system. We successfully detected renin in as little as 300ngmL(-1) using the PEP-on-DEP method. Thus, the generation and characterization of novel probes for unreachable target molecules by merging a newly identified peptide aptamer with electrochemical transduction allowed for the development of a more practical biosensor that, in principle, can be adapted to develop a portable, low-cost and mass-producible biosensor for point-of-care applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Controlling the type and the form of chip when machining steel

NASA Astrophysics Data System (ADS)

Gruby, S. V.; Lasukov, A. A.; Nekrasov, R. Yu; Politsinsky, E. V.; Arkhipova, D. A.

2016-08-01

The type of the chip produced in the process of machining influences many factors of production process. Controlling the type of chip when cutting metals is important for producing swarf chips and for easing its utilization as well as for protecting the machined surface, cutting tool and the worker. In the given work we provide the experimental data on machining structural steel with implanted tool. The authors show that it is possible to control the chip formation process to produce the required type of chip by selecting the material for machining the tool surface.

Characterization and performance of injection molded poly(methylmethacrylate) microchips for capillary electrophoresis

PubMed Central

Nikcevic, Irena; Lee, Se Hwan; Piruska, Aigars; Ahn, Chong H.; Ridgway, Thomas H.; Limbach, Patrick A.; Wehmeyer, K. R.; Heineman, William R.; Seliskar, Carl J.

2009-01-01

Injection molded poly(methylmethacrylate) (IM-PMMA), chips were evaluated as potential candidates for capillary electrophoresis disposable chip applications. Mass production and usage of plastic microchips depends on chip-to-chip reproducibility and on analysis accuracy. Several important properties of IM-PMMA chips were considered: fabrication quality evaluated by environmental scanning electron microscope imaging, surface quality measurements, selected thermal/electrical properties as indicated by measurement of the current versus applied voltage (I–V) characteristic, and the influence of channel surface treatments. Electroosmotic flow was also evaluated for untreated and O2 reactive ion etching (RIE) treated surface microchips. The performance characteristics of single lane plastic microchip capillary electrophoresis (MCE) separations were evaluated using a mixture of two dyes - fluorescein (FL) and fluorescein isothiocyanate (FITC). To overcome non-wettability of the native IM-PMMA surface, a modifier, polyethylene oxide was added to the buffer as a dynamic coating. Chip performance reproducibility was studied for chips with and without surface modification via the process of RIE with O2 and by varying the hole position for the reservoir in the cover plate or on the pattern side of the chip. Additionally, the importance of reconditioning steps to achieve optimal performance reproducibility was also examined. It was found that more reproducible quantitative results were obtained when normalized values of migration time, peak area and peak height of FL and FITC were used instead of actual measured parameters PMID:17477932

1-D grating based SPR biosensor for the detection of lung cancer biomarkers using Vroman effect

NASA Astrophysics Data System (ADS)

Teotia, Pradeep Kumar; Kaler, R. S.

2018-01-01

Grating based surface plasmon resonance waveguide biosensor have been reported for the detection of lung cancer biomarkers using Vroman effect. The proposed grating based multilayered biosensor is designed with high detection accuracy for Epidermal growth factor receptor (EGFR) and also analysed to show high detection accuracy with acceptable sensitivity for both cancer biomarkers. The introduction of periodic grating with multilayer metals generates a good resonance that make it possible for early detection of cancerous cells. Using finite difference time domain method, it is observed wavelength of biosensor get red-shifted on variations of the refractive index due to the presence of both the cancerous bio-markers. The reported detection accuracy and sensitivity of proposed biosensor is quite acceptable for both lung cancer biomarkers i.e. Carcinoembryonic antigen (CEA) and Epidermal growth factor receptor (EGFR) which further offer us label free early detection of lung cancer using these biomarkers.

High-Speed Lateral Flow Strategy for a Fast Biosensing with an Improved Selectivity and Binding Affinity.

PubMed

Cho, Dong Guk; Yoo, Haneul; Lee, Haein; Choi, Yeol Kyo; Lee, Minju; Ahn, Dong June; Hong, Seunghun

2018-05-10

We report a high-speed lateral flow strategy for a fast biosensing with an improved selectivity and binding affinity even under harsh conditions. In this strategy, biosensors were fixed at a location away from the center of a round shape disk, and the disk was rotated to create the lateral flow of a target solution on the biosensors during the sensing measurements. Experimental results using the strategy showed high reaction speeds, high binding affinity, and low nonspecific adsorptions of target molecules to biosensors. Furthermore, binding affinity between target molecules and sensing molecules was enhanced even in harsh conditions such as low pH and low ionic strength conditions. These results show that the strategy can improve the performance of conventional biosensors by generating high-speed lateral flows on a biosensor surface. Therefore, our strategy can be utilized as a simple but powerful tool for versatile bio and medical applications.

Simultaneous topographic and amperometric membrane mapping using an AFM probe integrated biosensor.

PubMed

Stanca, Sarmiza Elena; Csaki, Andrea; Urban, Matthias; Nietzsche, Sandor; Biskup, Christoph; Fritzsche, Wolfgang

2011-02-15

The investigation of the plasma membrane with intercorrelated multiparameter techniques is a prerequisite for understanding its function. Presented here, is a simultaneous electrochemical and topographic study of the cell membrane using a miniaturized amperometric enzymatic biosensor. The fabrication of this biosensor is also reported. The biosensor combines a scanning force microscopy (AFM) gold-coated cantilever and an enzymatic transducer layer of peroxidases (PODs). When these enzymes are brought in contact with the substrate, the specific redox reaction produces an electric current. The intensity of this current is detected simultaneously with the surface imaging. For sensor characterization, hydroquinone-2-carboxylic acid (HQ) is selected as an intrinsic source of H(2)O(2). HQ has been electrochemically regenerated by the reduction of antraquinone-2-carboxylic acid (AQ). The biosensor reaches the steady state value of the current intensity in 1 ± 0.2s. Copyright © 2010 Elsevier B.V. All rights reserved.

Biosensor based on tyrosinase immobilized on a single-walled carbon nanotube-modified glassy carbon electrode for detection of epinephrine

PubMed Central

Apetrei, Irina Mirela; Apetrei, Constantin

2013-01-01

A biosensor comprising tyrosinase immobilized on a single-walled carbon nanotube-modified glassy carbon electrode has been developed. The sensitive element, ie, tyrosinase, was immobilized using a drop-and-dry method followed by cross-linking. Tyrosinase maintained high bioactivity on this nanomaterial, catalyzing the oxidation of epinephrine to epinephrine-quinone, which was electrochemically reduced (−0.07 V versus Ag/AgCl) on the biosensor surface. Under optimum conditions, the biosensor showed a linear response in the range of 10–110 μM. The limit of detection was calculated to be 2.54 μM with a correlation coefficient of 0.977. The repeatability, expressed as the relative standard deviation for five consecutive determinations of 10−5 M epinephrine solution was 3.4%. A good correlation was obtained between results obtained by the biosensor and those obtained by ultraviolet spectrophotometric methods. PMID:24348034

Chip morphology as a performance predictor during high speed end milling of soda lime glass

NASA Astrophysics Data System (ADS)

Bagum, M. N.; Konneh, M.; Abdullah, K. A.; Ali, M. Y.

2018-01-01

Soda lime glass has application in DNA arrays and lab on chip manufacturing. Although investigation revealed that machining of such brittle material is possible using ductile mode under controlled cutting parameters and tool geometry, it remains a challenging task. Furthermore, ability of ductile machining is usually assed through machined surface texture examination. Soda lime glass is a strain rate and temperature sensitive material. Hence, influence on attainment of ductile surface due to adiabatic heat generated during high speed end milling using uncoated tungsten carbide tool is investigated in this research. Experimental runs were designed using central composite design (CCD), taking spindle speed, feed rate and depth of cut as input variable and tool-chip contact point temperature (Ttc) and the surface roughness (Rt) as responses. Along with machined surface texture, Rt and chip morphology was examined to assess machinability of soda lime glass. The relation between Ttc and chip morphology was examined. Investigation showed that around glass transition temperature (Tg) ductile chip produced and subsequently clean and ductile final machined surface produced.

Wood chips for dust control on surface-mine haul roads

Treesearch

George P., Jr. Williams

1979-01-01

On a coal haul spur road where water sprinkling was the primary method of dust control, the duration of control was increased tenfold by covering the road surface with a layer of wood chips. The chip blanket prevented existing dust-size particles from being kicked up and swept into plumes by passing traffic, insulated the road surface against evaporation and protected...

Grafting of Oligo(ethylene glycol)-Functionalized Calix[4]arene-Tetradiazonium Salts for Antifouling Germanium and Gold Surfaces.

PubMed

Blond, Pascale; Mattiuzzi, Alice; Valkenier, Hennie; Troian-Gautier, Ludovic; Bergamini, Jean-François; Doneux, Thomas; Goormaghtigh, Erik; Raussens, Vincent; Jabin, Ivan

2018-05-29

Biosensors that can determine protein concentration and structure are highly desired for biomedical applications. For the development of such biosensors, the use of Fourier transform infrared (FTIR) spectroscopy with the attenuated internal total reflection (ATR) configuration is particularly attractive, but it requires appropriate surface functionalization of the ATR optical element. Indeed, the surface has to specifically interact with a target protein in close contact with the optical element and must display antifouling properties to prevent nonspecific adsorption of other proteins. Here, we report robust monolayers of calix[4]arenes bearing oligo(ethylene glycol) (oEG) chains, which were grafted on germanium and gold surfaces via their tetradiazonium salts. The formation of monolayers of oEGylated calix[4]arenes was confirmed by AFM, IR, and contact angle measurements. The antifouling properties of these modified surfaces were studied by ATR-FTIR spectroscopy and fluorescence microscopy, and the nonspecific absorption of bovine serum albumin was found to be reduced by 85% compared to that of unmodified germanium. In other words, the organic coating by oEGylated calix[4]arenes provides remarkable antifouling properties, opening the way for the design of germanium- or gold-based biosensors.

Designing cellulosic and nanocellulosic sensors for interface with a protease sequestrant wound-dressing prototype: Implications of material selection for dressing and protease sensor design.

PubMed

Fontenot, Krystal R; Edwards, J Vincent; Haldane, David; Pircher, Nicole; Liebner, Falk; Condon, Brian D; Qureshi, Huzaifah; Yager, Dorne

2017-11-01

Interfacing nanocellulosic-based biosensors with chronic wound dressings for protease point of care diagnostics combines functional material properties of high specific surface area, appropriate surface charge, and hydrophilicity with biocompatibility to the wound environment. Combining a protease sensor with a dressing is consistent with the concept of an intelligent dressing, which has been a goal of wound-dressing design for more than a quarter century. We present here biosensors with a nanocellulosic transducer surface (nanocrystals, nanocellulose composites, and nanocellulosic aerogels) immobilized with a fluorescent elastase tripeptide or tetrapeptide biomolecule, which has selectivity and affinity for human neutrophil elastase present in chronic wound fluid. The specific surface area of the materials correlates with a greater loading of the elastase peptide substrate. Nitrogen adsorption and mercury intrusion studies revealed gas permeable systems with different porosities (28-98%) and pore sizes (2-50 nm, 210 µm) respectively, which influence water vapor transmission rates. A correlation between zeta potential values and the degree of protease sequestration imply that the greater the negative surface charge of the nanomaterials, the greater the sequestration of positively charged neutrophil proteases. The biosensors gave detection sensitivities of 0.015-0.13 units/ml, which are at detectable human neutrophil elastase levels present in chronic wound fluid. Thus, the physical and interactive biochemical properties of the nano-based biosensors are suitable for interfacing with protease sequestrant prototype wound dressings. A discussion of the relevance of protease sensors and cellulose nanomaterials to current chronic wound dressing design and technology is included.

Giant magnetoresistive biosensors for molecular diagnosis: surface chemistry and assay development

NASA Astrophysics Data System (ADS)

Yu, Heng; Osterfeld, Sebastian J.; Xu, Liang; White, Robert L.; Pourmand, Nader; Wang, Shan X.

2008-08-01

Giant magnetoresistive (GMR) biochips using magnetic nanoparticle as labels were developed for molecular diagnosis. The sensor arrays consist of GMR sensing strips of 1.5 μm or 0.75 μm in width. GMR sensors are exquisitely sensitive yet very delicate, requiring ultrathin corrosion-resistive passivation and efficient surface chemistry for oligonucleotide probe immobilization. A mild and stable surface chemistry was first developed that is especially suitable for modifying delicate electronic device surfaces, and a practical application of our GMR biosensors was then demonstrated for detecting four most common human papillomavirus (HPV) subtypes in plasmids. We also showed that the DNA hybridization time could potentially be reduced from overnight to about ten minutes using microfluidics.

Nano-particle enhanced impedimetric biosensor for detedtion of foodborne pathogens

NASA Astrophysics Data System (ADS)

Kim, G.; Om, A. S.; Mun, J. H.

2007-03-01

Recent outbreaks of foodborne illness have been increased the need for rapid and sensitive methods for detection of these pathogens. Conventional methods for pathogens detection and identification involve prolonged multiple enrichment steps. Even though some immunological rapid assays are available, these assays still need enrichment steps result in delayed detection. Biosensors have shown great potential for rapid detection of foodborne pathogens. They are capable of direct monitoring the antigen-antibody reactions in real time. Among the biosensors, impedimetric biosensors have been widely adapted as an analysis tool for the study of various biological binding reactions because of their high sensitivity and reagentless operation. In this study a nanoparticle-enhanced impedimetric biosensor for Salmonella enteritidis detection was developed which detected impedance changes caused by the attachment of the cells to the anti-Salmonella antibodies immobilized on interdigitated gold electrodes. Successive immobilization of neutravidin followed by anti-Salmonella antibodies was performed to the sensing area to create a biological detection surface. To enhance the impedance responses generated by antigen-antibody reactions, anti-Salmonella antibody conjugated nanoparticles were introduced on the sensing area. Using a portable impedance analyzer, the impedance across the interdigital electrodes was measured after the series of antigen-antibody bindings. Bacteria cells present in solution attached to capture antibodies and became tethered to the sensor surface. Attached bacteria cells changed the dielectric constant of the media between the electrodes thereby causing a change in measured impedance. Optimum input frequency was determined by analyzing frequency characteristics of the biosensor over ranges of applied frequencies from 10 Hz to 400 Hz. At 100 Hz of input frequency, the biosensor was most sensitive to the changes of the bacteria concentration and this frequency was used for the detection experiments. The biosensor was able to detect 106 CFU/mL in phosphate buffered saline (PBS) with a detection time of 3 minutes. Additional use of nanoparticles significantly enhanced the detection performance. By using the nanoparticles the biosensor could detect 104 CFU/mL of Salmonella enteritidis in PBS and 105 CFU/mL of cells in milk.

3-D readout-electronics packaging for high-bandwidth massively paralleled imager

DOEpatents

Kwiatkowski, Kris; Lyke, James

2007-12-18

Dense, massively parallel signal processing electronics are co-packaged behind associated sensor pixels. Microchips containing a linear or bilinear arrangement of photo-sensors, together with associated complex electronics, are integrated into a simple 3-D structure (a "mirror cube"). An array of photo-sensitive cells are disposed on a stacked CMOS chip's surface at a 45.degree. angle from light reflecting mirror surfaces formed on a neighboring CMOS chip surface. Image processing electronics are held within the stacked CMOS chip layers. Electrical connections couple each of said stacked CMOS chip layers and a distribution grid, the connections for distributing power and signals to components associated with each stacked CSMO chip layer.

A glucose biosensor based on direct electrochemistry of glucose oxidase immobilized on nitrogen-doped carbon nanotubes.

PubMed

Deng, Shengyuan; Jian, Guoqiang; Lei, Jianping; Hu, Zheng; Ju, Huangxian

2009-10-15

A novel biosensor for glucose was prepared by immobilizing glucose oxidase (GOx) on nitrogen-doped carbon nanotubes (CNx-MWNTs) modified electrode. The CNx-MWNTs membrane showed an excellent electrocatalytic activity toward the reduction of O(2) due to its diatomic side-on adsorption on CNx-MWNTs. The nitrogen doping accelerated the electron transfer from electrode surface to the immobilized GOx, leading to the direct electrochemistry of GOx. The biofunctional surface showed good biocompatibility, excellent electron-conductive network and large surface-to-volume ratio, which were characterized by scanning electron microscopy, contact angle and electrochemical impedance technique. The direct electron transfer of immobilized GOx led to stable amperometric biosensing for glucose with a linear range from 0.02 to 1.02 mM and a detection limit of 0.01 mM (S/N=3). These results indicated that CNx-MWNTs are good candidate material for construction of the third-generation enzyme biosensors based on the direct electrochemistry of immobilized enzymes.

Benzimidazole Carbamate Residues in Milk: Detection by SPR Biosensor; using a Modified QuEChERS Method for Extraction

USDA-ARS?s Scientific Manuscript database

A surface plasmon resonance (SPR) biosensor screening assay was developed and validated to detect 11 benzimidazole carbamate (BZT) veterinary drug residues in milk. The polyclonal antibody used was raised in sheep against a methyl 5 (6)-[(carboxypentyl)-thio]-2-benzimidazole carbamate protein conjug...

Detection of antibody-antigen reaction by silicon nitride slot-ring biosensors using protein G

NASA Astrophysics Data System (ADS)

Taniguchi, Tomoya; Hirowatari, Anna; Ikeda, Takeshi; Fukuyama, Masataka; Amemiya, Yoshiteru; Kuroda, Akio; Yokoyama, Shin

2016-04-01

Biosensors using ring resonators with silicon nitride (SiN) slot waveguides have been fabricated. The temperature coefficient of the resonance wavelength of the SiN resonator is 0.006 nm/°C, which is one order of magnitude smaller than that of Si. The sensitivity of the biosensor has been improved by using slot waveguide together with Si-binding protein (designated as Si-tag), which bonds to SiN or SiO2 surface, as an anchoring molecule to immobilize bioreceptors on the SiN rings in an oriented manner. Furthermore, the protein G, which strongly bonds to many kinds of mammalian antibodies only by mixing the antibody solution, is used to efficiently immobilize the antigen on the sensor surface. By means of these devises the sensitivity of the biosensor has been improved by factor of 10-100 compared with that of normal Si ring resonator sensors without slot. Then the detection of prostate specific antigen (PSA) with the sensitivity of ~1×10-8 g/ml, which is the concentration of strongly suspicious for the prostate cancer, has been achieved.

Amperometric Biosensor Based on Zirconium Oxide/Polyethylene Glycol/Tyrosinase Composite Film for the Detection of Phenolic Compounds.

PubMed

Ahmad, Nor Monica; Abdullah, Jaafar; Yusof, Nor Azah; Ab Rashid, Ahmad Hazri; Abd Rahman, Samsulida; Hasan, Md Rakibul

2016-06-29

A phenolic biosensor based on a zirconium oxide/polyethylene glycol/tyrosinase composite film for the detection of phenolic compounds has been explored. The formation of the composite film was expected via electrostatic interaction between hexacetyltrimethylammonium bromide (CTAB), polyethylene glycol (PEG), and zirconium oxide nanoparticles casted on screen printed carbon electrode (SPCE). Herein, the electrode was treated by casting hexacetyltrimethylammonium bromide on SPCE to promote a positively charged surface. Later, zirconium oxide was mixed with polyethylene glycol and the mixture was dropped cast onto the positively charged SPCE/CTAB. Tyrosinase was further immobilized onto the modified SPCE. Characterization of the prepared nanocomposite film and the modified SPCE surface was investigated by scanning electron microscopy (SEM), Electrochemical Impedance Spectroscopy (EIS), and Cyclic voltamogram (CV). The developed biosensor exhibits rapid response for less than 10 s. Two linear calibration curves towards phenol in the concentrations ranges of 0.075-10 µM and 10-55 µM with the detection limit of 0.034 µM were obtained. The biosensor shows high sensitivity and good storage stability for at least 30 days.

Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor

NASA Astrophysics Data System (ADS)

Su, Li-Chen; Tian, Ya-Chung; Chang, Ying-Feng; Chou, Chien; Lai, Chao-Sung

2014-01-01

In renal transplant patients, immunosuppressive therapy may result in the reactivation of polyomavirus BK (BKV), leading to polyomavirus-associated nephropathy (PVAN), which inevitably causes allograft failure. Since the treatment outcomes of PVAN remain unsatisfactory, early identification and continuous monitoring of BKV reactivation and reduction of immunosuppressants are essential to prevent PVAN development. The present study demonstrated that the developed dual-channel heterodyne-based surface plasmon resonance (SPR) biosensor is applicable for the rapid detection of urinary BKV. The use of a symmetrical reference channel integrated with the poly(ethylene glycol)-based low-fouling self-assembled monolayer to reduce the environmental variations and the nonspecific noise was proven to enhance the sensitivity in urinary BKV detection. Experimentally, the detection limit of the biosensor for BKV detection was estimated to be around 8500 copies/mL. In addition, urine samples from five renal transplant patients were tested to rapidly distinguish PVAN-positive and PVAN-negative renal transplant patients. By virtue of its simplicity, rapidity, and applicability, the SPR biosensor is a remarkable potential to be used for continuous clinical monitoring of BKV reactivation.

Layer-by-Layer Self-Assembling Gold Nanorods and Glucose Oxidase onto Carbon Nanotubes Functionalized Sol-Gel Matrix for an Amperometric Glucose Biosensor.

PubMed

Wu, Baoyan; Hou, Shihua; Miao, Zhiying; Zhang, Cong; Ji, Yanhong

2015-09-18

A novel amperometric glucose biosensor was fabricated by layer-by-layer self-assembly of gold nanorods (AuNRs) and glucose oxidase (GOD) onto single-walled carbon nanotubes (SWCNTs)-functionalized three-dimensional sol-gel matrix. A thiolated aqueous silica sol containing SWCNTs was first assembled on the surface of a cleaned Au electrode, and then the alternate self-assembly of AuNRs and GOD were repeated to assemble multilayer films of AuNRs-GOD onto SWCNTs-functionalized silica gel for optimizing the biosensor. Among the resulting glucose biosensors, the four layers of AuNRs-GOD-modified electrode showed the best performance. The sol-SWCNTs-(AuNRs- GOD)₄/Au biosensor exhibited a good linear range of 0.01-8 mM glucose, high sensitivity of 1.08 μA/mM, and fast amperometric response within 4 s. The good performance of the proposed glucose biosensor could be mainly attributed to the advantages of the three-dimensional sol-gel matrix and stereo self-assembly films, and the natural features of one-dimensional nanostructure SWCNTs and AuNRs. This study may provide a new facile way to fabricate the enzyme-based biosensor with high performance.

Methylamine-Sensitive Amperometric Biosensor Based on (His)6-Tagged Hansenula polymorpha Methylamine Oxidase Immobilized on the Gold Nanoparticles

PubMed Central

Stasyuk, Nataliya Ye.; Smutok, Oleh V.; Zakalskiy, Andriy E.; Zakalska, Oksana M.; Gonchar, Mykhailo V.

2014-01-01

A novel methylamine-selective amperometric bienzyme biosensor based on recombinant primary amine oxidase isolated from the recombinant yeast strain Saccharomyces cerevisiae and commercial horseradish peroxidase is described. Two amine oxidase preparations were used: free enzyme (AMO) and covalently immobilized on the surface of gold nanoparticles (AMO-nAu). Some bioanalytical parameters (sensitivity, selectivity, and storage stability) of the developed biosensors were investigated. The sensitivity for both sensors is high: 1450 ± 113 and 700 ± 30 A−1 ·M−1 ·m−2 for AMO-nAu biosensor, respectively. The biosensors exhibit the linear range from 15 μM to 150 μM (AMO-nAu) and from 15 μM to 60 μM (AMO). The developed biosensor demonstrated a good selectivity toward methylamine (MA) (signal for dimethylamine and trimethylamine is less than 5% and for ethylamine 15% compared to MA output) and reveals a satisfactory storage stability. The constructed amperometric biosensor was used for MA assay in real samples of fish products in comparison with chemical method. The values obtained with both approaches different methods demonstrated a high correlation. PMID:25136590

Determination of Organophosphate Pesticides at a Carbon Nanotube/Organophosphorus Hydrolase Electrochemical Biosensor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deo, R P.; Wang, Joseph; Block, I

2005-02-08

An amperometric biosensor for organophosphorus (OP) pesticides based on a carbon-nanotube (CNT) modified transducer and an organophosphorus hydrolase (OPH) biocatalyst is described. A bilayer approach with the OPH layer atop of the CNT film was used for preparing the CNT/OPH biosensor. The CNT layer leads to a greatly improved anodic detection of the enzymatically-generated p-nitrophenol product, including higher sensitivity and stability. The sensor performance was optimized with respect to the surface modification and operating conditions. Under the optimal conditions the biosensor was used to measure as low as 0.15 {micro}M paraoxon and 0.8 {micro}M methyl parathion with sensitivities of 25more » and 6 nA/{micro}M, respectively.« less

Piezoelectric detection of bilirubin based on bilirubin-imprinted titania film electrode.

PubMed

Yang, Zhengpeng; Yan, Jinlong; Zhang, Chunjing

2012-02-01

A novel quartz crystal microbalance (QCM) sensor with a high selectivity and sensitivity has been developed for bilirubin determination, based on the modification of bilirubin-imprinted titania film onto a quartz crystal by molecular imprinting and surface sol-gel techniques. The performance of the developed bilirubin biosensor was evaluated and the results indicated that a sensitive bilirubin biosensor could be fabricated. The obtained bilirubin biosensor presents high-selectivity monitoring of bilirubin, better reproducibility, shorter response time (30 min), wider linear range (0.1-50 μM), and lower detection limit (0.05 μM). The analytical application of the bilirubin biosensor confirms the feasibility of bilirubin determination in serum sample. Copyright © 2011 Elsevier Inc. All rights reserved.

Carbon Nanotubes (CNTs) for the Development of Electrochemical Biosensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yuehe; Yantasee, Wassana; Wang, Joseph

2005-01-01

Carbon nanotube (CNT) is a very attractive material for the development of biosensors because of its capability to provide strong electrocatalytic activity and minimize surface fouling of the sensors. This article reviews our recent developments of oxidase- and dehydrogenase-amperometric biosensors based on the immobilization of CNTs, the co-immobilization of enzymes on the CNTs/Nafion or the CNT/Teflon composite materials, or the attachment of enzymes on the controlled-density aligned CNT-nanoelectrode arrays. The excellent electrocatalytic activities of the CNTs on the redox reactions of hydrogen peroxide, nicotinamide adenine dinucleotide (NADH), and homocysteine have been demonstrated. Successful applications of the CNT-based biosensors reviewed hereinmore » include the low-potential detections of glucose, organophosphorus compounds, and alcohol.« less

An ultrasensitive lysozyme chemiluminescence biosensor based on surface molecular imprinting using ionic liquid modified magnetic graphene oxide/β-cyclodextrin as supporting material.

PubMed

Duan, Huimin; Wang, Xiaojiao; Wang, Yanhui; Sun, Yuanling; Li, Jianbo; Luo, Chuannan

2016-04-28

In this work, ionic liquid modified Fe3O4@dopamine/graphene oxide/β-cyclodextrin (ILs-Fe3O4@DA/GO/β-CD) was used as supporting material to synthesize surface molecularly imprinted polymer (SMIP) which then was introduced into chemiluminescence (CL) to achieve an ultrasensitive and selective biosensor for determination of lysozyme (Lys). ILs and β-CD was applied to provide multiple binding sites to prepare Lys SMIP and Fe3O4@DA was designed to make the product separate easily and prevent the aggregation of GO which could improve absorption capacity for its large specific surface area. The ILs-Fe3O4@DA/GO/β-CD-SMIP showed high adsorption capacity (Q = 101 mg/g) to Lys in the adsorption isotherm assays. The adsorption equilibrium was reached within 10 min for all the concentrations, attributing to the binding sites situated exclusively at the surface, and the adsorption model followed Langmuir isotherm. Under the suitable CL conditions, the proposed biosensor could response Lys linearly in the range of 1.0 × 10(-9)-8.0 × 10(-8) mg/mL with a detection limit of 3.0 × 10(-10) mg/mL. When used in practical samples in determination of Lys, the efficient biosensor exhibited excellent result with the recoveries ranging from 94% to 112%. Copyright © 2016 Elsevier B.V. All rights reserved.

Yeast surface displaying glucose oxidase as whole-cell biocatalyst: construction, characterization, and its electrochemical glucose sensing application.

PubMed

Wang, Hongwei; Lang, Qiaolin; Li, Liang; Liang, Bo; Tang, Xiangjiang; Kong, Lingrang; Mascini, Marco; Liu, Aihua

2013-06-18

The display of glucose oxidase (GOx) on yeast cell surface using a-agglutinin as an anchor motif was successfully developed. Both the immunochemical analysis and enzymatic assay showed that active GOx was efficiently expressed and translocated on the cell surface. Compared with conventional GOx, the yeast cell surface that displayed GOx (GOx-yeast) demonstrated excellent enzyme properties, such as good stability within a wide pH range (pH 3.5-11.5), good thermostability (retaining over 94.8% enzyme activity at 52 °C and 84.2% enzyme activity at 56 °C), and high d-glucose specificity. In addition, direct electrochemistry was achieved at a GOx-yeast/multiwalled-carbon-nanotube modified electrode, suggesting that the host cell of yeast did not have any adverse effect on the electrocatalytic property of the recombinant GOx. Thus, a novel electrochemical glucose biosensor based on this GOx-yeast was developed. The as-prepared biosensor was linear with the concentration of d-glucose within the range of 0.1-14 mM and a low detection limit of 0.05 mM (signal-to-noise ratio of S/N = 3). Moreover, the as-prepared biosensor is stable, specific, reproducible, simple, and cost-effective, which can be applicable for real sample detection. The proposed strategy to construct robust GOx-yeast may be applied to explore other oxidase-displaying-system-based whole-cell biocatalysts, which can find broad potential application in biosensors, bioenergy, and industrial catalysis.

A functional glycoprotein competitive recognition and signal amplification strategy for carbohydrate-protein interaction profiling and cell surface carbohydrate expression evaluation

NASA Astrophysics Data System (ADS)

Wang, Yangzhong; Chen, Zhuhai; Liu, Yang; Li, Jinghong

2013-07-01

A simple and sensitive carbohydrate biosensor has been suggested as a potential tool for accurate analysis of cell surface carbohydrate expression as well as carbohydrate-based therapeutics for a variety of diseases and infections. In this work, a sensitive biosensor for carbohydrate-lectin profiling and in situ cell surface carbohydrate expression was designed by taking advantage of a functional glycoprotein of glucose oxidase acting as both a multivalent recognition unit and a signal amplification probe. Combining the gold nanoparticle catalyzed luminol electrogenerated chemiluminescence and nanocarrier for active biomolecules, the number of cell surface carbohydrate groups could be conveniently read out. The apparent dissociation constant between GOx@Au probes and Con A was detected to be 1.64 nM and was approximately 5 orders of magnitude smaller than that of mannose and Con A, which would arise from the multivalent effect between the probe and Con A. Both glycoproteins and gold nanoparticles contribute to the high affinity between carbohydrates and lectin. The as-proposed biosensor exhibits excellent analytical performance towards the cytosensing of K562 cells with a detection limit of 18 cells, and the mannose moieties on a single K562 cell were determined to be 1.8 × 1010. The biosensor can also act as a useful tool for antibacterial drug screening and mechanism investigation. This strategy integrates the excellent biocompatibility and multivalent recognition of glycoproteins as well as the significant enzymatic catalysis and gold nanoparticle signal amplification, and avoids the cell pretreatment and labelling process. This would contribute to the glycomic analysis and the understanding of complex native glycan-related biological processes.A simple and sensitive carbohydrate biosensor has been suggested as a potential tool for accurate analysis of cell surface carbohydrate expression as well as carbohydrate-based therapeutics for a variety of diseases and infections. In this work, a sensitive biosensor for carbohydrate-lectin profiling and in situ cell surface carbohydrate expression was designed by taking advantage of a functional glycoprotein of glucose oxidase acting as both a multivalent recognition unit and a signal amplification probe. Combining the gold nanoparticle catalyzed luminol electrogenerated chemiluminescence and nanocarrier for active biomolecules, the number of cell surface carbohydrate groups could be conveniently read out. The apparent dissociation constant between GOx@Au probes and Con A was detected to be 1.64 nM and was approximately 5 orders of magnitude smaller than that of mannose and Con A, which would arise from the multivalent effect between the probe and Con A. Both glycoproteins and gold nanoparticles contribute to the high affinity between carbohydrates and lectin. The as-proposed biosensor exhibits excellent analytical performance towards the cytosensing of K562 cells with a detection limit of 18 cells, and the mannose moieties on a single K562 cell were determined to be 1.8 × 1010. The biosensor can also act as a useful tool for antibacterial drug screening and mechanism investigation. This strategy integrates the excellent biocompatibility and multivalent recognition of glycoproteins as well as the significant enzymatic catalysis and gold nanoparticle signal amplification, and avoids the cell pretreatment and labelling process. This would contribute to the glycomic analysis and the understanding of complex native glycan-related biological processes. Electronic supplementary information (ESI) available: Experimental details; characterization of probes; the influence of electrolyte pH; probe concentration and glucose concentration on the electrode ECL effect. See DOI: 10.1039/c3nr01598j

Novel label-free biosensing technology for monitoring of aqueous solutions (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kehl, Florian; Bielecki, Robert; Follonier, Stephane; Dorokhin, Denis

2016-03-01

Waste water, drinking water and other industrial water sources are more and more/increasingly polluted with a large variety of contaminants, such as pesticides or residuals of pharmaceuticals. These compounds can impact human and animal organisms and lead to serious health issues. Today, in order to analyze the presence and quantity of the abovementioned micropollutants, samples are typically sent to specialized centralized laboratories and their processing may take up to several days. In order to meet the demand for continuous and consistent monitoring of aqueous solutions we propose a novel label-free technology system comprising proprietary chip and reader device designs. The core of the system is constituted by a planar-grated-waveguide (PGW) chip. Label-free biosensors, based on PGWs are sensitive to effective refractive index changes caused by the adsorption of biomolecules (micropollutants) onto the sensor surface or due to refractive index changes of the bulk solution. The presented reader device operates with a novel readout concept based on a scanning MEMS mirror for the angular interrogation of input grating couplers at a high repetition rate. The reader has fully integrated optics, electronics and fluidics and at the same time consumes limited energy (portable, field use ready). In the recent experiments, the effectiveness of the technology has been demonstrated with various liquids and bioassays showing (i) an excellent refractometric sensitivity with a limit of detection towards effective refractive index changes of ▵neff < 2 x 10-7, and (ii) the capability to perform affinity measurements for large (<150 kDa) and small (<250 Da) molecules.

Thermoresponsive magnetic nano-biosensors for rapid measurements of inorganic arsenic and cadmium.

PubMed

Siddiki, Mohammad Shohel Rana; Shimoaoki, Shun; Ueda, Shunsaku; Maeda, Isamu

2012-10-18

Green fluorescent protein-tagged sensor proteins, ArsR-GFP and CadC-GFP, have been produced as biosensors for simple and low-cost quantification of As(III) or Cd(II). In this study, the sensor protein-promoter DNA complexes were reconstructed on the surfaces of magnetic particles of different sizes. After the surface modification all the particles could be attracted by magnets, and released different amounts of GFP-tagged protein, according to the metal concentrations within 5 min, which caused significant increases in fluorescence. A detection limit of 1 µg/L for As(III) and Cd(II) in purified water was obtained only with the nanoparticles exhibiting enough magnetization after heat treatment for 1 min. Therefore, thermoresponsive magnetic nano-biosensors offer great advantages of rapidity and sensitivity for the measurement of the toxic metals in drinking water.

An automatic chip structure optical inspection system for electronic components

NASA Astrophysics Data System (ADS)

Song, Zhichao; Xue, Bindang; Liang, Jiyuan; Wang, Ke; Chen, Junzhang; Liu, Yunhe

2018-01-01

An automatic chip structure inspection system based on machine vision is presented to ensure the reliability of electronic components. It consists of four major modules, including a metallographic microscope, a Gigabit Ethernet high-resolution camera, a control system and a high performance computer. An auto-focusing technique is presented to solve the problem that the chip surface is not on the same focusing surface under the high magnification of the microscope. A panoramic high-resolution image stitching algorithm is adopted to deal with the contradiction between resolution and field of view, caused by different sizes of electronic components. In addition, we establish a database to storage and callback appropriate parameters to ensure the consistency of chip images of electronic components with the same model. We use image change detection technology to realize the detection of chip images of electronic components. The system can achieve high-resolution imaging for chips of electronic components with various sizes, and clearly imaging for the surface of chip with different horizontal and standardized imaging for ones with the same model, and can recognize chip defects.

Hydrophobic interaction and charge accumulation at the diamond-electrolyte interface.

PubMed

Dankerl, M; Lippert, A; Birner, S; Stützel, E U; Stutzmann, M; Garrido, J A

2011-05-13

The hydrophobic interaction of surfaces with water is a well-known phenomenon, but experimental evidence of its influence on biosensor devices has been lacking. In this work we investigate diamond field-effect devices, reporting on Hall effect experiments and complementary simulations of the interfacial potential at the hydrogen-terminated diamond/aqueous electrolyte interface. The interfacial capacitance, derived from the gate-dependent Hall carrier concentration, can be modeled only when considering the hydrophobic nature of this surface and its influence on the structure of interfacial water. Our work demonstrates how profoundly the performance of potentiometric biosensor devices can be affected by their surfaces' hydrophobicity.

Enhanced sensitivity of surface plasmon resonance phase-interrogation biosensor by using oblique deposited silver nanorods.

PubMed

Chung, Hung-Yi; Chen, Chih-Chia; Wu, Pin Chieh; Tseng, Ming Lun; Lin, Wen-Chi; Chen, Chih-Wei; Chiang, Hai-Pang

2014-01-01

Sensitivity of surface plasmon resonance phase-interrogation biosensor is demonstrated to be enhanced by oblique deposited silver nanorods. Silver nanorods are thermally deposited on silver nanothin film by oblique angle deposition (OAD). The length of the nanorods can be tuned by controlling the deposition parameters of thermal deposition. By measuring the phase difference between the p and s waves of surface plasmon resonance heterodyne interferometer with different wavelength of incident light, we have demonstrated that maximum sensitivity of glucose detection down to 7.1 × 10(-8) refractive index units could be achieved with optimal deposition parameters of silver nanorods.

Development of optical WGM resonators for biosensors

NASA Astrophysics Data System (ADS)

Brice, I.; Pirktina, A.; Ubele, A.; Grundsteins, K.; Atvars, A.; Viter, R.; Alnis, J.

2017-12-01

Whispering Gallery Mode (WGM) resonators are very sensitive to nanoparticles attaching to the surface. We simulate this process using COMSOL Wave Optics module. Our spherical WGM resonators are produced by melting a tip of an optical fiber and we measure optical Q factors in the 105 range. Molecular oxygen lines of the air in the 760 nm region are used as reference markers when looking for the shifts of the WGM resonance lines. We demonstrate WGM microresonator surface coating with a layer of ZnO nanorods as well as with polystyrene microspheres. Coatings produce increased contact surface. Additional layer of antigens/antibodies will be coated to make high-specificity biosensors.

A biosensor based on photonic crystal surface waves with an independent registration of the liquid refractive index.

PubMed

Konopsky, Valery N; Alieva, Elena V

2010-01-15

A high-precision optical biosensor technique capable of independently determining the refractive index (RI) of liquids is presented. Photonic crystal surface waves were used to detect surface binding events, while an independent registration of the critical angle was used for accurate determination of the liquid RI. This technique was tested using binding of biotin molecules to a streptavidin monolayer at low and high biotin concentrations. The attained baseline noise is 5x10(-13) m/Hz(1/2) for adlayer thickness changes and 9x10(-8) RIU/Hz(1/2) for RI changes. Copyright 2009 Elsevier B.V. All rights reserved.

Biosensor Based on Self-Assembling Acetylcholinesterase on Carbon Nanotubes for Flow injection/Amperometric Detection of Organophosphate Pesticides and Nerve Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Guodong; Lin, Yuehe

A highly sensitive flow-injection amperometric biosensor for organophosphate pesticides and nerve agents based on self-assembly of acetylcholinesterase (AChE) on carbon nanotube (CNT)-modified glassy carbon (GC) electrode is described. AChE is immobilized on the negatively-charged CNT surface by alternatively assembling a cationic polydiallyldimethylammonium chloride (PDDA) layer and an AChE layer. Transmission electron microscopy images confirm the formation of layer-by-layer nanostructures on carboxyl functionalized CNTs. The unique sandwich-like structure (PDDA/AChE/PDDA) on the CNT surface formed by self-assembly provides a favorable microenvironment to keep the bioactivity of AChE and to prevent enzyme molecule leakage. The electrocatalytic activity of CNT leads to a greatlymore » improved electrochemical detection of the enzymatically generated thiocholine product, including a low oxidation overvoltage (+150 mV), higher sensitivity, and stability. The developed PDDA/AChE/PDDA/CNT/GC biosensor integrated into a flow injection system was used to monitor organophosphate pesticides and nerve agents, such as paraoxon. The sensor performance, including inhibition time and regeneration conditions, was optimized with respect to operating conditions. Under the optimal conditions, the biosensor was used to measure as low as 0.4 pM paraoxon with a 6-min inhibition time. The biosensor had excellent operational lifetime stability with no decrease in the activity of enzymes for more than 20 repeated measurements over a 1-week period. The developed biosensor system is an ideal tool for online monitoring of organophosphate pesticides and nerve agents.« less

Electrochemical Quartz Crystal Nanobalance (EQCN) Based Biosensor for Sensitive Detection of Antibiotic Residues in Milk.

PubMed

Bhand, Sunil; Mishra, Geetesh K

2017-01-01

An electrochemical quartz crystal nanobalance (EQCN), which provides real-time analysis of dynamic surface events, is a valuable tool for analyzing biomolecular interactions. EQCN biosensors are based on mass-sensitive measurements that can detect small mass changes caused by chemical binding to small piezoelectric crystals. Among the various biosensors, the piezoelectric biosensor is considered one of the most sensitive analytical techniques, capable of detecting antigens at picogram levels. EQCN is an effective monitoring technique for regulation of the antibiotics below the maximum residual limit (MRL). The analysis of antibiotic residues requires high sensitivity, rapidity, reliability and cost effectiveness. For analytical purposes the general approach is to take advantage of the piezoelectric effect by immobilizing a biosensing layer on top of the piezoelectric crystal. The sensing layer usually comprises a biological material such as an antibody, enzymes, or aptamers having high specificity and selectivity for the target molecule to be detected. The biosensing layer is usually functionalized using surface chemistry modifications. When these bio-functionalized quartz crystals are exposed to a particular substance of interest (e.g., a substrate, inhibitor, antigen or protein), binding interaction occurs. This causes a frequency or mass change that can be used to determine the amount of material interacted or bound. EQCN biosensors can easily be automated by using a flow injection analysis (FIA) setup coupled through automated pumps and injection valves. Such FIA-EQCN biosensors have great potential for the detection of different analytes such as antibiotic residues in various matrices such as water, waste water, and milk.

Recombinant antibodies and their use in biosensors.

PubMed

Zeng, Xiangqun; Shen, Zhihong; Mernaugh, Ray

2012-04-01

Inexpensive, noninvasive immunoassays can be used to quickly detect disease in humans. Immunoassay sensitivity and specificity are decidedly dependent upon high-affinity, antigen-specific antibodies. Antibodies are produced biologically. As such, antibody quality and suitability for use in immunoassays cannot be readily determined or controlled by human intervention. However, the process through which high-quality antibodies can be obtained has been shortened and streamlined by use of genetic engineering and recombinant antibody techniques. Antibodies that traditionally take several months or more to produce when animals are used can now be developed in a few weeks as recombinant antibodies produced in bacteria, yeast, or other cell types. Typically most immunoassays use two or more antibodies or antibody fragments to detect antigens that are indicators of disease. However, a label-free biosensor, for example, a quartz-crystal microbalance (QCM) needs one antibody only. As such, the cost and time needed to design and develop an immunoassay can be substantially reduced if recombinant antibodies and biosensors are used rather than traditional antibody and assay (e.g. enzyme-linked immunosorbant assay, ELISA) methods. Unlike traditional antibodies, recombinant antibodies can be genetically engineered to self-assemble on biosensor surfaces, at high density, and correctly oriented to enhance antigen-binding activity and to increase assay sensitivity, specificity, and stability. Additionally, biosensor surface chemistry and physical and electronic properties can be modified to further increase immunoassay performance above and beyond that obtained by use of traditional methods. This review describes some of the techniques investigators have used to develop highly specific and sensitive, recombinant antibody-based biosensors for detection of antigens in simple or complex biological samples.

Flexible Molybdenum Electrodes towards Designing Affinity Based Protein Biosensors

PubMed Central

Kamakoti, Vikramshankar; Panneer Selvam, Anjan; Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Prasad, Shalini

2016-01-01

Molybdenum electrode based flexible biosensor on porous polyamide substrates has been fabricated and tested for its functionality as a protein affinity based biosensor. The biosensor performance was evaluated using a key cardiac biomarker; cardiac Troponin-I (cTnI). Molybdenum is a transition metal and demonstrates electrochemical behavior upon interaction with an electrolyte. We have leveraged this property of molybdenum for designing an affinity based biosensor using electrochemical impedance spectroscopy. We have evaluated the feasibility of detection of cTnI in phosphate-buffered saline (PBS) and human serum (HS) by measuring impedance changes over a frequency window from 100 mHz to 1 MHz. Increasing changes to the measured impedance was correlated to the increased dose of cTnI molecules binding to the cTnI antibody functionalized molybdenum surface. We achieved cTnI detection limit of 10 pg/mL in PBS and 1 ng/mL in HS medium. The use of flexible substrates for designing the biosensor demonstrates promise for integration with a large-scale batch manufacturing process. PMID:27438863

Printable Electrochemical Biosensors: A Focus on Screen-Printed Electrodes and Their Application

PubMed Central

Yamanaka, Keiichiro; Vestergaard, Mun’delanji C.; Tamiya, Eiichi

2016-01-01

In this review we present electrochemical biosensor developments, focusing on screen-printed electrodes (SPEs) and their applications. In particular, we discuss how SPEs enable simple integration, and the portability needed for on-field applications. First, we briefly discuss the general concept of biosensors and quickly move on to electrochemical biosensors. Drawing from research undertaken in this area, we cover the development of electrochemical DNA biosensors in great detail. Through specific examples, we describe the fabrication and surface modification of printed electrodes for sensitive and selective detection of targeted DNA sequences, as well as integration with reverse transcription-polymerase chain reaction (RT-PCR). For a more rounded approach, we also touch on electrochemical immunosensors and enzyme-based biosensors. Last, we present some electrochemical devices specifically developed for use with SPEs, including USB-powered compact mini potentiostat. The coupling demonstrates the practical use of printable electrode technologies for application at point-of-use. Although tremendous advances have indeed been made in this area, a few challenges remain. One of the main challenges is application of these technologies for on-field analysis, which involves complicated sample matrices. PMID:27775661

Amperometric L-lysine biosensor based on carboxylated multiwalled carbon nanotubes-SnO2 nanoparticles-graphene composite

NASA Astrophysics Data System (ADS)

Kaçar, Ceren; Erden, Pınar Esra; Kılıç, Esma

2017-10-01

A novel matrix, carboxylated multiwalled carbon nanotubes-tin oxide nanoparticles-graphene-chitosan (c-MWCNTs-SnO2-GR-CS) composite, was prepared for biosensor construction. Lysine oxidase (LOx) enzyme was immobilized covalently on the surface of c-MWCNTs-GR-SnO2-CS composite modified glassy carbon electrode (GCE) using N-ethyl-N‧-(3-dimethyaminopropyl) carbodiimide (EDC) and N-hydroxyl succinimide (NHS). Effects of electrode composition and buffer pH on biosensor response were investigated to optimize the working conditions. The biosensor exhibited wide linear range (9.9 × 10-7 M-1.6 × 10-4 M), low detection limit (1.5 × 10-7 M), high sensitivity (55.20 μA mM-1 cm-2) and fast amperometric response (<25 s) at +0.70 V vs. Ag/AgCl. With good repeatability and long-term stability, the c-MWCNTs-SnO2-GR-CS based biosensor offered an alternative for L-lysine biosensing. The practical applicability of the biosensor in two dietary supplements has also been addressed.

An immuno-biosensor system based on quartz crystal microbalance for avian influenza virus detection

NASA Astrophysics Data System (ADS)

Liu, Shengping; Chen, Guoming; Zhou, Qi; Wei, Yunlong

2007-12-01

For the quick detection of Avian Influenza Virus (AIV), a biosensor based on Quartz Crystal Microbalance (QCM) was fabricated according to the specific bonding principle between antibody and antigen. Staphylococcal Protein A (SPA) was extracted from Staphylococcus and purified. Then SPA was coated on the surface of QCM for immobilizing AIV monoclonal antibodies. The use of AIV monoclonal antibody could enhance the specificity of the immuno-biosensor. A multi-channel piezoelectricity detection system for the immuno-biosensor was developed. The system can work for the quick detection of AIV antigen in the case of the entirely aqueous status owe to one special oscillating circuit designed in this work. The optimum conditions of SPA coating and AIV monoclonal antibody immobilization were investigated utilizing the multi-channel detection system. The preliminary application of the immuno-biosensor system for detection of AIV was evaluated. Results indicate that the immuno-biosensor system can detect the AIV antigens with a linear range of 3-200ng/ml. The system can accomplish the detection of AIV antigens around 40 minutes.

Amperometric Biosensor Based on Diamine Oxidase/Platinum Nanoparticles/Graphene/Chitosan Modified Screen-Printed Carbon Electrode for Histamine Detection.

PubMed

Apetrei, Irina Mirela; Apetrei, Constantin

2016-03-24

This work describes the development and optimization studies of a novel biosensor employed in the detection and quantification of histamine in freshwater fish samples. The proposed biosensor is based on a modified carbon screen-printed electrode with diamineoxidase, graphene and platinum nanoparticles, which detects the hydrogen peroxide formed by the chemical process biocatalysed by the enzyme diamine oxidase and immobilized onto the nanostructurated surface of the receptor element. The amperometric measurements with the biosensor have been implemented in buffer solution of pH 7.4, applying an optimal low potential of +0.4 V. The novel biosensor shows high sensitivity (0.0631 μA·μM), low detection limit (2.54 × 10(-8) M) and a broad linear domain from 0.1 to 300 μM. The applicability in natural complex samples and the analytical parameters of this enzyme sensor have been performed in the quantification of histamine in freshwater fish. An excellent correlation among results achieved with the developed biosensor and results found with the standard method for all freshwater fish samples has been achieved.

Amperometric Biosensor Based on Diamine Oxidase/Platinum Nanoparticles/Graphene/Chitosan Modified Screen-Printed Carbon Electrode for Histamine Detection

PubMed Central

Apetrei, Irina Mirela; Apetrei, Constantin

2016-01-01

This work describes the development and optimization studies of a novel biosensor employed in the detection and quantification of histamine in freshwater fish samples. The proposed biosensor is based on a modified carbon screen-printed electrode with diamineoxidase, graphene and platinum nanoparticles, which detects the hydrogen peroxide formed by the chemical process biocatalysed by the enzyme diamine oxidase and immobilized onto the nanostructurated surface of the receptor element. The amperometric measurements with the biosensor have been implemented in buffer solution of pH 7.4, applying an optimal low potential of +0.4 V. The novel biosensor shows high sensitivity (0.0631 μA·μM), low detection limit (2.54 × 10−8 M) and a broad linear domain from 0.1 to 300 μM. The applicability in natural complex samples and the analytical parameters of this enzyme sensor have been performed in the quantification of histamine in freshwater fish. An excellent correlation among results achieved with the developed biosensor and results found with the standard method for all freshwater fish samples has been achieved. PMID:27023541

Graphitized carbon nanofiber-Pt nanoparticle hybrids as sensitive tool for preparation of screen printing biosensors. Detection of lactate in wines and ciders.

PubMed

Loaiza, Oscar A; Lamas-Ardisana, Pedro J; Añorga, Larraitz; Jubete, Elena; Ruiz, Virginia; Borghei, Maryam; Cabañero, Germán; Grande, Hans J

2015-02-01

This work describes the fabrication of a new lactate biosensor. The strategy is based on the use of a novel hybrid nanomaterial for amperometric biosensors i.e. platinum nanoparticles (PtNps) supported on graphitized carbon nanofibers (PtNps/GCNF) prepared by chemical reduction of the Pt precursor at GCNF surfaces. The biosensors were constructed by covalent immobilization of lactate oxidase (LOx) onto screen printed carbon electrodes (SPCEs) modified with PtNps (PtNps/GCNF-SPCEs) using polyethyleneimine (PEI) and glutaraldehyde (GA). Experimental variables concerning both the biosensor design and the detection process were investigated for an optimal analytical performance. Lactate biosensors show good reproducibility (RSD 4.9%, n=10) and sensitivity (41,302±546) μA/Mcm(2), with a good limit of detection (6.9μM). Covalent immobilization of the enzyme allows the reuse of the biosensor for several measurements, converting them in a cheap alternative to the solid electrodes. The long-term stability of the biosensors was also evaluated. 90% of the signal was kept after 3months of storage at room temperature (RT), while 95% was retained after 18months at -20°C. These results demonstrate that the method provides sensitive electrochemical lactate biosensors where the stability of the enzymatic activity can be preserved for a long period of time in adequate storage conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Use of microring resonators for biospecific interaction analysis

NASA Astrophysics Data System (ADS)

Chalyan, Tatevik; Besselink, Geert A. J.; Heideman, Rene G.; Pavesi, Lorenzo

2017-08-01

Integrated optical biosensors based on Mach-Zehnder Interferometers and Microring Resonators are widely used for food/drug monitoring and protein studies thank to their high intrinsic sensitivity, easy integration and miniaturization, and low cost.1, 2 In this study, we present a system to perform antibody interaction analysis using a photonic chip made of an array of six microring resonators (MRRs) based on the TriPleX platform. A compact system is presented where the input light is provided by a Vertical Cavity Surface Emitting Laser (VCSEL) pigtailed to a single mode fiber and operating at a ≍ 850nm wavelength. The output signal is detected by PIN photodetectors placed in the optical signal read-out module (the so-called OSROM) and processed by an easy-to-use Fourier Transform algorithm. Bulk sensitivity (Sb=98+/-2.1 nm/RIU) and Limit of Detection (LOD=(7.5+/- 0.5) x10-6 RIU) are measured and appeared to be very similar for the six MRRs on the same chip,3 which is an important property for multianalyte detection. An analysis of the anti-biotin interaction with immobilized biotin is performed by using different concentrations of anti-biotin antibody. The dependence of the resonance wavelength shift from the antibody concentration, as well as the association and the dissociation rate constants are calculated. For the average dissociation constant (KD) of anti-biotin antibody toward immobilized biotin, a value of (1.9+/-0.5) x10-7M is estimated, which is of the same order of magnitude of other published data.4 Furthermore, the specificity of the interaction is confirmed by using negative control antibodies and by performing competition with free, i.e., dissolved, biotin. In addition, the functional surface of the sensors could be regenerated for repeated measurements up to eight times by using 10 mM glycine/HCl pH 1.5.

Detection of alprazolam with a lab on paper economical device integrated with urchin like Ag@ Pd shell nano-hybrids.

PubMed

Narang, Jagriti; Malhotra, Nitesh; Singhal, Chaitali; Mathur, Ashish; Pn, Anoop Krishna; Pundir, C S

2017-11-01

We present results of the studies relating to fabrication of a microfluidic biosensor chip based on urchin like Ag@ Pd shell nano-hybrids that is capable of sensing alprazolam through electrochemical detection. Using this chip we demonstrate, with high reliability and in a time efficient manner, the detection of alprazolam present in buffer solutions at clinically relevant concentrations. Methylene blue (MB) was also doped as redox transition substance for sensing alprazolam. Nano-hybrids modified EμPAD showed wide linear range 1-300ng/ml and low detection limit of 0.025ng/l. Low detection limit can further enhance its suitability for forensic application. Nano-hybrids modified EμPAD was also employed for determination of drug in real samples such as human urine. Reported facile lab paper approach integrated with urchin like Ag@ Pd shell nano-hybrids could be well applied for the determination of serum metabolites. Copyright © 2016 Elsevier B.V. All rights reserved.

Multi-spot porous silicon chip prepared from asymmetric electrochemical etching for human immunoglobin G sensor.

PubMed

Um, Sungyong; Cho, Bomin; Woo, Hee-Gweon; Sohn, Honglae

2011-08-01

Multi-spot porous silicon (MSPS)-based optical biosensor was developed to specify the biomolecules. MSPS chip was generated by an electrochemical etching of silicon wafer using an asymmetric electrode configuration in aqueous ethanolic HF solution and constituted with nine arrayed porous silicon. MSPS prepared from anisotropic etching conditions displayed the Fabry-Pérot fringe patterns which varied spatially across the porous silicon (PS). Each spot displayed different reflection resonances and different pore characteristics as a function of the lateral distance from the Pt counter electrode. The sensor system consists of the 3 x 3 spot array of porous silicon modified with Protein A. The system was probed with various fragments of an aqueous Human Immunoglobin G (Ig G) analyte. The sensor operated by measurement of the reflection patterns in the white light reflection spectrum of MSPS. Molecular binding and specificity was detected as a shift in wavelength of these Fabry-Pérot fringe patterns.

A CMOS-Compatible Poly-Si Nanowire Device with Hybrid Sensor/Memory Characteristics for System-on-Chip Applications

PubMed Central

Chen, Min-Cheng; Chen, Hao-Yu; Lin, Chia-Yi; Chien, Chao-Hsin; Hsieh, Tsung-Fan; Horng, Jim-Tong; Qiu, Jian-Tai; Huang, Chien-Chao; Ho, Chia-Hua; Yang, Fu-Liang

2012-01-01

This paper reports a versatile nano-sensor technology using “top-down” poly-silicon nanowire field-effect transistors (FETs) in the conventional Complementary Metal-Oxide Semiconductor (CMOS)-compatible semiconductor process. The nanowire manufacturing technique reduced nanowire width scaling to 50 nm without use of extra lithography equipment, and exhibited superior device uniformity. These n type polysilicon nanowire FETs have positive pH sensitivity (100 mV/pH) and sensitive deoxyribonucleic acid (DNA) detection ability (100 pM) at normal system operation voltages. Specially designed oxide-nitride-oxide buried oxide nanowire realizes an electrically Vth-adjustable sensor to compensate device variation. These nanowire FETs also enable non-volatile memory application for a large and steady Vth adjustment window (>2 V Programming/Erasing window). The CMOS-compatible manufacturing technique of polysilicon nanowire FETs offers a possible solution for commercial System-on-Chip biosensor application, which enables portable physiology monitoring and in situ recording. PMID:22666012

Nanocellulose-based biosensors: design, preparation, and activity of peptide-linked cotton cellulose nanocrystals having fluorimetric and colorimetric elastase detection sensitivity

USDA-ARS?s Scientific Manuscript database

Nanocrystalline cellulose is an amphiphilic, high surface area material that can be easily functionalized and is biocom-patible and eco-friendly. It has been used singularly and in combination with other nanomaterials to optimize biosensor design. The attachment of peptides and proteins to nanocryst...

MICROBIAL BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS USING RECOMBINANT ESCHERICHIA COLI WITH SURFACE-EXPRESSED ORGANOPHOSPHORUS HYDROLASE. 2. FIBER-OPTIC MICROBIAL BIOSENSOR. (R823663)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Electrochemical Glucose Biosensor Based on Glucose Oxidase Displayed on Yeast Surface.

PubMed

Wang, Hongwei; Lang, Qiaolin; Liang, Bo; Liu, Aihua

2015-01-01

The conventional enzyme-based biosensor requires chemical or physical immobilization of purified enzymes on electrode surface, which often results in loss of enzyme activity and/or fractions immobilized over time. It is also costly. A major advantage of yeast surface display is that it enables the direct utilization of whole cell catalysts with eukaryote-produced proteins being displayed on the cell surface, providing an economic alternative to traditional production of purified enzymes. Herein, we describe the details of the display of glucose oxidase (GOx) on yeast cell surface and its application in the development of electrochemical glucose sensor. In order to achieve a direct electrochemistry of GOx, the entire cell catalyst (yeast-GOx) was immobilized together with multiwalled carbon nanotubes on the electrode, which allowed sensitive and selective glucose detection.

Decapsulation Method for Flip Chips with Ceramics in Microelectronic Packaging

NASA Astrophysics Data System (ADS)

Shih, T. I.; Duh, J. G.

2008-06-01

The decapsulation of flip chips bonded to ceramic substrates is a challenging task in the packaging industry owing to the vulnerability of the chip surface during the process. In conventional methods, such as manual grinding and polishing, the solder bumps are easily damaged during the removal of underfill, and the thin chip may even be crushed due to mechanical stress. An efficient and reliable decapsulation method consisting of thermal and chemical processes was developed in this study. The surface quality of chips after solder removal is satisfactory for the existing solder rework procedure as well as for die-level failure analysis. The innovative processes included heat-sink and ceramic substrate removal, solder bump separation, and solder residue cleaning from the chip surface. In the last stage, particular temperatures were selected for the removal of eutectic Pb-Sn, high-lead, and lead-free solders considering their respective melting points.