Application of Microchip for Biomarker Analysis

NASA Astrophysics Data System (ADS)

Kataoka, Masatoshi; Yatsushiro, Shouki; Yamamura, Shouhei; Abe, Hiroko

Microchip technologies have received considerable attention, due to their competitive advantages, especially in regards to reduced sample and reagent consumption, analysis time, and easy operation. This approach has been successfully used to analyze DNA, amino acids, proteins, and carbohydrates. In the present study, we showed the potential of microchip technologies for the biomarker analysis, blood carbohydrate analysis on microchip electrophoresis, quantitative analysis of protein with antigen-antibody reaction on microchip, and the detection of malaria-infected erythrocyte with a cell microarray chip.

Integration of a Graphite/PMMA CompositeElectrode into a Poly(methyl methacrylate) (PMMA) Substrate for Electrochemical Detection in Microchips

PubMed Central

Regel, Anne; Lunte, Susan

2013-01-01

Traditional fabrication methods for polymer microchips, the bonding of two substrates together to form the microchip, can make the integration of carbon electrodes difficult. We have developed a simple and inexpensive method to integrate graphite/PMMA composite electrodes (GPCEs) into a PMMA substrate. These substrates can be bonded to other PMMA layers using a solvent-assisted thermal bonding method. The optimal composition of the GPCEs for electrochemical detection was determined using cyclic voltammetry with dopamine as a test analyte. Using the optimized GPCEs in an all-PMMA flow cell with flow injection analysis, it was possible to detect 50 nM dopamine under the best conditions. These electrodes were also evaluated for the detection of dopamine and catechol following separation by microchip electrophoresis (ME). PMID:23670816

Integration of On-Chip Peristaltic Pumps and Injection Valves with Microchip Electrophoresis and Electrochemical Detection

PubMed Central

Bowen, Amanda L; Martin, R. Scott

2010-01-01

A microfluidic approach that integrates peristaltic pumping from an on-chip reservoir with injection valves, microchip electrophoresis and electrochemical detection is described. Fabrication and operation of both the peristaltic pumps and injection valves were optimized to ensure efficient pumping and discrete injections. The final device uses the peristaltic pumps to continuously direct sample from a reservoir containing a mixture of analytes to injection valves that are coupled with microchip electrophoresis and amperometric detection. The separation and direct detection of dopamine and norepinephrine were possible with this approach and the utility of the device was demonstrated by monitoring the stimulated release of these neurotransmitters from a layer of cells introduced into the microchip. It is also shown that this pumping/reservoir approach can be expanded to multiple reservoirs and pumps, where one reservoir can be addressed individually or multiple reservoirs sampled simultaneously. PMID:20665914

Customized oligonucleotide microchips that convert multiple genetic information to simple patterns, are portable and reusable

DOEpatents

Mirzabekov, Andrei; Guschin, Dmitry Y.; Chik, Valentine; Drobyshev, Aleksei; Fotin, Alexander; Yershov, Gennadiy; Lysov, Yuri

2002-01-01

This invention relates to using customized oligonucleotide microchips as biosensors for the detection and identification of nucleic acids specific for different genes, organisms and/or individuals in the environment, in food and in biological samples. The microchips are designed to convert multiple bits of genetic information into simpler patterns of signals that are interpreted as a unit. Because of an improved method of hybridizing oligonucleotides from samples to microchips, microchips are reusable and transportable. For field study, portable laser or bar code scanners are suitable.

Recent developments in optical detection methods for microchip separations.

PubMed

Götz, Sebastian; Karst, Uwe

2007-01-01

This paper summarizes the features and performances of optical detection systems currently applied in order to monitor separations on microchip devices. Fluorescence detection, which delivers very high sensitivity and selectivity, is still the most widely applied method of detection. Instruments utilizing laser-induced fluorescence (LIF) and lamp-based fluorescence along with recent applications of light-emitting diodes (LED) as excitation sources are also covered in this paper. Since chemiluminescence detection can be achieved using extremely simple devices which no longer require light sources and optical components for focusing and collimation, interesting approaches based on this technique are presented, too. Although UV/vis absorbance is a detection method that is commonly used in standard desktop electrophoresis and liquid chromatography instruments, it has not yet reached the same level of popularity for microchip applications. Current applications of UV/vis absorbance detection to microchip separations and innovative approaches that increase sensitivity are described. This article, which contains 85 references, focuses on developments and applications published within the last three years, points out exciting new approaches, and provides future perspectives on this field.

Detection of enteropathogenic Escherichia coli by microchip capillary electrophoresis.

PubMed

Law, Wai S; Li, Sam F Y; Kricka, Larry J

2009-01-01

There is always a need to detect the presence of microorganisms, either as contaminants in food and pharmaceutical industries or bioindicators for disease diagnosis. Hence, it is important to develop efficient, rapid, and simple methods to detect microorganisms. Traditional culturing method is unsatisfactory due to its long incubation time. Molecular methods, although capable of providing a high degree of specificity, are not always useful in providing quick tests of presence or absence of microorganisms. Microchip elec-trophoresis has been recently employed to address problems associated with the detection of microorganisms due to its high versatility, selectivity, sensitivity, and short analysis times. In this work, the potential of PDMS-based microchip electrophoresis in the identification and characterization of microorganism was evaluated. Enteropathogenic E. coli (EPEC) was selected as the model microorganism. To obtain repeat-able separations, sample pretreatment was found to be essential. Microchip electrophoresis with laser-induced fluorescence detection could potentially revolutionize certain aspects of microbiology involving diagnosis, profiling of pathogens, environmental analysis, and many others areas of study.

Comparison of body temperature readings between an implantable microchip and a cloacal probe in lorikeets (Trichoglossus haematodus sp.).

PubMed

Hoskinson, Christine; McCain, Stephanie; Allender, Matthew C

2014-01-01

Body temperature readings can be a useful diagnostic tool for identifying the presence of subclinical disease. Traditionally, rectal or cloacal thermometry has been used to obtain body temperatures. The use of implantable microchips to obtain these temperatures has been studied in a variety of animals, but not yet in avian species. Initially, timepoint one (T₁), nine lorikeets were anesthetized via facemask induction with 5% isoflurane and maintained at 2-3% for microchip placement and body temperature data collection. Body temperature was measured at 0 and 2 min post-anesthetic induction both cloacally, using a Cardell veterinary monitor and also via implantable microchip, utilizing a universal scanner. On two more occasions, timepoints two and three (T₂, T₃), the same nine lorikeets were manually restrained to obtain body temperature readings both cloacally and via microchip, again at minutes 0 and 2. There was no statistical difference between body temperatures, for both methods, at T₁. Microchip temperatures were statistically different than cloacal temperatures at T₂ and T₃. Body temperatures at T₁, were statistically different from those obtained at T₂ and T₃ for both methods. Additional studies are warranted to verify the accuracy of microchip core body temperature readings in avian species. © 2014 Wiley Periodicals, Inc.

Amperometric detector designs for capillary electrophoresis microchips.

PubMed

Castaño-Alvarez, Mario; Fernández-Abedul, M Teresa; Costa-García, Agustín

2006-03-24

Electrochemical (EC) detection is a sensitive and miniaturisable detection mode for capillary electrophoresis (CE) microchips. Detection cell design is very important in order to ensure electrical isolation from the high separation voltage. Amperometric detectors with different designs have been developed for coupling EC detection to CE-microchips. Different working electrode alignment: in-channel or end-channel has been tested in conjunction with several materials: gold, platinum or carbon. The end-channel detector was based on a platinum or gold wire manually aligned at the exit of the separation channel. Thick- (screen-printed carbon electrode) and thin-film (sputtered gold film) electrodes have also been employed with this configuration, but with a different design that allowed the rapid replacement of the electrode. The in-channel detector was based on a gold film within the separation channel. A gold-based dual electrode detector, which combined for the first time in- and end-channel detection, has been also tested. These amperometric detectors have been evaluated in combination to poly(methylmethacrylate) (PMMA) and Topas (thermoplastic olefin polymer of amorphous structure) CE-microchips. Topas is a new and promising cyclic olefin copolymer with high chemical resistance. Relevant parameters of the polymer microchip separation such as precision, efficiency or resolution and amperometric detection were studied with the different detector designs using p-aminophenol and L-ascorbic acid as model analytes in Tris-based buffer pH 9.0.

Analysis of Anions in Ambient Aerosols by Microchip Capillary Electrophoresis

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

Liu, Yan; MacDonald, David A.; Yu, Xiao-Ying

2006-10-01

We describe a microchip capillary electrophoresis method for the analysis of nitrate and sulfate in ambient aerosols. Investigating the chemical composition of ambient aerosol particles is essential for understanding their sources and effects. Significant progress has been made towards developing mass spectrometry-based instrumentation for rapid qualitative analysis of aerosols. Alternative methods for rapid quantification of selected high abundance compounds are needed to augment the capacity for widespread routine analysis. Such methods could provide much higher temporal and spatial resolution than can be achieved currently. Inorganic anions comprise a large percentage of particulate mass with nitrate and sulfate among the mostmore » abundant species. While ion chromatography has proven very useful for analyzing extracts of time-integrated ambient aerosol samples collected on filters and for semi-continuous, on-line particle composition measurements, there is a growing need for development of new compact, inexpensive approaches to routine on-line aerosol ion analysis for deployment in spatially dense, atmospheric measurement networks. Microchip capillary electrophoresis provides the necessary speed and portability to address this need. In this report, on-column contact conductivity detection is used with hydrodynamic injection to create a simple microchip instrument for analysis of nitrate and sulfate. On-column contact conductivity detection was achieved using a Pd decoupler placed upstream from the working electrodes. Microchips containing two Au or Pd working electrodes showed a good linear range (5-500 µM) and low limits-of-detection for sulfate and nitrate with Au providing the lowest detection limits (1 µM) for both ions. The completed microchip system was used to analyze ambient aerosol filter samples. Nitrate and sulfate concentrations measured by the microchip matched the concentrations measured by ion chromatography.« less

Laser-induced fluorescence microscopic system using an optical parametric oscillator for tunable detection in microchip analysis.

PubMed

Kumemura, Momoko; Odake, Tamao; Korenaga, Takashi

2005-06-01

A laser-induced fluorescence microscopic system based on optical parametric oscillation has been constructed as a tunable detector for microchip analysis. The detection limit of sulforhodamine B (Ex. 520 nm, Em. 570 nm) was 0.2 mumol, which was approximately eight orders of magnitude better than with a conventional fluorophotometer. The system was applied to the determination of fluorescence-labeled DNA (Ex. 494 nm, Em. 519 nm) in a microchannel and the detection limit reached a single molecule. These results showed the feasibility of this system as a highly sensitive and tunable fluorescence detector for microchip analysis.

Rapid sample screening method for authenticity controlling vanilla flavors using a CE microchip approach with electrochemical detection.

PubMed

Avila, Mónica; González, María Cristina; Zougagh, Mohammed; Escarpa, Alberto; Ríos, Angel

2007-11-01

Five vanilla-related flavors of food significance, vanillic alcohol (VOH), ethyl maltol (EMA), maltol (MAL), ethyl vanillin (EVA) and vanillin (VAN), were separated using CE microchips with electrochemical detection (CE-ED microchips). A +2 kV driving voltage for both injection and separation operation steps, using a borate buffer (pH 9.5, 20 mM) and 1 M nitric acid in the detection reservoir allowed the selective and sensitive detection of the target analytes in less than 200 s with reproducible control of EOF (RSD(migration times)<3%). The analysis in selected real vanilla samples was focusing on VAN and EVA because VAN is a basic fragrance compound of the vanilla aroma, whereas EVA is an unequivocal proof of adulteration of vanilla flavors. Fast detection of all relevant flavors (200 s) with an acceptable resolution (R(s) >1.5) and a high accuracy (recoveries higher than 90%) were obtained with independence of the matrices and samples examined. These results showed the reliability of the method and the potential use of CE microchips in the food control field for fraudulent purposes.

Micromotor-based lab-on-chip immunoassays

NASA Astrophysics Data System (ADS)

García, Miguel; Orozco, Jahir; Guix, Maria; Gao, Wei; Sattayasamitsathit, Sirilak; Escarpa, Alberto; Merkoçi, Arben; Wang, Joseph

2013-01-01

Here we describe the first example of using self-propelled antibody-functionalized synthetic catalytic microengines for capturing and transporting target proteins between the different reservoirs of a lab-on-a-chip (LOC) device. A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost layer, is further functionalized with the antibody receptor to selectively recognize and capture the target protein. The new motor-based microchip immunoassay operations are carried out without any bulk fluid flow, replacing the common washing steps in antibody-based protein bioassays with the active transport of the captured protein throughout the different reservoirs, where each step of the immunoassay takes place. A first microchip format involving an `on-the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the selective capture of the target protein, in the presence of excess of non-target proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the direct visualization of the binding events. In a second approach the immuno-nanomotor captures and transports the microsphere-tagged antigen through a microchannel network. An anti-protein-A modified microengine is finally used to demonstrate the selective capture, transport and convenient label-free optical detection of a Staphylococcus aureus target bacteria (containing proteinA in its cell wall) in the presence of a large excess of non-target (Saccharomyces cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers considerable potential for diverse applications in clinical diagnostics, environmental and security monitoring fields.Here we describe the first example of using self-propelled antibody-functionalized synthetic catalytic microengines for capturing and transporting target proteins between the different reservoirs of a lab-on-a-chip (LOC) device. A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost layer, is further functionalized with the antibody receptor to selectively recognize and capture the target protein. The new motor-based microchip immunoassay operations are carried out without any bulk fluid flow, replacing the common washing steps in antibody-based protein bioassays with the active transport of the captured protein throughout the different reservoirs, where each step of the immunoassay takes place. A first microchip format involving an `on-the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the selective capture of the target protein, in the presence of excess of non-target proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the direct visualization of the binding events. In a second approach the immuno-nanomotor captures and transports the microsphere-tagged antigen through a microchannel network. An anti-protein-A modified microengine is finally used to demonstrate the selective capture, transport and convenient label-free optical detection of a Staphylococcus aureus target bacteria (containing proteinA in its cell wall) in the presence of a large excess of non-target (Saccharomyces cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers considerable potential for diverse applications in clinical diagnostics, environmental and security monitoring fields. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr32400h

Microchip ELISA coupled with cell phone to detect ovarian cancer HE4 biomarker in urine.

PubMed

Wang, ShuQi; Akbas, Ragip; Demirci, Utkan

2015-01-01

Ovarian cancer is a leading cause of death from gynecologic cancers in the USA, and early diagnosis can potentially increase 5-year survival rate. Detection of biomarkers derived from hyperplasia of epithelial tissue by enzyme-linked immunosorbent assay (ELISA) proves to be a practical way of early diagnosis of ovarian cancer. However, ELISA is commonly performed in a laboratory setting, and it cannot be used in a clinical setting for on-site consultation. We have shown a microchip ELISA that detects HE4, an ovarian cancer biomarker, from urine using a cell phone integrated with a mobile application for imaging and data analysis. In microchip ELISA, HE4 from urine was first absorbed on the surface; the primary and secondary antibodies were subsequently anchored on the surface via immuno-reaction; and addition of substrate led to color development because of enzymatic labeling. The microchip after color development was imaged using a cell phone, and the color intensity was analyzed by an integrated mobile application. By comparing with an ELISA standard curve, the concentration of HE4 was reported on the cell phone screen. The presented microchip ELISA coupled with a cell phone is portable as opposed to traditional ELISA, and this method can facilitate the detection of ovarian cancer at the point-of-care (POC).

Fundamentals and practice for ultrasensitive laser-induced fluorescence detection in microanalytical systems.

PubMed

Johnson, Mitchell E; Landers, James P

2004-11-01

Laser-induced fluorescence is an extremely sensitive method for detection in chemical separations. In addition, it is well-suited to detection in small volumes, and as such is widely used for capillary electrophoresis and microchip-based separations. This review explores the detailed instrumental conditions required for sub-zeptomole, sub-picomolar detection limits. The key to achieving the best sensitivity is to use an excitation and emission volume that is matched to the separation system and that, simultaneously, will keep scattering and luminescence background to a minimum. We discuss how this is accomplished with confocal detection, 90 degrees on-capillary detection, and sheath-flow detection. It is shown that each of these methods have their advantages and disadvantages, but that all can be used to produce extremely sensitive detectors for capillary- or microchip-based separations. Analysis of these capabilities allows prediction of the optimal means of achieving ultrasensitive detection on microchips.

Poly(dimethylsiloxane) microchip-based immunoassay with multiple reaction zones: Toward on-chip multiplex detection platform

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

Shao, Guocheng; Wang, Jun; Li, Zhaohui

2011-09-20

In this work, a poly(dimethylsiloxane) (PDMS) microchip-based immuno-sensing platform with integrated pneumatic micro valves is described. The microchip was fabricated with multiple layer soft lithography technology. By controlling the activation status of corresponding valves, reagent flows in the microchannel network can be well manipulated so that immuno-reactions only take place at designated reaction zones (DRZs). Four DRZs are included in the prototype microchip. Since these DRZs are all isolated from each other by micro valves, cross contamination is prevented. Using the inner surface of the all-PDMS microchannel as immunoassay substrate, on-chip sandwich format solid phase immunoassay was performed to demonstratemore » the feasibility of this immuno-sensing platform. Mouse IgG and fluorescein isothiocyanate (FITC) were used as the model analyte and the signal reporter respectively. Only 10 ul sample is needed for the assay and low detection limit of 5 ng/ml (≈33 pM) was achieved though low-cost polyclonal antibodies were used in our experiment for feasibility study only. The encouraging results from mouse IgG immunoassay proved the feasibility of our microchip design. With slight modification of the assay protocol, the same chip design can be used for multi-target detection and can provide a simple, cost-effective and integrated microchip solution for multiplex immunoassay applications.« less

CE microchips: an opened gate to food analysis.

PubMed

Escarpa, Alberto; González, María Cristina; Crevillén, Agustín González; Blasco, Antonio Javier

2007-03-01

CE microchips are the first generation of micrototal analysis systems (-TAS) emerging in the miniaturization scene of food analysis. CE microchips for food analysis are fabricated in both glass and polymer materials, such as PDMS and poly(methyl methacrylate) (PMMA), and use simple layouts of simple and double T crosses. Nowadays, the detection route preferred is electrochemical in both, amperometry and conductivity modes, using end-channel and contactless configurations, respectively. Food applications using CE microchips are now emerging since food samples present complex matrices, the selectivity being a very important challenge because the total integration of analytical steps into microchip format is very difficult. As a consequence, the first contributions that have recently appeared in the relevant literature are based primarily on fast separations of analytes of high food significance. These protocols are combined with different strategies to achieve selectivity using a suitable nonextensive sample preparation and/or strategically choosing detection routes. Polyphenolic compounds, amino acids, preservatives, and organic and inorganic ions have been studied using CE microchips. Thus, new and exciting future expectations arise in the domain of food analysis. However, several drawbacks could easily be found and assumed within the miniaturization map.

Allergen extracts and recombinant proteins: comparison of efficiency of in vitro allergy diagnostics using multiplex assay on a biological microchip.

PubMed

Smoldovskaya, Olga; Feyzkhanova, Guzel; Arefieva, Alla; Voloshin, Sergei; Ivashkina, Olga; Reznikov, Yuriy; Rubina, Alla

2016-01-01

Immunological test systems for diagnostics of type I hypersensitivity involve the following types of antigens: whole allergen extracts, individual highly purified proteins and their recombinant analogues. The goal of this study was to compare the results obtained with whole allergen extracts (birch pollen, cat dander, and timothy grass pollen) and their respective recombinant proteins in biochip-based immunoassay. Multiplex fluorescent immunoassay of 139 patients' blood serum samples was carried out using biological microchips (biochips). sIgE concentrations for the chosen allergens and their recombinant components were measured. ROC analysis was used for comparison of the results and determination of diagnostic accuracy. The results for the birch pollen extract and its recombinant allergens have shown that the diagnostic accuracy of the methods utilizing the whole allergen extract, its major component Bet v 1 and the combination of major and minor components (Bet v 1 and Bet v 2) was the same. Values for diagnostic accuracy for the cat dander extract and its major recombinant component Fel d 1 were equal. In contrast with birch pollen and cat dander allergens, using of recombinant components of timothy grass pollen (Phl p 1, Phl p 5, Phl p 7 and Phl p 12) did not allow reaching the diagnostic accuracy of using natural extract. Multiplex analysis of samples obtained from patients with allergy to birch pollen and cat dander using biological microchips has shown that comparable accuracy was observed for the assay with natural extracts and recombinant allergens. In the case of timothy grass allergen, using the recombinant components may be insufficient.

Polymer microchip CE of proteins either off- or on-chip labeled with chameleon dye for simplified analysis.

PubMed

Yu, Ming; Wang, Hsiang-Yu; Woolley, Adam T

2009-12-01

Microchip CE of proteins labeled either off- or on-chip with the "chameleon" CE dye 503 using poly(methyl methacrylate) microchips is presented. A simple dynamic coating using the cationic surfactant CTAB prevented nonspecific adsorption of protein and dye to the channel walls. The labeling reactions for both off- and on-chip labeling proceeded at room temperature without requiring heating steps. In off-chip labeling, a 9 ng/mL concentration detection limit for BSA, corresponding to a approximately 7 fg (100 zmol) mass detection limit, was obtained. In on-chip tagging, the free dye and protein were placed in different reservoirs of the microchip, and an extra incubation step was not needed. A 1 microg/mL concentration detection limit for BSA, corresponding to a approximately 700 fg (10 amol) mass detection limit, was obtained from this protocol. The earlier elution time of the BSA peak in on-chip labeling resulted from fewer total labels on each protein molecule. Our on-chip labeling method is an important part of automation in miniaturized devices.

A three-layer PMMA electrophoresis microchip with Pt microelectrodes insulated by a thin film for contactless conductivity detection.

PubMed

Liu, Junshan; Wang, Junyao; Chen, Zuanguang; Yu, Yong; Yang, Xiujuan; Zhang, Xianbin; Xu, Zheng; Liu, Chong

2011-03-07

A three-layer poly (methyl methacrylate) (PMMA) electrophoresis microchip integrated with Pt microelectrodes for contactless conductivity detection is presented. A 50 μm-thick PMMA film is used as the insulating layer and placed between the channel plate (containing the microchannel) and the electrode plate (containing the microelectrode). The three-layer structure facilitates the achievement of a thin insulating layer, obviates the difficulty of integrating microelectrodes on a thin film, and does not compromise the integration of microchips. To overcome the thermal and chemical incompatibilities of polymers and photolithographic techniques, a modified lift-off process was developed to integrate Pt microelectrodes onto the PMMA substrate. A novel two-step bonding method was created to assemble the complete PMMA microchip. A low limit of detection of 1.25 μg ml(-1) for Na(+) and high separation efficiency of 77,000 and 48,000 plates/m for Na(+) and K(+) were obtained when operating the detector at a low excitation frequency of 60 kHz.

Microchip electrophoresis with electrochemical detection for the determination of analytes in the dopamine metabolic pathway

PubMed Central

Saylor, Rachel A.; Reid, Erin A.; Lunte, Susan M.

2016-01-01

A method for the separation and detection of analytes in the dopamine metabolic pathway was developed using microchip electrophoresis with electrochemical detection. The microchip consisted of a 5 cm PDMS separation channel in a simple-t configuration. Analytes in the dopamine metabolic pathway were separated using a background electrolyte composed of 15 mM phosphate at pH 7.4, 15 mM SDS, and 2.5 mM boric acid. Two different microchip substrates using different electrode materials were compared for the analysis: a PDMS/PDMS device with a carbon fiber electrode and a PDMS/glass hybrid device with a pyrolyzed photoresist film carbon electrode. While the PDMS/PDMS device generated high separation efficiencies and good resolution, more reproducible migration times were obtained with the PDMS/glass hybrid device, making it a better choice for biological applications. Lastly, the optimized method was used to monitor L-DOPA metabolism in a rat brain slice. PMID:25958983

Rapid detection of EBOLA VP40 in microchip immunofiltration assay

NASA Astrophysics Data System (ADS)

Miethe, Peter; Gary, Dominik; Hlawatsch, Nadine; Gad, Anne-Marie

2015-05-01

In the spring of 2014, the Ebola virus (EBOV) strain Zaire caused a dramatic outbreak in several regions of West Africa. The RT-PCR and antigen capture diagnostic proved to be effective for detecting EBOV in blood and serum. In this paper, we present data of a rapid antigen capture test for the detection of VP40. The test was performed in a microfluidic chip for immunofiltration analysis. The chip integrates all necessary assay components. The analytical sensitivity of the rapid test was 8 ng/ml for recombinant VP40. In serum and whole blood samples spiked with virus culture material, the detection limit was 2.2 x 102 PFU/ml. The performance data of the rapid test (15 min) are comparable to that of the VP40 laboratory ELISA.

Integration of Microdialysis Sampling and Microchip Electrophoresis with Electrochemical Detection

PubMed Central

Mecker, Laura C.; Martin, R. Scott

2009-01-01

Here we describe the fabrication, optimization, and application of a microfluidic device that integrates microdialysis (MD) sampling, microchip electrophoresis (ME), and electrochemical detection (EC). The manner in which the chip is produced is reproducible and enables the fixed alignment of the MD/ME and ME/EC interfaces. Poly(dimethylsiloxane) (PDMS) -based valves were used for the discrete injection of sample from the hydrodynamic MD dialysate stream into a separation channel for analysis with ME. To enable the integration of ME with EC detection, a palladium decoupler was used to isolate the high voltages associated with electrophoresis from micron-sized carbon ink detection electrodes. Optimization of the ME/EC interface was needed to allow the use of biologically appropriate perfusate buffers containing high salt content. This optimization included changes in the fabrication procedure, increases in the decoupler surface area, and a programmed voltage shutoff. The ability of the MD/ME/EC system to sample a biological system was demonstrated by using a linear probe to monitor the stimulated release of dopamine from a confluent layer of PC 12 cells. To our knowledge, this is the first report of a microchip-based system that couples microdialysis sampling with microchip electrophoresis and electrochemical detection. PMID:19551945

A review of microdialysis coupled to microchip electrophoresis for monitoring biological events

PubMed Central

Saylor, Rachel A.; Lunte, Susan M.

2015-01-01

Microdialysis is a powerful sampling technique that enables monitoring of dynamic processes in vitro and in vivo. The combination of microdialysis with chromatographic or electrophoretic methods yields along with selective detection methods yields a “separation-based sensor” capable of monitoring multiple analytes in near real time. Analysis of microdialysis samples requires techniques that are fast (<1 min), have low volume requirements (nL–pL), and, ideally, can be employed on-line. Microchip electrophoresis fulfills these requirements and also permits the possibility of integrating sample preparation and manipulation with detection strategies directly on-chip. Microdialysis coupled to microchip electrophoresis has been employed for monitoring biological events in vivo and in vitro. This review discusses technical considerations for coupling microdialysis sampling and microchip electrophoresis, including various interface designs, and current applications in the field. PMID:25637011

Microchannel-electrode alignment and separation parameters comparison in microchip capillary electrophoresis by scanning electrochemical microscopy.

PubMed

Wang, Kang; Xia, Xing-Hua

2006-03-31

The end of separation channel in a microchip was electrochemically mapped using the feedback imaging mode of scanning electrochemical microscopy (SECM). This method provides a convenient way for microchannel-electrode alignment in microchip capillary electrophoresis. Influence of electrode-to-channel positions on separation parameters in this capillary electrophoresis-electrochemical detection (CE-ED) was then investigated. For the trapezoid shaped microchannel, detection in the central area resulted in the best apparent separation efficiency and peak shape. In the electrode-to-channel distance ranging from 65 to 15mum, the limiting peak currents of dopamine increased with the decrease of the detection distance due to the limited diffusion and convection of the sample band. Results showed that radial position and axial distance of the detection electrode to microchannel was important for the improvement of separation parameters in CE amperometric detection.

Polymer microchip capillary electrophoresis of proteins either off- or on-chip labeled with chameleon dye for simplified analysis

PubMed Central

Yu, Ming; Wang, Hsiang-Yu; Woolley, Adam

2009-01-01

Microchip capillary electrophoresis of proteins labeled either off- or on-chip with the “chameleon” CE dye 503 using poly(methyl methacrylate) microchips is presented. A simple dynamic coating using the cationic surfactant cetyltrimethyl ammonium bromide prevented nonspecific adsorption of protein and dye to the channel walls. The labeling reactions for both off- and on-chip labeling proceeded at room temperature without requiring heating steps. In off-chip labeling, a 9 ng/mL concentration detection limit for bovine serum albumin (BSA), corresponding to a ~7 fg (100 zmol) mass detection limit, was obtained. In on-chip tagging, the free dye and protein were placed in different reservoirs of the microchip, and an extra incubation step was not needed. A 1 μg/mL concentration detection limit for BSA, corresponding to a ~700 fg (10 amol) mass detection limit, was obtained from this protocol. The earlier elution time of the BSA peak in on-chip labeling resulted from fewer total labels on each protein molecule. Our on-chip labeling method is an important part of automation in miniaturized devices. PMID:19924700

Sensitive, label-free protein assay using 1-ethyl-3-methylimidazolium tetrafluoroborate-supported microchip electrophoresis with laser-induced fluorescence detection.

PubMed

Xu, Yuanhong; Li, Jing; Wang, Erkang

2008-05-01

Based on the dimer-monomer equilibrium movement of the fluorescent dye Pyronin Y (PY), a rapid, simple, highly sensitive, label-free method for protein detection was developed by microchip electrophoresis with LIF detection. PY formed a nonfluorescent dimer induced by the premicellar aggregation of an anionic surfactant, SDS, however, the fluorescence intensity of the system increased dramatically when proteins such as BSA, bovine hemoglobin, cytochrome c, and trypsin were added to the solution due to the transition of dimer to fluorescent monomer. Furthermore, 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF4) instead of PBS was applied as running buffers in microchip electrophoresis. Due to the excellent properties of EMImBF4, not only nonspecific protein adsorption was more efficiently suppressed, but also approximately ten-fold higher fluorescence intensity enhancement was obtained than that using PBS. Under the optimal conditions, detection limits for BSA, bovine hemoglobin, cytochrome c, and trypsin were 1.00x10(-6), 2x10(-6), 7x10(-7), and 5x10(-7) mg/mL, respectively. Thus, without covalent modification of the protein, a protein assay method with high sensitivity was achieved on microchips.

Integration of Microchip Electrophoresis with Electrochemical Detection Using an Epoxy-Based Molding Method to Embed Multiple Electrode Materials

PubMed Central

Johnson, Alicia S.; Selimovic, Asmira; Martin, R. Scott

2012-01-01

This paper describes the use of epoxy-encapsulated electrodes to integrate microchip-based electrophoresis with electrochemical detection. Devices with various electrode combinations can easily be developed. This includes a palladium decoupler with a downstream working electrode material of either gold, mercury/gold, platinum, glassy carbon, or a carbon fiber bundle. Additional device components such as the platinum wires for the electrophoresis separation and the counter electrode for detection can also be integrated into the epoxy base. The effect of the decoupler configuration was studied in terms of the separation performance, detector noise, and the ability to analyze samples of a high ionic strength. The ability of both glassy carbon and carbon fiber bundle electrodes to analyze a complex mixture was demonstrated. It was also shown that a PDMS-based valving microchip can be used along with the epoxy embedded electrodes to integrate microdialysis sampling with microchip electrophoresis and electrochemical detection, with the microdialysis tubing also being embedded in the epoxy substrate. This approach enables one to vary the detection electrode material as desired in a manner where the electrodes can be polished and modified in a similar fashion to electrochemical flow cells used in liquid chromatography. PMID:22038707

Fast analysis of domoic acid using microchip electrophoresis with laser-induced fluorescence detection.

PubMed

Cheng, Yongqiang; Guo, Cuilian; Zhao, Bin; Yang, Li

2017-04-01

A fast and effective method was developed to detect domoic acid based upon microchip electrophoresis combined with laser-induced fluorescence detection. Through study of the gated injection process on the cross channel of the microchip, the low-voltage mode with relatively longer sample loading time was adopted to reduce the sample discrimination and improve the signal sensitivity. Fluorescein isothiocyanate was used as the derivatizing reagent for domoic acid. Under the optimized conditions, domoic acid was completely separated in 60 s with separation efficiency of 1.35 × 10 5  m -1 . The calibration curve was obtained in the range of 1.0 × 10 -9 to 1.0 × 10 -7  mol/L, and the detection limit reached 2.8 × 10 -10  mol/L. This developed method was successfully applied to analyze domoic acid in real samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microchip assays for screening monoclonal antibody product quality.

PubMed

Chen, Xiaoyu; Tang, Kaiyan; Lee, Maximilian; Flynn, Gregory C

2008-12-01

Microchip CE-SDS was evaluated as a high-throughput alternative to conventional CE-SDS for monitoring monoclonal antibody protein quality. A commercial instrument (LabChip) 90) was used to separate dodecyl sulfate coated proteins through a sieving polymer based on the proteins' sizes. Under reducing conditions, the microchip CE-SDS separation was similar to that of conventional CE-SDS, providing reasonable resolution of the non-glycosylated and the glycosylated heavy chains. The fluorescence detection on LabChip 90 using non-covalent fluorescent labeling method was about as sensitive as the 220 nm UV detection used in a conventional CE instrument. A simple glycan typing assay was developed for the reducing microchip CE-SDS format. Antibodies, either pure or in crude cell culture media are treated with Endoglycosidase H, which specifically cleaves the hybrid and high mannose type glycans. A heavy chain migration shift on reducing CE-SDS resulting from the loss of glycan is used to measure the level of high mannose/hybrid type glycans as a percentage of the total glycans. Microchip CE-SDS, under both non-reducing and reducing conditions, can be used in a variety of antibody product screening assays. The microchip analyses provide sufficient resolution and sensitivity for this purpose but on a time scale approximately 70 times faster (41 s versus 50 min per sample) than conventional CE separation under typical operational conditions.

Inner structure detection by optical tomography technology based on feedback of microchip Nd:YAG lasers.

PubMed

Xu, Chunxin; Zhang, Shulian; Tan, Yidong; Zhao, Shijie

2013-05-20

We describe a new optical tomography technology based on feedback of microchip Nd:YAG lasers. In the case of feedback light frequency-shifted, light can be magnified by a fact of 10(6) in the Nd:YAG microchip lasers, which makes it possible to realize optical tomography with a greater depth than current optical tomography. The results of the measuring and imaging of kinds of samples are presented, which demonstrate the feasibility and potential of this approach in the inner structure detection. The system has a lateral resolution of ~1 μm, a vertical resolution of 15 μm and a longitudinal scanning range of over 10mm.

A compactly integrated laser-induced fluorescence detector for microchip electrophoresis.

PubMed

Li, Hai-Fang; Lin, Jin-Ming; Su, Rong-Guo; Uchiyama, Katsumi; Hobo, Toshiyuki

2004-06-01

A simple and easy-to-use integrated laser-induced fluorescence detector for microchip electrophoresis was constructed and evaluated. The fluid channels and optical fiber channels in the glass microchip were fabricated using standard photolithographic techniques and wet chemical etching. A 473 nm diode-pumped laser was used as the excitation source, and the collimation and collection optics and mirrors were discarded by using a multimode optical fiber to couple the excitation light straight into the microchannel and placing the microchip directly on the top of the photomultiplier tube. A combination of filter systems was incorporated into a poly(dimethylsiloxane) layer, which was reversibly sealed to the bottom of the microchip to eliminate the scattering excitation light reaching to the photomultiplier tube. Fluorescein/calcein samples were taken as model analytes to evaluate the performance with respect to design factors. The detection limits were 0.05 microM for fluorescein and 0.18 microM for calcein, respectively. The suitability of this simple detector for fluorescence detection was demonstrated by baseline separation of fluorescein isothiocyanate (FITC)-labeled arginine, phenylalanine, and glycine and FITC within 30 s at separation length of 3.8 cm and electrical field strength of 600 V/cm.

Micromotor-based lab-on-chip immunoassays.

PubMed

García, Miguel; Orozco, Jahir; Guix, Maria; Gao, Wei; Sattayasamitsathit, Sirilak; Escarpa, Alberto; Merkoçi, Arben; Wang, Joseph

2013-02-21

Here we describe the first example of using self-propelled antibody-functionalized synthetic catalytic microengines for capturing and transporting target proteins between the different reservoirs of a lab-on-a-chip (LOC) device. A new catalytic polymer/Ni/Pt microtube engine, containing carboxy moieties on its mixed poly(3,4-ethylenedioxythiophene) (PEDOT)/COOH-PEDOT polymeric outermost layer, is further functionalized with the antibody receptor to selectively recognize and capture the target protein. The new motor-based microchip immunoassay operations are carried out without any bulk fluid flow, replacing the common washing steps in antibody-based protein bioassays with the active transport of the captured protein throughout the different reservoirs, where each step of the immunoassay takes place. A first microchip format involving an 'on-the-fly' double-antibody sandwich assay (DASA) is used for demonstrating the selective capture of the target protein, in the presence of excess of non-target proteins. A secondary antibody tagged with a polymeric-sphere tracer allows the direct visualization of the binding events. In a second approach the immuno-nanomotor captures and transports the microsphere-tagged antigen through a microchannel network. An anti-protein-A modified microengine is finally used to demonstrate the selective capture, transport and convenient label-free optical detection of a Staphylococcus aureus target bacteria (containing proteinA in its cell wall) in the presence of a large excess of non-target (Saccharomyces cerevisiae) cells. The resulting nanomotor-based microchip immunoassay offers considerable potential for diverse applications in clinical diagnostics, environmental and security monitoring fields.

Diagnosis of Periodontal Diseases by Biomarkers

NASA Astrophysics Data System (ADS)

Kido, Jun-Ichi; Hino, Mami; Bando, Mika; Hiroshima, Yuka

Many middle aged and old persons take periodontal diseases that mainly cause teeth loss and result in some systemic diseases. The prevention of periodontal diseases is very important for oral and systemic health, but the present diagnostic examination is not fully objective and suitable. To diagnose periodontal diseases exactly, some biomarkers shown inflammation, tissue degradation and bone resorption, in gingival crevicular fluid (GCF) and saliva are known. We demonstrated that GCF levels of calprotectin, inflammation-related protein, and carboxy-terminal propeptide of type I procollagen, bone metabolism-related protein, were associated with clinical condition of periodontal diseases, and suggested that these proteins may be useful biomarkers for periodontal diseases. Recently, determinations of genes and proteins by using microdevices are studied for diagnosis of some diseases. We detected calprotectin protein by chemiluminescent immunoassay on a microchip and showed the possibility of specific and quantitative detection of calprotectin in a very small amount of GCF. To determine plural markers in GCF by using microdevices contributes to develop accurate, objective diagnostic system of periodontal diseases.

Coupling Microdialysis Sampling to Microchip Electrophoresis in a Reversibly Sealed Device

PubMed Central

Mecker, Laura C.; Martin, R. Scott

2007-01-01

In this paper, we describe the fabrication and characterization of a reversibly sealed microchip device that is used to couple microdialysis sampling to microchip electrophoresis. The ability to interface microdialysis sampling and microchip electrophoresis in a device that is amenable to reversible sealing is advantageous from a repeated use standpoint. Commercially available tubing coming from the microdialysis probe is directly inserted into the chip and flow from the probe is interfaced to the electrophoresis portion of the device through integrated pneumatic valves. Fluorescence detection was used to characterize the poly(dimethylsiloxane)-based device in terms of injection reproducibility. It was found that the entire system (microdialysis probe and microchip device) has a concentration response lag time of 170 sec. Microdialysis sampling followed by an electrophoretic separation of amino acids derivatized with naphthalene-2,3-dicarboxaldehyde/cyanide was also demonstrated. PMID:18836517

Integration of serpentine channels for microchip electrophoresis with a palladium decoupler and electrochemical detection

PubMed Central

Bowen, Amanda L; Martin, R. Scott

2010-01-01

While it has been shown that microchip electrophoresis with electrochemical detection can be used to separate and detect electroactive species, there is a need to increase the separation performance of these devices so that complex mixtures can be routinely analyzed. Previous work in microchip electrophoresis has demonstrated that increasing the separation channel length leads to an increase in resolution between closely eluting analytes. This paper details the use of lengthened serpentine microchannels for microchip electrophoresis and electrochemical detection where a palladium decoupler is used to ground the separation voltage so that the working electrodes remain in the fluidic network. In this work, palladium electrodepositions were used to increase the decoupler surface area and more efficiently dissipate hydrogen produced at the decoupler. Dopamine and norepinephrine, which only differ in structure by a hydroxyl group, were used as model analytes. It was found that increasing the separation channel length led to improvements in both resolution and the number of theoretical plates for these analytes. The use of a bi-layer valving device, where PDMS-based valves are utilized for the injection process, along with serpentine microchannels and amperometric detection resulted in a multi-analyte separation and an average of 28,700 theoretical plates. It was also shown that the increased channel length is beneficial when separating and detecting analytes from a high ionic strength matrix. This was demonstrated by monitoring the stimulated release of neuro-transmitters from a confluent layer of PC 12 cells. PMID:19739137

Integrated Micro-Chip Amino Acid Chirality Detector for MOD

NASA Technical Reports Server (NTRS)

Glavin, D. P.; Bada, J. L.; Botta, O.; Kminek, G.; Grunthaner, F.; Mathies, R.

2001-01-01

Integration of a micro-chip capillary electrophoresis analyzer with a sublimation-based extraction technique, as used in the Mars Organic Detector (MOD), for the in-situ detection of amino acids and their enantiomers on solar system bodies. Additional information is contained in the original extended abstract.

Polymeric microchip for the simultaneous determination of anions and cations by hydrodynamic injection using a dual-channel sequential injection microchip electrophoresis system.

PubMed

Gaudry, Adam J; Nai, Yi Heng; Guijt, Rosanne M; Breadmore, Michael C

2014-04-01

A dual-channel sequential injection microchip capillary electrophoresis system with pressure-driven injection is demonstrated for simultaneous separations of anions and cations from a single sample. The poly(methyl methacrylate) (PMMA) microchips feature integral in-plane contactless conductivity detection electrodes. A novel, hydrodynamic "split-injection" method utilizes background electrolyte (BGE) sheathing to gate the sample flows, while control over the injection volume is achieved by balancing hydrodynamic resistances using external hydrodynamic resistors. Injection is realized by a unique flow-through interface, allowing for automated, continuous sampling for sequential injection analysis by microchip electrophoresis. The developed system was very robust, with individual microchips used for up to 2000 analyses with lifetimes limited by irreversible blockages of the microchannels. The unique dual-channel geometry was demonstrated by the simultaneous separation of three cations and three anions in individual microchannels in under 40 s with limits of detection (LODs) ranging from 1.5 to 24 μM. From a series of 100 sequential injections the %RSDs were determined for every fifth run, resulting in %RSDs for migration times that ranged from 0.3 to 0.7 (n = 20) and 2.3 to 4.5 for peak area (n = 20). This system offers low LODs and a high degree of reproducibility and robustness while the hydrodynamic injection eliminates electrokinetic bias during injection, making it attractive for a wide range of rapid, sensitive, and quantitative online analytical applications.

Trace analysis of D-tyrosine in biological samples by microchip electrophoresis with laser induced fluorescence detection.

PubMed

Huang, Yong; Shi, Ming; Zhao, Shulin; Liang, Hong

2011-11-01

A rapid and sensitive microchip electrophoresis (MCE) method with laser induced fluorescence (LIF) detection has been developed for the quantification of D-tyrosine (Tyr) in biological samples. The assay was performed using a MCE-LIF system with glass/poly(dimethylsiloxane) (PDMS) hybrid microchip after pre-column derivatization of amino acids with fluorescein isothiocyanate (FITC). Chiral separation of the derivatives was achieved by cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) using γ-CD as chiral selector in the running buffer. D/L-Tyr enantiomer was well separated in less than 140s. The limit of detection (S/N=3) was 3.3 × 10(-8) M. Using the present method, D-Tyr level in human plasma was found to vary significantly from normal humans to patients suffering from renal failure. Copyright © 2011 Elsevier B.V. All rights reserved.

PCR amplification on microarrays of gel immobilized oligonucleotides

DOEpatents

Strizhkov, Boris; Tillib, Sergei; Mikhailovich, Vladimir; Mirzabekov, Andrei

2003-11-04

The invention relates two general methods for performing PCR amplification, combined with the detection and analysis of the PCR products on a microchip. In the first method, the amplification occurs both outside and within a plurality of gel pads on a microchip, with at least one oligonucleotide primer immobilized in a gel pad. In the second method, PCR amplification also takes place within gel pads on a microchip, but the pads are surrounded by a hydrophobic liquid such as that which separates the individual gel pads into environments which resemble micro-miniaturized test tubes.

Microchip-based Integration of Cell Immobilization, Electrophoresis, Post-column Derivatization, and Fluorescence Detection for Monitoring the Release of Dopamine from PC 12 Cells

PubMed Central

Li, Michelle W.; Martin, R. Scott

2008-01-01

In this paper, we describe the fabrication and evaluation of a multilayer microchip device that can be used to quantitatively measure the amount of catecholamines released from PC 12 cells immobilized within the same device. This approach allows immobilized cells to be stimulated on-chip and, through rapid actuation of integrated microvalves, the products released from the cells are repeatedly injected into the electrophoresis portion of the microchip, where the analytes are separated based upon mass and charge and detected through post-column derivatization and fluorescence detection. Following optimization of the post-column derivatization detection scheme (using naphthalene-2,3-dicarboxaldehyde and 2-β-mercaptoethanol), off-chip cell stimulation experiments were performed to demonstrate the ability of this device to detect dopamine from a population of PC 12 cells. The final 3-dimensional device that integrates an immobilized PC 12 cell reactor with the bilayer continuous flow sampling/electrophoresis microchip was used to continuously monitor the on-chip stimulated release of dopamine from PC 12 cells. Similar dopamine release was seen when stimulating on-chip versus off-chip yet the on-chip immobilization studies could be carried out with 500 times fewer cells in a much reduced volume. While this paper is focused on PC 12 cells and neurotransmitter analysis, the final device is a general analytical tool that is amenable to immobilization of a variety of cell lines and analysis of various released analytes by electrophoretic means. PMID:18810283

The Optimization of Electrophoresis on a Glass Microfluidic Chip and its Application in Forensic Science.

PubMed

Han, Jun P; Sun, Jing; Wang, Le; Liu, Peng; Zhuang, Bin; Zhao, Lei; Liu, Yao; Li, Cai X

2017-11-01

Microfluidic chips offer significant speed, cost, and sensitivity advantages, but numerous parameters must be optimized to provide microchip electrophoresis detection. Experiments were conducted to study the factors, including sieving matrices (the concentration and type), surface modification, analysis temperature, and electric field strengths, which all impact the effectiveness of microchip electrophoresis detection of DNA samples. Our results showed that the best resolution for ssDNA was observed using 4.5% w/v (7 M urea) lab-fabricated LPA gel, dynamic wall coating of the microchannel, electrophoresis temperatures between 55 and 60°C, and electrical fields between 350 and 450 V/cm on the microchip-based capillary electrophoresis (μCE) system. One base-pair resolution could be achieved in the 19-cm-length microchannel. Furthermore, both 9947A standard genomic DNA and DNA extracted from blood spots were demonstrated to be successfully separated with well-resolved DNA peaks in 8 min. Therefore, the microchip electrophoresis system demonstrated good potential for rapid forensic DNA analysis. © 2017 American Academy of Forensic Sciences.

Fast electrophoretic analysis of individual mitochondria using microchip capillary electrophoresis with laser induced fluorescence detection.

PubMed

Duffy, Ciarán F; MacCraith, Brian; Diamond, Dermot; O'Kennedy, Richard; Arriaga, Edgar A

2006-08-01

The analysis of mitochondria by capillary electrophoresis usually takes longer than 20 min per replicate which may compromise the quality of the mitochondria due to degradation. In addition, low sample consumption may be beneficial in the analysis of rare or difficult samples. In this report, we demonstrate the ability to analyze individual mitochondrial events in picoliter-volume samples (approximately 80 pL) taken from a bovine liver preparation using microchip capillary electrophoresis with laser-induced fluorescence detection (micro-chip CE-LIF). Using a commercial "double-T" glass microchip, the sample was electrokinetically loaded in the "double-T" intersection and then subjected to electrophoretic separation along the main separation channel. In order to decrease interactions of mitochondria with channel walls during the analysis, poly(vinyl alcohol) was used as a dynamic coating. This procedure eliminates the need for complicated covalent surface modifications within the channels that were previously used in capillary electrophoresis methods. For analysis, mitochondria, isolated from bovine liver tissue, were selectively labelled using 10-nonyl acridine orange (NAO). The results consist of electropherograms where each mitochondrial event is a narrow spike (240 +/- 44 ms). While the spike intensity is representative of its NAO content, its migration time is used to calculate and describe its electrophoretic mobility, which is a property still largely unexplored for intracellular organelles. The five-fold decrease in separation time (4 min for microchip versus 20 min for capillary electrophoresis) makes microchip electrophoretic separations of organelles a faster, sensitive, low-sample volume alternative for the characterization of individual organelle properties and for investigations of subcellular heterogeneity.

Encapsulation of Fluidic Tubing and Microelectrodes in Microfluidic Devices: Integrating Off-Chip Process and Coupling Conventional Capillary Electrophoresis with Electrochemical Detection

PubMed Central

Becirovic, Vedada; Doonan, Steven R.; Martin, R. Scott

2013-01-01

In this paper, an approach to fabricate epoxy or polystyrene microdevices with encapsulated tubing and electrodes is described. Key features of this approach include a fixed alignment between the fluidic tubing and electrodes, the ability to polish the device when desired, and the low dead volume nature of the fluidic interconnects. It is shown that a variety of tubing can be encapsulated with this approach, including fused silica capillary, polyetheretherketone (PEEK), and perfluoroalkoxy (PFA), with the resulting tubing/microchip interface not leading to significant band broadening or plug dilution. The applicability of the devices with embedded tubing is demonstrated by integrating several off-chip analytical methods to the microchip. This includes droplet transfer, droplet desegmentation, and microchip-based flow injection analysis. Off-chip generated droplets can be transferred to the microchip with minimal coalescence, while flow injection studies showed improved peak shape and sensitivity when compared to the use of fluidic interconnects with an appreciable dead volume. Importantly, it is shown that this low dead volume approach can be extended to also enable the integration of conventional capillary electrophoresis (CE) with electrochemical detection. This is accomplished by embedding fused silica capillary along with palladium (for grounding the electrophoresis voltage) and platinum (for detection) electrodes. With this approach, up to 128,000 theoretical plates for dopamine was possible. In all cases, the tubing and electrodes are housed in a rigid base; this results in extremely robust devices that will be of interest to researchers wanting to develop microchips for use by non-experts. PMID:24159363

Encapsulation of Fluidic Tubing and Microelectrodes in Microfluidic Devices: Integrating Off-Chip Process and Coupling Conventional Capillary Electrophoresis with Electrochemical Detection.

PubMed

Becirovic, Vedada; Doonan, Steven R; Martin, R Scott

2013-08-21

In this paper, an approach to fabricate epoxy or polystyrene microdevices with encapsulated tubing and electrodes is described. Key features of this approach include a fixed alignment between the fluidic tubing and electrodes, the ability to polish the device when desired, and the low dead volume nature of the fluidic interconnects. It is shown that a variety of tubing can be encapsulated with this approach, including fused silica capillary, polyetheretherketone (PEEK), and perfluoroalkoxy (PFA), with the resulting tubing/microchip interface not leading to significant band broadening or plug dilution. The applicability of the devices with embedded tubing is demonstrated by integrating several off-chip analytical methods to the microchip. This includes droplet transfer, droplet desegmentation, and microchip-based flow injection analysis. Off-chip generated droplets can be transferred to the microchip with minimal coalescence, while flow injection studies showed improved peak shape and sensitivity when compared to the use of fluidic interconnects with an appreciable dead volume. Importantly, it is shown that this low dead volume approach can be extended to also enable the integration of conventional capillary electrophoresis (CE) with electrochemical detection. This is accomplished by embedding fused silica capillary along with palladium (for grounding the electrophoresis voltage) and platinum (for detection) electrodes. With this approach, up to 128,000 theoretical plates for dopamine was possible. In all cases, the tubing and electrodes are housed in a rigid base; this results in extremely robust devices that will be of interest to researchers wanting to develop microchips for use by non-experts.

Further improvement of hydrostatic pressure sample injection for microchip electrophoresis.

PubMed

Luo, Yong; Zhang, Qingquan; Qin, Jianhua; Lin, Bingcheng

2007-12-01

Hydrostatic pressure sample injection method is able to minimize the number of electrodes needed for a microchip electrophoresis process; however, it neither can be applied for electrophoretic DNA sizing, nor can be implemented on the widely used single-cross microchip. This paper presents an injector design that makes the hydrostatic pressure sample injection method suitable for DNA sizing. By introducing an assistant channel into the normal double-cross injector, a rugged DNA sample plug suitable for sizing can be successfully formed within the cross area during the sample loading. This paper also demonstrates that the hydrostatic pressure sample injection can be performed in the single-cross microchip by controlling the radial position of the detection point in the separation channel. Rhodamine 123 and its derivative as model sample were successfully separated.

DNA analysis using an integrated microchip for multiplex PCR amplification and electrophoresis for reference samples.

PubMed

Le Roux, Delphine; Root, Brian E; Reedy, Carmen R; Hickey, Jeffrey A; Scott, Orion N; Bienvenue, Joan M; Landers, James P; Chassagne, Luc; de Mazancourt, Philippe

2014-08-19

A system that automatically performs the PCR amplification and microchip electrophoretic (ME) separation for rapid forensic short tandem repeat (STR) forensic profiling in a single disposable plastic chip is demonstrated. The microchip subassays were optimized to deliver results comparable to conventional benchtop methods. The microchip process was accomplished in sub-90 min compared with >2.5 h for the conventional approach. An infrared laser with a noncontact temperature sensing system was optimized for a 45 min PCR compared with the conventional 90 min amplification time. The separation conditions were optimized using LPA-co-dihexylacrylamide block copolymers specifically designed for microchip separations to achieve accurate DNA size calling in an effective length of 7 cm in a plastic microchip. This effective separation length is less than half of other reports for integrated STR analysis and allows a compact, inexpensive microchip design. This separation quality was maintained when integrated with microchip PCR. Thirty samples were analyzed conventionally and then compared with data generated by the microfluidic chip system. The microfluidic system allele calling was 100% concordant with the conventional process. This study also investigated allelic ladder consistency over time. The PCR-ME genetic profiles were analyzed using binning palettes generated from two sets of allelic ladders run three and six months apart. Using these binning palettes, no allele calling errors were detected in the 30 samples demonstrating that a microfluidic platform can be highly consistent over long periods of time.

Microchip transponder thermometry for monitoring core body temperature of antelope during capture.

PubMed

Rey, Benjamin; Fuller, Andrea; Hetem, Robyn S; Lease, Hilary M; Mitchell, Duncan; Meyer, Leith C R

2016-01-01

Hyperthermia is described as the major cause of morbidity and mortality associated with capture, immobilization and restraint of wild animals. Therefore, accurately determining the core body temperature of wild animals during capture is crucial for monitoring hyperthermia and the efficacy of cooling procedures. We investigated if microchip thermometry can accurately reflect core body temperature changes during capture and cooling interventions in the springbok (Antidorcas marsupialis), a medium-sized antelope. Subcutaneous temperature measured with a temperature-sensitive microchip was a weak predictor of core body temperature measured by temperature-sensitive data loggers in the abdominal cavity (R(2)=0.32, bias >2 °C). Temperature-sensitive microchips in the gluteus muscle, however, provided an accurate estimate of core body temperature (R(2)=0.76, bias=0.012 °C). Microchips inserted into muscle therefore provide a convenient and accurate method to measure body temperature continuously in captured antelope, allowing detection of hyperthermia and the efficacy of cooling procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Liquid Chromatography-Mass Spectrometry Interface for Detection of Extraterrestrial Organics

NASA Technical Reports Server (NTRS)

Southard, Adrian E.; Getty, Stephanie A.; Balvin, Manuel; Cook, Jamie E.; Espiritu, Ana Mellina; Kotecki, Carl; Towner, Deborah W.; Dworkin, J. P.; Glavin, Daniel P.; Mahaffy, Paul R.;

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.

Identification of chemical warfare agents using a portable microchip-based detection device

NASA Astrophysics Data System (ADS)

Petkovic-Duran, K.; Swallow, A.; Sexton, B. A.; Glenn, F.; Zhu, Y.

2011-12-01

Analysis of chemical warfare agents (CWAs) and their degradation products is an important verification component in support of the Chemical Weapons Convention and urgently demanding rapid and reliable analytical methods. A portable microchip electrophoresis (ME) device with contactless conductivity (CCD) detection was developed for the in situ identification of CWA and their degradation products. A 10mM MES/His, 0.4mM CTAB - based separation electrolyte accomplished the analysis of Sarin (GB), Tabun( GA) and Soman (GD) in less than 1 min, which is the fastest screening of nerve agents achieved with portable ME and CCD based detection methods to date. Reproducibility of detection was successfully demonstrated on simultaneous detection of GB (200ppm) and GA (278ppm). Reasonable agreement for the four consecutive runs was achieved with the mean peak time for Sarin of 29.15s, and the standard error of 0.58s or 2%. GD and GA were simultaneously detected with their degradation products methylphosphonic acid (MPA), pinacolyl methylphosphonic acid (PMPA) and O-Ethyl Phosphorocyanidate (GAHP and GAHP1) respectively. The detection limit for Sarin was around 35ppb. To the best of our knowledge this is the best result achieved in microchip electrophoresis and contactless conductivity based detection to date.

Serial processing of biological reactions using flow-through microfluidic devices: coupled PCR/LDR for the detection of low-abundant DNA point mutations.

PubMed

Hashimoto, Masahiko; Barany, Francis; Xu, Feng; Soper, Steven A

2007-09-01

We have fabricated a flow-through biochip consisting of passive elements for the analysis of single base mutations in genomic DNA using polycarbonate (PC) as the substrate. The biochip was configured to carry out two processing steps on the input sample, a primary polymerase chain reaction (PCR) followed by an allele-specific ligation detection reaction (LDR) for scoring the presence of low abundant point mutations in genomic DNA. The operation of the device was demonstrated by detecting single nucleotide polymorphisms in gene fragments (K-ras) that carry high diagnostic value for colorectal cancers. The effect of carryover from the primary PCR on the subsequent LDR was investigated in terms of LDR yield and fidelity. We found that a post-PCR treatment step prior to the LDR phase of the assay was not essential. As a consequence, a thermal cycling microchip was used for a sequential PCR/LDR in a simple continuous-flow format, in which the following three steps were carried out: (1) exponential amplification of the gene fragments from genomic DNA; (2) mixing of the resultant PCR product(s) with an LDR cocktail via a Y-shaped passive micromixer; and (3) ligation of two primers (discriminating primer that carried the complement base to the mutation locus being interrogated and a common primer) only when the particular mutation was present in the genomic DNA. We successfully demonstrated the ability to detect one mutant DNA in 1000 normal sequences with the integrated microfluidic system. The PCR/LDR assay using the microchip performed the entire assay at a relatively fast processing speed: 18.7 min for 30 rounds of PCR, 4.1 min for 13 rounds of LDR (total processing time = ca. 22.8 min) and could screen multiple mutations simultaneously in a multiplexed format. In addition, the low cost of the biochip due to the fact that it was fabricated from polymers using replication technologies and consisted of passive elements makes the platform amenable to clinical diagnostics, where one-time use devices are required to eliminate false positives resulting from carryover contamination.

Blinded study determination of high sensitivity and specificity microchip electrophoresis–SSCP/HA to detect mutations in the p53 gene

PubMed Central

Hestekin, Christa N.; Lin, Jennifer S.; Senderowicz, Lionel; Jakupciak, John P.; O’Connell, Catherine; Rademaker, Alfred; Barron, Annelise E.

2012-01-01

Knowledge of the genetic changes that lead to disease has grown and continues to grow at a rapid pace. However, there is a need for clinical devices that can be used routinely to translate this knowledge into the treatment of patients. Use in a clinical setting requires high sensitivity and specificity (>97%) in order to prevent misdiagnoses. Single strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) are two DNA-based, complementary methods for mutation detection that are inexpensive and relatively easy to implement. However, both methods are most commonly detected by slab gel electrophoresis, which can be labor-intensive, time-consuming, and often the methods are unable to produce high sensitivity and specificity without the use of multiple analysis conditions. Here we demonstrate the first blinded study using microchip electrophoresis-SSCP/HA. We demonstrate the ability of microchip electrophoresis-SSCP/HA to detect with 98% sensitivity and specificity >100 samples from the p53 gene exons 5–9 in a blinded study in an analysis time of less than 10 minutes. PMID:22002021

Contactless conductivity detector for microchip capillary electrophoresis

NASA Technical Reports Server (NTRS)

Pumera, Martin; Wang, Joseph; Opekar, Frantisek; Jelinek, Ivan; Feldman, Jason; Lowe, Holger; Hardt, Steffen; Svehla, D. (Principal Investigator)

2002-01-01

A microfabricated electrophoresis chip with an integrated contactless conductivity detection system is described. The new contactless conductivity microchip detector is based on placing two planar sensing aluminum film electrodes on the outer side of a poly(methyl methacrylate) (PMMA) microchip (without contacting the solution) and measuring the impedance of the solution in the separation channel. The contactless route obviates problems (e.g., fouling, unwanted reactions) associated with the electrode-solution contact, offers isolation of the detection system from high separation fields, does not compromise the separation efficiency, and greatly simplifies the detector fabrication. Relevant experimental variables, such as the frequency and amplitude of the applied ac voltage or the separation voltage, were examined and optimized. The detector performance was illustrated by the separation of potassium, sodium, barium, and lithium cations and the chloride, sulfate, fluoride, acetate, and phosphate anions. The response was linear (over the 20 microM-7 mM range) and reproducible (RSD = 3.4-4.9%; n = 10), with detection limits of 2.8 and 6.4 microM (for potassium and chloride, respectively). The advantages associated with the contactless conductivity detection, along with the low cost of the integrated PMMA chip/detection system, should enhance the power and scope of microfluidic analytical devices.

Detection of Plasmodium Aldolase Using a Smartphone and Microfluidic Enzyme Linked Immunosorbent Assay

PubMed Central

2017-01-01

Background Malaria control efforts are limited in rural areas. A low-cost system to monitor response without the use of electricity is needed. Plasmodium aldolase is a malaria biomarker measured using enzyme linked immunosorbent assay (ELISA) techniques. A three-part system using ELISA was developed consisting of a microfluidic chip, hand crank centrifuge, and a smartphone. Methods A circular microfluidic chip was fabricated using clear acrylic and a CO2 laser. A series of passive valves released reagents at precise times based upon centrifugal force. Color change was measured via smartphone camera using an application programmed in Java. The microchip was compared to a standard 96-well sandwich ELISA. Results Results from standard ELISA were compared to microchip at varying concentrations (1–10 ng/mL). Over 15 different microfluidic patterns were tested, and a final prototype of the chip was created. The prototype microchip was compared to standard sandwich ELISA (n = 20) using samples of recombinant aldolase. Color readings of standard ELISA and microfluidic microchip showed similar results. Conclusion A low-cost microfluidic system could detect and follow therapeutic outcomes in rural areas and identify resistant strains. PMID:29057138

On-Chip Magnetic Bead Manipulation and Detection Using a Magnetoresistive Sensor-Based Micro-Chip: Design Considerations and Experimental Characterization

PubMed Central

Gooneratne, Chinthaka P.; Kodzius, Rimantas; Li, Fuquan; Foulds, Ian G.; Kosel, Jürgen

2016-01-01

The remarkable advantages micro-chip platforms offer over cumbersome, time-consuming equipment currently in use for bio-analysis are well documented. In this research, a micro-chip that includes a unique magnetic actuator (MA) for the manipulation of superparamagnetic beads (SPBs), and a magnetoresistive sensor for the detection of SPBs is presented. A design methodology, which takes into account the magnetic volume of SPBs, diffusion and heat transfer phenomena, is presented with the aid of numerical analysis to optimize the parameters of the MA. The MA was employed as a magnetic flux generator and experimental analysis with commercially available COMPEL™ and Dynabeads® demonstrated the ability of the MA to precisely transport a small number of SPBs over long distances and concentrate SPBs to a sensing site for detection. Moreover, the velocities of COMPEL™ and Dynabead® SPBs were correlated to their magnetic volumes and were in good agreement with numerical model predictions. We found that 2.8 μm Dynabeads® travel faster, and can be attracted to a magnetic source from a longer distance, than 6.2 μm COMPEL™ beads at magnetic flux magnitudes of less than 10 mT. The micro-chip system could easily be integrated with electronic circuitry and microfluidic functions, paving the way for an on-chip biomolecule quantification device. PMID:27571084

On-Chip Magnetic Bead Manipulation and Detection Using a Magnetoresistive Sensor-Based Micro-Chip: Design Considerations and Experimental Characterization.

PubMed

Gooneratne, Chinthaka P; Kodzius, Rimantas; Li, Fuquan; Foulds, Ian G; Kosel, Jürgen

2016-08-26

The remarkable advantages micro-chip platforms offer over cumbersome, time-consuming equipment currently in use for bio-analysis are well documented. In this research, a micro-chip that includes a unique magnetic actuator (MA) for the manipulation of superparamagnetic beads (SPBs), and a magnetoresistive sensor for the detection of SPBs is presented. A design methodology, which takes into account the magnetic volume of SPBs, diffusion and heat transfer phenomena, is presented with the aid of numerical analysis to optimize the parameters of the MA. The MA was employed as a magnetic flux generator and experimental analysis with commercially available COMPEL™ and Dynabeads(®) demonstrated the ability of the MA to precisely transport a small number of SPBs over long distances and concentrate SPBs to a sensing site for detection. Moreover, the velocities of COMPEL™ and Dynabead(®) SPBs were correlated to their magnetic volumes and were in good agreement with numerical model predictions. We found that 2.8 μm Dynabeads(®) travel faster, and can be attracted to a magnetic source from a longer distance, than 6.2 μm COMPEL™ beads at magnetic flux magnitudes of less than 10 mT. The micro-chip system could easily be integrated with electronic circuitry and microfluidic functions, paving the way for an on-chip biomolecule quantification device.

Microchip integrating magnetic nanoparticles for allergy diagnosis.

PubMed

Teste, Bruno; Malloggi, Florent; Siaugue, Jean-Michel; Varenne, Anne; Kanoufi, Frederic; Descroix, Stéphanie

2011-12-21

We report on the development of a simple and easy to use microchip dedicated to allergy diagnosis. This microchip combines both the advantages of homogeneous immunoassays i.e. species diffusion and heterogeneous immunoassays i.e. easy separation and preconcentration steps. In vitro allergy diagnosis is based on specific Immunoglobulin E (IgE) quantitation, in that way we have developed and integrated magnetic core-shell nanoparticles (MCSNPs) as an IgE capture nanoplatform in a microdevice taking benefit from both their magnetic and colloidal properties. Integrating such immunosupport allows to perform the target analyte (IgE) capture in the colloidal phase thus increasing the analyte capture kinetics since both immunological partners are diffusing during the immune reaction. This colloidal approach improves 1000 times the analyte capture kinetics compared to conventional methods. Moreover, based on the MCSNPs' magnetic properties and on the magnetic chamber we have previously developed the MCSNPs and therefore the target can be confined and preconcentrated within the microdevice prior to the detection step. The MCSNPs preconcentration factor achieved was about 35,000 and allows to reach high sensitivity thus avoiding catalytic amplification during the detection step. The developed microchip offers many advantages: the analytical procedure was fully integrated on-chip, analyses were performed in short assay time (20 min), the sample and reagents consumption was reduced to few microlitres (5 μL) while a low limit of detection can be achieved (about 1 ng mL(-1)).

Improved hydrostatic pressure sample injection by tilting the microchip towards the disposable miniaturized CE device.

PubMed

Wang, Wei; Zhou, Fang; Zhao, Liang; Zhang, Jian-Rong; Zhu, Jun-Jie

2008-02-01

A simple method of hydrostatic pressure sample injection towards a disposable microchip CE device was developed. The liquid level in the sample reservoir was higher than that in the sample waste reservoir (SWR) by tilting microchip and hydrostatic pressure was generated, the sample was driven to pass through injection channel into SWR. After sample loading, the microchip was levelled for separation under applied high separation voltage. Effects of tilted angle, initial liquid height and injection duration on electrophoresis were investigated. With enough injection duration, the injection result was little affected by tilted angle and initial liquid heights in the reservoirs. Injection duration for obtaining a stable sample plug was mainly dependent on the tilted angle rather than the initial height of liquid. Experimental results were consistent with theoretical prediction. Fluorescence observation and electrochemical detection of dopamine and catechol were employed to verify the feasibility of tilted microchip hydrostatic pressure injection. Good reproducibility of this injection method was obtained. Because the instrumentation was simplified and no additional hardware was needed in this technology, the proposed method would be potentially useful in disposable devices.

Recent progress in microchip electrophoresis-mass spectrometry.

PubMed

Kitagawa, Fumihiko; Otsuka, Koji

2011-06-25

This review highlights the methodological and instrumental developments in microchip electrophoresis (MCE)-mass spectrometry (MS) from 1997. In MCE-MS, the development of ionization interface is one of the most important issues to realize highly sensitive detection and high separation efficiency. Among several interfaces, electrospray ionization (ESI) has been mainly employed to MCE-MS since a simple structure of the ESI interface is suitable for coupling with the microchips. Although the number of publications is still limited, laser desorption ionization (LDI) interface has also been developed for MCE-MS. The characteristics of the ESI and LDI interfaces applied to the electrophoresis microchips are presented in this review. The scope of applications in MCE-MS covers mainly biogenic compounds such as bioactive amines, peptides, tryptic digests and proteins. This review provides a comprehensive table listing the applications in MCE-MS. Copyright © 2010 Elsevier B.V. All rights reserved.

Use of epoxy-embedded electrodes to integrate electrochemical detection with microchip-based analysis systems.

PubMed

Selimovic, Asmira; Johnson, Alicia S; Kiss, István Z; Martin, R Scott

2011-04-01

A new method of fabricating electrodes for microchip devices that involves the use of Teflon molds and a commercially available epoxy to embed electrodes of various sizes and compositions is described. The resulting epoxy base can be polished to generate a fresh electrode and sealed against poly(dimethylsiloxane) (PDMS)-based fluidic structures. Microchip-based flow injection analysis was used to characterize the epoxy-embedded electrodes. It was shown that gold electrodes can be amalgamated with liquid mercury and the resulting mercury/gold electrode is used to selectively detect glutathione from lysed red blood cells. The ability to encapsulate multiple electrode materials of differing compositions enabled the integration of microchip electrophoresis with electrochemical detection. Finally, a unique feature of this approach is that the electrode connection is made from the bottom of the epoxy base. This enables the creation of three-dimensional gold pillar electrodes (65 μm in diameter and 27 μm in height) that can be integrated within a fluidic network. As compared with the use of a flat electrode of a similar diameter, the use of the pillar electrode led to improvements in both the sensitivity (72.1 pA/μM for the pillar versus 4.2 pA/μM for the flat electrode) and limit of detection (20 nM for the pillar versus 600 nM for the flat electrode), with catechol being the test analyte. These epoxy-embedded electrodes hold promise for the creation of inexpensive microfluidic devices that can be used to electrochemically detect biologically important analytes in a manner where the electrodes can be polished and a fresh electrode surface is generated as desired. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Capillary liquid chromatography-microchip atmospheric pressure chemical ionization-mass spectrometry.

PubMed

Ostman, Pekka; Jäntti, Sirkku; Grigoras, Kestas; Saarela, Ville; Ketola, Raimo A; Franssila, Sami; Kotiaho, Tapio; Kostiainen, Risto

2006-07-01

A miniaturized nebulizer chip for capillary liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (capillary LC-microchip APCI-MS) is presented. The APCI chip consists of two wafers, a silicon wafer and a Pyrex glass wafer. The silicon wafer has a DRIE etched through-wafer nebulizer gas inlet, an edge capillary insertion channel, a stopper, a vaporizer channel and a nozzle. The platinum heater electrode and pads for electrical connection were patterned on to the Pyrex glass wafer. The two wafers were joined by anodic bonding, creating a microchip version of an APCI-source. The sample inlet capillary from an LC column is directly connected to the vaporizer channel of the APCI chip. The etched nozzle in the microchip forms a narrow sample plume, which is ionized by an external corona needle, and the formed ions are analyzed by a mass spectrometer. The nebulizer chip enables for the first time the use of low flow rate separation techniques with APCI-MS. The performance of capillary LC-microchip APCI-MS was tested with selected neurosteroids. The capillary LC-microchip APCI-MS provides quantitative repeatability and good linearity. The limits of detection (LOD) with a signal-to-noise ratio (S/N) of 3 in MS/MS mode for the selected neurosteroids were 20-1000 fmol (10-500 nmol l(-1)). LODs (S/N = 3) with commercial macro APCI with the same compounds using the same MS were about 10 times higher. Fast heat transfer allows the use of the optimized temperature for each compound during an LC run. The microchip APCI-source provides a convenient and easy method to combine capillary LC to any API-MS equipped with an APCI source. The advantages and potentials of the microchip APCI also make it a very attractive interface in microfluidic APCI-MS.

A simple and highly sensitive spectroscopic fluorescence-detection system for multi-channel plastic-microchip electrophoresis based on side-entry laser-beam zigzag irradiation.

PubMed

Anazawa, Takashi; Uchiho, Yuichi; Yokoi, Takahide; Chalkidis, George; Yamazaki, Motohiro

2017-06-27

A five-color fluorescence-detection system for eight-channel plastic-microchip electrophoresis was developed. In the eight channels (with effective electrophoretic lengths of 10 cm), single-stranded DNA fragments were separated (with single-base resolution up to 300 bases within 10 min), and seventeen-loci STR genotyping for forensic human identification was successfully demonstrated. In the system, a side-entry laser beam is passed through the eight channels (eight A channels), with alternately arrayed seven sacrificial channels (seven B channels), by a technique called "side-entry laser-beam zigzag irradiation." Laser-induced fluorescence from the eight A channels and Raman-scattered light from the seven B channels are then simultaneously, uniformly, and spectroscopically detected, in the direction perpendicular to the channel array plane, through a transmission grating and a CCD camera. The system is therefore simple and highly sensitive. Because the microchip is fabricated by plastic-injection molding, it is inexpensive and disposable and thus suitable for actual use in various fields.

Determination of morphine and codeine in urine using poly(dimethylsiloxane) microchip electrophoresis with electrochemical detection.

PubMed

Zhang, Qian-Li; Xu, Jing-Juan; Li, Xiang-Yun; Lian, Hong-Zhen; Chen, Hong-Yuan

2007-01-04

In this paper, a poly(dimethylsiloxane) (PDMS) microchip with electrochemical (EC) detection was developed for rapid separation and detection of morphine and codeine. It was found that morphine and codeine were well separated within 140 s in phosphate buffer solution (PBS) (pH 6.6, 40 mM)-beta-cyclodextrin (beta-CD) (20 mM)-acetonitrile (30%, v/v). The detection limit was 0.2 microM for morphine and 1 microM for codeine. The protocol was successfully applied to monitoring the amount of morphine and codeine in human urine. Compared with the conventional methods, the presented method had many advantages such as lower instrument cost, less reagent consumption and shorter analysis time.

Design and operation of a portable scanner for high performance microchip capillary array electrophoresis.

PubMed

Scherer, James R; Liu, Peng; Mathies, Richard A

2010-11-01

We have developed a compact, laser-induced fluorescence detection scanner, the multichannel capillary array electrophoresis portable scanner (McCAEPs) as a platform for electrophoretic detection and control of high-throughput, integrated microfluidic devices for genetic and other analyses. The instrument contains a confocal optical system with a rotary objective for detecting four different fluorescence signals, a pneumatic system consisting of two pressure/vacuum pumps and 28 individual addressable solenoid valves for control of on-chip microvalves and micropumps, four Polymerase Chain Reaction (PCR) temperature control systems, and four high voltage power supplies for electrophoresis. The detection limit of the instrument is ~20 pM for on-chip capillary electrophoresis of fluorescein dyes. To demonstrate the system performance for forensic short tandem repeat (STR) analysis, two experiments were conducted: (i) electrophoretic separation and detection of STR samples on a 96-lane microfabricated capillary array electrophoresis microchip. Fully resolved PowerPlex(®) 16 STR profiles amplified from 1 ng of 9947A female standard DNA were successfully obtained; (ii) nine-plex STR amplification, sample injection, separation, and fluorescence detection of 100-copy 9948 male standard DNA in a single integrated PCR- capillary electrophoresis microchip. These results demonstrate that the McCAEPs can be used as a versatile control and detection instrument that operates integrated microfluidic devices for high-performance forensic human identification.

Design and operation of a portable scanner for high performance microchip capillary array electrophoresis

NASA Astrophysics Data System (ADS)

Scherer, James R.; Liu, Peng; Mathies, Richard A.

2010-11-01

We have developed a compact, laser-induced fluorescence detection scanner, the multichannel capillary array electrophoresis portable scanner (McCAEPs) as a platform for electrophoretic detection and control of high-throughput, integrated microfluidic devices for genetic and other analyses. The instrument contains a confocal optical system with a rotary objective for detecting four different fluorescence signals, a pneumatic system consisting of two pressure/vacuum pumps and 28 individual addressable solenoid valves for control of on-chip microvalves and micropumps, four Polymerase Chain Reaction (PCR) temperature control systems, and four high voltage power supplies for electrophoresis. The detection limit of the instrument is ˜20 pM for on-chip capillary electrophoresis of fluorescein dyes. To demonstrate the system performance for forensic short tandem repeat (STR) analysis, two experiments were conducted: (i) electrophoretic separation and detection of STR samples on a 96-lane microfabricated capillary array electrophoresis microchip. Fully resolved PowerPlex® 16 STR profiles amplified from 1 ng of 9947A female standard DNA were successfully obtained; (ii) nine-plex STR amplification, sample injection, separation, and fluorescence detection of 100-copy 9948 male standard DNA in a single integrated PCR- capillary electrophoresis microchip. These results demonstrate that the McCAEPs can be used as a versatile control and detection instrument that operates integrated microfluidic devices for high-performance forensic human identification.

Evaluation of a Portable Microchip Electrophoresis Fluorescence Detection System for the Analysis of Amino Acid Neurotransmitters in Brain Dialysis Samples

PubMed Central

OBORNY, Nathan J.; COSTA, Elton E. Melo; SUNTORNSUK, Leena; ABREU, Fabiane C.; LUNTE, Susan M.

2016-01-01

A portable fluorescence detection system for use with microchip electrophoresis was developed and compared to a benchtop system. Using this system, six neuroactive amines commonly found in brain dialysate—arginine, citrulline, taurine, histamine, glutamate, and aspartate—were derivatized offline with naphthalene-2,3-dicarboxaldehyde/cyanide, separated electrophoretically, and detected by fluorescence. Limits of detection for the analytes of interest were 50nM – 250nM for the benchtop system and 250 nM – 1.3 μM for the portable system, both of which were adequate for analyte determination in brain microdialysis samples. The portable system was then demonstrated for the detection of the same six amines in a rat brain microdialysis sample. PMID:26753703

A Sol-Gel-Modified Poly(methyl methacrylate) Electrophoresis Microchip with a Hydrophilic Channel Wall

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

Chen, Gang; Xu, Xuejiao; Lin, Yuehe

2007-07-27

A sol-gel method was employed to fabricate a poly(methyl methacrylate) (PMMA) electrophoresis microchip that contains a hydrophilic channel wall. To fabricate such a device, tetraethoxysilane (TEOS) was injected into the PMMA channel and was allowed to diffuse into the surface layer for 24 h. After removing the excess TEOS, the channel was filled with an acidic solution for 3 h. Subsequently, the channel was flushed with water and was pretreated in an oven to obtain a sol-gel-modified PMMA microchip. The water contact angle for the sol-gel-modified PMMA was 27.4° compared with 66.3° for the pure PMMA. In addition, the electro-osmoticmore » flow increased from 2.13×10-4 cm2 V-1 s-1 for the native-PMMA channel to 4.86×10-4 cm2 V-1 s-1 for the modified one. The analytical performance of the sol-gel-modified PMMA microchip was demonstrated for the electrophoretic separation of several purines, coupled with amperometric detection. The separation efficiency of uric acid increased to 74 882.3 m-1 compared with 14 730.5 m-1 for native-PMMA microchips. The result of this simple modification is a significant improvement in the performance of PMMA for microchip electrophoresis and microfluidic applications.« less

In-channel amperometric detection for microchip electrophoresis using a wireless isolated potentiostat

PubMed Central

Gunasekara, Dulan B.; Hulvey, Matthew K.; Lunte, Susan M.

2012-01-01

The combination of microchip electrophoresis (ME) with amperometric detection leads to a number of analytical challenges that are associated with isolating the detector from the high voltages used for the separation. While methods such as end-channel alignment and the use of decouplers have been employed, they have limitations. A less common method has been to utilize an electrically isolated potentiostat. This approach allows placement of the working electrode directly in the separation channel without using a decoupler. This paper explores the use of microchip electrophoresis and electrochemical detection (ME-EC) with an electrically isolated potentiostat for the separation and in-channel detection of several biologically important anions. The separation employed negative polarity voltages and tetradecyltrimethylammonium bromide (TTAB, as a buffer modifier) for the separation of nitrite (NO2-), glutathione (GSH), ascorbic acid (AA), and tyrosine (Tyr). A half-wave potential (E½) shift of approximately negative 500 mV was observed for NO2- and H2O2 standards in the in-channel configuration compared to end channel. Higher separation efficiencies were observed for both NO2- and H2O2 with the in-channel detection configuration. The limits of detection were approximately two-fold lower and the sensitivity was approximately two-fold higher for in-channel detection of nitrite when compared to end-channel. The application of this microfluidic device for the separation and detection of biomarkers related to oxidative stress is described. PMID:21437918

Determination of trace amount of cyanobacterial toxin in water by microchip based enzyme-linked immunosorbent assay.

PubMed

Pyo, Dongjin; Hahn, Jong Hoon

2009-01-01

Routine monitoring of microcystin in natural waters is difficult because the concentration of the toxin is usually lower than the detection limits. As a more sensitive detection method for microcystin, we developed a microchip based enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibodies. New monoclonal antibodies against the microcystin leucine-arginine variant (MCLR), a cyclic peptide toxin of the freshwater cyanobacterium Microcystis aeruginosa, were prepared from cloned hybridoma cell lines. We used keyhole limpet hemocyanin(KLH)-conjugated MCLR as an immunogen for the production of mouse monoclonal antibody. The immunization, cell fusion, and screening of hybridoma cells producing anti-MCLR antibody were conducted. Since the ELISA test was highly sensitive, the newly developed microchip based ELISA can be suitable for the trace analysis of cyanobacterial hepatotoxins, microcystins in water. The linear responses of monoclonal antibodies with different concentrations of microcystin LR were established between 0.025 and 0.3 ng/mL.

Variability of microchip capillary electrophoresis with conductivity detection.

PubMed

Tantra, Ratna; Robinson, Kenneth; Sikora, Aneta

2014-02-01

Microfluidic CE with conductivity detection platforms could have an impact on the future development of smaller, faster and portable devices. However, for the purpose of reliable identification and quantification, there is a need to understand the degree of irreproducibility associated with the analytical technique. In this study, a protocol was developed to remove baseline drift problems sometimes observed in such devices. The protocol, which consisted of pre-conditioning steps prior to analysis, was used to further assess measurement variability from 24 individual microchips fabricated from six separate batches of glass substrate. Results show acceptable RSD percentage for retention time measurements but large variability in their corresponding peak areas (with some microchips having variability of ∼50%). Sources of variability were not related to substrate batch but possibly to a number of factors such as applied voltage fluctuations or variations in microchannel quality, for example surface roughness that will subsequently affect microchannel dimensions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Side-entry laser-beam zigzag irradiation of multiple channels in a microchip for simultaneous and highly sensitive detection of fluorescent analytes.

PubMed

Anazawa, Takashi; Yokoi, Takahide; Uchiho, Yuichi

2015-09-01

A simple and highly sensitive technique for laser-induced fluorescence detection on multiple channels in a plastic microchip was developed, and its effectiveness was demonstrated by laser-beam ray-trace simulations and experiments. In the microchip, with refractive index nC, A channels and B channels are arrayed alternately and respectively filled with materials with refractive indexes nA for electrophoresis analysis and nB for laser-beam control. It was shown that a laser beam entering from the side of the channel array traveled straight and irradiated all A channels simultaneously and effectively because the refractive actions by the A and B channels were counterbalanced according to the condition nA < nC < nB. This technique is thus called "side-entry laser-beam zigzag irradiation". As a demonstration of the technique, when nC = 1.53, nA = 1.41, nB = 1.66, and the cross sections of both eight A channels and seven B channels were the same isosceles trapezoids with 97° base angle, laser-beam irradiation efficiency on the eight A channels by the simulations was 89% on average and coefficient of variation was 4.4%. These results are far superior to those achieved by other conventional methods such as laser-beam expansion and scanning. Furthermore, fluorescence intensity on the eight A channels determined by the experiments agreed well with that determined by the simulations. Therefore, highly sensitive and uniform fluorescence detection on eight A channels was achieved. It is also possible to fabricate the microchips at low cost by plastic-injection molding and to make a simple and compact detection system, thereby promoting actual use of the proposed side-entry laser-beam zigzag irradiation in various fields.

Comparative Profiling of N-Glycans Isolated from Serum Samples of Ovarian Cancer Patients and Analyzed by Microchip Electrophoresis

PubMed Central

Mitra, Indranil; Alley, William R.; Goetz, John A.; Vasseur, Jacqueline A.; Novotny, Milos V.; Jacobson, Stephen C.

2013-01-01

Ovarian cancer is the fifth leading cause of cancer-related mortalities for women in the United States and the most lethal gynecological cancer. Aberrant glycosylation has been linked to several human diseases, including ovarian cancer, and accurate measurement of changes in glycosylation may provide relevant diagnostic and prognostic information. In this work, we used microchip electrophoresis coupled with laser-induced fluorescence detection to determine quantitative differences among the N-glycan profiles of control individuals and late-stage recurrent ovarian cancer patients prior to and after an experimental drug treatment that combined docetaxel and imatinib mesylate. N-Glycans were enzymatically released from 5-μL aliquots of serum samples, labeled with the anionic fluorescent tag, 8-aminopyrene-1,3,6-trisulfonic acid, and analyzed on microfluidic devices. A 22-cm long separation channel, operated at 1250 V/cm, generated analysis times less than 100 s, separation efficiencies up to 8 × 105 plates (3.6 × 106 plates/m), and migration time reproducibilities better than 0.1% relative standard deviation after peak alignment. Principal component analysis (PCA) and analysis of variance (ANOVA) tests showed significant differences between the control and both pre- and post-treatment cancer samples and subtle differences between the pre- and post-treatment cancer samples. Area-under-the curve (AUC) values from receiver operating characteristics (ROC) tests were used to evaluate the diagnostic merit of N-glycan peaks, and specific N-glycan peaks used in combination provided AUCs > 0.90 (highly accurate test) when the control and pre-treatment cancer samples and control and post-treatment samples were compared. PMID:23984816

Design and Fabrication of a PDMS Microchip Based Immunoassay

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

Shao, Guocheng; Wang, Wanjun; Wang, Jun

2010-07-01

In this paper, we describe the design and fabrication process of a polydimethylsiloxane (PDMS) microchip for on-chip multiplex immunoassay application. The microchip consists of a PDMS microfluidic channel layer and a micro pneumatic valve control layer. By selectively pressurizing the pneumatic microvalves, immuno reagents were controlled to flow and react in certain fluidic channel sites. Cross contamination was prevented by tightly closed valves. Our design was proposed to utilize PDMS micro channel surface as the solid phase immunoassay substrate and simultaneously detect four targets antigens on chip. Experiment result shows that 20psi valve pressure is sufficient to tightly close amore » 200µm wide micro channel with flow rate up to 20µl/min.« less

Novel Time-Resolved Fluorescence Europium Nanoparticle Immunoassay for Detection of Human Immunodeficiency Virus-1 Group O Viruses Using Microplate and Microchip Platforms.

PubMed

Haleyur Giri Setty, Mohan Kumar; Liu, Jikun; Mahtani, Prerna; Zhang, Panhe; Du, Bingchen; Ragupathy, Viswanath; Devadas, Krishnakumar; Hewlett, Indira K

2016-06-01

Accurate detection and quantification of HIV-1 group O viruses have been challenging for currently available HIV assays. We have developed a novel time-resolved fluorescence (TRF) europium nanoparticle immunoassay for HIV-1 group O detection using a conventional microplate enzyme-linked immunosorbent assay (ELISA) and a microchip platform. We screened several antibodies for optimal reactivity with several HIV-1 group O strains and identified antibodies that can detect all the strains of HIV-1 group O that were available for testing. The antibodies were used to develop a conventional ELISA format assay and an in-house developed europium nanoparticle-based assay for sensitivity. The method was evaluated on both microwell plate and microchip platforms. We identified two specific and sensitive antibodies among the six we screened. The antibodies, C65691 and ANT-152, were able to quantify 15 and detect all 17 group O viruses, respectively, as they were broadly cross-reactive with all HIV-1 group O strains and yielded better signals compared with other antibodies. We have developed a sensitive assay that reflects the actual viral load in group O samples by using an appropriate combination of p24 antibodies that enhance group O detection and a highly sensitive TRF-based europium nanoparticle for detection. The combination of ANT-152 and C65690M in the ratio 3:1 was able to give significantly higher signals in our europium-based assay compared with using any single antibody.

Magnetic bead droplet immunoassay of oligomer amyloid β for the diagnosis of Alzheimer's disease using micro-pillars to enhance the stability of the oil-water interface.

PubMed

Kim, Jeong Ah; Kim, Moojong; Kang, Sung Min; Lim, Kun Taek; Kim, Tae Song; Kang, Ji Yoon

2015-05-15

Despite scientific progress in the study of Alzheimer's disease (AD), it is still challenging to develop a robust and sensitive methodology for the early diagnosis of AD due to the lack of a decisive biomarker in blood. Recent reports on the oligomer amyloid β (Aβ) as a biomarker demonstrated its possibility for identifying early onset of AD in patients, but its low concentration in blood requires highly reliable detection techniques. To overcome the low reliability and labor-intensive procedures of conventional enzyme-linked immunosorbent assay (ELISA), we present a magnetic bead-droplet immunoassay platform for simple and highly sensitive detection of oligomer Aβ for the diagnosis of AD. This microchip consists of chambers that contain water-based reagents or oil for consecutive assay procedures, and there are arrays of micro-pillars fabricated between the two adjacent chambers to form robust water-oil interfaces. With the aid of these micro-pillars, magnetic beads can stably pass through each chamber by linearly actuating a magnet along the microchip. The robust water-oil interface and simple procedures of the assay make it possible to obtain reliable results from this microchip. The intensity of the fluorescence at the read-out chamber increased quantitatively and linearly, depending on the amount of serially-diluted standard Aβ solution. The results of the assay indicated that the limit of detection was about 10 pg/mL even though it was done with manual manipulation of the magnet. This platform simplified the complicated ELISA procedure and achieved high sensitivity that was no lower than that of the conventional magnetic bead immunoassay. The magnetic bead-droplet platform reduced the assay time to 45 min, and it also reduced the amount of antibody usage in a single diagnosis significantly (10-30 ng of antibody per single assay). Consequently, this microfluidic chip has strong potential as a feasible system for use in the diagnosis of AD with a fast and easy immunoassay process, since the suggested platform can be automated with ease for point-of-care testing as well as high-throughput diagnostic equipment. Copyright © 2014 Elsevier B.V. All rights reserved.

Integrated hybrid polystyrene-polydimethylsiloxane device for monitoring cellular release with microchip electrophoresis and electrochemical detection

PubMed Central

Johnson, Alicia S.; Mehl, Benjamin T.; Martin, R. Scott

2015-01-01

In this work, a polystyrene (PS)-polydimethylsiloxane (PDMS) hybrid device was developed to enable the integration of cell culture with analysis by microchip electrophoresis and electrochemical detection. It is shown that this approach combines the fundamental advantages of PDMS devices (the ability to integrate pumps and valves) and PS devices (the ability to permanently embed fluidic tubing and electrodes). The embedded fused-silica capillary enables high temporal resolution measurements from off-chip cell culture dishes and the embedded electrodes provide close to real-time analysis of small molecule neurotransmitters. A novel surface treatment for improved (reversible) adhesion between PS and PDMS is described using a chlorotrimethylsilane stamping method. It is demonstrated that a Pd decoupler is efficient at handling the high current (and cathodic hydrogen production) resulting from use of high ionic strength buffers needed for cellular analysis; thus allowing an electrophoretic separation and in-channel detection. The separation of norepinephrine (NE) and dopamine (DA) in highly conductive biological buffers was optimized using a mixed surfactant system. This PS-PDMS hybrid device integrates multiple processes including continuous sampling from a cell culture dish, on-chip pump and valving technologies, microchip electrophoresis, and electrochemical detection to monitor neurotransmitter release from PC 12 cells. PMID:25663849

Deep UV laser-induced fluorescence detection of unlabeled drugs and proteins in microchip electrophoresis.

PubMed

Schulze, Philipp; Ludwig, Martin; Kohler, Frank; Belder, Detlev

2005-03-01

Deep UV fluorescence detection at 266-nm excitation wavelength has been realized for sensitive detection in microchip electrophoresis. For this purpose, an epifluorescence setup was developed enabling the coupling of a deep UV laser into a commercial fluorescence microscope. Deep UV laser excitation utilizing a frequency quadrupled pulsed laser operating at 266 nm shows an impressive performance for native fluorescence detection of various compounds in fused-silica microfluidic devices. Aromatic low molecular weight compounds such as serotonin, propranolol, a diol, and tryptophan could be detected at low-micromolar concentrations. Deep UV fluorescence detection was also successfully employed for the detection of unlabeled basic proteins. For this purpose, fused-silica chips dynamically coated with hydroxypropylmethyl cellulose were employed to suppress analyte adsorption. Utilizing fused-silica chips permanently coated with poly(vinyl alcohol), it was also possible to separate and detect egg white chicken proteins. These data show that deep UV fluorescence detection significantly widens the application range of fluorescence detection in chip-based analysis techniques.

Monitoring the enzymatic conversion of urea to ammonium by conventional or microchip capillary electrophoresis with contactless conductivity detection.

PubMed

Schuchert-Shi, Aiping; Hauser, Peter C

2008-05-15

Capillary electrophoresis with contactless conductivity detection was used to directly quantify the ammonium produced in the enzymatic conversion of urea with urease. This allowed the characterization of the reaction without having to use more elaborate indirect optical methods for quantification. The maximum rate of reaction, V(max), was determined as 5.1 mmol x mL(-1) x min(-1), and the Michaelis-Menten constant, K(m), was determined as 16 mM. Furthermore, the method was successfully applied to the determination of urea in clinical samples of human blood by using a conventional capillary and a microchip device.

Microchip electrophoresis with amperometric detection for a novel determination of phenolic compounds in olive oil.

PubMed

Godoy-Caballero, María del Pilar; Acedo-Valenzuela, María Isabel; Galeano-Díaz, Teresa; Costa-García, Agustín; Fernández-Abedul, María Teresa

2012-11-07

The relevance of the development of microchip electrophoresis applications in the field of food analysis is considered in this work. A novel method to determine important phenolic compounds in extra virgin olive oil samples using a miniaturized chemical analysis system is presented in this paper. Three interesting phenolic compounds in olive oil and fruit (tyrosol, hydroxytyrosol and oleuropein glucoside) were studied by end-channel amperometric detection using a 100 μm gold wire as working electrode in glass microchip electrophoresis. The electrochemical behavior of these compounds was studied and the medium to carry out their detection was selected (0.1 M aqueous sulfuric acid). The best conditions for the separation were achieved in sodium tetraborate (10% methanol, pH 9.50) with different concentrations for the sample and the running buffer in order to allow the sample stacking phenomenon. The injection was carried out using 600 V for 3 s and the separation voltage was set at 1000 V. The quality of the method was evaluated through its analytical figures of merit and by its performance on real extra virgin olive oil samples. Determination of these compounds was carried out using the standard addition calibration method with good recoveries.

Simultaneous detection of 19 K-ras mutations by free-solution conjugate electrophoresis of ligase detection reaction products on glass microchips

PubMed Central

Albrecht, Jennifer Coyne; Kotani, Akira; Lin, Jennifer S.; Soper, Steven A.; Barron, Annelise E.

2015-01-01

We demonstrate here the power and flexibility of free-solution conjugate electrophoresis (FSCE) as a method of separating DNA fragments by electrophoresis with no sieving polymer network. Previous work introduced the coupling of FSCE with ligase detection reaction (LDR) to detect point mutations, even at low abundance compared to the wild-type DNA. Here, four large drag-tags are used to achieve free-solution electrophoretic separation of 19 LDR products ranging in size from 42–66 nt that correspond to mutations in the K-ras oncogene. LDR-FSCE enabled electrophoretic resolution of these 19 LDR-FSCE products by CE in 13.5 minutes (E = 310 V/cm) and by microchip electrophoresis in 140 seconds (E = 350 V/cm). The power of FSCE is demonstrated in the unique characteristic of free-solution separations where the separation resolution is constant no matter the electric field strength. By microchip electrophoresis, the electric field was increased to the maximum of the power supply (E = 700 V/cm), and the 19 LDR-FSCE products were separated in < 70 seconds with almost identical resolution to the separation at E = 350 V/cm. These results will aid the goal of screening K-ras mutations on integrated “sample-in/answer-out” devices with amplification, LDR, and detection all on one platform. PMID:23192597

Rapid determination of gizzerosine in fish meals using microchip capillary electrophoresis with laser-induced fluorescence detection.

PubMed

Xiao, Meng-Wei; Bai, Xiao-Lin; Xu, Pei-Li; Zhao, Yan; Yang, Li; Liu, Yi-Ming; Liao, Xun

2017-05-01

Sensitive detection of gizzerosine, a causative agent for deadly gizzard erosion in chicken feeds, is very important to the poultry industry. In this work, a new method was developed based on microchip capillary electrophoresis (MCE) with laser-induced fluorescence (LIF) detection for rapid analysis of gizzerosine, a biogenic amine in fish meals. The MCE separation was performed on a glass microchip using sodium dodecyl sulfate (SDS) as dynamic coating modifier. Separation conditions, including running buffer pH and concentration, SDS concentration, and the separation voltage were investigated to achieve fast and sensitive quantification of gizzerosine. The assay proposed was very quick and could be completed within 65 s. A linear calibration curve was obtained in the range from 0.04 to 1.8 μg ml -1 gizzerosine. The detection limit was 0.025 μg ml -1 (0.025 mg kg -1 ), which was far more sensitive than those previously reported. Gizzerosine was well separated from other endogenous components in fish meal samples. Recovery of gizzerosine from this sample matrix (n = 3) was determined to be 97.2-102.8%. The results from analysing fish meal samples indicated that the present MCE-LIF method might hold the potential for rapid detection of gizzerosine in poultry feeds.

Use of a Corona Discharge to Selectively Pattern a Hydrophilic/Hydrophobic Interface for Integrating Segmented Flow with Microchip Electrophoresis and Electrochemical Detection

PubMed Central

Filla, Laura A.; Kirkpatrick, Douglas C.; Martin, R. Scott

2011-01-01

Segmented flow in microfluidic devices involves the use of droplets that are generated either on- or off-chip. When used with off-chip sampling methods, segmented flow has been shown to prevent analyte dispersion and improve temporal resolution by periodically surrounding an aqueous flow stream with an immiscible carrier phase as it is transferred to the microchip. To analyze the droplets by methods such as electrochemistry or electrophoresis, a method to “desegment” the flow into separate aqueous and immiscible carrier phase streams is needed. In this paper, a simple and straightforward approach for this desegmentation process was developed by first creating an air/water junction in natively hydrophobic and perpendicular PDMS channels. The air-filled channel was treated with a corona discharge electrode to create a hydrophilic/hydrophobic interface. When a segmented flow stream encounters this interface, only the aqueous sample phase enters the hydrophilic channel, where it can be subsequently analyzed by electrochemistry or microchip-based electrophoresis with electrochemical detection. It is shown that the desegmentation process does not significantly degrade the temporal resolution of the system, with rise times as low as 12 s reported after droplets are recombined into a continuous flow stream. This approach demonstrates significant advantages over previous studies in that the treatment process takes only a few minutes, fabrication is relatively simple, and reversible sealing of the microchip is possible. This work should enable future studies where off-chip processes such as microdialysis can be integrated with segmented flow and electrochemical-based detection. PMID:21718004

Complexity and performance of on-chip biochemical assays

NASA Astrophysics Data System (ADS)

Kopf-Sill, Anne R.; Nikiforov, Theo; Bousse, Luc J.; Nagle, Rob; Parce, J. W.

1997-03-01

The use of microchips for performing biochemical processes has the potential to reduce reagent use and thus assay costs, increase throughput, and automate complex processes. We are building a multifunctional platform that provides sensing and actuation functions for a variety of microchip- based biochemical and analytical processes. Here we describe recent experiments that include on-chip dilution, reagent mixing, reaction, separation, and detection for important classes of biochemical assays. Issues in chip design and control are discussed.

Direct detection of cancer biomarkers in blood using a "place n play" modular polydimethylsiloxane pump.

PubMed

Zhang, Honglian; Li, Gang; Liao, Lingying; Mao, Hongju; Jin, Qinghui; Zhao, Jianlong

2013-01-01

Cancer biomarkers have significant potential as reliable tools for the early detection of the disease and for monitoring its recurrence. However, most current methods for biomarker detection have technical difficulties (such as sample preparation and specific detector requirements) which limit their application in point of care diagnostics. We developed an extremely simple, power-free microfluidic system for direct detection of cancer biomarkers in microliter volumes of whole blood. CEA and CYFRA21-1 were chosen as model cancer biomarkers. The system automatically extracted blood plasma from less than 3 μl of whole blood and performed a multiplex sample-to-answer assay (nano-ELISA (enzyme-linked immunosorbent assay) technique) without the use of external power or extra components. By taking advantage of the nano-ELISA technique, this microfluidic system detected CEA at a concentration of 50 pg/ml and CYFRA21-1 at a concentration of 60 pg/ml within 60 min. The combination of PnP polydimethylsiloxane (PDMS) pump and nano-ELISA technique in a single microchip system shows great promise for the detection of cancer biomarkers in a drop of blood.

Pulse laser head with monolithic thermally bonded microchip operating at 1.5 μm wavelength

NASA Astrophysics Data System (ADS)

Młyńczak, Jarosław; Kopczyński, Krzysztof; Belghachem, Nabil; Kisielewski, Jarosław; Stepień, Ryszard; Wychowaniec, Marek; Galas, Jacek; Litwin, Dariusz; CzyŻewski, Adam

2016-12-01

On the basis of thermally bonded Er,Yb:glass/Co:MALO microchip a laser head pumped by fiber coupled laser diode was designed. The performance of the laser head were investigated and the main output parameters were determined. The energy over 40 μJ in 3.8 ns pulse with repetition rate of 0.735 kHz was achieved. The laser head characterized by such parameters can successfully be used in tele-detection applications.

Novel Time-Resolved Fluorescence Europium Nanoparticle Immunoassay for Detection of Human Immunodeficiency Virus-1 Group O Viruses Using Microplate and Microchip Platforms

PubMed Central

Liu, Jikun; Mahtani, Prerna; Zhang, Panhe; Du, Bingchen; Ragupathy, Viswanath; Devadas, Krishnakumar

2016-01-01

Abstract Accurate detection and quantification of HIV-1 group O viruses have been challenging for currently available HIV assays. We have developed a novel time-resolved fluorescence (TRF) europium nanoparticle immunoassay for HIV-1 group O detection using a conventional microplate enzyme-linked immunosorbent assay (ELISA) and a microchip platform. We screened several antibodies for optimal reactivity with several HIV-1 group O strains and identified antibodies that can detect all the strains of HIV-1 group O that were available for testing. The antibodies were used to develop a conventional ELISA format assay and an in-house developed europium nanoparticle-based assay for sensitivity. The method was evaluated on both microwell plate and microchip platforms. We identified two specific and sensitive antibodies among the six we screened. The antibodies, C65691 and ANT-152, were able to quantify 15 and detect all 17 group O viruses, respectively, as they were broadly cross-reactive with all HIV-1 group O strains and yielded better signals compared with other antibodies. We have developed a sensitive assay that reflects the actual viral load in group O samples by using an appropriate combination of p24 antibodies that enhance group O detection and a highly sensitive TRF-based europium nanoparticle for detection. The combination of ANT-152 and C65690M in the ratio 3:1 was able to give significantly higher signals in our europium-based assay compared with using any single antibody. PMID:26978478

Precise determination of N-acetylcysteine in pharmaceuticals by microchip electrophoresis.

PubMed

Rudašová, Marína; Masár, Marián

2016-01-01

A novel microchip electrophoresis method for the rapid and high-precision determination of N-acetylcysteine, a pharmaceutically active ingredient, in mucolytics has been developed. Isotachophoresis separations were carried out at pH 6.0 on a microchip with conductivity detection. The methods of external calibration and internal standard were used to evaluate the results. The internal standard method effectively eliminated variations in various working parameters, mainly run-to-run fluctuations of an injected volume. The repeatability and accuracy of N-acetylcysteine determination in all mucolytic preparations tested (Solmucol 90 and 200, and ACC Long 600) were more than satisfactory with the relative standard deviation and relative error values <0.7 and <1.9%, respectively. A recovery range of 99-101% of N-acetylcysteine in the analyzed pharmaceuticals predetermines the proposed method for accurate analysis as well. This work, in general, indicates analytical possibilities of microchip isotachophoresis for the quantitative analysis of simplified samples such as pharmaceuticals that contain the analyte(s) at relatively high concentrations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative aspects of microchip isotachophoresis for high precision determination of main components in pharmaceuticals.

PubMed

Hradski, Jasna; Chorváthová, Mária Drusková; Bodor, Róbert; Sabo, Martin; Matejčík, Štefan; Masár, Marián

2016-12-01

Although microchip electrophoresis (MCE) is intended to provide reliable quantitative data, so far there is only limited attention paid to these important aspects. This study gives a general overview of key aspects to be followed to reach high-precise determination using isotachophoresis (ITP) on the microchip with conductivity detection. From the application point of view, the procedure for the determination of acetate, a main component in the pharmaceutical preparation buserelin acetate, was developed. Our results document that run-to-run fluctuations in the sample injection volume limit the reproducibility of quantitation based on the external calibration. The use of a suitable internal standard (succinate in this study) improved the repeatability of the precision of acetate determination from six to eight times. The robustness of the procedure was studied in terms of impact of fluctuations in various experimental parameters (driving current, concentration of the leading ions, pH of the leading electrolyte and buffer impurities) on the precision of the ITP determination. The use of computer simulation programs provided means to assess the ITP experiments using well-defined theoretical models. A long-term validity of the calibration curves on two microchips and two MCE equipments was verified. This favors ITP over other microchip electrophoresis techniques, when chip-to-chip or equipment-to-equipment transfer of the analytical method is required. The recovery values in the range of 98-101 % indicate very accurate determination of acetate in buserelin acetate, which is used in the treatment of hormone-dependent tumors. This study showed that microchip ITP is suitable for reliable determination of main components in pharmaceutical preparations.

Evaluation of pain and inflammation associated with hot iron branding and microchip transponder injection in horses.

PubMed

Lindegaard, Casper; Vaabengaard, Dorte; Christophersen, Mogens T; Ekstøm, Claus T; Fjeldborg, Julie

2009-07-01

To compare effects of hot iron branding and microchip transponder injection regarding aversive behavioral reactions indicative of pain and inflammation in horses. 7 adult horses. In a randomized controlled clinical crossover study, behavioral reactions to hot iron branding and microchip transponder injection were scored by 4 observers. Local and systemic inflammation including allodynia were assessed and compared by use of physiologic and biochemical responses obtained repeatedly for the 168-hour study period. Serum cortisol concentration was measured repeatedly throughout the first 24 hours of the study. Sham treatments were performed 1 day before and 7 days after treatments. Hot iron branding elicited a significantly stronger aversive reaction indicative of pain than did microchip transponder injection (odds ratio [OR], 12.83). Allodynia quantified by means of skin sensitivity to von Frey monofilaments was significantly greater after hot iron branding than after microchip transponder injection (OR, 2.59). Neither treatment induced signs of spontaneously occurring pain that were observed during the remaining study period, and neither treatment induced increased serum cortisol concentrations. Comparison with sham treatments indicated no memory of an unpleasant event. The hot iron branding areas had significantly increased skin temperature and swelling (OR, 14.6). Systemic inflammation as measured via serum amyloid A concentration was not detected after any of the treatments. Microchip transponder injection induced less signs of pain and inflammation and did not seem to pose a higher long-term risk than hot iron branding. Consequently, results indicated that hot iron branding does inflict more pain and should be abandoned where possible.

Enhanced Microchip Electrophoresis Separations Combined with Electrochemical Detection Utilizing a Capillary Embedded in Polystyrene.

PubMed

Mehl, Benjamin T; Martin, R Scott

2018-01-07

The ability to use microchip-based electrophoresis for fast, high-throughput separations provides researchers with a tool for close-to real time analysis of biological systems. While PDMS-based electrophoresis devices are popular, the separation efficiency is often an issue due to the hydrophobic nature of PDMS. In this study, a hybrid microfluidic capillary device was fabricated to utilize the positive features of PDMS along with the electrophoretic performance of fused silica. A capillary loop was embedded in a polystyrene base that can be coupled with PDMS microchannels at minimal dead volume interconnects. A method for cleaning out the capillaries after a wet-polishing step was devised through the use of 3D printed syringe attachment. By comparing the separation efficiency of fluorescein and CBI-glycine with both a PDMS-based serpentine device and the embedded capillary loop device, it was shown that the embedded capillary loop device maintained higher theoretical plates for both analytes. A Pd decoupler with a carbon or Pt detection electrode were embedded along with the loop allowing integration of the electrophoretic separation with electrochemical detection. A series of catecholamines were separated to show the ability to resolve similar analytes and detect redox active species. The release of dopamine and norepinephrine from PC 12 cells was also analyzed showing the compatibility of these improved microchip separations with high ionic cell buffers associated with cell culture.

Hand-held analyser based on microchip electrophoresis with contactless conductivity detection for measurement of chemical warfare agent degradation products

NASA Astrophysics Data System (ADS)

Duran, Karolina-Petkovic; Zhu, Yonggang; Chen, Chuanpin; Swallow, Anthony; Stewart, Robert; Hoobin, Pam; Leech, Patrick; Ovenden, Simon

2008-12-01

This paper reports on the development of a hand-held device for on-site detection of organophosphonate nerve agent degradation products. This field-deployable analyzer relies on efficient microchip electrophoresis separation of alkyl methylphosphonic acids and their sensitive contactless conductivity detection. Miniaturized, low-powered design is coupled with promising analytical performance for separating the breakdown products of chemical warfare agents such as Soman, Sarin and VX . The detector has a detection limit of about 10 μg/mL and has a good linear response in the range 10-300 μg/mL concentration range. Applicability to environmental samples is demonstrated .The new hand-held analyzer offers great promise for converting conventional ion chromatography or capillary electrophoresis sophisticated systems into a portable forensic laboratory for faster, simpler and more reliable on-site screening.

Chemical and biological threat-agent detection using electrophoresis-based lab-on-a-chip devices.

PubMed

Borowsky, Joseph; Collins, Greg E

2007-10-01

The ability to separate complex mixtures of analytes has made capillary electrophoresis (CE) a powerful analytical tool since its modern configuration was first introduced over 25 years ago. The technique found new utility with its application to the microfluidics based lab-on-a-chip platform (i.e., microchip), which resulted in ever smaller footprints, sample volumes, and analysis times. These features, coupled with the technique's potential for portability, have prompted recent interest in the development of novel analyzers for chemical and biological threat agents. This article will comment on three main areas of microchip CE as applied to the separation and detection of threat agents: detection techniques and their corresponding limits of detection, sampling protocol and preparation time, and system portability. These three areas typify the broad utility of lab-on-a-chip for meeting critical, present-day security, in addition to illustrating areas wherein advances are necessary.

A new microcolumn-type microchip for examining the expression of chimeric fusion genes using a nucleic acid sandwich hybridization technique.

PubMed

Ohnishi, Michihiro; Sasaki, Naoyuki; Kishimoto, Takuya; Watanabe, Hidetoshi; Takagi, Masatoshi; Mizutani, Shuki; Kishii, Noriyuki; Yasuda, Akio

2014-11-01

We report a new type of microcolumn installed in a microchip. The architecture allows use of a nucleic acid sandwich hybridization technique to detect a messenger RNA (mRNA) chain as a target. Data are presented that demonstrate that the expression of a chimeric fusion gene can be detected. The microcolumn was filled with semi-transparent microbeads made of agarose gel that acted as carriers, allowing increased efficiency of the optical detection of fluorescence from the microcolumn. The hybrid between the target trapped on the microbeads and a probe DNA labeled with a fluorescent dye was detected by measuring the intensity of the fluorescence from the microcolumn directly. These results demonstrate an easy and simple method for determining the expression of chimeric fusion genes with no preamplification. Copyright © 2014 Elsevier B.V. All rights reserved.

Competitive immunoassay of phenobarbital by microchip electrophoresis with laser induced fluorescence detection.

PubMed

Huang, Yong; Zhao, Shulin; Shi, Ming; Liu, Jinwen; Liang, Hong

2011-05-23

A microchip electrophoresis method with laser induced fluorescence detection was developed for the immunoassay of phenobarbital. The detection was based on the competitive immunoreaction between analyte phenobarbital and fluorescein isothiocyanate (FITC) labeled phenobarbital with a limited amount of antibody. The assay was developed by varying the borate concentration, buffer pH, separation voltage, and incubation time. A running buffer system containing 35 mM borate and 15 mM sodium dodecyl sulfate (pH 9.5), and 2800 V separation voltage provided analysis conditions for a high-resolution, sensitive, and repeatable assay of phenobarbital. Free FITC-labeled phenobarbital and immunocomplex were separated within 30s. The calibration curve for phenobarbital had a detection limit of 3.4 nM and a range of 8.6-860.0 nM. The assay could be used to determine the phenobarbital plasma concentration in clinical plasma sample. Copyright © 2011 Elsevier B.V. All rights reserved.

Detection system of capillary array electrophoresis microchip based on optical fiber

NASA Astrophysics Data System (ADS)

Yang, Xiaobo; Bai, Haiming; Yan, Weiping

2009-11-01

To meet the demands of the post-genomic era study and the large parallel detections of epidemic diseases and drug screening, the high throughput micro-fluidic detection system is needed urgently. A scanning laser induced fluorescence detection system based on optical fiber has been established by using a green laser diode double-pumped solid-state laser as excitation source. It includes laser induced fluorescence detection subsystem, capillary array electrophoresis micro-chip, channel identification unit and fluorescent signal processing subsystem. V-shaped detecting probe composed with two optical fibers for transmitting the excitation light and detecting induced fluorescence were constructed. Parallel four-channel signal analysis of capillary electrophoresis was performed on this system by using Rhodamine B as the sample. The distinction of different samples and separation of samples were achieved with the constructed detection system. The lowest detected concentration is 1×10-5 mol/L for Rhodamine B. The results show that the detection system possesses some advantages, such as compact structure, better stability and higher sensitivity, which are beneficial to the development of microminiaturization and integration of capillary array electrophoresis chip.

Microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse-transcription polymerase chain reaction for the rapid detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens.

PubMed

Jia, Ruan; Chengjun, Sun; Heng, Chen; Chen, Zhou; Yuanqian, Li; Yongxin, Li

2015-07-01

Enterovirus 71 and Coxsackievirus A16 are the main pathogens causing hand-foot-mouth disease. In this paper, microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse transcript-polymerase chain reaction has been developed for the detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens. The specific reverse transcription-polymerase chain reaction amplicons labeled with SYBR Orange were separated by microchip capillary electrophoresis and detected by laser induced fluorescence detector within 7 min. The intraday and interday relative standard deviation of migration time for DNA Marker was in the range of 1.36-2.94 and 2.78-3.96%, respectively. The detection limits were as low as 2.06 × 10(3) copies/mL for Enterovirus 71 and 5 × 10(3) copies/mL for Coxsackievirus A16. No cross-reactivity was observed with rotavirus, astrovirus, norovirus, and adenovirus, which showed good specificity of the method. This assay was validated using 100 throat swab specimens that were detected by real-time reverse-transcript polymerase chain reaction in parallel and the two methods produced the same results. This study provided a rapid, sensitive and specific method for the detection of Enterovirus 71 and Coxsackievirus A16, which make a contribution to significant time and cost saving for the identification and treatment of patients. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Amperometric Detection in Microchip Electrophoresis Devices: Effect of Electrode Material and Alignment on Analytical Performance

PubMed Central

Fischer, David J.; Hulvey, Matthew K.; Regel, Anne R.; Lunte, Susan M.

2012-01-01

The fabrication and evaluation of different electrode materials and electrode alignments for microchip electrophoresis with electrochemical (EC) detection is described. The influences of electrode material, both metal and carbon-based, on sensitivity and limits of detection (LOD) were examined. In addition, the effects of working electrode alignment on analytical performance (in terms of peak shape, resolution, sensitivity, and LOD) were directly compared. Using dopamine (DA), norepinephrine (NE), and catechol (CAT) as test analytes, it was found that pyrolyzed photoresist electrodes with end-channel alignment yielded the lowest limit of detection (35 nM for DA). In addition to being easier to implement, end-channel alignment also offered better analytical performance than off-channel alignment for the detection of all three analytes. In-channel electrode alignment resulted in a 3.6-fold reduction in peak skew and reduced peak tailing by a factor of 2.1 for catechol in comparison to end-channel alignment. PMID:19802847

In-channel electrochemical detection in the middle of microchannel under high electric field.

PubMed

Kang, Chung Mu; Joo, Segyeong; Bae, Je Hyun; Kim, Yang-Rae; Kim, Yongseong; Chung, Taek Dong

2012-01-17

We propose a new method for performing in-channel electrochemical detection under a high electric field using a polyelectrolytic gel salt bridge (PGSB) integrated in the middle of the electrophoretic separation channel. The finely tuned placement of a gold working electrode and the PGSB on an equipotential surface in the microchannel provided highly sensitive electrochemical detection without any deterioration in the separation efficiency or interference of the applied electric field. To assess the working principle, the open circuit potentials between gold working electrodes and the reference electrode at varying distances were measured in the microchannel under electrophoretic fields using an electrically isolated potentiostat. In addition, "in-channel" cyclic voltammetry confirmed the feasibility of electrochemical detection under various strengths of electric fields (∼400 V/cm). Effective separation on a microchip equipped with a PGSB under high electric fields was demonstrated for the electrochemical detection of biological compounds such as dopamine and catechol. The proposed "in-channel" electrochemical detection under a high electric field enables wider electrochemical detection applications in microchip electrophoresis.

Discrimination of Bacillus anthracis from closely related microorganisms by analysis of 16S and 23S rRNA with oligonucleotide microchips

DOEpatents

Bavykin, Sergei G.; Mirzabekova, legal representative, Natalia V.; Mirzabekov, deceased, Andrei D.

2007-12-04

The present invention relates to methods and compositions for using nucleotide sequence variations of 16S and 23S rRNA within the B. cereus group to discriminate a highly infectious bacterium B. anthracis from closely related microorganisms. Sequence variations in the 16S and 23S rRNA of the B. cereus subgroup including B. anthracis are utilized to construct an array that can detect these sequence variations through selective hybridizations and discriminate B. cereus group that includes B. anthracis. Discrimination of single base differences in rRNA was achieved with a microchip during analysis of B. cereus group isolates from both single and in mixed samples, as well as identification of polymorphic sites. Successful use of a microchip to determine the appropriate subgroup classification using eight reference microorganisms from the B. cereus group as a study set, was demonstrated.

Discrimination of Bacillus anthracis from closely related microorganisms by analysis of 16S and 23S rRNA with oligonucleotide microchips

DOEpatents

Bavykin, Sergei G.; Mirzabekov, Andrei D.

2007-10-30

The present invention is directed to a novel method of discriminating a highly infectious bacterium Bacillus anthracis from a group of closely related microorganisms. Sequence variations in the 16S and 23S rRNA of the B. cereus subgroup including B. anthracis are utilized to construct an array that can detect these sequence variations through selective hybridizations. The identification and analysis of these sequence variations enables positive discrimination of isolates of the B. cereus group that includes B. anthracis. Discrimination of single base differences in rRNA was achieved with a microchip during analysis of B. cereus group isolates from both single and in mixed probes, as well as identification of polymorphic sites. Successful use of a microchip to determine the appropriate subgroup classification using eight reference microorganisms from the B. cereus group as a study set, was demonstrated.

Problems Associated with the Microchip Data of Stray Dogs and Cats Entering RSPCA Queensland Shelters

PubMed Central

Lancaster, Emily; Rand, Jacquie; Collecott, Sheila; Paterson, Mandy

2015-01-01

Simple Summary Microchip identification has become an important tool to reunite stray dogs and cats with their owners, and is now compulsory in most states of Australia. Improvement of the microchipping system in Australia is limited by a lack of published Australian data documenting the problems experienced by shelter staff when using microchip data to contact the owner of a stray animal. In this study we determine the character and frequency of inaccurate microchip data to identify weaknesses in the current microchipping system. This information could be used to develop strategies that increase the accuracy of microchip data that will increase the reclaiming of stray animals. Abstract A lack of published information documenting problems with the microchip data for the reclaiming of stray animals entering Australian shelters limits improvement of the current microchipping system. A retrospective study analysing admission data for stray, adult dogs (n = 7258) and cats (n = 6950) entering the Royal Society for the Prevention of Cruelty to Animals (RSPCA) Queensland between January 2012 and December 2013 was undertaken to determine the character and frequency of microchip data problems and their impact on outcome for the animal. Only 28% of dogs and 9% of cats were microchipped, and a substantial proportion (37%) had problems with their data, including being registered to a previous owner or organisation (47%), all phone numbers incorrect/disconnected (29%), and the microchip not registered (14%). A higher proportion of owners could be contacted when the microchip had no problems, compared to those with problems (dogs, 93% vs. 70%; cats, 75% vs. 41%). The proportion of animals reclaimed declined significantly between microchipped animals with no data problems, microchipped animals with data problems and non-microchipped animals—87%, 69%, and 37%, respectively, for dogs and 61%, 33%, and 5%, respectively, for cats. Strategies are needed to increase the accuracy of microchip data to facilitate the reclaiming of stray dogs and cats. PMID:26479238

Microchip electrophoresis with background electrolyte containing polyacrylic acid and high content organic solvent in cyclic olefin copolymer microchips for easily adsorbed dyes.

PubMed

Wei, Xuan; Sun, Ping; Yang, Shenghong; Zhao, Lei; Wu, Jing; Li, Fengyun; Pu, Qiaosheng

2016-07-29

Plastic microchips can significantly reduce the fabrication cost but the adsorption of some analytes limits their application. In this work, background electrolyte containing ionic polymer and high content of organic solvent was adopted to eliminate the analyte adsorption and achieve highly efficient separation in microchip electrophoresis. Two dyes, rhodamine 6G (Rh6G) and rhodamine B (RhB) were used as the model analytes. By using methanol as the organic solvent and polyacrylic acid (PAA) as a multifunctional additive, successful separation of the two dyes within 75μm id. microchannels was realized. The role of PAA is multiple, including viscosity regulator, selectivity modifier and active additive for counteracting analyte adsorption on the microchannel surface. The number of theoretical plate of 7.0×10(5)/m was attained within an effective separation distance of 2cm using background electrolyte consisting 80% methanol, 0.36% PAA and 30mmol/L phosphate at pH 5.0. Under optimized conditions, relative standard deviations of Rh6G and RhB detection (n=5) were no more than 1.5% for migration time and 2.0% for peak area, respectively. The limit of detection (S/N=3) was 0.1nmol/L for Rh6G. The proposed technique was applied in the determination of both Rh6G and RhB in chilli powder and lipstick samples with satisfactory recoveries of 81.3-103.7%. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a microchip-pulsed electrochemical method for rapid determination of L-DOPA and tyrosine in Mucuna pruriens.

PubMed

Li, Xinchun; Chen, Zuanguang; Yang, Fan; Pan, Jianbin; Li, Yinbao

2013-05-01

L-3,4-dihydroxyphenylalanine (L-DOPA) is a well-recognized therapeutic compound to Parkinson's disease. Tyrosine is a precursor for the biosynthesis of L-DOPA, both of which are widely found in traditional medicinal material, Mucuna pruriens. In this paper, we described a validated novel analytical method based on microchip capillary electrophoresis with pulsed electrochemical detection for the simultaneous measurement of L-DOPA and tyrosine in M. pruriens. This protocol adopted end-channel amperometric detection using platinum disk electrode on a homemade glass/polydimethylsiloxane electrophoresis microchip. The background buffer consisted of 10 mM borate (pH 9.5) and 0.02 mM cetyltrimethylammonium bromide, which can produce an effective resolution for the two analytes. In the optimal condition, sufficient electrophoretic separation and sensitive detection for the target analytes can be realized within 60 s. Both tyrosine and L-DOPA yielded linear response in the concentration range of 5.0-400 μM (R(2) > 0.99), and the LOD were 0.79 and 1.1 μM, respectively. The accuracy and precision of the established method were favorable. The present method shows several merits such as facile apparatus, high speed, low cost and minimal pollution, and provides a means for the pharmacologically active ingredients assay in M. pruriens. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Miniaturized multiplex label-free electronic chip for rapid nucleic acid analysis based on carbon nanotube nanoelectrode arrays

NASA Technical Reports Server (NTRS)

Koehne, Jessica E.; Chen, Hua; Cassell, Alan M.; Ye, Qi; Han, Jie; Meyyappan, Meyya; Li, Jun

2004-01-01

BACKGROUND: Reducing cost and time is the major concern in clinical diagnostics, particularly in molecular diagnostics. Miniaturization technologies have been recognized as promising solutions to provide low-cost microchips for diagnostics. With the recent advancement in nanotechnologies, it is possible to further improve detection sensitivity and simplify sample preparation by incorporating nanoscale elements in diagnostics devices. A fusion of micro- and nanotechnologies with biology has great potential for the development of low-cost disposable chips for rapid molecular analysis that can be carried out with simple handheld devices. APPROACH: Vertically aligned multiwalled carbon nanotubes (MWNTs) are fabricated on predeposited microelectrode pads and encapsulated in SiO2 dielectrics with only the very end exposed at the surface to form an inlaid nanoelectrode array (NEA). The NEA is used to collect the electrochemical signal associated with the target molecules binding to the probe molecules, which are covalently attached to the end of the MWNTs. CONTENT: A 3 x 3 microelectrode array is presented to demonstrate the miniaturization and multiplexing capability. A randomly distributed MWNT NEA is fabricated on each microelectrode pad. Selective functionalization of the MWNT end with a specific oligonucleotide probe and passivation of the SiO2 surface with ethylene glycol moieties are discussed. Ru(bpy)2+ -mediator-amplified guanine oxidation is used to directly measure the electrochemical signal associated with target molecules. SUMMARY: The discussed MWNT NEAs have ultrahigh sensitivity in direct electrochemical detection of guanine bases in the nucleic acid target. Fewer than approximately 1000 target nucleic acid molecules can be measured with a single microelectrode pad of approximately 20 x 20 microm2, which approaches the detection limit of laser scanners in fluorescence-based DNA microarray techniques. MWNT NEAs can be easily integrated with microelectronic circuitry and microfluidics for development of a fully automated system for rapid molecular analysis with minimum cost.

Fast and simultaneous detection of prominent natural antioxidants using analytical microsystems for capillary electrophoresis with a glassy carbon electrode: a new gateway to food environments.

PubMed

Blasco, Antonio Javier; Barrigas, Inés; González, María Cristina; Escarpa, Alberto

2005-12-01

This paper examines for the first time the analytical possibilities of fast and simultaneous detection of prominent natural antioxidants including examples of flavonoids and vitamins using a CE microchip with electrochemical detection (ED). Unpinched injection conditions, zone electrophoretic separation and amperometric detection were carefully assayed and optimised. Analysis involved the zone electrophoretic separation of arbutin, (+)-catechin and ascorbic acid in less than 4 min using a borate buffer (pH 9.0, 50 mM), employing 2 kV as the separation voltage and +1.0 V as the detection potential. In addition, the separation of different 'couples' of natural antioxidants of food significance including (+)-catechin and ascorbic acid, (+)-catechin and rutin, as well as arbutin and phlorizdin is proposed. To demonstrate the potential and future role of CE microsystems, analytical possibilities and a new route in the raw sample analysis are presented. The preliminary results obtained allow the proposal of CE-ED microchips as a real gateway to microanalysis in foods.

Measurement of Nitrogen Mustard Degredation Products by Poly(dimethylsiloxane) Microchip Electrophoresis with Contactless Conductivity Detection

EPA Science Inventory

The potential risk of human exposure from an accidental or intentional release of CWAs into a civilian population continues to drive the need for screening and monitoring techniques for these compounds. In particular, rapid and reliable methods for detecting CWAs such as the nitr...

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

PubMed

Yu, Stephanie C Y; Chan, K C Allen; Zheng, Yama W L; Jiang, Peiyong; Liao, Gary J W; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y; Go, Attie T J I; van Vugt, John M G; Minekawa, Ryoko; Oudejans, Cees B M; Nicolaides, Kypros H; Chiu, Rossa W K; Lo, Y M Dennis

2014-06-10

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring.

Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing

PubMed Central

Yu, Stephanie C. Y.; Chan, K. C. Allen; Zheng, Yama W. L.; Jiang, Peiyong; Liao, Gary J. W.; Sun, Hao; Akolekar, Ranjit; Leung, Tak Y.; Go, Attie T. J. I.; van Vugt, John M. G.; Minekawa, Ryoko; Oudejans, Cees B. M.; Nicolaides, Kypros H.; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2014-01-01

Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the use of DNA fragment size as a diagnostic parameter. This approach is dependent on the fact that circulating fetal DNA molecules are generally shorter than the corresponding maternal DNA molecules. First, we performed plasma DNA size analysis using paired-end massively parallel sequencing and microchip-based capillary electrophoresis. We demonstrated that the fetal DNA fraction in maternal plasma could be deduced from the overall size distribution of maternal plasma DNA. The fetal DNA fraction is a critical parameter affecting the accuracy of noninvasive prenatal testing using maternal plasma DNA. Second, we showed that fetal chromosomal aneuploidy could be detected by observing an aberrant proportion of short fragments from an aneuploid chromosome in the paired-end sequencing data. Using this approach, we detected fetal trisomy 21 and trisomy 18 with 100% sensitivity (T21: 36/36; T18: 27/27) and 100% specificity (non-T21: 88/88; non-T18: 97/97). For trisomy 13, the sensitivity and specificity were 95.2% (20/21) and 99% (102/103), respectively. For monosomy X, the sensitivity and specificity were both 100% (10/10 and 8/8). Thus, this study establishes the principle of size-based molecular diagnostics using plasma DNA. This approach has potential applications beyond noninvasive prenatal testing to areas such as oncology and transplantation monitoring. PMID:24843150

Pencil graphite leads as simple amperometric sensors for microchip electrophoresis.

PubMed

Natiele Tiago da Silva, Eiva; Marques Petroni, Jacqueline; Gabriel Lucca, Bruno; Souza Ferreira, Valdir

2017-11-01

In this work we demonstrate, for the first time, the use of inexpensive commercial pencil graphite leads as simple amperometric sensors for microchip electrophoresis. A PDMS support containing one channel was fabricated through soft lithography and sanded pencil graphite leads were inserted into this channel to be used as working electrodes. The electrochemical and morphological characterization of the sensor was carried out. The graphite electrode was coupled to PDMS microchips in end-channel configuration and electrophoretic experiments were performed using nitrite and ascorbate as probe analytes. The analytes were successfully separated and detected in well-defined peaks with satisfactory resolution using the microfluidic platform proposed. The repeatability of the pencil graphite electrode was satisfactory (RSD values of 1.6% for nitrite and 12.3% for ascorbate, regarding the peak currents) and its lifetime was estimated to be ca. 700 electrophoretic runs over a cost of ca. $ 0.05 per electrode. The limits of detection achieved with this system were 2.8 μM for nitrite and 5.7 μM for ascorbate. For proof of principle, the pencil graphite electrode was employed for the real analysis of well water samples and nitrite was successfully quantified at levels below its maximum contaminant level established in Brazil and US. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Low-temperature microchip nonaqueous capillary electrophoresis of aliphatic primary amines: applications to Titan chemistry.

PubMed

Cable, Morgan L; Stockton, Amanda M; Mora, Maria F; Willis, Peter A

2013-01-15

We demonstrate microchip nonaqueous capillary electrophoresis (μNACE) analysis of primary aliphatic amines (C1-C18) in ethanol down to -20 °C as a first step in adapting microfluidic protocols for in situ analysis on Titan. To our knowledge, this is the first report of a nonaqueous separation at -20 °C on-chip. Limits of detection (LODs) ranged from 1.0 nM to 2.6 nM, and we identified several primary amines ranging in length from C2 to C16 in Titan aerosol analogue (tholin) samples; new amines were also detected in a tholin sample exposed to oxygen and liquid water. This preliminary work validates the sensitivity and efficacy of microfluidic chemical analysis of complex organics with relevance to Titan aerosols and surface deposits.

Determination of foodborne pathogenic bacteria by multiplex PCR-microchip capillary electrophoresis with genetic algorithm-support vector regression optimization.

PubMed

Li, Yongxin; Li, Yuanqian; Zheng, Bo; Qu, Lingli; Li, Can

2009-06-08

A rapid and sensitive method based on microchip capillary electrophoresis with condition optimization of genetic algorithm-support vector regression (GA-SVR) was developed and applied to simultaneous analysis of multiplex PCR products of four foodborne pathogenic bacteria. Four pairs of oligonucleotide primers were designed to exclusively amplify the targeted gene of Vibrio parahemolyticus, Salmonella, Escherichia coli (E. coli) O157:H7, Shigella and the quadruplex PCR parameters were optimized. At the same time, GA-SVR was employed to optimize the separation conditions of DNA fragments in microchip capillary electrophoresis. The proposed method was applied to simultaneously detect the multiplex PCR products of four foodborne pathogenic bacteria under the optimal conditions within 8 min. The levels of detection were as low as 1.2 x 10(2) CFU mL(-1) of Vibrio parahemolyticus, 2.9 x 10(2) CFU mL(-1) of Salmonella, 8.7 x 10(1) CFU mL(-1) of E. coli O157:H7 and 5.2 x 10(1) CFU mL(-1) of Shigella, respectively. The relative standard deviation of migration time was in the range of 0.74-2.09%. The results demonstrated that the good resolution and less analytical time were achieved due to the application of the multivariate strategy. This study offers an efficient alternative to routine foodborne pathogenic bacteria detection in a fast, reliable, and sensitive way.

Analysis of anabolic steroids in urine by gas chromatography-microchip atmospheric pressure photoionization-mass spectrometry with chlorobenzene as dopant.

PubMed

Hintikka, Laura; Haapala, Markus; Kuuranne, Tiia; Leinonen, Antti; Kostiainen, Risto

2013-10-18

A gas chromatography-microchip atmospheric pressure photoionization-tandem mass spectrometry (GC-μAPPI-MS/MS) method was developed for the analysis of anabolic androgenic steroids in urine as their trimethylsilyl derivatives. The method utilizes a heated nebulizer microchip in atmospheric pressure photoionization mode (μAPPI) with chlorobenzene as dopant, which provides high ionization efficiency by producing abundant radical cations with minimal fragmentation. The performance of GC-μAPPI-MS/MS was evaluated with respect to repeatability, linearity, linear range, and limit of detection (LOD). The results confirmed the potential of the method for doping control analysis of anabolic steroids. Repeatability (RSD<10%), linearity (R(2)≥0.996) and sensitivity (LODs 0.05-0.1ng/mL) were acceptable. Quantitative performance of the method was tested and compared with that of conventional GC-electron ionization-MS, and the results were in good agreement. Copyright © 2013 Elsevier B.V. All rights reserved.

Rapid fabrication of poly(dimethylsiloxane)-based microchip capillary electrophoresis devices using CO2 laser ablation.

PubMed

Fogarty, Barbara A; Heppert, Kathleen E; Cory, Theodore J; Hulbutta, Kalonie R; Martin, R Scott; Lunte, Susan M

2005-06-01

The use of CO(2) laser ablation for the patterning of capillary electrophoresis (CE) microchannels in poly(dimethylsiloxane)(PDMS) is described. Low-cost polymer devices were produced using a relatively inexpensive CO(2) laser system that facilitated rapid patterning and ablation of microchannels. Device designs were created using a commercially available software package. The effects of PDMS thickness, laser focusing, power, and speed on the resulting channel dimensions were investigated. Using optimized settings, the smallest channels that could be produced averaged 33 microm in depth (11.1% RSD, N= 6) and 110 microm in width (5.7% RSD, N= 6). The use of a PDMS substrate allowed reversible sealing of microchip components at room temperature without the need for cleanroom facilities. Using a layer of pre-cured polymer, devices were designed, ablated, and assembled within minutes. The final devices were used for microchip CE separation and detection of the fluorescently labeled neurotransmitters aspartate and glutamate.

Microchip-Based Organophosphorus Detection Using Bienzyme Bioelectrocatalysis

NASA Astrophysics Data System (ADS)

Han, Yong Duk; Jeong, Chi Yong; Lee, Jun Hee; Lee, Dae-Sik; Yoon, Hyun C.

2012-06-01

We have developed a microsystem for the detection of organophosphorus (OP) compounds using acetylcholine esterase (AchE) and choline oxidase (ChOx) bienzyme bioelectrocatalysis. Because AchE is irreversibly inhibited by OP pesticides, the change in AchE activity with OP treatment can be traced to determine OP concentration. Polymer-associated ChOx immobilization on the working electrode surface and magnetic microparticle (MP)-assisted AchE deposition methods were employed to create an AchE-ChOx bienzyme-modified biosensing system. ChOx was immobilized on the micropatterned electrodes using poly(L-lysine), glutaraldehyde, and amine-rich interfacial surface. AchE was immobilized on the MP surface via Schiff's base formation, and the enzyme-modified MPs were deposited on the working electrode using a magnet under the microfluidic channel. The bioelectrocatalytic reaction between AchE-ChOx bienzyme cascade and the ferrocenyl electron shuttle was successfully used to detect OP with the developed microchip. This provides a self-contained and relatively easy method for OP detection. It requires minimal time and a small sample size, and has potential analytic applications in pesticides and chemical warfare agents.

Band-broadening suppressed effect in long turned geometry channel and high-sensitive analysis of DNA sample by using floating electrokinetic supercharging on a microchip.

PubMed

Xu, Zhongqi; Murata, Kenji; Arai, Akihiro; Hirokawa, Takeshi

2010-03-12

A featured microchip owning three big reservoirs and long turned geometry channel was designed to improve the detection limit of DNA fragments by using floating electrokinetic supercharging (FEKS) method. The novel design matches the FEKS preconcentration needs of a large sample volume introduction with electrokinetic injection (EKI), as well as long duration of isotachophoresis (ITP) process to enrich low concentration sample. In the curved channel [ approximately 45.6 mm long between port 1 (P1) and the intersection point of two channels], EKI and ITP were performed while the side port 3 (P3) was electrically floated. The turn-induced band broadening with or without ITP process was investigated by a computer simulation (using CFD-ACE+ software) when the analytes traveling through the U-shaped geometry. It was found that the channel curvature determined the extent of band broadening, however, which could be effectively eliminated by the way of ITP. After the ITP-stacked zones passed the intersection point from P1, they were rapidly destacked for separation and detection from ITP to zone electrophoresis by using leading ions from P3. The FEKS carried on the novel chip successfully contributed to higher sensitivities of DNA fragments in comparison with our previous results realized on either a single channel or a cross microchip. The analysis of low concentration 50 bp DNA step ladders (0.23 mugml after 1500-fold diluted) was achieved with normal UV detection at 260 nm. The obtained limit of detections (LODs) were on average 100 times better than using conventional pinched injection, down to several ngml for individual DNA fragment.

A disposable laser print-cut-laminate polyester microchip for multiplexed PCR via infra-red-mediated thermal control.

PubMed

Ouyang, Yiwen; Duarte, Gabriela R M; Poe, Brian L; Riehl, Paul S; dos Santos, Fernando M; Martin-Didonet, Claudia C G; Carrilho, Emanuel; Landers, James P

2015-12-11

Infrared (IR)-mediated thermal cycling system, a method proven to be a effective for sub-μL scale polymerase chain reaction (PCR) on microchips, has been integrated with DNA extraction and separation on a glass microchip in a fully integrated micro Total Analysis System by Easley et al., in 2006. IR-PCR has been demonstrated on both glass and PMMA microdevices where the fabrication (bonding) is not trivial. Polyester-toner (PeT) microfluidic devices have significant potential as cost-effective, disposable microdevices as a result of the ease of fabrication (∼$0.25 USD and <10 min per device) and availability of commercial substrates. For the first time, we demonstrate here the thermal cycling in PeT microchips on the IR-PCR system. Undesirable IR absorption by the black-toner bonding layer was eliminated with a spatial filter in the form of an aluminum foil mask. The solution heating rate for a black PeT microchip using a tungsten lamp was 10.1 ± 0.7 °C s(-1) with a cooling rate of roughly -12 ± 0.9 °C s(-1) assisted by forced air cooling. Dynamic surface passivation strategies allowed the successful amplification of a 520 bp fragment of the λ-phage genome (in 11 min) and a 1500 bp region of Azospirillum brasilense. Using a centrosymmetric chamber configuration in a multichamber PeT microchip, homogenous temperature distribution over all chambers was achieved with inter-chamber temperature differences at annealing, extension and denaturing steps of less than ±2 °C. The effectiveness of the multichamber system was demonstrated with the simultaneous amplification of a 390 bp amplicon of human β-globin gene in five PeT PCR microchambers. The relative PCR amplification efficiency with a human β-globin DNA fragment ranged from 70% to 90%, in comparison to conventional thermal cyclers, with an inter-chamber standard deviation of ∼10%. Development of PeT microchips for IR-PCR has the potential to provide rapid, low-volume amplification while also integrating PCR with extraction upstream and separation/detection downstream. Copyright © 2015. Published by Elsevier B.V.

Capillary Electrophoresis Chips for Fingerprinting Endotoxin Chemotypes and Subclasses.

PubMed

Kocsis, Béla; Makszin, Lilla; Kilár, Anikó; Péterfi, Zoltán; Kilár, Ferenc

2017-01-01

Endotoxins (lipopolysaccharides, LPS; lipooligosaccharides, LOS) are components of the envelope of Gram-negative bacteria. These molecules, responsible for both advantageous and harmful biological activity of these microorganisms, are highly immunogenic and directly involved in numerous bacterial diseases in humans, such as Gram-negative sepsis. The characterization of endotoxins is of importance, since their physiological and pathophysiological effects depend on their chemical structure. The differences among the LPS from different bacterial serotypes and their mutants include variations mainly within the composition and length or missing of their O-polysaccharide chains. Microchip electrophoretic methodology enables the structural characterization of LPS molecules from several bacteria and the quantitative evaluation of components of endotoxin extracts. The improved microchip electrophoretic method is based on the direct labeling of endotoxins by covalent binding of a fluorescent dye. The classification of the S-type LPSs can be done according to their electrophoretic profiles, which are characteristics of the respective bacterial strains. According to the number, distribution, and the relative amounts of components in an endotoxin extract, it is possible to differentiate between the S-type endotoxins from different Gram-negative bacterial strains. The microchip electrophoresis affords high-resolution separation of pure and partially purified (e.g., obtained from whole-cell lysate) S and R endotoxins. This microchip technique provides a new, standardizable, fast, and sensitive method for the detection of endotoxins and for the quantitative evaluation of components of an endotoxin extract.

Rapid detection of a cocaine-binding aptamer using biological nanopores on a chip.

PubMed

Kawano, Ryuji; Osaki, Toshihisa; Sasaki, Hirotaka; Takinoue, Masahiro; Yoshizawa, Satoko; Takeuchi, Shoji

2011-06-08

This paper describes a methodology for the rapid and highly selective detection of cocaine using a membrane protein channel combined with a DNA aptamer. The DNA aptamer recognizes the cocaine molecule with high selectivity. We successfully detected a low concentration of cocaine (300 ng/mL, the drug test cutoff limit) within 60 s using a biological nanopore embedded in a microchip.

A Contactless Capacitance Detection System for Microchip Capillary Electrophoresis

NASA Astrophysics Data System (ADS)

Wu, Peter

2008-05-01

The design, construction and operation of a simple, inexpensive and compact high voltage power supply for use in conjunction with a simple cross, capillary electrophoresis microchip is presented. The detection system utilizes a single high voltage power supply (15 kV), a voltage divider network for obtaining the required voltages for enabling a gated injection valve, and two high voltage relays for switching between the open and closed gate sequences of the injection. The system is used to determine sodium monofluoroacetate (MFA) concentration in diluted fruit juices and tap water. A separation buffer consisting of 20 mM citric acid and histidine at pH 3.5 enabled the detection of the anion in diluted apple juice, cranberry juice, and orange juice without lengthy sample pretreatments. Limit of detection in diluted juices and tap water were determined to be 125, 167, 138, and 173 mg/L for tap water, apple juice, cranberry juice, and orange juice, respectively, based upon an S/N of 3:1. The total analysis time for detecting the MFA anion in fruit juices was less than 5 min, which represents a considerable reduction in analysis time compared to other analytical methods currently used in food analysis.

Determination of ammonium on an integrated microchip with LED-induced fluorescence detection.

PubMed

Xue, Shuhua; Uchiyama, Katsumi; Li, Hai-Fang

2012-01-01

A simply fabricated microfluidic device integrated with a fluorescence detection system has been developed for on-line determination of ammonium in aqueous samples. A 365-nm light-emitting diode (LED) as an excitation source and a minor band pass filter were mounted into a polydimethylsiloxane (PDMS)-based microchip for the purpose of miniaturization of the entire analytical system. The ammonium sample reacted with o-phthaldialdehyde (OPA) on-chip with sodium sulfite as reducing reagent to produce a fluorescent isoindole derivative, which can emit fluorescence signal at about 425 nm when excited at 365 nm. Effects of pH, flow rate of solutions, concentrations of OPA-reagent, phosphate and sulfite salt were investigated. The calibration curve of ammonium in the range of 0.018-1.8 microg/mL showed a good linear relationship with R2 = 0.9985, and the detection limit was (S/N = 3) 3.6 x 10(-4) microg/mL. The relative standard deviation was 2.8% (n = 11) by calculating at 0.18 microg/mL ammonium for repeated detection. The system was applied to determine the ammonium concentration in rain and river waters, even extent to other analytes fluorescence detection by the presented device.

Microchip Module for Blood Sample Preparation and Nucleic Acid Amplification Reactions

PubMed Central

Yuen, Po Ki; Kricka, Larry J.; Fortina, Paolo; Panaro, Nicholas J.; Sakazume, Taku; Wilding, Peter

2001-01-01

A computer numerical control-machined plexiglas-based microchip module was designed and constructed for the integration of blood sample preparation and nucleic acid amplification reactions. The microchip module is comprised of a custom-made heater-cooler for thermal cycling, a series of 254 μm × 254 μm microchannels for transporting human whole blood and reagents in and out of an 8–9 μL dual-purpose (cell isolation and PCR) glass-silicon microchip. White blood cells were first isolated from a small volume of human whole blood (<3 μL) in an integrated cell isolation–PCR microchip containing a series of 3.5-μm feature-sized “weir-type” filters, formed by an etched silicon dam spanning the flow chamber. A genomic target, a region in the human coagulation Factor V gene (226-bp), was subsequently directly amplified by microchip-based PCR on DNA released from white blood cells isolated on the filter section of the microchip mounted onto the microchip module. The microchip module provides a convenient means to simplify nucleic acid analyses by integrating two key steps in genetic testing procedures, cell isolation and PCR and promises to be adaptable for additional types of integrated assays. PMID:11230164

Functionality of veterinary identification microchips following low- (0.5 tesla) and high-field (3 tesla) magnetic resonance imaging.

PubMed

Piesnack, Susann; Frame, Mairi E; Oechtering, Gerhard; Ludewig, Eberhard

2013-01-01

The ability to read patient identification microchips relies on the use of radiofrequency pulses. Since radiofrequency pulses also form an integral part of the magnetic resonance imaging (MRI) process, the possibility of loss of microchip function during MRI scanning is of concern. Previous clinical trials have shown microchip function to be unaffected by MR imaging using a field strength of 1 Tesla and 1.5. As veterinary MRI scanners range widely in field strength, this study was devised to determine whether exposure to lower or higher field strengths than 1 Tesla would affect the function of different types of microchip. In a phantom study, a total of 300 International Standards Organisation (ISO)-approved microchips (100 each of three different types: ISO FDX-B 1.4 × 9 mm, ISO FDX-B 2.12 × 12 mm, ISO HDX 3.8 × 23 mm) were tested in a low field (0.5) and a high field scanner (3.0 Tesla). A total of 50 microchips of each type were tested in each scanner. The phantom was composed of a fluid-filled freezer pack onto which a plastic pillow and a cardboard strip with affixed microchips were positioned. Following an MRI scan protocol simulating a head study, all of the microchips were accurately readable. Neither 0.5 nor 3 Tesla imaging affected microchip function in this study. © 2013 Veterinary Radiology & Ultrasound.

MICROCHIP ENZYMATIC ASSAY OF ORGANOPHOSPHATE NERVE AGENTS. (R830900)

EPA Science Inventory

An on-chip enzymatic assay for screening organophosphate (OP) nerve agents, based on a pre-column reaction of organophosphorus hydrolase (OPH), electrophoretic separation of the phosphonic acid products, and their contactless-conductivity detection, is described. Factors affec...

Physiological and behavioural responses of young horses to hot iron branding and microchip implantation.

PubMed

Erber, R; Wulf, M; Becker-Birck, M; Kaps, S; Aurich, J E; Möstl, E; Aurich, C

2012-02-01

Branding is the traditional and well-established method used to mark horses, but recently microchip transponders for implantation have become available. In this study, behaviour, physiological stress variables and skin temperature in foals were determined in response to hot-iron branding (n=7) and microchip implantation (n=7). Salivary cortisol concentrations increased in response to branding (1.8 ± 0.2 ng/mL) and microchip implantation (1.4 ± 0.1ng/mL), but cortisol release over time did not differ. In response to both manipulations there was a transient increase in heart rate (P<0.001) and heart rate variability (P<0.01). Branding and microchip implantation induced a comparable aversive behaviour (branding, score 3.86 ± 0.85; microchip, score 4.00 ± 0.82). Both techniques thus caused similar physiological and behavioural changes indicative of stress. Acutely, implantation of a microchip was as stressful as branding in foals. Branding caused a necrotising skin burn lasting at least 7 days. Moreover branding, but not microchip implantation (P<0.001), was accompanied by a generalized increase in skin temperature which was comparable to low degree post-burn hypermetabolism in humans. Copyright © 2011 Elsevier Ltd. All rights reserved.

Microchips and controlled-release drug reservoirs.

PubMed

Staples, Mark

2010-01-01

This review summarizes and updates the development of implantable microchip-containing devices that control dosing from drug reservoirs integrated with the devices. As the expense and risk of new drug development continues to increase, technologies that make the best use of existing therapeutics may add significant value. Trends of future medical care that may require advanced drug delivery systems include individualized therapy and the capability to automate drug delivery. Implantable drug delivery devices that promise to address these anticipated needs have been constructed in a variety of ways using micro- and nanoelectromechanical systems (MEMS or NEMS)-based technology. These devices expand treatment options for addressing unmet medical needs related to dosing. Within the last few years, advances in several technologies (MEMS or NEMS fabrication, materials science, polymer chemistry, and data management) have converged to enable the construction of miniaturized implantable devices for controlled delivery of therapeutic agents from one or more reservoirs. Suboptimal performance of conventional dosing methods in terms of safety, efficacy, pain, or convenience can be improved with advanced delivery devices. Microchip-based implantable drug delivery devices allow localized delivery by direct placement of the device at the treatment site, delivery on demand (emergency administration, pulsatile, or adjustable continuous dosing), programmable dosing cycles, automated delivery of multiple drugs, and dosing in response to physiological and diagnostic feedback. In addition, innovative drug-medical device combinations may protect labile active ingredients within hermetically sealed reservoirs. Copyright (c) 2010 John Wiley & Sons, Inc.

Single-cell codetection of metabolic activity, intracellular functional proteins, and genetic mutations from rare circulating tumor cells.

PubMed

Zhang, Yu; Tang, Yin; Sun, Shuai; Wang, Zhihua; Wu, Wenjun; Zhao, Xiaodong; Czajkowsky, Daniel M; Li, Yan; Tian, Jianhui; Xu, Ling; Wei, Wei; Deng, Yuliang; Shi, Qihui

2015-10-06

The high glucose uptake and activation of oncogenic signaling pathways in cancer cells has long made these features, together with the mutational spectrum, prime diagnostic targets of circulating tumor cells (CTCs). Further, an ability to characterize these properties at a single cell resolution is widely believed to be essential, as the known extensive heterogeneity in CTCs can obscure important correlations in data obtained from cell population-based methods. However, to date, it has not been possible to quantitatively measure metabolic, proteomic, and genetic data from a single CTC. Here we report a microchip-based approach that allows for the codetection of glucose uptake, intracellular functional proteins, and genetic mutations at the single-cell level from rare tumor cells. The microchip contains thousands of nanoliter grooves (nanowells) that isolate individual CTCs and allow for the assessment of their glucose uptake via imaging of a fluorescent glucose analog, quantification of a panel of intracellular signaling proteins using a miniaturized antibody barcode microarray, and retrieval of the individual cell nuclei for subsequent off-chip genome amplification and sequencing. This approach integrates molecular-scale information on the metabolic, proteomic, and genetic status of single cells and permits the inference of associations between genetic signatures, energy consumption, and phosphoproteins oncogenic signaling activities in CTCs isolated from blood samples of patients. Importantly, this microchip chip-based approach achieves this multidimensional molecular analysis with minimal cell loss (<20%), which is the bottleneck of the rare cell analysis.

A method for UV-bonding in the fabrication of glass electrophoretic microchips.

PubMed

Huang, Z; Sanders, J C; Dunsmor, C; Ahmadzadeh, H; Landers, J P

2001-10-01

This paper presents an approach for the development of methodologies amenable to simple and inexpensive microchip fabrication, potentially applicable to dissimilar materials bonding and chip integration. The method involves a UV-curable glue that can be used for glass microchip fabrication bonding at room temperature. This involves nothing more than fabrication of glue "guide channels" into the microchip architecture that upon exposure to the appropriate UV light source, bonds the etched plate and cover plate together. The microchip performance was verified by capillary zone electrophoresis (CZE) of small fluorescent molecules with no microchannel surface modification carried out, as well as with a DNA fragment separation following surface modification. The performance of these UV-bonded electrophoretic microchips indicates that this method may provide an alternative to high temperature bonding.

Biological cell controllable patch-clamp microchip

NASA Astrophysics Data System (ADS)

Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long

2010-12-01

A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.

Blinded study determination of high sensitivity and specificity microchip electrophoresis-SSCP/HA to detect mutations in the p53 gene.

PubMed

Hestekin, Christa N; Lin, Jennifer S; Senderowicz, Lionel; Jakupciak, John P; O'Connell, Catherine; Rademaker, Alfred; Barron, Annelise E

2011-11-01

Knowledge of the genetic changes that lead to disease has grown and continues to grow at a rapid pace. However, there is a need for clinical devices that can be used routinely to translate this knowledge into the treatment of patients. Use in a clinical setting requires high sensitivity and specificity (>97%) in order to prevent misdiagnoses. Single-strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) are two DNA-based, complementary methods for mutation detection that are inexpensive and relatively easy to implement. However, both methods are most commonly detected by slab gel electrophoresis, which can be labor-intensive, time-consuming, and often the methods are unable to produce high sensitivity and specificity without the use of multiple analysis conditions. Here, we demonstrate the first blinded study using microchip electrophoresis (ME)-SSCP/HA. We demonstrate the ability of ME-SSCP/HA to detect with 98% sensitivity and specificity >100 samples from the p53 gene exons 5-9 in a blinded study in an analysis time of <10 min. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of the Separation of NDA-Derivatized Methylarginines by Capillary and Microchip Electrophoresis

PubMed Central

Linz, Thomas H.; Snyder, Christa M.; Lunte, Susan M.

2013-01-01

The methylated arginines (MAs) monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) have been shown to be independent predictors of cardiovascular disease. This article describes progress regarding the development of an analytical method capable of rapidly analyzing MAs using capillary electrophoresis (CE) and microchip electrophoresis (MCE) with laser-induced fluorescence (LIF) detection. Several parameters including buffer composition and separation voltage were optimized to achieve an ideal separation. The analytes of interest were derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) to produce fluorescent 1-cyanobenz[f]isoindole (CBI) derivatives and then subjected to CE analysis. Baseline resolution of SDMA, ADMA, MMA, and arginine was achieved in less than 8 min. The limits of detection for SDMA, ADMA, MMA, and arginine were determined to be 15, 20, 25, and 5 nM, respectively, which are well below the expected plasma concentrations. The CE separation method was then transferred to a glass MCE device with LIF detection. MAs were baseline resolved in 3 min on-chip using a 14 cm separation channel with detection limits of approximately 10 nM for each species. To the best of the authors’ knowledge, this is the first report of the separation of MAs by MCE. PMID:22357605

A micro-scale plasma spectrometer for space and plasma edge applications (invited)

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

Scime, E. E., E-mail: escime@wvu.edu; Keesee, A. M.; Elliott, D.

2016-11-15

A plasma spectrometer design based on advances in lithography and microchip stacking technologies is described. A series of curved plate energy analyzers, with an integrated collimator, is etched into a silicon wafer. Tests of spectrometer elements, the energy analyzer and collimator, were performed with a 5 keV electron beam. The measured collimator transmission and energy selectivity were in good agreement with design targets. A single wafer element could be used as a plasma processing or fusion first wall diagnostic.

Effects of radiation from a radiofrequency identification (RFID) microchip on human cancer cells.

PubMed

Lai, Henry C; Chan, Ho Wing; Singh, Narendra P

2016-01-01

Radiofrequency identification (RFID) microchips are used to remotely identify objects, e.g. an animal in which a chip is implanted. A passive RFID microchip absorbs energy from an external source and emits a radiofrequency identification signal which is then decoded by a detector. In the present study, we investigated the effect of the radiofrequency energy emitted by a RFID microchip on human cancer cells. Molt-4 leukemia, BT474 breast cancer, and HepG2 hepatic cancer cells were exposed in vitro to RFID microchip-emitted radiofrequency field for 1 h. Cells were counted before and after exposure. Effects of pretreatment with the spin-trap compound N-tert-butyl-alpha-phenylnitrone or the iron-chelator deferoxamine were also investigated. Results We found that the energy effectively killed/retarded the growth of the three different types of cancer cells, and the effect was blocked by the spin-trap compound or the iron-chelator, whereas an inactive microchip and energy from the external source had no significant effect on the cells. Conclusions Data of the present study suggest that radiofrequency field from the microchip affects cancer cells via the Fenton Reaction. Implantation of RFID microchips in tumors may provide a new method for cancer treatment.

Detection and counting of a submicrometer particle in liquid flow by self-mixing microchip Yb:YAG laser velocimetry.

PubMed

Ohtomo, Takayuki; Sudo, Seiichi; Otsuka, Kenju

2016-09-20

We observed intermittent modulation by scattered light from a single submicrometer particle moving in the flow channel using a self-mixing microchip Yb:YAG laser Doppler velocimeter (LDV) under lateral beam access. The Doppler-shift frequency chirping (i.e., velocity change) was identified in accordance with a particle passage through the beam focus. Single particle counting, which obeys the Poisson distribution, was performed successfully over a long period of time. The experimental results have been reproduced by a numerical simulation. The LDV signal was increased over 20 dB for a 202-nm particle without chirping by collinear beam access with the laser beam axis aligned along the flow direction.

Monitoring Cellular Events in Living Mast Cells Stimulated with an Extremely Small Amount of Fluid on a Microchip

NASA Astrophysics Data System (ADS)

Munaka, Tatsuya; Abe, Hirohisa; Kanai, Masaki; Sakamoto, Takashi; Nakanishi, Hiroaki; Yamaoka, Tetsuji; Shoji, Shuichi; Murakami, Akira

2006-07-01

We successfully developed a measurement system for real-time analysis of cellular function using a newly designed microchip. This microchip was equipped with a micro cell incubation chamber (240 nl) and was stimulated by a very small amount of stimuli (as small as 24 nl). Using the microchip system, cultivation of mast cells was successfully carried out. Monitoring of the cellular events after stimulation with an extremely small amount of fluid on a microchip was performed. This system could be applicable for various types of cellular analysis including real-time monitoring of cellular response by stimulation.

CARBON NANOTUBE/COPPER COMPOSITE ELECTRODES FOR CAPILLARY ELECTROPHORESIS MICROCHIP DETECTION OF CARBOHYDRATES. (R830900)

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...

CAPILLARY ELECTROPHORESIS MICROCHIPS FOR RAPID SEPARATION AND DETECTION OF ORGANOPHOSPHATE NERVE AGENTS. (R828160)

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...

Comparison of Digital Rectal and Microchip Transponder Thermometry in Ferrets (Mustela putorius furo)

PubMed Central

Maxwell, Branden M; Brunell, Marla K; Olsen, Cara H; Bentzel, David E

2016-01-01

Body temperature is a common physiologic parameter measured in both clinical and research settings, with rectal thermometry being implied as the ‘gold standard.’ However, rectal thermometry usually requires physical or chemical restraint, potentially causing falsely elevated readings due to animal stress. A less stressful method may eliminate this confounding variable. The current study compared 2 types of digital rectal thermometers—a calibrated digital thermometer and a common digital thermometer—with an implantable subcutaneous transponder microchip. Microchips were implanted subcutaneously between the shoulder blades of 16 ferrets (8 male, 8 female), and temperatures were measured twice from the microchip reader and once from each of the rectal thermometers. Results demonstrated the microchip temperature readings had very good to good correlation and agreement to those from both of the rectal thermometers. This study indicates that implantable temperature-sensing microchips are a reliable alternative to rectal thermometry for monitoring body temperature in ferrets. PMID:27177569

Ultrasensitive Nanoelectrospray Ionization-Mass Spectrometry using Poly(dimethylsiloxane) Microchips with Monolithically Integrated Emitters

PubMed Central

Sun, Xuefei; Kelly, Ryan T.; Tang, Keqi; Smith, Richard D.

2010-01-01

Summary Poly(dimethylsiloxane) (PDMS) is a widely used substrate for microfluidic devices, as it enables facile fabrication and has other distinctive properties. However, for applications requiring highly sensitive nanoelectrospray ionization mass spectrometry (nanoESI-MS) detection, the use of PDMS microdevices has been hindered by a large chemical background in the mass spectra that originates from the leaching of uncross-linked oligomers and other contaminants from the substrate. A more general challenge is that microfluidic devices containing monolithically integrated electrospray emitters are frequently unable to operate stably in the nanoflow regime where the best sensitivity is achieved. In this report, we extracted the contaminants from PDMS substrates using a series of solvents, eliminating the background observed when untreated PDMS microchips are used for nanoESI-MS, such that peptides at concentrations of 1 nM were readily detected. Optimization of the integrated emitter geometry enabled stable operation at flow rates as low as 10 nL/min. PMID:20617264

Analysis of mutations in oral poliovirus vaccine by hybridization with generic oligonucleotide microchips.

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

Proudnikov, D.; Kirillov, E.; Chumakov, K.

2000-01-01

This paper describes use of a new technology of hybridization with a micro-array of immobilized oligonucleotides for detection and quantification of neurovirulent mutants in Oral Poliovirus Vaccine (OPV). We used a micro-array consisting of three-dimensional gel-elements containing all possible hexamers (total of 4096 probes). Hybridization of fluorescently labelled viral cDNA samples with such microchips resulted in a pattern of spots that was registered and quantified by a computer-linked CCD camera, so that the sequence of the original cDNA could be deduced. The method could reliably identify single point mutations, since each of them affected fluorescence intensity of 12 micro-array elements.more » Micro-array hybridization of DNA mixtures with varying contents of point mutants demonstrated that the method can detect as little as 10% of revertants in a population of vaccine virus. This new technology should be useful for quality control of live viral vaccines, as well as for other applications requiring identification and quantification of point mutations.« less

Authenticity screening of seized whiskey samples using electrophoresis microchips coupled with contactless conductivity detection.

PubMed

Rezende, Kariolanda C A; Moreira, Roger Cardoso; Logrado, Lucio Paulo Lima; Talhavini, Márcio; Coltro, Wendell K T

2016-10-01

This report describes for the first time the use of microchip electrophoresis (ME) devices integrated with capacitively coupled contactless conductivity detection (C 4 D) to investigate the authenticity of seized whiskey samples, which were probably adulterated by simple dilution with tap water. The proposed microfluidic platform was explored for the monitoring of anionic species (Cl - and F - ) in both original and tampered samples. The best separations were achieved within 70 s using a running buffer composed of lactic acid and histidine (pH = 5.9). ME-C 4 D devices were used to analyze samples from three different brands (five samples each). Based on the presence of inorganic anions like Cl - , F - , SO 4 2- and NO 2 - in different amounts, the authenticity of seized whiskeys was compared to original samples. According to the reported data, the proposed microfluidic platform can be useful to help regulatory authorities in the investigation and monitoring of authenticity of commercialized whiskey beverages. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental comparison of autodyne and heterodyne laser interferometry using an Nd:YVO₄ microchip laser.

PubMed

Jacquin, Olivier; Lacot, Eric; Glastre, Wilfried; Hugon, Olivier; Guillet de Chatellus, Hugues

2011-08-01

Using an Nd:YVO₄ microchip laser with a relaxation frequency in the megahertz range, we have experimentally compared a heterodyne interferometer based on a Michelson configuration with an autodyne interferometer based on the laser optical feedback imaging (LOFI) method regarding their signal-to-noise ratios. In the heterodyne configuration, the beating between the reference beam and the signal beam is realized outside the laser cavity, while in the autodyne configuration, the wave beating takes place inside the laser cavity, and the relaxation oscillations of the laser intensity then play an important part. For a given laser output power, object under investigation, and detection noise level, we have determined the amplification gain of the LOFI interferometer compared to the heterodyne interferometer. LOFI interferometry is demonstrated to show higher performance than heterodyne interferometry for a wide range of laser powers and detection levels of noise. The experimental results are in good agreement with the theoretical predictions.

Microchip Immunoaffinity Electrophoresis of Antibody-Thymidine Kinase 1 Complex

PubMed Central

Pagaduan, Jayson V.; Ramsden, Madison; O’Neill, Kim; Woolley, Adam T.

2015-01-01

Thymidine kinase-1 (TK1) is an important cancer biomarker whose serum levels are elevated in early cancer development. We developed a microchip electrophoresis immunoaffinity assay to measure recombinant purified TK1 (pTK1) using an antibody that binds to human TK1. We fabricated poly(methyl methacrylate) microfluidic devices to test the feasibility of detecting antibody (Ab)-pTK1 immune complexes as a step towards TK1 analysis in clinical serum samples. We were able to separate immune complexes from unbound antibodies using 0.5X phosphate buffer saline (pH 7.4) containing 0.01% Tween-20, with 1% w/v methylcellulose that acts as a dynamic surface coating and sieving matrix. Separation of the antibody and Ab-pTK1 complex was observed within a 5 mm effective separation length. This method of detecting pTK1 is easy to perform, requires only a 10 μL sample volume, and takes just 1 minute for separation. PMID:25486911

Infrared microchip and signal receiver being developed

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

Not Available

1990-01-01

ORNL researchers have developed both a solar-powered microtransmitter system that emits an infrared signal as well as a prototype detection system that detect the signal from a distance at least twice as far as can be sent by current transmitters of comparable size. This technology can be used to study mating and foraging habits of Africanized bees, as well as a number of other applications.

Simultaneous analysis of vascular norepinephrine and ATP release using an integrated microfluidic system.

PubMed

Townsend, Alexandra D; Wilken, Gerald H; Mitchell, Kyle K; Martin, R Scott; Macarthur, Heather

2016-06-15

Sympathetic nerves are known to release three neurotransmitters: norepinephrine, ATP, and neuropeptide Y that play a role in controlling vascular tone. This paper focuses on the co-release of norepinephrine and ATP from the mesenteric arterial sympathetic nerves of the rat. In this paper, a quantification technique is described that allows simultaneous detection of norepinephrine and ATP in a near-real-time fashion from the isolated perfused mesenteric arterial bed of the rat. Simultaneous detection is enabled with 3-D printing technology, which is shown to help integrate the perfusate with different detection methods (norepinephrine by microchip-based amperometery and ATP by on-line chemiluminescence). Stimulated levels relative to basal levels of norepinephrine and ATP were found to be 363nM and 125nM, respectively (n=6). The limit of detection for norepinephrine is 80nM using microchip-based amperometric detection. The LOD for on-line ATP detection using chemiluminescence is 35nM. In previous studies, the co-transmitters have been separated and detected with HPLC techniques. With HPLC, the samples from biological preparations have to be derivatized for ATP detection and require collection time before analysis. Thus real-time measurements are not made and the delay in analysis by HPLC can cause degradation. In conclusion, the method described in the paper can be used to successfully detect norepinephrine and ATP simultaneously and in a near-real-time fashion. Copyright © 2016 Elsevier B.V. All rights reserved.

Second Microchip Gets Ready for Launch

NASA Image and Video Library

2018-01-24

Second dime-size microchip carrying 1.6 million names gets processed for installation onto the InSight lander. Technicians at Lockheed Martin Space in Littleton, Colorado installed a microchip with 1.6 million names submitted by the public to ride along with NASA's InSight mission to Mars. The chip was installed on Jan. 23, 2018. This joins another microchip that was previously installed that included 800,000 names for a grand total of 2.4 million names going to Mars as early as May 5, 2018. The microchip including names from the NASA InSight mission's "Send Your Name to Mars" campaign was affixed to the spacecraft with a special glue. https://photojournal.jpl.nasa.gov/catalog/PIA22237

A layered microchip conductance detector with through-layer access to detection fields and high sensitivity to dielectric constant.

PubMed

Suganuma, Y; Dhirani, A-A

2011-04-01

The present study explores a novel apertured microchip conductance detector (AMCD) that is sensitive to dielectric constant. Fashioned on silicon oxide/silicon using optical microlithography, the detector has novel parallel-plate geometry with a top mesh electrode, a middle apertured insulator, and a bottom conducting electrode. This monolithic apertured architecture is planar and may be provided with a thin insulator layer enabling large capacitances, while the top mesh electrode and middle apertured-insulator enable access to regions of the capacitor where electric fields are strong. Hence, the detector is sensitive yet mechanically robust. To test its response, the AMCD was immersed in various solvents, namely water, methanol, acetonitrile, and hexanes. Its response was found to vary in proportion to the solvents' respective dielectric constants. The AMCD was also able to distinguish quantitatively the presence of various molecules in solution, including molecules with chromophores [such as acetylsalicylic acid (ASA)] in methanol and those without chrompohores [such as polyethylene glycol 200 Daltons (PEG200)] in methanol or water. The universal nature of dielectric constant and the microchip detector's sensitivity point to a wide range of potential applications. © 2011 American Institute of Physics

Optical resolution photoacoustic microscopy using novel high-repetition-rate passively Q-switched microchip and fiber lasers.

PubMed

Shi, Wei; Kerr, Shaun; Utkin, Ilya; Ranasinghesagara, Janaka; Pan, Lei; Godwal, Yogesh; Zemp, Roger J; Fedosejevs, Robert

2010-01-01

Optical-resolution photoacoustic microscopy (OR-PAM) is a novel imaging technology for visualizing optically absorbing superficial structures in vivo with lateral spatial resolution determined by optical focusing rather than acoustic detection. Since scanning of the illumination spot is required, OR-PAM imaging speed is limited by both scanning speed and laser pulse repetition rate. Unfortunately, lasers with high repetition rates and suitable pulse durations and energies are not widely available and can be cost-prohibitive and bulky. We are developing compact, passively Q-switched fiber and microchip laser sources for this application. The properties of these lasers are discussed, and pulse repetition rates up to 100 kHz are demonstrated. OR-PAM imaging was conducted using a previously developed photoacoustic probe, which enabled flexible scanning of the focused output of the lasers. Phantom studies demonstrate the ability to image with lateral spatial resolution of 7±2 μm with the microchip laser system and 15±5 μm with the fiber laser system. We believe that the high pulse repetition rates and the potentially compact and fiber-coupled nature of these lasers will prove important for clinical imaging applications where real-time imaging performance is essential.

Simple, rapid and, cost-effective fabrication of PDMS electrophoresis microchips using poly(vinyl acetate) as photoresist master.

PubMed

Lobo-Júnior, Eulício O; Gabriel, Ellen F M; Dos Santos, Rodrigo A; de Souza, Fabrício R; Lopes, Wanderson D; Lima, Renato S; Gobbi, Angelo L; Coltro, Wendell K T

2017-01-01

This study describes a simple, rapid, and cost-effective fabrication of PDMS electrophoresis microchips using poly(vinyl acetate) (PVAc) emulsion as photoresist master. High-relief microfluidic structures were defined on poly(vinyl acetate) previously deposited on printed circuit boards surfaces without cleanroom facilities and sophisticated instrumentation. After a UV exposure, channels with heights ranging from 30 to 140 μm were obtained by controlling the emulsion mass deposited on the master surface. The developing stage was performed using water rather than the organic solvents that are applied for conventional masks. The surface morphology was characterized by optical imaging, profilometry, and SEM. Based on the achieved results, the proposed method offers suitable reproducibility for the prototyping of electrophoresis microchips in PDMS. The feasibility of the resulting PDMS electrophoresis chips was successfully demonstrated with the separation of major inorganic cations within 100 s using a contactless conductivity detection system. The separation efficiencies ranged from ca. 67 900 to 125 600 plates/m. Due to the satisfactory performance and simplified instrumentation, we believe this fabrication protocol presents potential to be implemented in any chemical, biochemical, or biological laboratory. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of in-channel amperometric detection using a dual-channel microchip electrophoresis device and a two-electrode potentiostat for reverse polarity separations

PubMed Central

Meneses, Diogenes; Gunasekara, Dulan B.; Pichetsurnthorn, Pann; da Silva, José A. F.; de Abreu, Fabiane C.; Lunte, Susan M.

2015-01-01

In-channel amperometric detection combined with dual-channel microchip electrophoresis is evaluated using a two-electrode isolated potentiostat for reverse polarity separations. The device consists of two separate channels with the working and reference electrodes placed at identical positions relative to the end of the channel, enabling noise subtraction. In previous reports of this configuration, normal polarity and a three-electrode detection system were used. In the two-electrode detection system described here, the electrode in the reference channel acts as both the counter and reference. The effect of electrode placement in the channels on noise and detector response was investigated using nitrite, tyrosine, and hydrogen peroxide as model compounds. The effects of electrode material and size and type of reference electrode on noise and the potential shift of hydrodynamic voltammograms for the model compounds were determined. In addition, the performance of two- and three-electrode configurations using Pt and Ag/AgCl reference electrodes was compared. Although the signal was attenuated with the Pt reference, the noise was also significantly reduced. It was found that lower LOD were obtained for all three compounds with the dual-channel configuration compared to single-channel, in-channel detection. The dual-channel method was then used for the detection of nitrite in a dermal microdialysis sample obtained from a sheep following nitroglycerin administration. PMID:25256669

In vitro evaluation of a passive radio frequency identification microchip implanted in human molars subjected to compression forces, for forensic purposes of human identification

PubMed Central

Moreno, Freddy; Vallejo, Diego; Garzón, Herney; Moreno, Sandra

2013-01-01

Objective: To evaluate the in vitro behavior of a passive Radio Frequency Identification (RFID) microchip implanted in human molars subjected to compression forces to determine its technical and clinical viability. Materials and Methods: In vitro experimental study to evaluate the physical behavior of a passive RFID microchip (VeriChip™) implanted in human molars through resin restoration (Filtek P90™ Silorane 3M-ESPE®) to determine the clinical and technical possibilities of the implant and the viability to withstand compression forces exerted by the stomatognathic system during mastication. Results: Through the ANOVA test, it was found that the teeth on which a microchip was implanted show great resistance to compressive forces. It was also evident that teeth with microchips implanted in Class V cavities are more resistant than those implanted in Class I cavities. Conclusions: Although microchip dimensions are big, requiring a sufficiently large cavity, from the biomechanical point of view it is plausible to implant a microchip in a Class V cavity employing restoration material based on resin for forensic purposes of human identification. PMID:24255554

Megawatt level UV output from [110] Cr⁴⁺:YAG passively Q-switched microchip laser.

PubMed

Bhandari, Rakesh; Taira, Takunori

2011-11-07

Recent development of megawatt peak power, giant pulse microchip lasers has opened new opportunities for efficient wavelength conversion, provided the output of the microchip laser is linearly polarized. We obtain > 2 MW peak power, 260 ps, 100 Hz pulses at 266 nm by fourth harmonic conversion of a linearly polarized Nd:YAG microchip laser that is passively Q-switched with [110] cut Cr⁴⁺:YAG. The SHG and FHG conversion efficiencies are 85% and 51%, respectively.

Pr:YAlO(3) microchip laser.

PubMed

Fibrich, Martin; Jelínková, Helena; Sulc, Jan; Nejezchleb, Karel; Skoda, Václav

2010-08-01

A cw Pr:YAlO(3) microchip-laser operation in the near-IR spectral region is reported. A microchip resonator was formed by dielectric mirrors directly deposited on the Pr:YAlO(3) crystal surfaces. For active medium pumping, a GaN laser diode providing up to 1W of output power at approximately 448 nm was used. 139mW of laser radiation at 747nm wavelength has been extracted from the microchip-laser system. Slope efficiency related to the incident pumping power was approximately 25%.

Separation and detection of VX and its methylphosphonic acid degradation products on a microchip using indirect laser-induced fluorescence.

PubMed

Heleg-Shabtai, Vered; Gratziany, Natzach; Liron, Zvi

2006-05-01

The application of indirect LIF (IDLIF) technique for on-chip electrophoretic separation and detection of the nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and its major phosphonic degradation products, ethyl methylphosphonic acid (EMPA) and methylphosphonic acid (MPA) was demonstrated. Separation and detection of MPA degradation products of VX and the nerve agent isopropyl methylphosphonofluoridate (GB) are presented. The negatively charged dye eosin was found to be a good fluorescent marker for both the negatively charged phosphonic acids and the positively charged VX, and was chosen as the IDLIF visualization fluorescent dye. Separation and detection of VX, EMPA, and MPA in a simple-cross microchip were completed within less than a minute, and consumed only a 50 pL sample volume. A characteristic system peak that appeared in all IDLIF electropherograms served as an internal standard that increased the reliability of peak identification. The negative peak of both VX and the MPAs is in agreement with indirect detection theory and with previous reports in the literature. The LOD of VX and EMPA by IDLIF was 30 and 37 microM, respectively. Despite the fact that the detection sensitivity is relatively low, the rapid simultaneous on-chip analysis of both VX and its degradation products as well as the separation and detection of the MPA degradation products of both VX and GB, increases detection reliability and may present a choice when sensitivity is not critical compared with speed and simplicity of the assay.

Pneumatic Microvalve-Based Hydrodynamic Sample Injection for High-Throughput, Quantitative Zone Electrophoresis in Capillaries

PubMed Central

2015-01-01

A hybrid microchip/capillary electrophoresis (CE) system was developed to allow unbiased and lossless sample loading and high-throughput repeated injections. This new hybrid CE system consists of a poly(dimethylsiloxane) (PDMS) microchip sample injector featuring a pneumatic microvalve that separates a sample introduction channel from a short sample loading channel, and a fused-silica capillary separation column that connects seamlessly to the sample loading channel. The sample introduction channel is pressurized such that when the pneumatic microvalve opens briefly, a variable-volume sample plug is introduced into the loading channel. A high voltage for CE separation is continuously applied across the loading channel and the fused-silica capillary separation column. Analytes are rapidly separated in the fused-silica capillary, and following separation, high-sensitivity MS detection is accomplished via a sheathless CE/ESI-MS interface. The performance evaluation of the complete CE/ESI-MS platform demonstrated that reproducible sample injection with well controlled sample plug volumes could be achieved by using the PDMS microchip injector. The absence of band broadening from microchip to capillary indicated a minimum dead volume at the junction. The capabilities of the new CE/ESI-MS platform in performing high-throughput and quantitative sample analyses were demonstrated by the repeated sample injection without interrupting an ongoing separation and a linear dependence of the total analyte ion abundance on the sample plug volume using a mixture of peptide standards. The separation efficiency of the new platform was also evaluated systematically at different sample injection times, flow rates, and CE separation voltages. PMID:24865952

Electrochromatography on acrylate-based monolith in cyclic olefin copolymer microchip: a cost-effective and easy-to-use technology.

PubMed

Ladner, Yoann; Crétier, Gérard; Faure, Karine

2012-10-01

This article shows that there is great interest in using an electrochromatographic microchip made of hexyl acrylate (HA) based porous monolith cast within the channel of a cyclic olefin copolymer (COC) device. The monolith is simultaneously in situ synthesized and anchored to the inner walls of the channel in less than 10 min. By appropriate choice of light intensity used during the synthesis, the separation efficiency obtained for nonpolar solutes such as polycyclic aromatic hydrocarbons (PAH) is increased up to 250 000 plates/m. The performance of this HA-filled COC microchip was investigated for a wide range of analytes of varying nature. The reversed-phase separation of four aflatoxins is obtained in less than 2 min. The baseline separation of a mixture of neurotransmitters including six amino acids and two catecholamines is possible thanks to the superimposition of the differences in electrophoretic mobility on the chromatographic process. The durability of the system at pH 13 allows the separation of five biogenic amines and the quantitative determination of two of them in numerous wine samples. The feasibility of on-line preconcentration is also demonstrated. Hydrophilic surface modification of COC channel via UV-photografting with poly(ethylene glycol) methacrylate (PEGMA) before in situ synthesis of HA, is necessary to reduce the adsorption of very hydrophobic solutes such as PAH during enrichment. The detection limit of fluoranthene is decreased down to less than 1 ppb with a preconcentration of 4.5 h on the HA-filled PEGMA functionalized COC microchip. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pneumatic Microvalve-Based Hydrodynamic Sample Injection for High-Throughput, Quantitative Zone Electrophoresis in Capillaries

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

Kelly, Ryan T.; Wang, Chenchen; Rausch, Sarah J.

2014-07-01

A hybrid microchip/capillary CE system was developed to allow unbiased and lossless sample loading and high throughput repeated injections. This new hybrid CE system consists of a polydimethylsiloxane (PDMS) microchip sample injector featuring a pneumatic microvalve that separates a sample introduction channel from a short sample loading channel and a fused silica capillary separation column that connects seamlessly to the sample loading channel. The sample introduction channel is pressurized such that when the pneumatic microvalve opens briefly, a variable-volume sample plug is introduced into the loading channel. A high voltage for CE separation is continuously applied across the loading channelmore » and the fused silica capillary separation column. Analytes are rapidly separated in the fused silica capillary with high resolution. High sensitivity MS detection after CE separation is accomplished via a sheathless CE/ESI-MS interface. The performance evaluation of the complete CE/ESI-MS platform demonstrated that reproducible sample injection with well controlled sample plug volumes could be achieved by using the PDMS microchip injector. The absence of band broadening from microchip to capillary indicated a minimum dead volume at the junction. The capabilities of the new CE/ESI-MS platform in performing high throughput and quantitative sample analyses were demonstrated by the repeated sample injection without interrupting an ongoing separation and a good linear dependence of the total analyte ion abundance on the sample plug volume using a mixture of peptide standards. The separation efficiency of the new platform was also evaluated systematically at different sample injection times, flow rates and CE separation voltages.« less

Fibrosarcoma adjacent to the site of microchip implantation in a cat.

PubMed

Daly, Meighan K; Saba, Corey F; Crochik, Sonia S; Howerth, Elizabeth W; Kosarek, Carrie E; Cornell, Karen K; Roberts, Royce E; Northrup, Nicole C

2008-04-01

A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.

Wavelength locking of CW and Q-switched Er(3+) microchip lasers to acetylene absorption lines using pump-power modulation.

PubMed

Brunel, Marc; Vallet, Marc

2007-02-19

We show that modulating the diode-pump power of a microchip solid-state laser enables to lock its wavelength to a reference molecular line. The method is applied to two different types of Er,Yb:glass monolithic microchip lasers operating at 1.53 microm. First, wavelength locking of a continuous-wave dual-polarization microchip laser to acetylene absorption lines is demonstrated, without using any additional modulator, internal or external. We then show that, remarkably, this simple method is also suitable for stabilizing a passively Q-switched microchip laser. A pulsed wavelength stability of 10(-8) over 1 hour is readily observed. Applications to lidars and to microwave photonics are discussed.

Laser diode side-pumped Nd:YVO4 microchip laser with film-etched microcavity mirrors.

PubMed

Li, Jiyang; Niu, Yanxiong; Chen, Sanbin; Tan, Yidong

2017-10-01

Microchip lasers are applied as the light sources on various occasions with the end-pumping scheme. However, the vibration, the temperature drift, or the mechanical deformation of the pumping light in laser diodes in the end-pumping scheme will lead to instability in the microchip laser output, which causes errors and malfunctioning in the optic systems. In this paper, the side-pumping scheme is applied for improving the disturbance-resisting ability of the microchip laser. The transverse mode and the frequency purity of the laser output are tested. To ensure unicity in the frequency of the laser output, numerical simulations based on Fresnel-Kirchhoff diffraction theory are conducted on the parameters of the microchip laser cavity. Film-etching technique is applied to restrain the area of the film and form the microcavity mirrors. The laser output with microcavity mirrors is ensured to be in single frequency and with good beam quality, which is significant in the applications of microchip lasers as the light sources in optical systems.

Automatic Feature Selection and Improved Classification in SICADA Counterfeit Electronics Detection

DTIC Science & Technology

2017-03-20

The SICADA methodology was developed to detect such counterfeit microelectronics by collecting power side channel data and applying machine learning...to identify counterfeits. This methodology has been extended to include a two-step automated feature selection process and now uses a one-class SVM...classifier. We describe this methodology and show results for empirical data collected from several types of Microchip dsPIC33F microcontrollers

Multichannel microchip electrophoresis device fabricated in polycarbonate with an integrated contact conductivity sensor array.

PubMed

Shadpour, Hamed; Hupert, Mateusz L; Patterson, Donald; Liu, Changgeng; Galloway, Michelle; Stryjewski, Wieslaw; Goettert, Jost; Soper, Steven A

2007-02-01

A 16-channel microfluidic chip with an integrated contact conductivity sensor array is presented. The microfluidic network consisted of 16 separation channels that were hot-embossed into polycarbonate (PC) using a high-precision micromilled metal master. All channels were 40 microm deep and 60 microm wide with an effective separation length of 40 mm. A gold (Au) sensor array was lithographically patterned onto a PC cover plate and assembled to the fluidic chip via thermal bonding in such a way that a pair of Au microelectrodes (60 microm wide with a 5 microm spacing) was incorporated into each of the 16 channels and served as independent contact conductivity detectors. The spacing between the corresponding fluidic reservoirs for each separation channel was set to 9 mm, which allowed for loading samples and buffers to all 40 reservoirs situated on the microchip in only five pipetting steps using an 8-channel pipettor. A printed circuit board (PCB) with platinum (Pt) wires was used to distribute the electrophoresis high-voltage to all reservoirs situated on the fluidic chip. Another PCB was used for collecting the conductivity signals from the patterned Au microelectrodes. The device performance was evaluated using microchip capillary zone electrophoresis (mu-CZE) of amino acid, peptide, and protein mixtures as well as oligonucleotides that were separated via microchip capillary electrochromatography (mu-CEC). The separations were performed with an electric field (E) of 90 V/cm and were completed in less than 4 min in all cases. The conductivity detection was carried out using a bipolar pulse voltage waveform with a pulse amplitude of +/-0.6 V and a frequency of 6.0 kHz. The conductivity sensor array concentration limit of detection (SNR = 3) was determined to be 7.1 microM for alanine. The separation efficiency was found to be 6.4 x 10(4), 2.0 x 10(3), 4.8 x 10(3), and 3.4 x 10(2) plates for the mu-CEC of the oligonucleotides and mu-CZE of the amino acids, peptides, and proteins, respectively, with an average channel-to-channel migration time reproducibility of 2.8%. The average resolution obtained for mu-CEC of the oligonucleotides and mu-CZE of the amino acids, peptides, and proteins was 4.6, 1.0, 0.9, and 1.0, respectively. To the best of our knowledge, this report is the first to describe a multichannel microchip electrophoresis device with integrated contact conductivity sensor array.

Rapid analysis of perchlorate in drinking water at parts per billion levels using microchip electrophoresis.

PubMed

Gertsch, Jana C; Noblitt, Scott D; Cropek, Donald M; Henry, Charles S

2010-05-01

A microchip capillary electrophoresis (MCE) system has been developed for the determination of perchlorate in drinking water. The United States Environmental Protection Agency (USEPA) recently proposed a health advisory limit for perchlorate in drinking water of 15 parts per billion (ppb), a level requiring large, sophisticated instrumentation, such as ion chromatography coupled with mass spectrometry (IC-MS), for detection. An inexpensive, portable system is desired for routine online monitoring applications of perchlorate in drinking water. Here, we present an MCE method using contact conductivity detection for perchlorate determination. The method has several advantages, including reduced analysis times relative to IC, inherent portability, high selectivity, and minimal sample pretreatment. Resolution of perchlorate from more abundant ions was achieved using zwitterionic, sulfobetaine surfactants, N-hexadecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate (HDAPS) and N-tetradecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate (TDAPS). The system performance and the optimization of the separation chemistry, including the use of these surfactants to resolve perchlorate from other anions, are discussed in this work. The system is capable of detection limits of 3.4 +/- 1.8 ppb (n = 6) in standards and 5.6 +/- 1.7 ppb (n = 6) in drinking water.

Microchip Lasers

DTIC Science & Technology

2016-10-31

microchip laser : (top) schematic and (bottom) photograph of working device mounted on 12.7-mm- dia. post. switch 17 (355-nm UV ), 1.5 µJ of fourth......USA E-mail: zayhowski@ll.mit.edu Abstract Microchip lasers are a rich family of solid-state lasers defined by their small size, robust integration

Apparatus for Precise Indium-Bump Bonding of Microchips

NASA Technical Reports Server (NTRS)

Wild, Larry; Mulder, Jerry; Alvarado, Nicholas

2005-01-01

An improved apparatus has been designed and built for use in precise positioning and pressing of a microchip onto a substrate (which could, optionally, be another microchip) for the purpose of indium-bump bonding. The apparatus (see figure) includes the following: A stereomicroscope, A stage for precise positioning of the microchip in rotation angle (theta) about the nominally vertical pressing axis and in translation along two nominally horizontal coordinate axes (x and y), and An actuator system that causes a bonding tip to press the microchip against the substrate with a precisely controlled force. In operation, the microscope and the stage are used to position the microchip under the bonding tip and to align the indium bumps on the chip and the substrate, then the actuator system is used to apply a prescribed bonding force for a prescribed time. The improved apparatus supplants a partly similar prior apparatus that operated with less precision and repeatability, producing inconsistent and unreliable bonds. Results of the use of the prior apparatus included broken microchips, uneven bonds, and bonds characterized, variously, by overcompression or undercompression. In that apparatus, the bonding force was generated and controlled by use of a micrometer head positioned over the center of a spring-loaded scale, and the force was applied to the microchip via the scale, which was equipped for digital readout of the force. The inconsistency of results was attributed to the following causes: It was not possible to control the bonding force with sufficient precision or repeatability. Particularly troublesome was the inability to control the force at levels less than the weight of 150 g. Excessive compliance in the spring-loaded scale, combined with deviations from parallelarity of the substrate and bonding-tip surfaces, gave rise to nonuniformity in the pressure applied to the microchip, thereby generating excessive stresses and deformations in the microchip. In the improved apparatus, the bonding tip and the components that hold the substrate and the microchip are more rigid and precise than in the prior apparatus, so as to ensure less deviation from parallelarity of the bonding-tip and substrate surfaces, thereby ensuring more nearly uniform distribution of bonding force over the area of the microchip. The bonding force is now applied through, and measured by, a load cell that makes it possible to exert finer control over the force. The force can be set at any value between 0 and the weight of 800 g in increments of 0.2 g.

Production of Microchips from Polystyrene Plates

ERIC Educational Resources Information Center

Pace, Sarah Lindsey

2009-01-01

Currently manufactured microchips are expensive to make, require specialized equipment, and leave a large environmental footprint. To counter this, an alternative procedure that is cheaper and leaves a smaller environmental footprint should be made. The goal of this research project is to develop a process that creates microchips from polystyrene…

Metrics for TRUST in Integrated Circuits

DTIC Science & Technology

2008-06-01

metrics; Trojan ; detection Introduction In the Defense Science Board report, “DSB Task Force on High Performance Microchip Supply” [1] several...BETAINV C m M m= − + − + Where Ptd | lower is a lower bound on Ptd with confidence C, m is the number of detected Trojan transistors, and M is the...total number of Trojan transistors. From this relationship, in order to establish Ptd = 90% at 90% confidence on a single test article, we must

Photonic crystal microchip laser

NASA Astrophysics Data System (ADS)

Gailevicius, D.; Koliadenko, V.; Purlys, V.; Peckus, M.; Taranenko, V.; Staliunas, K.

2017-02-01

The microchip lasers, being sources of coherent light, suffer from one serious drawback: low spatial quality of the beam, strongly reducing the brightness of emitted radiation. Attempts to improve the beam quality, such as pump-beam guiding, external feedback, either strongly reduce the emission power, or drastically increase the size and complexity of the lasers. Here we propose that specially designed photonic crystal in the cavity of a microchip laser, can significantly improve the beam quality. We experimentally show that a microchip laser, due to spatial filtering functionality of intracavity photonic crystal, improves the beam quality factor M2 reducing it by factor of 2, and thus increase the brightness of radiation by a factor of 4. This comprises a new kind of laser, the "photonic crystal microchip laser", a very compact and efficient light source emitting high spatial high brightness radiation.

Photonic Crystal Microchip Laser.

PubMed

Gailevicius, Darius; Koliadenko, Volodymyr; Purlys, Vytautas; Peckus, Martynas; Taranenko, Victor; Staliunas, Kestutis

2016-09-29

The microchip lasers, being very compact and efficient sources of coherent light, suffer from one serious drawback: low spatial quality of the beam strongly reducing the brightness of emitted radiation. Attempts to improve the beam quality, such as pump-beam guiding, external feedback, either strongly reduce the emission power, or drastically increase the size and complexity of the lasers. Here it is proposed that specially designed photonic crystal in the cavity of a microchip laser, can significantly improve the beam quality. Experiments show that a microchip laser, due to spatial filtering functionality of intracavity photonic crystal, improves the beam quality factor M 2 reducing it by a factor of 2, and increase the brightness of radiation by a factor of 3. This comprises a new kind of laser, the "photonic crystal microchip laser", a very compact and efficient light source emitting high spatial quality high brightness radiation.

Capillary electrophoresis-electrochemical detection microchip device and supporting circuits

DOEpatents

Jackson, Douglas J [New Albany, IN; Roussel, Jr., Thomas J.; Crain, Mark M [Georgetown, IN; Baldwin, Richard P [Louisville, KY; Keynton, Robert S [Louisville, KY; Naber, John F [Prospect, KY; Walsh, Kevin M [Louisville, KY; Edelen, John G [Versailles, KY

2008-03-18

The present invention is a capillary electrophoresis device, comprising a substrate; a first channel in the substrate, and having a buffer arm and a detection arm; a second channel in the substrate intersecting the first channel, and having a sample arm and a waste arm; a buffer reservoir in fluid communication with the buffer arm; a waste reservoir in fluid communication with the waste arm; a sample reservoir in fluid communication with the sample arm; and a detection reservoir in fluid communication with the detection arm. The detection arm and the buffer arm are of substantially equal length.

InSight's Second Microchip

NASA Image and Video Library

2018-01-23

Technicians at Lockheed Martin Space in Littleton, Colorado installed a microchip with 1.6 million names submitted by the public to ride along with NASA's InSight mission to Mars. The chip was installed on Jan. 23, 2018. This joins another microchip that was previously installed that included 800,000 names for a grand total of 2.4 million names going to Mars as early as May 5, 2018. The microchip including names from the NASA InSight mission's "Send Your Name to Mars" campaign was affixed to the spacecraft with a special glue. https://photojournal.jpl.nasa.gov/catalog/PIA22206

Nanostructured gold microelectrodes for SERS and EIS measurements by incorporating ZnO nanorod growth with electroplating

PubMed Central

Zong, Xianli; Zhu, Rong; Guo, Xiaoliang

2015-01-01

In this paper, a fine gold nanostructure synthesized on selective planar microelectrodes in micro-chip is realized by using an advanced hybrid fabrication approach incorporating growth of nanorods (NRs) with gold electroplating. By this developed nanostructure, integration of in-situ surface-enhanced Raman spectroscopy (SERS) detection with electrochemical impedance spectroscopy (EIS) measurement for label-free, nondestructive, real-time and rapid monitoring on a single cell has been achieved. Moreover, parameters of Au nanostructures such as size of nanoholes/nanogaps can be controllably adjusted in the fabrication. We have demonstrated a SERS enhancement factor of up to ~2.24 × 106 and double-layer impedance decrease ratio of 90% ~ 95% at low frequency range below 200 kHz by using nanostructured microelectrodes. SERS detection and in-situ EIS measurement of a trapped single cell by using planar microelectrodes are realized to demonstrate the compatibility, multi-functions, high-sensitivity and simplicity of the micro-chip system. This dual function platform integrating SERS and EIS is of great significance in biological, biochemical and biomedical applications. PMID:26558325

A high-throughput solid-phase extraction microchip combined with inductively coupled plasma-mass spectrometry for rapid determination of trace heavy metals in natural water.

PubMed

Shih, Tsung-Ting; Hsieh, Cheng-Chuan; Luo, Yu-Ting; Su, Yi-An; Chen, Ping-Hung; Chuang, Yu-Chen; Sun, Yuh-Chang

2016-04-15

Herein, a hyphenated system combining a high-throughput solid-phase extraction (htSPE) microchip with inductively coupled plasma-mass spectrometry (ICP-MS) for rapid determination of trace heavy metals was developed. Rather than performing multiple analyses in parallel for the enhancement of analytical throughput, we improved the processing speed for individual samples by increasing the operation flow rate during SPE procedures. To this end, an innovative device combining a micromixer and a multi-channeled extraction unit was designed. Furthermore, a programmable valve manifold was used to interface the developed microchip and ICP-MS instrumentation in order to fully automate the system, leading to a dramatic reduction in operation time and human error. Under the optimized operation conditions for the established system, detection limits of 1.64-42.54 ng L(-1) for the analyte ions were achieved. Validation procedures demonstrated that the developed method could be satisfactorily applied to the determination of trace heavy metals in natural water. Each analysis could be readily accomplished within just 186 s using the established system. This represents, to the best of our knowledge, an unprecedented speed for the analysis of trace heavy metal ions. Copyright © 2016 Elsevier B.V. All rights reserved.

Parallel confocal detection of single biomolecules using diffractive optics and integrated detector units.

PubMed

Blom, H; Gösch, M

2004-04-01

The past few years we have witnessed a tremendous surge of interest in so-called array-based miniaturised analytical systems due to their value as extremely powerful tools for high-throughput sequence analysis, drug discovery and development, and diagnostic tests in medicine (see articles in Issue 1). Terminologies that have been used to describe these array-based bioscience systems include (but are not limited to): DNA-chip, microarrays, microchip, biochip, DNA-microarrays and genome chip. Potential technological benefits of introducing these miniaturised analytical systems include improved accuracy, multiplexing, lower sample and reagent consumption, disposability, and decreased analysis times, just to mention a few examples. Among the many alternative principles of detection-analysis (e.g.chemiluminescence, electroluminescence and conductivity), fluorescence-based techniques are widely used, examples being fluorescence resonance energy transfer, fluorescence quenching, fluorescence polarisation, time-resolved fluorescence, and fluorescence fluctuation spectroscopy (see articles in Issue 11). Time-dependent fluctuations of fluorescent biomolecules with different molecular properties, like molecular weight, translational and rotational diffusion time, colour and lifetime, potentially provide all the kinetic and thermodynamic information required in analysing complex interactions. In this mini-review article, we present recent extensions aimed to implement parallel laser excitation and parallel fluorescence detection that can lead to even further increase in throughput in miniaturised array-based analytical systems. We also report on developments and characterisations of multiplexing extension that allow multifocal laser excitation together with matched parallel fluorescence detection for parallel confocal dynamical fluorescence fluctuation studies at the single biomolecule level.

Production, Cost and Chip Characteristics of In-Woods Microchipping

Treesearch

J. Thompson; W. Sprinkle

2013-01-01

Emerging markets for biomass have increased the interest in producing microchips in the field. As a component of a large United States Department of Energy (DOE) funded project, microchipping has been trialed on a limited scale. The goal of the research was to evaluate the production, cost and chip characteristics of a mobile disc chipper configured to produce...

Correlative fluorescence and scanning transmission electron microscopy of quantum dot-labeled proteins on whole cells in liquid.

PubMed

Peckys, Diana B; Bandmann, Vera; de Jonge, Niels

2014-01-01

Correlative fluorescence microscopy combined with scanning transmission electron microscopy (STEM) of cells fully immersed in liquid is a new methodology with many application areas. Proteins, in live cells immobilized on microchips, are labeled with fluorescent quantum dot nanoparticles. In this protocol, the epidermal growth factor receptor (EGFR) is labeled. The cells are fixed after a selected labeling time, for example, 5 min as needed to form EGFR dimers. The microchip with cells is then imaged with fluorescence microscopy. Thereafter, STEM can be accomplished in two ways. The microchip with the labeled cells and one microchip with a spacer are assembled into a special microfluidic device and imaged with dedicated high-voltage STEM. Alternatively, thin edges of cells can be studied with environmental scanning electron microscopy with a STEM detector, by placing a microchip with cells in a cooled wet environment. © 2014 Elsevier Inc. All rights reserved.

Characteristics of High-Resolution Hemoglobin Measurement Microchip Integrated with Signal Processing Circuit

NASA Astrophysics Data System (ADS)

Noda, Toshihiko; Takao, Hidekuni; Ashiki, Mitsuaki; Ebi, Hiroyuki; Sawada, Kazuaki; Ishida, Makoto

2004-04-01

In this study, a microchip for measurement of hemoglobin in human blood has been proposed, fabricated and evaluated. The measurement principle of hemoglobin is based on the “cyanmethemoglobin method” that calculates the cyanmethemoglobin concentration by absorption photometry. A glass/silicon/silicon structure was used for the microchip. The middle silicon layer includes flow channels, and 45° mirrors formed at each end of the flow channels. Photodiodes and metal oxide semiconductor (MOS) integrated circuits were fabricated on the bottom silicon layer. The performance of the microchip for hemoglobin measurement was evaluated using a solution of red food color instead of a real blood sample. The fabricated microchip exhibited a similar performance to a nonminiaturized absorption cell which has the same optical path length. Signal processing output varied with solution concentration from 5.32 V to 5.55 V with very high stability due to differential signal processing.

Photonic Crystal Microchip Laser

NASA Astrophysics Data System (ADS)

Gailevicius, Darius; Koliadenko, Volodymyr; Purlys, Vytautas; Peckus, Martynas; Taranenko, Victor; Staliunas, Kestutis

2016-09-01

The microchip lasers, being very compact and efficient sources of coherent light, suffer from one serious drawback: low spatial quality of the beam strongly reducing the brightness of emitted radiation. Attempts to improve the beam quality, such as pump-beam guiding, external feedback, either strongly reduce the emission power, or drastically increase the size and complexity of the lasers. Here it is proposed that specially designed photonic crystal in the cavity of a microchip laser, can significantly improve the beam quality. Experiments show that a microchip laser, due to spatial filtering functionality of intracavity photonic crystal, improves the beam quality factor M2 reducing it by a factor of 2, and increase the brightness of radiation by a factor of 3. This comprises a new kind of laser, the “photonic crystal microchip laser”, a very compact and efficient light source emitting high spatial quality high brightness radiation.

Photonic Crystal Microchip Laser

PubMed Central

Gailevicius, Darius; Koliadenko, Volodymyr; Purlys, Vytautas; Peckus, Martynas; Taranenko, Victor; Staliunas, Kestutis

2016-01-01

The microchip lasers, being very compact and efficient sources of coherent light, suffer from one serious drawback: low spatial quality of the beam strongly reducing the brightness of emitted radiation. Attempts to improve the beam quality, such as pump-beam guiding, external feedback, either strongly reduce the emission power, or drastically increase the size and complexity of the lasers. Here it is proposed that specially designed photonic crystal in the cavity of a microchip laser, can significantly improve the beam quality. Experiments show that a microchip laser, due to spatial filtering functionality of intracavity photonic crystal, improves the beam quality factor M2 reducing it by a factor of 2, and increase the brightness of radiation by a factor of 3. This comprises a new kind of laser, the “photonic crystal microchip laser”, a very compact and efficient light source emitting high spatial quality high brightness radiation. PMID:27683066

Acupuncture injection for field amplified sample stacking and glass microchip-based capillary gel electrophoresis.

PubMed

Ha, Ji Won; Hahn, Jong Hoon

2017-02-01

Acupuncture sample injection is a simple method to deliver well-defined nanoliter-scale sample plugs in PDMS microfluidic channels. This acupuncture injection method in microchip CE has several advantages, including minimization of sample consumption, the capability of serial injections of different sample solutions into the same microchannel, and the capability of injecting sample plugs into any desired position of a microchannel. Herein, we demonstrate that the simple and cost-effective acupuncture sample injection method can be used for PDMS microchip-based field amplified sample stacking in the most simplified straight channel by applying a single potential. We achieved the increase in electropherogram signals for the case of sample stacking. Furthermore, we present that microchip CGE of ΦX174 DNA-HaeⅢ digest can be performed with the acupuncture injection method on a glass microchip while minimizing sample loss and voltage control hardware. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An integrated CMOS high voltage supply for lab-on-a-chip systems.

PubMed

Behnam, M; Kaigala, G V; Khorasani, M; Marshall, P; Backhouse, C J; Elliott, D G

2008-09-01

Electrophoresis is a mainstay of lab-on-a-chip (LOC) implementations of molecular biology procedures and is the basis of many medical diagnostics. High voltage (HV) power supplies are necessary in electrophoresis instruments and are a significant part of the overall system cost. This cost of instrumentation is a significant impediment to making LOC technologies more widely available. We believe one approach to overcoming this problem is to use microelectronic technology (complementary metal-oxide semiconductor, CMOS) to generate and control the HV. We present a CMOS-based chip (3 mm x 2.9 mm) that generates high voltages (hundreds of volts), switches HV outputs, and is powered by a 5 V input supply (total power of 28 mW) while being controlled using a standard computer serial interface. Microchip electrophoresis with laser induced fluorescence (LIF) detection is implemented using this HV CMOS chip. With the other advancements made in the LOC community (e.g. micro-fluidic and optical devices), these CMOS chips may ultimately enable 'true' LOC solutions where essentially all the microfluidics, photonics and electronics are on a single chip.

Recent advancements in chemical luminescence-based lab-on-chip and microfluidic platforms for bioanalysis.

PubMed

Mirasoli, Mara; Guardigli, Massimo; Michelini, Elisa; Roda, Aldo

2014-01-01

Miniaturization of analytical procedures through microchips, lab-on-a-chip or micro total analysis systems is one of the most recent trends in chemical and biological analysis. These systems are designed to perform all the steps in an analytical procedure, with the advantages of low sample and reagent consumption, fast analysis, reduced costs, possibility of extra-laboratory application. A range of detection technologies have been employed in miniaturized analytical systems, but most applications relied on fluorescence and electrochemical detection. Chemical luminescence (which includes chemiluminescence, bioluminescence, and electrogenerated chemiluminescence) represents an alternative detection principle that offered comparable (or better) analytical performance and easier implementation in miniaturized analytical devices. Nevertheless, chemical luminescence-based ones represents only a small fraction of the microfluidic devices reported in the literature, and until now no review has been focused on these devices. Here we review the most relevant applications (since 2009) of miniaturized analytical devices based on chemical luminescence detection. After a brief overview of the main chemical luminescence systems and of the recent technological advancements regarding their implementation in miniaturized analytical devices, analytical applications are reviewed according to the nature of the device (microfluidic chips, microchip electrophoresis, lateral flow- and paper-based devices) and the type of application (micro-flow injection assays, enzyme assays, immunoassays, gene probe hybridization assays, cell assays, whole-cell biosensors). Copyright © 2013 Elsevier B.V. All rights reserved.

Microchip electrophoresis with laser-induced fluorescence detection for the determination of the ratio of nitric oxide to superoxide production in macrophages during inflammation.

PubMed

Caruso, Giuseppe; Fresta, Claudia G; Siegel, Joseph M; Wijesinghe, Manjula B; Lunte, Susan M

2017-07-01

It is well known that excessive production of reactive oxygen and nitrogen species is linked to the development of oxidative stress-driven disorders. In particular, nitric oxide (NO) and superoxide (O 2 •- ) play critical roles in many physiological and pathological processes. This article reports the use of 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate and MitoSOX Red in conjunction with microchip electrophoresis and laser-induced fluorescence detection for the simultaneous detection of NO and O 2 •- in RAW 264.7 macrophage cell lysates following different stimulation procedures. Cell stimulations were performed in the presence and absence of cytosolic (diethyldithiocarbamate) and mitochondrial (2-methoxyestradiol) superoxide dismutase (SOD) inhibitors. The NO/O 2 •- ratios in macrophage cell lysates under physiological and proinflammatory conditions were determined. The NO/O 2 •- ratios were 0.60 ± 0.07 for unstimulated cells pretreated with SOD inhibitors, 1.08 ± 0.06 for unstimulated cells in the absence of SOD inhibitors, and 3.14 ± 0.13 for stimulated cells. The effect of carnosine (antioxidant) or Ca 2+ (intracellular messenger) on the NO/O 2 •- ratio was also investigated. Graphical Abstract Simultaneous detection of nitric oxide and superoxide in macrophage cell lysates.

[Rapid Detection of Adenovirus in Fecal Samples by Capillary Electrophoresis-laser Induced Fluorescence and Microchip Capillary Electrophoresis-laser Induced Fluorescence].

PubMed

Ruan, Jia; Ren, Dong-xia; Yang, Dan-ni; Long, Pin-pin; Zhao, Hong-yue; Wang, Yi-qi; Li, Yong-xin

2015-07-01

To establish a rapid and sensitive method based on polymerase chain reaction (PCR) combined with capillary electrophoresis-laser induced fluorescence (CE-LIF) and microchip capillary electrophoresis-laser induced fluorescence (MCE-LIF) for detecting adenoviruses in fecal samples. The DNA of adenovirus in fecal samples were extracted by the commercial kits and the conserved region of hexon gene was selected as the target gene and amplified by PCR reaction. After labeling highly sensitive nucleic acid fluorescent dye SYBR Gold and SYBR Orange respectively, PCR amplification products were separated by CE and MCE under the optimized condition and detected by LIF detector. PCR amplification products could be detected within 9 min by CE-LIF and 6 min by MCE-LIF under the optimized separation condition. The sequenced PCR product showed good specificity in comparison with the prototype sequences from NCBI. The intraday and inter-day relative standard deviation (RSD) of the size (bp) of the target DNA was in the range of 1.14%-1.34% and 1.27%- 2.76%, respectively, for CE-LIF, and 1.18%-1.48% and 2.85%-4.06%, respectively, for MCE-LIF. The detection limits was 2.33 x 10(2) copies/mL for CE-LIF and 2.33 x 10(3) copies/mL for MCE-LIF. The two proposed methods were applied to detect fecal samples, both showing high accuracy. The two proposed methods of PCR-CE-LIF and PCR-MCE-LIF can detect adenovirus in fecal samples rapidly, sensitively and specifically.

Ligase Detection Reaction for the Analysis of Point Mutations using Free Solution Conjugate Electrophoresis in a Polymer Microfluidic Device

PubMed Central

Sinville, Rondedrick; Coyne, Jennifer; Meagher, Robert J.; Cheng, Yu-Wei; Barany, Francis; Barron, Annelise; Soper, Steven A.

2010-01-01

We have developed a new method for the analysis of low abundant point mutations in genomic DNA using a combination of an allele-specific ligase detection reaction (LDR) with free-solution conjugate electrophoresis (FSCE) to generate and analyze the genetic products. FSCE eliminates the need for a polymer sieving matrix by conjugating chemically synthesized polyamide “drag-tags” onto the LDR primers. The additional drag of the charge-neutral drag-tag breaks the linear scaling of the charge-to-friction ratio of DNA and enables size-based separations of DNA in free solution using electrophoresis with no sieving matrix. We successfully demonstrate the conjugation of polyamide drag-tags onto a set of four LDR primers designed to probe the K-ras oncogene for mutations highly associated with colorectal cancer, the simultaneous generation of fluorescently-labeled LDR/drag-tagged (LDR-dt) products in a multiplexed, single-tube format with mutant:wild-type ratios as low as 1:100, respectively, and the single-base, high-resolution separation of all four LDR-dt products. Separations were conducted in free solution with no polymer network using both a commercial capillary array electrophoresis (CAE) system and a poly(methylmethacrylate), PMMA, microchip replicated via hot-embossing with only a Tris-based running buffer containing additives to suppress the electroosmotic flow (EOF). Typical analysis times for LDR-dt conjugates were 11 min using the CAE system and as low as 85 s for the PMMA microchips. With resolution comparable to traditional gel-based CAE, FSCE along with microchip electrophoresis decreased the separation time by more than a factor of 40. PMID:19053073

Monitoring carnosine uptake by RAW 264.7 macrophage cells using microchip electrophoresis with fluorescence detection

PubMed Central

Fresta, Claudia G.; Hogard, Michael L.; Caruso, Giuseppe; Melo Costa, Elton E.; Lazzarino, Giuseppe; Lunte, Susan M.

2017-01-01

Carnosine, a dipeptide found in a variety of tissues, is believed to possess antioxidant properties. It serves as a scavenger of reactive nitrogen and oxygen species (RNOS), which are important stress mediators of pro-inflammatory conditions and can lead to macrophage activation. In this study, intracellular concentrations of carnosine in murine RAW 264.7 macrophage cells were determined using microchip electrophoresis with laser-induced fluorescence detection following derivatization with naphthalene-2,3-dicarboxaldehyde and cyanide. The method was linear from 25 nM to 5 μM with a limit of detection in cell lysate samples of 65 nM. Using the method of standard additions, the basal intracellular content of carnosine in macrophage cells was determined to be 0.079 ± 0.02 nmol/106 cells. The uptake of carnosine by these cells was then investigated under both physiological and pro-inflammatory conditions. There was a 2.8-fold increase in carnosine uptake for macrophages exposed to lipopolysaccharide and interferon-γ prior to incubation, compared to the controls. This suggests that macrophages may use carnosine uptake as a defense mechanism under pro-inflammatory conditions. Future studies will investigate the role of the carnosine transporter in carnosine uptake and its possible correlation with cell morphological changes observed after stimulation. PMID:29104617

Enhanced amine and amino acid analysis using Pacific Blue and the Mars Organic Analyzer microchip capillary electrophoresis system.

PubMed

Chiesl, Thomas N; Chu, Wai K; Stockton, Amanda M; Amashukeli, Xenia; Grunthaner, Frank; Mathies, Richard A

2009-04-01

The fluorescent amine reactive probe Pacific Blue succinimidyl ester (PB) is used for the detection of trace amounts of amines and amino acids by microchip capillary electrophoresis on the Mars Organic Analyzer (MOA). The spectral and chemical properties of PB provide a 200-fold increase in sensitivity and improved resolution compared to fluorescamine derivatization. With the use of cross injection and PB labeling, the MOA detected amino acids at concentrations as low as 75 pM (sub-parts-per-trillion). Micellar electrokinetic chromatography (MEKC) which separates PB-labeled amino acids by their hydrophobicity is also demonstrated. The optimized MEKC conditions (45 mM CHAPSO, pH 6 at 5 degrees C) effectively separated amines and 25 amino acids with enantiomeric resolution of alanine, serine, and citrulline. Samples from the Yungay Hills region in the Atacama Desert, Chile, and from the Murchison meteorite are successfully analyzed using both techniques, and amino acids are found in the parts-per-billion range. Abiotic amino acids such as beta-alanine and epsilon-aminocaprioc acid are detected along with several neutral and acidic amino acids in the Murchison sample. The Atacama Desert sample is found to contain homochiral L-alanine and L-serine indicating the presence of extant or recently extinct life.

Structure of the Anthrax Research Literature

DTIC Science & Technology

2006-01-01

4; identification 4; staphylococcus - aureus 3; pharmacology & pharmacy 3; microbiology 3; pharmacology & pharmacy 2; biotechnology & applied...proteins 4; microbiology 4; escherichia-coli 4; bacillus-anthracis 4; cell-wall 3; staphylococcus - aureus 3 Country usa 9; france 7; england 2...pathogen detection using a microchip PCR array Instrument 199 In vitro selection of DNA aptamers to anthrax spores with electrochemiluminescence

Monolithic thermally bonded Er3+, Yb3+:glass/Co2+:MgAl2O4 microchip lasers

NASA Astrophysics Data System (ADS)

Mlynczak, Jaroslaw; Belghachem, Nabil

2015-12-01

The highest ever reported 10 kW peak power in monolithic thermally bonded Er3+, Yb3+:glass/Co2+:MgAl2O4 microchip laser was achieved. To show the superiority of monolithic microchip lasers over those with external mirrors the laser generation characteristics of the same samples in both cases were compared.

[Comparison of susceptibility artifacts generated by microchips with different geometry at 1.5 Tesla magnet resonance imaging. A phantom pilot study referring to the ASTM standard test method F2119-07].

PubMed

Dengg, S; Kneissl, S

2013-01-01

Ferromagnetic material in microchips, used for animal identification, causes local signal increase, signal void or distortion (susceptibility artifact) on MR images. To measure the impact of microchip geometry on the artifact's size, an MRI phantom study was performed. Microchips of the labels Datamars®, Euro-I.D.® and Planet-ID® (n  =  15) were placed consecutively in a phantom and examined with respect to the ASTM Standard Test Method F2119-07 using spin echo (TR 500 ms, TE 20 ms), gradient echo (TR 300 ms, TE 15 ms, flip angel 30°) and otherwise constant imaging parameters (slice thickness 3 mm, field of view 250 x 250 mm, acquisition matrix 256 x 256 pixel, bandwidth 32 kHz) at 1.5 Tesla. Image acquisition was undertaken with a microchip positioned in the x- and z-direction and in each case with a phase-encoding direction in the y- and z-direction. The artifact size was determined with a) a measurement according to the test method F2119-07 using a homogeneous point operation, b) signal intensity measurement according to Matsuura et al. and c) pixel counts in the artifact according to Port and Pomper. There was a significant difference in artifact size between the three microchips tested (Wilcoxon p = 0.032). A two- to three-fold increase in microchip volume generated an up to 76% larger artifact, depending on the sequence type, phase-encoding direction and chip position to B0. The smaller the microchip geometry, the less is the susceptibility artifact. Spin echoes (SE) generated smaller artifacts than gradient echoes (GE). In relation to the spatial measurement of the artifact, the switch in phase-encoding direction had less influence on the artifact size in GE- than in SE-sequences. However, the artifact shape and direction of SE-sequences can be changed by altering the phase. The artifact size, caused by the microchip, plays a major clinical role in the evaluation of MRI from the head, shoulder and neck regions.

Bottom-up fabrication of paper-based microchips by blade coating of cellulose microfibers on a patterned surface.

PubMed

Gao, Bingbing; Liu, Hong; Gu, Zhongze

2014-12-23

We report a method for the bottom-up fabrication of paper-based capillary microchips by the blade coating of cellulose microfibers on a patterned surface. The fabrication process is similar to the paper-making process in which an aqueous suspension of cellulose microfibers is used as the starting material and is blade-coated onto a polypropylene substrate patterned using an inkjet printer. After water evaporation, the cellulose microfibers form a porous, hydrophilic, paperlike pattern that wicks aqueous solution by capillary action. This method enables simple, fast, inexpensive fabrication of paper-based capillary channels with both width and height down to about 10 μm. When this method is used, the capillary microfluidic chip for the colorimetric detection of glucose and total protein is fabricated, and the assay requires only 0.30 μL of sample, which is 240 times smaller than for paper devices fabricated using photolithography.

A ultra-small-angle self-mixing sensor system with high detection resolution and wide measurement range

NASA Astrophysics Data System (ADS)

Yang, Bo; Wang, Dehui; Zhou, Lin; Wu, Shuang; Xiang, Rong; Zhang, Wenhua; Gui, Huaqiao; Liu, Jianguo; Wang, Huanqing; Lu, Liang; Yu, Benli

2017-06-01

The self-mixing technique based on the traditional reflecting mirror has been demonstrated with great merit for angle sensing applications. Here we demonstrate a modified self-reflection-mixing angle measurement system by combine a right-angle prism to self-mixing angle measurement. In our system, the wavelength is crucial to the angle measurement resolution. For a microchip solid-state laser, the measurement resolution can reach 0.49 mrad, while the resolution for the He-Ne laser is 0.53 mrad. In addition, the ranges in the system with the microchip solid-state laser and He-Ne laser are up to 22 mrad and 24.9 mrad respectively. This modified angle measurement system effectively combines the advantage of self-mixing measurement system with a compact structure, providing interesting features such as of high requisition of resolution and precision.

Microchip electrophoresis for wine analysis.

PubMed

Gomez, Federico J V; Silva, M Fernanda

2016-12-01

The present critical review provides a summary of representative articles describing the analysis of wine by microchip electrophoresis. Special emphasis has been given to those compounds able to provide background information to achieve the differentiation of wines according to botanical origin, provenance, vintage and quality or assure wine authentication. This review focuses on capillary electrophoresis (CE) microchips dedicated to the analysis of wine covering all the contributions concerning this area. The most relevant compounds in wine analysis such as phenols, organic acids, inorganic species, aldehydes, sugars, alcohols, and neuroactive amines were considered. Moreover, a special section is dedicated to the potential of CE microchip for wine classification. Indeed, potential directions for the future are discussed.

Generating electrospray from microchip devices using electroosmotic pumping

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

Ramsey, R.S.; Ramsey, J.M.

1997-03-15

A method of generating electrospray from solutions emerging from small channels etched on planer substrates in described. The fluids are delivered using electroosmotically induced pressures and are sprayed electrostatically from the terminus of a channel by applying an electrical potential of sufficient amplitude to generate the electrospray between the microchip and a conductor spaced from the channel terminus. No major modification of the microchip is required other than to expose a channel opening. The principles that regulate the fluid delivery are described and demonstrated. A spectrum for a test compound, tetrabutylammonium iodide, that was continuously electrophoresed was obtained by couplingmore » the microchip to an ion trap mass spectrometer. 35 refs., 6 figs.« less

Generation of Ince-Gaussian beams in highly efficient, nanosecond Cr, Nd:YAG microchip lasers

NASA Astrophysics Data System (ADS)

Dong, J.; Ma, J.; Ren, Y. Y.; Xu, G. Z.; Kaminskii, A. A.

2013-08-01

Direct generation of higher-order Ince-Gaussian (IG) beams from laser-diode end-pumped Cr, Nd:YAG self-Q-switched microchip lasers was achieved with high efficiency and high repetition rate. An average output power of over 2 W was obtained at an absorbed pump power of 8.2 W a corresponding optical-to-optical efficiency of 25% was achieved. Various IG modes with nanosecond pulse width and peak power of over 2 kW were obtained in laser-diode pumped Cr, Nd:YAG microchip lasers under different pump power levels by applying a tilted, large area pump beam. The effect of the inversion population distribution induced by the tilted pump beam and nonlinear absorption of Cr4+-ions for different pump power levels on the oscillation of higher-order IG modes in Cr, Nd:YAG microchip lasers is addressed. The higher-order IG mode oscillation has a great influence on the laser performance of Cr, Nd:YAG microchip lasers.

A hydrodynamic microchip for formation of continuous cell chains

NASA Astrophysics Data System (ADS)

Khoshmanesh, Khashayar; Zhang, Wei; Tang, Shi-Yang; Nasabi, Mahyar; Soffe, Rebecca; Tovar-Lopez, Francisco J.; Rajadas, Jayakumar; Mitchell, Arnan

2014-05-01

Here, we demonstrate the unique features of a hydrodynamic based microchip for creating continuous chains of model yeast cells. The system consists of a disk shaped microfluidic structure, containing narrow orifices that connect the main channel to an array of spoke channels. Negative pressure provided by a syringe pump draws fluid from the main channel through the narrow orifices. After cleaning process, a thin layer of water is left between the glass substrate and the polydimethylsiloxane microchip, enabling leakage beneath the channel walls. A mechanical clamp is used to adjust the operation of the microchip. Relaxing the clamp allows leakage of liquid beneath the walls in a controllable fashion, leading to formation of a long cell chain evenly distributed along the channel wall. The unique features of the microchip are demonstrated by creating long chains of yeast cells and model 15 μm polystyrene particles along the side wall and analysing the hydrogen peroxide induced death of patterned cells.

A low timing jitter picosecond microchip laser pumped by pulsed LD

NASA Astrophysics Data System (ADS)

Wang, Sha; Wang, Yan-biao; Feng, Guoying; Zhou, Shou-huan

2016-07-01

SESAM passively Q-switched microchip laser is a very promising instrument to replace mode locked lasers to obtain picosecond pulses. The biggest drawback of a passively Q-switched microchip laser is its un-avoided large timing jitter, especially when the pump intensity is low, i.e. at low laser repetition rate range. In order to obtain a low timing jitter passively Q-switched picosecond microchip laser in the whole laser repetition rate range, a 1000 kHz pulsed narrow bandwidth Fiber Bragg Grating (FBG) stablized laser diode was used as the pump source. By tuning the pump intensity, we could control the output laser frequency. In this way, we achieved a very low timing jitter passively Q-switched picosecond laser at 2.13 mW, 111.1 kHz. The relative timing jitter was only 0.0315%, which was around 100 times smaller compared with a cw LD pumped microchip working at hundred kilohertz repetition rate frequency range.

Chemiluminescence Resonance Energy Transfer-based Detection for Microchip Electrophoresis

PubMed Central

Huang, Yong; Shi, Ming; Liu, Rongjun

2010-01-01

Since the channels in micro- and nanofluidic devices are extremely small, a sensitive detection is required following microchip electrophoresis (MCE). This work describes a highly sensitive and yet universal detection scheme based on chemiluminescence resonance energy transfer (CRET) for MCE. It was found that an efficient CRET occurred between a luminol donor and a CdTe quantum dot (QD) acceptor in the luminol-NaBrO-QD system, and that it was sensitively suppressed by the presence of certain organic compounds of biological interest including biogenic amines and thiols, amino acids, organic acids, and steroids. These findings allowed developing sensitive MCE-CL assays for the tested compounds. The proposed MCE-CL methods showed desired analytical figures of merit such as a wide concentration range of linear response. Detection limits obtained were ~10−9 M for biogenic amines including dopamine and epinephrine, and ~ 10−8 M for biogenic thiols (e.g. glutathione and acetylcysteine), organic acids (i.e. ascorbic acid and uric acid), estrogens, and native amino acids. These were 10 to 1000 times more sensitive than those of previously reported MCE-based methods with chemiluminescence, electrochemical, or laser induced fluorescence detection for quantifying corresponding compounds. To evaluate the applicability of the present MCE-CL method for analyzing real biological samples, it was used to determine amino acids in individual human red blood cells. Nine amino acids including Lys, Ser, Ala, Glu, Trp, etc. were detected. The contents ranged from 3 to 31 amol /cell. The assay proved to be simple, quick, reproducible, and very sensitive. PMID:20121202

Simultaneous Detection of Yersinia Enterocolitica and Listeria Monocytogenes in Foodstuffs by Capillary Electrophoresis and Microchip Capillary Electrophoresis Laser-Induced Fluorescence Detector.

PubMed

Li, Yongru; Su, Hongwei; Lan, Yajia

2018-05-29

Background: Food safety is one of the most important public health problems in the world,and pathogenic bacterium is a major factor causing serious foodborne diseases. Objective: Two methods of duplex PCR combined with capillary electrophoresis laser-induced fluorescence detector (CE-LIF) and microchip capillary electrophoresis laser-induced fluorescence detector (MCE-LIF) have been developed for the simultaneous detection of Yersinia enterocolitica and Listeria monocytogenes in various foods. The specific conservative sequences of these two bacteria were amplified. Methods: After labelled with nucleic acid dye SYBR Gold and SYBR Orange, the PCR products were analyzed by CE-LIF and MCE-LIF, respectively. Under the optimal conditions, the detection of PCR products of the target bacteria was achieved in less than 15 min by CE-LIF and within 6 min by MCE-LIF. Results: The alignment analysis demonstrated that the PCR products had good agreement with the sequences published in GenBank. The CE-LIF method could detect 10 CFU/mL Y. enterocolitica and L. monocytogenes , and the MCE-LIF method could detect 100 CFU/mL Y. enterocolitica and L. monocytogenes . The intraday precisions of migration time and peak area of DNA markers and PCR products were in the range of 1.13 to 1.18% and 1.60 to 6.29%, respectively, for CE-LIF and 1.18 to 1.48% and 2.85 to 4.06%, respectively, for MCE-LIF. Conclusions : The proposed methods could be applied to target bacterial detection infood samples rapidly, sensitively, and specifically. Highlights : Two new methods based on CE and MCE have been developed for the simultaneous detection of Y. enterocolitica and L. monocytogenes in foodstuffs, and they can detect the bacteria directly without any enrichment because of their high sensitivity.

12  mJ Yb:YAG/Cr:YAG microchip laser.

PubMed

Guo, Xiaoyang; Tokita, Shigeki; Kawanaka, Junji

2018-02-01

We have developed a quasi-continuous wave diode end-pumped cryogenically cooled Yb:YAG/Cr:YAG passively Q-switched microchip laser. A maximum energy of 12.1 mJ with 3.7 MW of peak power was obtained. To the best of our knowledge, this is the highest energy and peak power obtained by an Yb:YAG/Cr:YAG microchip laser so far.

Microfluidic channel-based wireless charging and communication platform for microsensors with miniaturized onboard antenna

NASA Astrophysics Data System (ADS)

Duan, G.; Zhao, X.; Seren, H. R.; Chen, C.; Li, A.; Zhang, X.

2016-12-01

A double layer spiral antenna with side length of 380 μm was fabricated by a multi-step electroplating process, and integrated with a commercialized passive RFID chip to realize the RF power harvesting and communication functions of a microsensor. To power up and communicate with the microchips, a single layer spiral reader antenna was fabricated on top of a glass substrate with side length of 1 mm. The microchips and the reader antenna were both optimized at the frequency of 915 MHz. Due to the small size of the reader antenna, the strength of the magnetic field decreased dramatically along the axial direction of the reader antenna, which limited the working distance to within 1 mm. To enclose the microchips within the reading range, a three-layer microfluidic channel was designed and fabricated. The channel and cover layers were fabricated by laser cutting of acrylic sheets, and bonded with the glass substrate to form the channel. To operate multiple microchips simultaneously, separation and focusing function units were also designed. Low loss pump oil was used to transport the microchips flowing inside the channel. Within the reading area, the microchips were powered up, and their ID information was retrieved and displayed on the computer interface successfully.

Analysis of carbonaceous biomarkers with the Mars Organic Analyzer microchip capillary electrophoresis system: aldehydes and ketones.

PubMed

Stockton, Amanda M; Tjin, Caroline Chandra; Huang, Grace L; Benhabib, Merwan; Chiesl, Thomas N; Mathies, Richard A

2010-11-01

A microchip CE method is developed for the analysis of two oxidized forms of carbon, aldehydes and ketones, with the Mars Organic Analyzer (MOA). Fluorescent derivitization is achieved in ∼ 15 min by hydrazone formation with Cascade Blue hydrazide in 30 mM borate pH 5-6. The microchip CE separation and analysis method is optimized via separation in 30 mM borate buffer, pH 9.5, at 20°C. A carbonyl standard consisting of ten aldehydes and ketones found in extraterrestrial matter is successfully separated; the resulting LOD depends on the reactivity of the compound and range from 70 pM for formaldehyde to 2 μM for benzophenone. To explore the utility of this method for analyzing complex samples, analyses of several fermented beverages are conducted, identifying ten aldehydes and ketones ranging from 30 nM to 5 mM. A Martian regolith simulant sample, consisting of a basalt matrix spiked with soluble ions and acetone, is designed and analyzed, but acetone is found to have a limited detectable lifetime under simulant Martian conditions. This work establishes the capability of the MOA for studying aldehydes and ketones, a critical class of oxidized organic molecules of interest in planetary and in terrestrial environmental and health studies. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spectroscopy and microchip laser operation of Tm, Ho:KYW crystals with different Ho concentrations

NASA Astrophysics Data System (ADS)

Gusakova, N. V.; Kurilchik, S. V.; Yasukevich, A. S.; Kisel, V. E.; Dashkevich, V. I.; Orlovich, V. A.; Pavlyuk, A. A.; Vatnik, S. M.; Bagaev, S. N.; Kuleshov, N. V.

2018-02-01

The spectroscopic properties of Tm, Ho:KYW crystals with different Ho concentrations were investigated. The diode-pumped microchip laser operation of Tm (5 at.%), Ho (0.5 at.%):KYW and Tm (5 at.%), Ho (1 at.%):KYW was demonstrated. The highest, to our knowledge, output power of 480 mW with slope efficiency of 31% for CW Tm (5 at.%), Ho (0.5 at.%):KYW microchip laser was obtained.

Microchip systems for immunoassay: an integrated immunoreactor with electrophoretic separation for serum theophylline determination.

PubMed

Chiem, N H; Harrison, D J

1998-03-01

A glass microchip is described in which reagents and serum samples for competitive immunoassay of serum theophylline can be mixed, reacted, separated, and analyzed. The device functions as an automated microfluidic immunoassay system, creating a lab-on-a-chip. Electroosmotic pumping was used to control first the mixing of 50-fold-diluted serum sample with labeled theophylline tracer in a 1:1 ratio, followed by 1:1 mixing and reaction with anti-theophylline antibody. The 51-nL on-chip mixer gave the same concentration as dilution performed off-chip, within 3%. A 100-pL plug of the reacted solution was then injected into an electrophoresis separation channel integrated within the same chip. Measurements of free and bound tracer by fluorescence detection gave linear calibration curves of signal vs log[theophylline] between 0 and 40 mg/L, with a slope of 0.52 +/- 0.03 and an intercept of -0.04 +/- 0.04 after a 90-s reaction time. A detection limit of 0.26 mg/L in serum (expressed before the dilution step, actual concentration of 1.3 micrograms/L at the detector) was obtained. Recovery values were 107% +/- 8% for 15 mg/L serum samples.

Polycyclic aromatic hydrocarbon analysis with the Mars organic analyzer microchip capillary electrophoresis system.

PubMed

Stockton, Amanda M; Chiesl, Thomas N; Scherer, James R; Mathies, Richard A

2009-01-15

The Mars Organic Analyzer (MOA), a portable microchip capillary electrophoresis (CE) instrument developed for sensitive amino acid analysis on Mars, is used to analyze laboratory standards and real-world samples for polycyclic aromatic hydrocarbons (PAHs). The microfabricated CE separation and analysis method for these hydrophobic analytes is optimized, resulting in a separation buffer consisting of 10 mM sulfobutylether-beta-cyclodextrin, 40 mM methyl-beta-cyclodextrin, 5 mM carbonate buffer at pH 10, 5 degrees C. A PAH standard consisting of seven PAHs found in extraterrestrial matter and two terrestrial PAHs is successfully baseline separated. Limits of detection for the components of the standard ranged from 2000 ppm to 6 ppb. Analysis of an environmental contamination standard from Lake Erie and of a hydrothermal vent chimney sample from the Guaymas Basin agreed with published composition. A Martian analogue sample from the Yungay Hills region of the Atacama Desert was analyzed and found to contain 9,10-diphenylanthracene, anthracene, anthanthrene, fluoranthene, perylene, and benzo[ghi]fluoranthene at ppm levels. This work establishes the viability of the MOA for detecting and analyzing PAHs in in situ planetary exploration.

Multiplex detection of quality indicator molecule targets in urine using programmable hairpin probes based on a simple double-T type microchip electrophoresis platform and isothermal polymerase-catalyzed target recycling.

PubMed

Zhou, Lingying; Gan, Ning; Wu, Yongxiang; Hu, Futao; Lin, Jianyuan; Cao, Yuting; Wu, Dazhen

2018-05-29

Recently, it has been crucial to be able to detect and quantify small molecular targets simultaneously in biological samples. Herein, a simple and conventional double-T type microchip electrophoresis (MCE) based platform for the multiplex detection of quality indicator molecule targets in urine, using ampicillin (AMPI), adenosine triphosphate (ATP) and estradiol (E2) as models, was developed. Several programmable hairpin probes (PHPs) were designed for detecting different targets and triggering isothermal polymerase-catalyzed target recycling (IPCTR) for signal amplification. Based on the target-responsive aptamer structure of PHP (Domain I), target recognition can induce PHP conformational transition and produce extension duplex DNA (dsDNA), assisted by primers & Bst polymerase. Afterwards, the target can be displaced to react with another PHP and initiate the next cycle. After several rounds of reaction, the dsDNA can be produced in large amounts by IPCTR. Three targets can be simultaneously converted to dsDNA fragments with different lengths, which can be separated and detected using MCE. Thus, a simple double-T type MCE based platform was successfully built for the homogeneous detection of multiplex targets in one channel. Under optimal conditions, the assay exhibited high throughput (48 samples per hour at most, not including reaction time) and sensitivity to three targets in urine with a detection limit of 1 nM (ATP), 0.05 nM (AMPI) and 0.1 nM (E2) respectively. The multiplex assay was successfully employed for the above three targets in several urine samples and combined the advantages of the high specificity of programmable hairpin probes, the excellent signal amplification of IPCTR, and the high through-put of MCE which can be employed for screening in biochemical analysis.

Sensitive detection of C-reactive protein in serum by immunoprecipitation-microchip capillary gel electrophoresis.

PubMed

Herwig, Ela; Marchetti-Deschmann, Martina; Wenz, Christian; Rüfer, Andreas; Redl, Heinz; Bahrami, Soheyl; Allmaier, Günter

2015-06-01

Sepsis represents a significant cause of mortality in intensive care units. Early diagnosis of sepsis is essential to increase the survival rate of patients. Among others, C-reactive protein (CRP) is commonly used as a sepsis marker. In this work we introduce immune precipitation combined with microchip capillary gel electrophoresis (IP-MCGE) for the detection and quantification of CRP in serum samples. First high-abundance proteins (HSA, IgG) are removed from serum samples using affinity spin cartridges, and then the remaining proteins are labeled with a fluorescence dye and incubated with an anti-CRP antibody, and the antigen/antibody complex is precipitated with protein G-coated magnetic beads. After precipitation the complex is eluted from the beads and loaded onto the MCGE system. CRP could be reliably detected and quantified, with a detection limit of 25 ng/μl in serum samples and 126 pg/μl in matrix-free samples. The overall sensitivity (LOQ = 75 ng/μl, R(2) = 0.9668) of the method is lower than that of some specially developed methods (e.g., immune radiometric assay) but is comparable to those of clinically accepted ELISA methods. The straightforward sample preparation (not prone to mistakes), reduced sample and reagent volumes (including the antibodies), and high throughput (10 samples/3 h) are advantages and therefore IP-MCGE bears potential for point-of-care diagnosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrically controlled microvalves to integrate microchip polymerase chain reaction and capillary electrophoresis.

PubMed

Kaigala, Govind V; Hoang, Viet N; Backhouse, Christopher J

2008-07-01

Microvalves are key in realizing portable miniaturized diagnostic platforms. We present a scalable microvalve that integrates well with standard lab on a chip (LOC) implementations, yet which requires essentially no external infrastructure for its operation. This electrically controlled, phase-change microvalve is used to integrate genetic amplification and analysis via capillary electrophoresis--the basis of many diagnostics. The microvalve is actuated using a polymer (polyethylene glycol, PEG) that exhibits a large volumetric change between its solid and liquid phases. Both the phase change of the PEG and the genetic amplification via polymerase chain reaction (PCR) are thermally controlled using thin film resistive elements that are patterned using standard microfabrication methods. By contrast with many other valve technologies, these microvalves and their control interface scale down in size readily. The novelty here lies in the use of fully integrated microvalves that require only electrical connections to realize a portable and inexpensive genetic analysis platform.

A linearly-polarized Nd:YVO4/KTP microchip green laser.

PubMed

Jung, C; Yu, B-A; Kim, I-S; Lee, Y L; Yu, N E; Ko, D-K

2009-10-26

We described the principle and the fabrication of a Nd:YVO(4)/KTP microchip for the linearly-polarized green laser and verified its availability by manufacturing and characterizing the green laser using the microchip. Under the driving condition having the modulation frequency of 60 Hz and the duty ratio of 25%, the laser showed the stable linear polarization, the maximum average power of 37 mW, yielding the high electrical-to-optical efficiency of 10.9%.

A simple strategy for in situ fabrication of a smart hydrogel microvalve within microchannels for thermostatic control.

PubMed

Lin, Shuo; Wang, Wei; Ju, Xiao-Jie; Xie, Rui; Chu, Liang-Yin

2014-08-07

Self-regulation of temperature in microchip systems is crucial for their applications in biomedical fields such as cell culture and biomolecule synthesis as well as those cases that require constant temperature conditions. Here we report on a simple and versatile approach for in situ fabrication of a smart hydrogel microvalve within a microchip for thermostatic control. The thermo-responsive hydrogel microvalve enables the "on-off" switch by sensing temperature fluctuations to control the fluid flux as well as the fluid heat exchange for self-regulation of the temperature at a constant range. Such temperature self-regulation is demonstrated by integrating the microvalve-incorporated microchip into the flow circulation loop of a micro-heat-exchanging system for thermostatic control. Moreover, the microvalve-incorporated microchip is employed for culturing cells under temperature self-regulation. The smart microvalve shows great potential as a temperature controller for applications that require thermostatic conditions. This approach offers a facile and flexible strategy for in situ fabricating hydrogel microvalves within microchips as chemostats and microreactors for biomedical applications.

Detection technique of targets for missile defense system

NASA Astrophysics Data System (ADS)

Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong

2009-11-01

Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.

Electrophoretically mediated microanalysis of leucine aminopeptidase using two-photon excited fluorescence detection on a microchip.

PubMed

Zugel, S A; Burke, B J; Regnier, F E; Lytle, F E

2000-11-15

Two-photon excited fluorescence detection was performed on a microfabricated electrophoresis chip. A calibration curve of the fluorescent tag beta-naphthylamine was performed, resulting in a sensitivity of 2.5 x 10(9) counts M(-1) corresponding to a detection limit of 60 nM. Additionally, leucine aminopeptidase was assayed on the chip using electrophoretically mediated microanalysis. The differential electroosmotic mobilities of the enzyme and substrate, L-leucine beta-naphthylamide, allowed for efficient mixing in an open channel, resulting in the detection of a 30 nM enzyme solution under constant potential. A zero potential incubation for 1 min yielded a calculated detection limit of 4 nM enzyme.

Comparison of rectal, microchip transponder, and infrared thermometry techniques for obtaining body temperature in the laboratory rabbit (Oryctolagus cuniculus).

PubMed

Chen, Patty H; White, Charles E

2006-01-01

This study compared rabbit rectal thermometry with 4 other thermometry techniques: an implantable microchip temperature transponder, an environmental noncontact infrared thermometer, a tympanic infrared thermometer designed for use on humans, and a tympanic infrared thermometer designed for use on animals. The microchip transponder was implanted between the shoulder blades; the environmental noncontact infrared thermometer recorded results from the base of the right pinna and the left inner thigh, and the tympanic infrared thermometer temperatures were taken from the right ear. Results from each technique were compared to determine agreement between the test modality and the rectal temperature. The practicality and reliability of the modalities were reviewed also. According to this study, the implantable microchip transponder measurements agreed most closely with the rectal temperature.

Microchip-associated fibrosarcoma in a cat.

PubMed

Carminato, Antonio; Vascellari, Marta; Marchioro, Wendy; Melchiotti, Erica; Mutinelli, Franco

2011-12-01

A 9-year-old, neutered male cat was presented for a subcutaneous mass on the neck. After surgical removal of the mass, a pet identification microchip was found within the tumour. Histological examination of the mass revealed typical features of the feline postinjection sarcoma. The cat had never received injections at the tumour site; all routine vaccinations were administered in the hindlimbs. Few cases of sarcomas developing at the site of microchip application have been reported in animals, although the contributory role of vaccine administrations has not been ruled out. This is the first report of a microchip-associated fibrosarcoma in a cat. Adherence to American Association of Feline Practitioners vaccination guidelines, avoiding the interscapular area, enabled confirmation of the definitive aetiology of the neoplasia. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

Rectangular pulsed LD pumped saturable output coupler (SOC) Q-switched microchip laser

NASA Astrophysics Data System (ADS)

Wang, Yan-biao; Wang, Sha; Feng, Guo-ying; Zhou, Shou-huan

2017-02-01

We studied the cw LD and rectangular pulsed LD pumped saturable output coupler (SOC) passively Q-switched Nd:YVO4 transmission microchip laser experimentally. We demonstrated that the SOC passively Q-switched Nd:YVO4 transmission microchip laser pumped by a highly stabilized narrow bandwidth pulsed LD has a much lower timing jitter than pumped by a continuous wave (CW) LD, especially at low output frequency regime. By changing the pump beam size in the rectangular shape pulsed pump scheme, the output frequency can be achieved from 333.3 kHz to 71.4 kHz, while the relative timing jitter decreased from 0.09865% to 0.03115% accordingly. Additionally, the microchip laser has a good stability of output power, the power fluctuation below 2%.

Integration of Multiple Components in Polystyrene-based Microfluidic Devices Part 1: Fabrication and Characterization

PubMed Central

Johnson, Alicia S.; Anderson, Kari B.; Halpin, Stephen T.; Kirkpatrick, Douglas C.; Spence, Dana M.; Martin, R. Scott

2012-01-01

In Part I of a two-part series, we describe a simple, and inexpensive approach to fabricate polystyrene devices that is based upon melting polystyrene (from either a Petri dish or powder form) against PDMS molds or around electrode materials. The ability to incorporate microchannels in polystyrene and integrate the resulting device with standard laboratory equipment such as an optical plate reader for analyte readout and micropipettors for fluid propulsion is first described. A simple approach for sample and reagent delivery to the device channels using a standard, multi-channel micropipette and a PDMS-based injection block is detailed. Integration of the microfluidic device with these off-chip functions (sample delivery and readout) enables high throughput screens and analyses. An approach to fabricate polystyrene-based devices with embedded electrodes is also demonstrated, thereby enabling the integration of microchip electrophoresis with electrochemical detection through the use of a palladium electrode (for a decoupler) and carbon-fiber bundle (for detection). The device was sealed against a PDMS-based microchannel and used for the electrophoretic separation and amperometric detection of dopamine, epinephrine, catechol, and 3,4-dihydroxyphenylacetic acid. Finally, these devices were compared against PDMS-based microchips in terms of their optical transparency and absorption of an anti-platelet drug, clopidogrel. Part I of this series lays the foundation for Part II, where these devices were utilized for various on-chip cellular analysis. PMID:23120747

Development of an On-animal Separation-based Sensor for Monitoring Drug Metabolism in Freely Roaming Sheep

PubMed Central

Scott, David E.; Willis, Sean D.; Gabbert, Seth; Johnson, Dave A.; Naylor, Erik; Janle, Elsa M.; Krichevsky, Janice E.; Lunte, Craig E.; Lunte, Susan M.

2015-01-01

The development of an on-animal separation-based sensor that can be employed for monitoring drug metabolism in a freely roaming sheep is described. The system consists of microdialysis sampling coupled directly to microchip electrophoresis with electrochemical detection (MD-ME-EC). Separations were accomplished using an all-glass chip with integrated platinum working and reference electrodes. Discrete samples from the microdialysis flow were introduced into the electrophoresis chip using a flow-gated injection approach. Electrochemical detection was accomplished in-channel using a two-electrode isolated potentiostat. Nitrite was separated by microchip electrophoresis using reverse polarity and a run buffer consisting of 50 mM phosphate at pH 7.4. The entire system was under telemetry control. The system was first tested with rats to monitor the production of nitrite following introduction of nitroglycerin into the subdermal tissue using a linear probe. The data acquired using the on-line MD-ME-EC system was compared to that obtained off-line analysis by liquid chromatography with electrochemical detection (LC-EC), using a second microdialysis probe implanted parallel to the first probe in the same animal. The MD-ME-EC device was then used on-animal to monitor the subdermal metabolism of nitroglycerin in sheep. The ultimate goal is to use this device to simultaneously monitor drug metabolism and behavior in a freely roaming animal. PMID:25697221

Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells.

PubMed

Ramirez, Lisa; Herschkowitz, Jason I; Wang, Jun

2016-09-01

Cellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only available in a laboratory setting and don't have the portability to meet the needs in point-of-care cancer diagnostics. Towards that application, we have developed a portable single-cell system that is comprised of a microchip and an adjustable clamp, so on-chip operation only needs pipetting and adjusting of clamping force. Up to 10 proteins can be quantitated from each cell with hundreds of single-cell assays performed in parallel from one chip operation. We validated the technology and analyzed the oncogenic signatures of cancer stem cells by quantitating both aldehyde dehydrogenase (ALDH) activities and 5 signaling proteins in single MDA-MB-231 breast cancer cells. The technology has also been used to investigate the PI3K pathway activities of brain cancer cells expressing mutant epidermal growth factor receptor (EGFR) after drug intervention targeting EGFR signaling. Our portable single-cell system will potentially have broad application in the preclinical and clinical settings for cancer diagnosis in the future.

Apparatus and method for performing microfluidic manipulations for chemical analysis

DOEpatents

Ramsey, J. Michael

1999-01-01

A microchip apparatus and method provide fluidic manipulations for a variety of applications, including sample injection for microchip liquid chromatography. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis is performed in channels formed in the substrate. Injections are made by electro-osmotically pumping sample through the injection channel that crosses the separation channel, followed by a switching of the potentials to force a plug into the separation channel.

Apparatus and method for performing microfluidic manipulations for chemical analysis

DOEpatents

Ramsey, J. Michael

2002-01-01

A microchip apparatus and method provide fluidic manipulations for a variety of applications, including sample injection for microchip liquid chromatography. The microchip is fabricated using standard photolitographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis is performed in channels formed in the substrate. Injections are made by electro-osmotically pumping sample through the injection channel that crosses the separation channel, followed by a switching of the potentials to force a plug into the separation channel.

12 mJ Yb:YAG/Cr:YAG microchip laser

NASA Astrophysics Data System (ADS)

Guo, Xiaoyang; Tokita, Shigeki; Kawanaka, Junji

2018-02-01

By cryogenically cooling the Yb:YAG/Cr:YAG medium, one can break through the damage limit of Yb:YAG/Cr:YAG passively Q-switched microchip lasers at room temperature and thus achieve a shorter minimum pulse duration. In the proof of principle experiment we carried out, a 160.6 ps pulse duration was obtained. To the best of our knowledge, this is the first realization of sub-200 ps pulse operation for an Yb:YAG/Cr:YAG microchip laser

Practical application of pulsed "eye-safe" microchip laser to laser rangefinders

NASA Astrophysics Data System (ADS)

Młyńczak, J.; Kopczyński, K.; Mierczyk, Z.; Zygmunt, M.; Natkański, S.; Muzal, M.; Wojtanowski, J.; Kirwil, P.; Jakubaszek, M.; Knysak, P.; Piotrowski, W.; Zarzycka, A.; Gawlikowski, A.

2013-09-01

The paper describes practical application of pulsed microchip laser generating at 1535-nm wavelength to a laser rangefinder. The complete prototype of a laser rangefinder was built and investigated in real environmental conditions. The measured performance of the device is discussed. To build the prototype of a laser rangefinder at a reasonable price and shape a number of basic considerations had to be done. These include the mechanical and optical design of a microchip laser and the opto-mechanical construction of the rangefinder.

Melting analysis on microbeads in rapid temperature-gradient inside microchannels for single nucleotide polymorphisms detectiona)

PubMed Central

Li, Kan-Chien; Ding, Shih-Torng; Lin, En-Chung; Wang, Lon (Alex); Lu, Yen-Wen

2014-01-01

A continuous-flow microchip with a temperature gradient in microchannels was utilized to demonstrate spatial melting analysis on microbeads for clinical Single Nucleotide Polymorphisms (SNPs) genotyping on animal genomic DNA. The chip had embedded heaters and thermometers, which created a rapid and yet stable temperature gradient between 60 °C and 85 °C in a short distance as the detection region. The microbeads, which served as mobile supports carrying the target DNA and fluorescent dye, were transported across the temperature gradient. As the surrounding temperature increased, the fluorescence signals of the microbeads decayed with this relationship being acquired as the melting curve. Fast DNA denaturation, as a result of the improved heat transfer and thermal stability due to scaling, was also confirmed. Further, each individual microbead could potentially bear different sequences and pass through the detection region, one by one, for a series of melting analysis, with multiplex, high-throughput capability being possible. A prototype was tested with target DNA samples in different genotypes (i.e., wild and mutant types) with a SNP location from Landrace sows. The melting temperatures were obtained and compared to the ones using a traditional tube-based approach. The results showed similar levels of SNP discrimination, validating our proposed technique for scanning homozygotes and heterozygotes to distinguish single base changes for disease research, drug development, medical diagnostics, agriculture, and animal production. PMID:25553186

Sample preparation and detection device for infectious agents

DOEpatents

Miles, Robin R.; Wang, Amy W.; Fuller, Christopher K.; Lemoff, Asuncion V.; Bettencourt, Kerry A.; Yu, June

2003-06-10

A sample preparation and analysis device which incorporates both immunoassays and PCR assays in one compact, field-portable microchip. The device provides new capabilities in fluid and particle control which allows the building of a fluidic chip with no moving parts, thus decreasing fabrication cost and increasing the robustness of the device. The device can operate in a true continuous (not batch) mode. The device incorporates magnetohydrodynamic (MHD) pumps to move the fluid through the system, acoustic mixing and fractionation, dielectropheretic (DEP) sample concentration and purification, and on-chip optical detection capabilities.

Sub-micron surface plasmon resonance sensor systems

NASA Technical Reports Server (NTRS)

Glazier, James A. (Inventor); Amarie, Dragos (Inventor)

2012-01-01

A sensor for detecting the presence of a target analyte, ligand or molecule in a test fluid, comprising a light transmissive substrate on which an array of surface plasmon resonant (SPR) elements is mounted is described. A multi-channel sensor for detecting the presence of several targets with a single microchip sensor is described. A multi-channel sensor including collections of SPR elements which are commonly functionalized to one of several targets is also described. The detectors sense changes in the resonant response of the SPR elements indicative of binding with the targets.

Sub-micron surface plasmon resonance sensor systems

NASA Technical Reports Server (NTRS)

Amarie, Dragos (Inventor); Glazier, James A. (Inventor)

2011-01-01

A sensor for detecting the presence of a target analyte, ligand or molecule in a test fluid, comprising a light transmissive substrate on which an array of surface plasmon resonant (SPR) elements is mounted is described. A multichannel sensor for detecting the presence of several targets with a single microchip sensor is described. A multichannel sensor including collections of SPR elements which are commonly functionalized to one of several targets is also described. The detectors sense changes in the resonant response of the SPR elements indicative of binding with the targets.

Sub-micron surface plasmon resonance sensor systems

NASA Technical Reports Server (NTRS)

Glazier, James A. (Inventor); Dragnea, Bogdan (Inventor); Amarie, Dragos (Inventor)

2010-01-01

A sensor for detecting the presence of a target analyte, ligand or molecule in a test fluid, comprising a light transmissive substrate on which an array of surface plasmon resonant (SPR) elements is mounted is described. A multi-channel sensor for detecting the presence of several targets with a single microchip sensor is described. A multi-channel sensor including collections of SPR elements which are commonly functionalized to one of several targets is also described. The detectors sense changes in the resonant response of the SPR elements indicative of binding with the targets.

Sub-micron surface plasmon resonance sensor systems

NASA Technical Reports Server (NTRS)

Amarie, Dragos (Inventor); Glazier, James A. (Inventor); Dragnea, Bogdan (Inventor)

2010-01-01

A sensor for detecting the presence of a target analyte, ligand or molecule in a test fluid, comprising a light transmissive substrate on which an array of surface plasmon resonant (SPR) elements is mounted is described. A multi-channel sensor for detecting the presence of several targets with a single micro-chip sensor is described. A multi-channel sensor including collections of SPR elements which are commonly functionalized to one of several targets is also described. The detectors sense changes in the resonant response of the SPR elements indicative of binding with the targets.

Sub-micron surface plasmon resonance sensor systems

NASA Technical Reports Server (NTRS)

Glazier, James A. (Inventor); Amarie, Dragos (Inventor)

2011-01-01

A sensor for detecting the presence of a target analyte, ligand or molecule in a test fluid, comprising a light transmissive substrate on which an array of surface plasmon resonant (SPR) elements is mounted is described. A multi-channel sensor for detecting the presence of several targets with a single micro-chip sensor is described. A multi-channel sensor including collections of SPR elements which are commonly functionalized to one of several targets is also described. The detectors sense changes in the resonant response of the SPR elements indicative of binding with the targets.

50 CFR 21.21 - Import and export permits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with an implanted microchip for identification. (d) Falconry birds covered under a CITES “pet passport... and Wildlife Service leg band issued by the Service, including any raptor with an implanted microchip...

Fabrication and Characterization of All-Polystyrene Microfluidic Devices with Integrated Electrodes and Tubing.

PubMed

Pentecost, Amber M; Martin, R Scott

2015-01-01

A new method of fabricating all-polystyrene devices with integrated electrodes and fluidic tubing is described. As opposed to expensive polystyrene (PS) fabrication techniques that use hot embossing and bonding with a heated lab press, this approach involves solvent-based etching of channels and lamination-based bonding of a PS cover, all of which do not need to occur in a clean room. PS has been studied as an alternative microchip substrate to PDMS, as it is more hydrophilic, biologically compatible in terms of cell adhesion, and less prone to absorption of hydrophobic molecules. The etching/lamination-based method described here results in a variety of all-PS devices, with or without electrodes and tubing. To characterize the devices, micrographs of etched channels (straight and intersected channels) were taken using confocal and scanning electron microscopy. Microchip-based electrophoresis with repetitive injections of fluorescein was conducted using a three-sided PS (etched pinched, twin-tee channel) and one-sided PDMS device. Microchip-based flow injection analysis, with dopamine and NO as analytes, was used to characterize the performance of all-PS devices with embedded tubing and electrodes. Limits of detection for dopamine and NO were 130 nM and 1.8 μM, respectively. Cell immobilization studies were also conducted to assess all-PS devices for cellular analysis. This paper demonstrates that these easy to fabricate devices can be attractive alternative to other PS fabrication methods for a wide variety of analytical and cell culture applications.

Pretreatment method for immunoassay of polychlorinated biphenyls in transformer oil using multilayer capillary column and microfluidic liquid-liquid partitioning.

PubMed

Aota, Arata; Date, Yasumoto; Terakado, Shingo; Ohmura, Naoya

2013-01-01

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that are present in the insulating oil inside a large number of transformers. To aid in eliminating PCB-contaminated transformers, PCBs in oil need to be measured using a rapid and cost-effective analytical method. We previously reported a pretreatment method for the immunoassay of PCBs in oil using a large-scale multilayer column and a microchip with multiple microrecesses, which permitted concentrated solvent extraction. In this paper, we report on a more rapid and facile pretreatment method, without an evaporation process, by improving the column and the microchip. In a miniaturized column, the decomposition and separation of oil were completed in 2 min. PCBs can be eluted from the capillary column at concentrations seven-times higher than those from the previous column. The total volume of the microrecesses was increased by improving the microrecess structure, the enabling extraction of four-times the amount of PCBs achieved with the previous system. By interfacing the capillary column with the improved microchip, PCBs in the eluate from the column were extracted into dimethyl sulfoxide in microrecesses with high enrichment and without the need for evaporation. Pretreatment was completed within 20 min. The pretreated oil was analyzed using a flow-based kinetic exclusion immunoassay. The limit of detection of PCBs in oil was 0.15 mg kg(-1), which satisfies the criterion set in Japan of 0.5 mg kg(-1).

Elastomeric Microchip Electrospray Emitter for Stable Cone-Jet Mode Operation in the Nano-Flow Regime

PubMed Central

Kelly, Ryan T.; Tang, Keqi; Irimia, Daniel; Toner, Mehmet; Smith, Richard D.

2009-01-01

Despite widespread interest in combining lab-on-a-chip technologies with mass spectrometry (MS)-based analyses, the coupling of microfluidics to electrospray ionization (ESI)-MS remains challenging. We report a robust, integrated poly(dimethylsiloxane) microchip interface for ESI-MS using simple and widely accessible microfabrication procedures. The interface uses an auxiliary channel to provide electrical contact for the stable cone-jet electrospray without sample loss or dilution. The electric field at the channel terminus is enhanced by two vertical cuts that cause the interface to taper to a line rather than to a point, and the formation of a small Taylor cone at the channel exit ensures sub-nL post-column dead volumes. Cone-jet mode electrospray was demonstrated for up to 90% aqueous solutions and for extended durations. Comparable ESI-MS sensitivities were achieved using both microchip and conventional fused silica capillary emitters, but stable cone-jet mode electrosprays could be established over a far broader range of flow rates (from 50-1000 nL/min) and applied potentials using the microchip emitters. This attribute of the microchip emitter should simplify electrospray optimization and make the stable electrospray more resistant to external perturbations. PMID:18419138

Integrated microchip incorporating atomic magnetometer and microfluidic channel for NMR and MRI

DOEpatents

Ledbetter, Micah P [Oakland, CA; Savukov, Igor M [Los Alamos, NM; Budker, Dmitry [El Cerrito, CA; Shah, Vishal K [Plainsboro, NJ; Knappe, Svenja [Boulder, CO; Kitching, John [Boulder, CO; Michalak, David J [Berkeley, CA; Xu, Shoujun [Houston, TX; Pines, Alexander [Berkeley, CA

2011-08-09

An integral microfluidic device includes an alkali vapor cell and microfluidic channel, which can be used to detect magnetism for nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Small magnetic fields in the vicinity of the vapor cell can be measured by optically polarizing and probing the spin precession in the small magnetic field. This can then be used to detect the magnetic field of in encoded analyte in the adjacent microfluidic channel. The magnetism in the microfluidic channel can be modulated by applying an appropriate series of radio or audio frequency pulses upstream from the microfluidic chip (the remote detection modality) to yield a sensitive means of detecting NMR and MRI.

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

Strizhkov, B. N.; Drobyshev, A. L.; Mikhailovich, V. M.

PCR amplification on a microarray of gel-immobilized primers (microchip) has been developed. One of a pair of PCR primers was immobilized inside a separate microchip polyacrylamide porous gel pad of 0.1 x 0.1 x 0.02 (or 0.04) micron in size and 0.2 (or 0.4) nL in volume. The amplification was carried out simultaneously both in solution covering the microchip array and inside gel pads. Each gel pad contained the immobilized forward primers, while the fluorescently labeled reverse primers, as well as all components of the amplification reaction, diffused into the gel pads from the solution. To increase the amplification efficiency,more » the forward primers were also added into the solution. The kinetics of amplification was measured in real time in parallel for all gel pads with a fluorescent microscope equipped with a charge-coupled device (CCD) camera. The accuracy of the amplification was assessed by using the melting curves obtained for the duplexes formed by the labeled amplification product and the gel-immobilized primers during the amplification process; alternatively, the duplexes were produced by hybridization of the extended immobilized primers with labeled oligonucleotide probes. The on-chip amplification was applied to detect the anthrax toxin genes and the plasmid-borne beta-lactamase gene responsible for bacterial ampicillin resistance. The allele-specific type of PCR amplification was used to identify the Shiga toxin gene and discriminate it from the Shiga-like one. The genomic mutations responsible for rifampicin resistance of the Mycobacterium tuberculosis strains were detected by the same type of PCR amplification of the rpoB gene fragment isolated from sputum of tuberculosis patients. The on-chip PCR amplification has been shown to be a rapid, inexpensive and powerful tool to test genes responsible for bacterial toxin production and drug resistance, as well as to reveal point nucleotide mutations.« less

Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis

DOEpatents

Ramsey, J. Michael

2000-01-01

A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis

DOEpatents

Ramsey, J. Michael

2000-01-01

A microchip laboratory system and method proved fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis

DOEpatents

Ramsey, J. Michael

2002-01-01

A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis

DOEpatents

Ramsey, J. Michael

1999-01-01

A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Application of Microchip Electrophoresis for Clinical Tests

NASA Astrophysics Data System (ADS)

Yatsushiro, Shouki; Kataoka, Masatoshi

Microchip electrophoresis has recently attracted much attention in the field of nuclear acid analysis due to its high efficiency, ease of operation, low consumption of samples and reagents, and relatively low costs. In addition, the analysis has expanded to an analytical field like not only the analysis of DNA but also the analysis of RNA, the protein, the sugar chain, and the cellular function, etc. In this report, we showed that high-performance monitoring systems for human blood glucose levels and α-amylase activity in human plasma using microchip electrophoresis.

Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis

DOEpatents

Ramsey, J.M.

1999-01-12

A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel. 46 figs.

> 6 MW peak power at 532 nm from passively Q-switched Nd:YAG/Cr4+:YAG microchip laser.

PubMed

Bhandari, Rakesh; Taira, Takunori

2011-09-26

Megawatt peak power, giant pulse microchip lasers are attractive for wavelength conversion, provided their output is linearly polarized. We use a [110] cut Cr(4+):YAG for passively Q-switched Nd:YAG microchip laser to obtain a stable, linearly polarized output. Further, we optimize the conditions for second harmonic generation at 532 nm wavelength to achieve > 6 MW peak power, 1.7 mJ, 265 ps, 100 Hz pulses with a conversion efficiency of 85%. © 2011 Optical Society of America

A general microchip surface modification approach using a spin-coated polymer resist film doped with hydroxypropyl cellulose.

PubMed

Sun, Xiuhua; Yang, Weichun; Geng, Yanli; Woolley, Adam T

2009-04-07

We have developed a simple and effective method for surface modification of polymer microchips by entrapping hydroxypropyl cellulose (HPC) in a spin-coated thin film on the surface. Poly(methyl methacrylate-8.5-methacrylic acid), a widely available commercial resist formulation, was utilized as a matrix for dissolving HPC and providing adherence to native polymer surfaces. Various amounts of HPC (0.1-2.0%) dissolved in the copolymer and spun on polymer surfaces were evaluated. The modified surfaces were characterized by contact angle measurement, X-ray photoelectron spectroscopy and atomic force microscopy. The developed method was applied on both poly(methyl methacrylate) and cyclic olefin copolymer microchips. A fluorescently labeled myoglobin digest, binary protein mixture, and human serum sample were all separated in these surface-modified polymer microdevices. Our work exhibits an easy and reliable way to achieve favorable biomolecular separation performance in polymer microchips.

A general microchip surface modification approach using a spin-coated polymer resist film doped with hydroxypropyl cellulose

PubMed Central

Sun, Xiuhua; Yang, Weichun; Geng, Yanli; Woolley, Adam T.

2009-01-01

We have developed a simple and effective method for surface modification of polymer microchips by entrapping hydroxypropyl cellulose (HPC) in a spin-coated thin film on the surface. Poly(methyl methacrylate-8.5-methacrylic acid), a widely available commercial resist formulation, was utilized as a matrix for dissolving HPC and providing adherence to native polymer surfaces. Various amounts of HPC (0.1–2.0%) dissolved in the copolymer and spun on polymer surfaces were evaluated. The modified surfaces were characterized by contact angle measurement, X-ray photoelectron spectroscopy and atomic force microscopy. The developed method was applied on both poly(methyl methacrylate) and cyclic olefin copolymer microchips. A fluorescently labeled myoglobin digest, binary protein mixture, and human serum sample were all separated in these surface-modified polymer microdevices. Our work exhibits an easy and reliable way to achieve favorable biomolecular separation performance in polymer microchips. PMID:19294306

A Cr4+:YAG passively Q-switched Nd:YVO4 microchip laser for controllable high-order Hermite-Gaussian modes

NASA Astrophysics Data System (ADS)

Dong, Jun; He, Yu; Bai, Sheng-Chuang; Ueda, Ken-ichi; Kaminskii, Alexander A.

2016-09-01

A nanosecond, high peak power, passively Q-switched laser for controllable Hermite-Gaussian (HG) modes has been achieved by manipulating the saturated inversion population inside the gain medium. The stable HG modes are generated in a Cr4+:YAG passively Q-switched Nd:YVO4 microchip laser by applying a tilted pump beam. The asymmetrical saturated inversion population distribution inside the Nd:YVO4 crystal for desirable HG modes is manipulated by choosing the proper pump beam diameter and varying pump power. A HG9,8 mode passively Q-switched Nd:YVO4 microchip laser with average output power of 265 mW has been obtained. Laser pulses with a pulse width of 7.3 ns and peak power of over 1.7 kW working at 21 kHz have been generated in the passively Q-switched Nd:YVO4 microchip laser.

Solid State Research

DTIC Science & Technology

2005-06-21

266-nm, l-,W, 500-ps laser pulse from a frequency-quadrupled Nd:YAG microchip laser operating at 10 kHz. Fluorescence and elastic scattering from the...on Solid State Research xv Organization xxiii QUANTUM ELECTRONICS 1.1 Fluorescence-Cued Laser -Induced Breakdown Spectroscopy Detection of Bioaerosols...2. ELECTRO-OfI’ICAL MATERIALS AND DEVICES 2.1 Narrow-Linewidth, High-Power 1556-nm Slab-Coupled Optical Waveguide External-Cavity Laser 7 3

Single-pair fluorescence resonance energy transfer analysis of mRNA transcripts for highly sensitive gene expression profiling in near real time.

PubMed

Peng, Zhiyong; Young, Brandon; Baird, Alison E; Soper, Steven A

2013-08-20

Expression analysis of mRNAs transcribed from certain genes can be used as important sources of biomarkers for in vitro diagnostics. While the use of reverse transcription quantitative PCR (RT-qPCR) can provide excellent analytical sensitivity for monitoring transcript numbers, more sensitive approaches for expression analysis that can report results in near real-time are needed for many critical applications. We report a novel assay that can provide exquisite limits-of-quantitation and consists of reverse transcription (RT) followed by a ligase detection reaction (LDR) with single-pair fluorescence resonance energy transfer (spFRET) to provide digital readout through molecular counting. For this assay, no PCR was employed, which enabled short assay turnaround times. To facilitate implementation of the assay, a cyclic olefin copolymer (COC) microchip, which was fabricated using hot embossing, was employed to carry out the LDR in a continuous flow format with online single-molecule detection following the LDR. As demonstrators of the assay's utility, MMP-7 mRNA was expression profiled from several colorectal cancer cell lines. It was found that the RT-LDR/spFRET assay produced highly linear calibration plots even in the low copy number regime. Comparison to RT-qPCR indicated a better linearity over the low copy number range investigated (10-10,000 copies) with an R(2) = 0.9995 for RT-LDR/spFRET and R(2) = 0.98 for RT-qPCR. In addition, differentiating between copy numbers of 10 and 50 could be performed with higher confidence using RT-LDR/spFRET. To demonstrate the short assay turnaround times obtainable using the RT-LDR/spFRET assay, a two thermal cycle LDR was carried out on amphiphysin gene transcripts that can serve as important diagnostic markers for ischemic stroke. The ability to supply diagnostic information on possible stroke events in short turnaround times using RT-LDR/spFRET will enable clinicians to treat patients effectively with appropriate time-sensitive therapeutics.

Single-Pair Fret Analysis of mRNA Transcripts for Highly Sensitive Gene Expression Profiling in Near Real Time

PubMed Central

Peng, Zhiyong; Young, Brandon; Baird, Alison E.; Soper, Steven A.

2013-01-01

Expression analysis of mRNAs transcribed from certain genes can be used as important sources of biomarkers for in vitro diagnostics. While the use of reverse transcription quantitative PCR (RT-qPCR) can provide excellent analytical sensitivity for monitoring transcript numbers, more sensitive approaches for expression analysis that can report results in near real-time are needed for many critical applications. We report a novel assay that can provide exquisite limits-of-quantitation and consists of reverse transcription (RT) followed by a ligase detection reaction (LDR) with single-pair fluorescence resonance energy transfer (spFRET) to provide digital readout through molecular counting. For this assay, no PCR was employed, which enabled short assay turnaround times. To facilitate implementation of the assay, a cyclic olefin copolymer (COC) microchip, which was fabricated using hot embossing, was employed to carry out the LDR in a continuous flow format with on-line single-molecule detection following the LDR. As demonstrators of the assay's utility, MMP-7 mRNA was expression profiled from several colorectal cancer cell lines. It was found that the RT-LDR/spFRET assay produced highly linear calibration plots even in the low copy number regime. Comparison to RT-qPCR indicated a better linearity over the low copy number range investigated (10 − 10,000 copies) with an R2 = 0.9995 for RT-LDR/spFRET and R2 = 0.98 for RT-qPCR. In addition, differentiating between copy numbers of 10 and 50 could be performed with higher confidence using RT-LDR/spFRET. To demonstrate the short assay turnaround times obtainable using the RT-LDR/spFRET assay, a 2 thermal cycle LDR was carried out on amphiphysin gene transcripts that can serve as important diagnostic markers for ischemic stroke. The ability to supply diagnostic information on possible stroke events in short turnaround times using RT-LDR/spFRET will enable clinicians to treat patients effectively with appropriate time-sensitive therapeutics. PMID:23869556

On-Chip Spyhole Nanoelectrospray Ionization Mass Spectrometry for Sensitive Biomarker Detection in Small Volumes

NASA Astrophysics Data System (ADS)

Zhong, Xiaoqin; Qiao, Liang; Stauffer, Géraldine; Liu, Baohong; Girault, Hubert H.

2018-03-01

A polyimide microfluidic chip with a microhole emitter (Ø 10-12 μm) created on top of a microchannel by scanning laser ablation has been designed for nanoelectrospray ionization (spyhole-nanoESI) to couple microfluidics with mass spectrometry. The spyhole-nanoESI showed higher sensitivity compared to standard ESI and microESI from the end of the microchannel. The limits of detection (LOD) for peptide with the spyhole-nanoESI MS reached 50 pM, which was 600 times lower than that with standard ESI. The present microchip emitter allows the analysis of small volumes of samples. As an example, a small cell lung cancer biomarker, neuron-specific enolase (NSE), was detected by monitoring the transition of its unique peptide with the spyhole-nanoESI MS/MS. NSE at 0.2 nM could be well identified with a signal to noise ratio (S/N) of 50, and thereby its LOD was estimated to be 12 pM. The potential application of the spyhole-nanoESI MS/MS in cancer diagnosis was further demonstrated with the successful detection of 2 nM NSE from 1 μL of human serum. Before the detection, the serum sample spiked with NSE was first depleted with immune spin column, then desalted by centrifugal filter device, and finally digested by trypsin, without any other complicated preparation steps. The concentration matched the real condition of clinical samples. In addition, the microchips can be disposable to avoid any cross contamination. The present technique provides a highly efficient way to couple microfluidics with MS, which brings additional values to various microfluidics and MS-based analysis.

Analytical Chemistry and the Microchip.

ERIC Educational Resources Information Center

Lowry, Robert K.

1986-01-01

Analytical techniques used at various points in making microchips are described. They include: Fourier transform infrared spectrometry (silicon purity); optical emission spectroscopy (quantitative thin-film composition); X-ray photoelectron spectroscopy (chemical changes in thin films); wet chemistry, instrumental analysis (process chemicals);…

Science and Technology of Bio-Inert Thin Films as Hermetic-Encapsulating Coatings for Implantable Biomedical Devices: Application to Implantable Microchip in the Eye for the Artificial Retina

NASA Astrophysics Data System (ADS)

Auciello, Orlando; Shi, Bing

Extensive research has been devoted to the development of neuron prostheses and hybrid bionic systems to establish links between the nervous system and electronic or robotic prostheses with the main focus of restoring motor and sensory functions in blind patients. Artificial retinas, one type of neural prostheses we are currently working on, aim to restore some vision in blind patients caused by retinitis picmentosa or macular degeneration, and in the future to restore vision at the level of face recognition, if not more. Currently there is no hermetic microchip-size coating that provides a reliable, long-term (years) performance as encapsulating coating for the artificial retina Si microchip to be implanted inside the eye. This chapter focuses on the critical topics relevant to the development of a robust, long-term artificial retina device, namely the science and technology of hermetic bio-inert encapsulating coatings to protect a Si microchip implanted in the human eye from being attacked by chemicals existing in the eye's saline environment. The work discussed in this chapter is related to the development of a novel ultrananocrystalline diamond (UNCD) hermetic coating, which exhibited no degradation in rabbit eyes. The material synthesis, characterization, and electrochemical properties of these hermetic coatings are reviewed for application as encapsulating coating for the artificial retinal microchips implantable inside the human eye. Our work has shown that UNCD coatings may provide a reliable hermetic bio-inert coating technology for encapsulation of Si microchips implantable in the eye specifically and in the human body in general. Electrochemical tests of the UNCD films grown under CH4/Ar/H2 (1%) plasma exhibit the lowest leakage currents (˜7 × 10-7 A/cm2) in a saline solution simulating the eye environment. This leakage is incompatible with the functionality of the first-generation artificial retinal microchip. However, the growth of UNCD on top of the Si microchip passivated by a silicon nitride layer or the oxide layers is also under investigation in our group as introduced in this chapter. The electrochemically induced leakage will be reduced by at least one to three orders of magnitude to the range of 10-10 A/cm2, which is compatible with reliable, long-term implants.

Extending the upper temperature range of gas chromatography with all-silicon microchip columns using a heater/clamp assembly.

PubMed

Ghosh, Abhijit; Johnson, Jacob E; Nuss, Johnathan G; Stark, Brittany A; Hawkins, Aaron R; Tolley, Luke T; Iverson, Brian D; Tolley, H Dennis; Lee, Milton L

2017-09-29

Miniaturization of gas chromatography (GC) instrumentation is of interest because it addresses current and future issues relating to compactness, portability and field application. While incremental advancements continue to be reported in GC with columns fabricated in microchips (referred to in this paper as "microchip columns"), the current performance is far from acceptable. This lower performance compared to conventional GC is due to factors such as pooling of the stationary phase in corners of non-cylindrical channels, adsorption of sensitive compounds on incompletely deactivated surfaces, shorter column lengths and less than optimum interfacing to injector and detector. In this work, a GC system utilizing microchip columns was developed that solves the latter challenge, i.e., microchip interfacing to injector and detector. A microchip compression clamp was constructed to heat the microchip (i.e., primary heater), and seal the injector and detector fused silica interface tubing to the inlet and outlet ports of the microchip channels with minimum extra-column dead volume. This clamp allowed occasional operation up to 375°C and routine operation up to 300°C. The compression clamp was constructed of a low expansion alloy, Kovar™, to minimize leaking due to thermal expansion mismatch at the interface during repeated thermal cycling, and it was tested over several months for more than one hundred injections without forming leaks. A 5.9m long microcolumn with rectangular cross section of 158μm×80μm, which approximately matches a 100μm i.d. cylindrical fused silica column, was fabricated in a silicon wafer using deep reactive ion etching (DRIE) and high temperature fusion bonding; finally, the channel was coated statically with a 1% vinyl, 5% phenyl, 94% methylpolysiloxane stationary phase. High temperature separations of C10-C40 n-alkanes and a commercial diesel sample were demonstrated using the system under both temperature programmed GC (TPGC) and thermal gradient GC (TGGC) conditions. TGGC analysis of a complex essential oil sample was also demonstrated. Addition of a secondary heater and polyimide insulation proved to be helpful in achieving the desired elution temperature without having to raise the primary heater temperature above 300°C for high boiling point compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of carbonaceous biomarkers with the Mars Organic Analyzer microchip capillary electrophoresis system: carboxylic acids.

PubMed

Stockton, Amanda M; Tjin, Caroline Chandra; Chiesl, Thomas N; Mathies, Richard A

2011-01-01

The oxidizing surface chemistry on Mars argues that any comprehensive search for organic compounds indicative of life requires methods to analyze higher oxidation states of carbon with very low limits of detection. To address this goal, microchip capillary electrophoresis (μCE) methods were developed for analysis of carboxylic acids with the Mars Organic Analyzer (MOA). Fluorescent derivatization was achieved by activation with the water soluble 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) followed by reaction with Cascade Blue hydrazide in 30 mM borate, pH 3. A standard containing 12 carboxylic acids found in terrestrial life was successfully labeled and separated in 30 mM borate at pH 9.5, 20 °C by using the MOA CE system. Limits of detection were 5-10 nM for aliphatic monoacids, 20 nM for malic acid (diacid), and 230 nM for citric acid (triacid). Polyacid benzene derivatives containing 2, 3, 4, and 6 carboxyl groups were also analyzed. In particular, mellitic acid was successfully labeled and analyzed with a limit of detection of 300 nM (5 ppb). Analyses of carboxylic acids sampled from a lava tube cave and a hydrothermal area demonstrated the versatility and robustness of our method. This work establishes that the MOA can be used for sensitive analyses of a wide range of carboxylic acids in the search for extraterrestrial organic molecules. © Mary Ann Liebert, Inc.

25 CFR 542.8 - What are the minimum internal control standards for pull tabs?

Code of Federal Regulations, 2011 CFR

2011-04-01

... microchip reader, the reader shall be tested periodically to determine that it is correctly reading the bar code or microchip. (iii) If the electronic equipment returns a voucher or a payment slip to the player...

R&D 100, 2016: T-Quake – Quantum-Mechanical Transmitter/Receiver Microchip

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

Tauke-Pedretti, Anna; Camacho, Ryan; Thayer, Gayle

2016-11-07

Applying advanced microfabrication techniques and innovative microdesign, the Sandia Enabled Communications and Authentication Network (SECANT) team has designed and produced photonic microchips capable of sending, receiving, and processing quantum signals for applications in cyber and physical security.

Reduction of timing jitter in passively Q-switched microchip lasers using self-injection seeding.

PubMed

Steinmetz, Alexander; Nodop, Dirk; Martin, Andreas; Limpert, Jens; Tünnermann, Andreas

2010-09-01

We present an efficient, simple, and passive technique for the reduction of timing jitter in passively Q-switched microchip lasers via self-injection seeding using a fiber delay line. The presented approach mitigates one inherent issue of passively Q-switched lasers without the need for active stabilization. At a repetition rate of a few hundred kilohertz and pulse duration of approximately 200 ps delivered by a microchip laser, the rms jitter is reduced from several nanoseconds down to 20 ps, hence, significantly below the pulse duration of the laser source.

Sub-nanosecond Yb:KLu(WO₄)₂ microchip laser.

PubMed

Loiko, P; Serres, J M; Mateos, X; Yumashev, K; Yasukevich, A; Petrov, V; Griebner, U; Aguiló, M; Díaz, F

2016-06-01

A diode-pumped Yb:KLu(WO₄)₂ microchip laser passively Q-switched by a Cr⁴⁺:YAG saturable absorber generated a maximum average output power of 590 mW at 1031 nm with a slope efficiency of 55%. The pulse characteristics were 690 ps/47.6 μJ at a pulse repetition frequency of 12.4 kHz. The output beam had an excellent circular profile with M²<1.05. Yb:KLu(WO₄)₂ is very promising for ultrathin sub-ns microchip lasers.

Deformation-induced release of ATP from erythrocytes in a poly(dimethylsiloxane)-based microchip with channels that mimic resistance vessels.

PubMed

Price, Alexander K; Fischer, David J; Martin, R Scott; Spence, Dana M

2004-08-15

The ability of nitric oxide to relax smooth muscle cells surrounding resistance vessels in vivo is well documented. Here, we describe a series of studies designed to quantify amounts of adenosine triphosphate (ATP), a known stimulus of NO production in endothelial cells, released from erythrocytes that are mechanically deformed as these cells traverse microbore channels in lithographically patterned microchips. Results indicate that micromolar amounts of ATP are released from erythrocytes flowing through channels having cross sectional dimensions of 60 x 38 micron (2.22 +/- 0.50 microM ATP). Microscopic images indicate that erythrocytes, when being pumped through the microchip channels, migrate toward the center of the channels, leaving a cell-free or skimming layer at the walls of the channel, a profile known to exist in circulatory vessels in vivo. A comparison of the amounts of ATP released from RBCs mechanically deformed in microbore tubing (2.54 +/- 0.15 microM) vs a microchip (2.59 +/- 0.32 microM) suggests that channels in microchips may serve as functional biomimics of the microvasculature. Control studies involving diamide, a membrane-stiffening agent, suggest that the RBC-derived ATP is not due to cell lysis but rather physical deformation.

Highly-efficient multi-watt Yb:CaLnAlO4 microchip lasers

NASA Astrophysics Data System (ADS)

Loiko, Pavel; Serres, Josep Maria; Mateos, Xavier; Xu, Xiaodong; Xu, Jun; Yumashev, Konstantin; Griebner, Uwe; Petrov, Valentin; Aguiló, Magdalena; Díaz, Francesc; Major, Arkady

2017-02-01

Tetragonal rare-earth calcium aluminates, CaLnAlO4 where Ln = Gd or Y (CALGO and CALYO, respectively), are attractive laser crystal hosts due to their locally disordered structure and high thermal conductivity. In the present work, we report on highly-efficient power-scalable microchip lasers based on 8 at.% Yb:CALGO and 3 at.% Yb:CALYO crystals grown by the Czochralski method. Pumped by an InGaAs laser diode at 978 nm, the 6 mm-long Yb:CALGO microchip laser generated 7.79 W at 1057-1065 nm with a slope efficiency of η = 84% (with respect to the absorbed pump power) and an optical-to-optical efficiency of ηopt = 49%. The 3 mm-long Yb:CALYO microchip laser generated 5.06 W at 1048-1056 nm corresponding to η = 91% and ηopt = 32%. Both lasers produced linearly polarized output (σ- polarization) with an almost circular beam profile and beam quality factors M2 x,y <1.1. The output performance of the developed lasers was modeled yielding a loss coefficient as low as 0.004-0.007 cm-1. The results indicate that the Yb3+- doped calcium aluminates are very promising candidates for high-peak-power passively Q-switched microchip lasers.

Conductivity detection for monitoring mixing reactions in microfluidic devices.

PubMed

Liu, Y; Wipf, D O; Henry, C S

2001-08-01

A conductivity detector was coupled to poly(dimethylsiloxane)-glass capillary electrophoresis microchips to monitor microfluidic flow. Electroosmotic flow was investigated with both conductivity detection (CD) and the current monitoring method. No significant variation was observed between these methods, but CD showed a lower relative standard deviation. Gradient mixing experiments were employed to investigate the relationship between the electrolyte conductivity and the electrolyte concentration. A good linear response of conductivity to concentration was obtained for solutions whose difference in concentrations were less than 27 mM. The new system holds great promise for precision mixing in microfluidic devices using electrically driven flows.

A Novel Protocol to Analyze Short- and Long-Chain Fatty Acids Using Nonaqueous Microchip Capillary Electrophoresis

NASA Technical Reports Server (NTRS)

Cable, M. L.; Stockton, A. M.; Mora, Maria F; Willis, P. A.

2013-01-01

We propose a new protocol to identify and quantify both short- and long-chain saturated fatty acids in samples of astrobiological interest using non-aqueous microchip capillary electrophoresis (micronNACE) with laser induced fluorescence (LIF).

R&D 100, 2016: T-Quake – Quantum-Mechanical Transmitter/Receiver Microchip

ScienceCinema

Tauke-Pedretti, Anna; Camacho, Ryan; Thayer, Gayle

2018-06-13

Applying advanced microfabrication techniques and innovative microdesign, the Sandia Enabled Communications and Authentication Network (SECANT) team has designed and produced photonic microchips capable of sending, receiving, and processing quantum signals for applications in cyber and physical security.

50 CFR 23.56 - What U.S. CITES document conditions do I need to follow?

Code of Federal Regulations, 2011 CFR

2011-10-01

... CITES document correspond. If a microchip is used, we may, if necessary, ask the importer, exporter, or re-exporter to have equipment on hand to read the microchip at the time of import, export, or re...

50 CFR 23.56 - What U.S. CITES document conditions do I need to follow?

Code of Federal Regulations, 2010 CFR

2010-10-01

... CITES document correspond. If a microchip is used, we may, if necessary, ask the importer, exporter, or re-exporter to have equipment on hand to read the microchip at the time of import, export, or re...

On-Campus Projects: Inventing a Microchip.

ERIC Educational Resources Information Center

Basta, Nicholas

1985-01-01

In response to growth of microelectronics and changes in microchip design/manufacturing technology, universities are supporting class projects for students. Approximately 50 schools now conduct such programs which have resulted from earlier National Science Foundation sponsorship. Major advantages for the students include designing experience,…

Novel label-free and high-throughput microchip electrophoresis platform for multiplex antibiotic residues detection based on aptamer probes and target catalyzed hairpin assembly for signal amplification.

PubMed

Wang, Ye; Gan, Ning; Zhou, You; Li, Tianhua; Hu, Futao; Cao, Yuting; Chen, Yinji

2017-11-15

Novel label-free and multiplex aptasensors have been developed for simultaneous detection of several antibiotics based on a microchip electrophoresis (MCE) platform and target catalyzed hairpin assembly (CHA) for signal amplification. Kanamycin (Kana) and oxytetracycline (OTC) were employed as models for testing the system. These aptasensors contained six DNA strands termed as Kana aptamer-catalysis strand (Kana apt-C), Kana inhibit strand (Kana inh), OTC aptamer-catalysis strand (OTC apt-C), OTC inhibit strand (OTC inh), hairpin structures H1 and H2 which were partially complementary. Upon the addition of Kana or OTC, the binding event of aptamer and target triggered the self-assembly between H1 and H2, resulting in the formation of many H1-H2 complexes. They could show strong signals which represented the concentration of Kana or OTC respectively in the MCE system. With the help of the well-designed and high-quality CHA amplification, the assay could yield 300-fold amplified signal comparing that from non-amplified system. Under optimal conditions, this assay exhibited a linear correlation in the ranges from 0.001ngmL -1 to 10ngmL -1 , with the detection limits of 0.7pgmL -1 and 0.9pgmL -1 (S/N=3) toward Kana and OTC, respectively. The platform has the following advantages: firstly, the aptamer probes can be fabricated easily without labeling signal tags for MCE detection; Secondly, the targets can just react with probes and produce the amplified signal in one-pot. Finally, the targets can be simultaneously detected within 10min in different channels, thus high-throughput measurement can be achieved. Based on this work, it is estimated that this detection platform will be universally served as a simple, sensitive and portable platform for antibiotic contaminants detection in biological and environmental samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-Sterilizing and Regeneratable Microchip for the Precise Capture and Recovery of Viable Circulating Tumor Cells from Patients with Cancer.

PubMed

Hui, Lanlan; Su, Yi; Ye, Tingting; Liu, Zhao; Tian, Qingchang; He, Chuanjiang; Zhao, Yueqi; Chen, Pu; Wang, Xiaojia; Han, Weidong; Luo, Yan; Wang, Ben

2018-01-10

Cancer cells metastasize and are transported in the bloodstream, easily reaching any site in the body through the blood circulation. A method designed to assess the number of circulating tumor cells (CTCs) should be validated as a clinical tool for predicting the response to therapy and monitoring the disease progression in patients with cancer. Although CTCs are detectable in many cases, they remain unavailable for clinic usage because of their high testing cost, tedious operation, and poor clinical relevance. Herein, we developed a regeneratable microchip for isolating CTCs, which is available for robust cell heterogeneity assays on-site without the need for a sterile environment. The ivy-like hierarchical roughened zinc oxide (ZnO) nanograss interface was synthesized and directly integrated into the microfluidic devices and enables effective CTC capture and flexible, nontoxic CTC release during incubation in a mildly acidic solution, thus enabling cellular and molecular analyses. The microchip can be regenerated and recycled to capture CTCs with the remaining ZnO without affecting the efficiency, even after countless cycles of cell release. Moreover, microbial infection is avoided during its storage, distribution, and even in the open space usage, which ideally appeals to the demands of point-of-care (POC) and home testing and meets to the requirements for blood examinations in undeveloped or resource-limited settings. Furthermore, the findings generated using this platform based on the cocktail of antiepithelial cell adhesion molecule and antivimentin antibodies indicate that CTC capture was more precise and reasonable for patients with advanced cancer.

Microfluidic biosensing systems. Part I. Development and optimisation of enzymatic chemiluminescent micro-biosensors based on silicon microchips.

PubMed

Davidsson, Richard; Genin, Frédéric; Bengtsson, Martin; Laurell, Thomas; Emnéus, Jenny

2004-10-01

Chemiluminescent (CL) enzyme-based flow-through microchip biosensors (micro-biosensors) for detection of glucose and ethanol were developed for the purpose of monitoring real-time production and release of glucose and ethanol from microchip immobilised yeast cells. Part I of this study focuses on the development and optimisation of the micro-biosensors in a microfluidic sequential injection analysis (microSIA) system. Glucose oxidase (GOX) or alcohol oxidase (AOX) was co-immobilised with horseradish peroxidase (HRP) on porous silicon flow through microchips. The hydrogen peroxide produced from oxidation of the corresponding analyte (glucose or ethanol) took part in the chemiluminescent (CL) oxidation of luminol catalysed by HRP enhanced by addition of p-iodophenol (PIP). All steps in the microSIA system, including control of syringe pump, multiposition valve (MPV) and data readout, were computer controlled. The influence of flow rate and luminol- and PIP concentration were investigated using a 2(3)-factor experiment using the GOX-HRP sensor. It was found that all estimated single factors and the highest order of interaction were significant. The optimum was found at 250 microM luminol and 150 microM PIP at a flow rate of 18 microl min(-1), the latter as a compromise between signal intensity and analysis time. Using the optimised system settings one sample was processed within 5 min. Two different immobilisation chemistries were investigated for both micro-biosensors based on 3-aminopropyltriethoxsilane (APTS)- or polyethylenimine (PEI) functionalisation followed by glutaraldehyde (GA) activation. GOX-HRP micro-biosensors responded linear in a log-log format within the range 10-1000 microM glucose. Both had an operational stability of at least 8 days, but the PEI-GOX-HRP sensor was more sensitive. The AOX-HRP micro-biosensors responded linear (log-log) in the range between 1 and 10 mM ethanol, but the PEI-AOX-HRP sensor was in general more sensitive. Both sensors had an operational stability of at least 8 h, but with a half-life of 2-3 days.

Microchip capillary gel electrophoresis using programmed field strength gradients for the ultra-fast analysis of genetically modified organisms in soybeans.

PubMed

Kim, Yun-Jeong; Chae, Joon-Seok; Chang, Jun Keun; Kang, Seong Ho

2005-08-12

We have developed a novel method for the ultra-fast analysis of genetically modified organisms (GMOs) in soybeans by microchip capillary gel electrophoresis (MCGE) using programmed field strength gradients (PFSG) in a conventional glass double-T microchip. Under the programmed electric field strength and 0.3% poly(ethylene oxide) sieving matrix, the GMO in soybeans was analyzed within only 11 s of the microchip. The MCGE-PFSG method was a program that changes the electric field strength during GMO analysis, and was also applied to the ultra-fast analysis of PCR products. Compared to MCGE using a conventional and constantly applied electric field, the MCGE-PFSG analysis generated faster results without the loss of resolving power and reproducibility for specific DNA fragments (100- and 250-bp DNA) of GM-soybeans. The MCGE-PFSG technique may prove to be a new tool in the GMO analysis due to its speed, simplicity, and high efficiency.

Multiphoton lithography using a high-repetition rate microchip laser.

PubMed

Ritschdorff, Eric T; Shear, Jason B

2010-10-15

Multiphoton lithography (MPL) provides a means to create prototype, three-dimensional (3D) materials for numerous applications in analysis and cell biology. A major impediment to the broad adoption of MPL in research laboratories is its reliance on high peak-power light sources, a requirement that typically has been met using expensive femtosecond titanium:sapphire lasers. Development of affordable microchip laser sources has the potential to substantially extend the reach of MPL, but previous lasers have provided relatively low pulse repetition rates (low kilohertz range), thereby limiting the rate at which microforms could be produced using this direct-write approach. In this report, we examine the MPL capabilities of a new, high-repetition-rate (36.6 kHz) microchip Nd:YAG laser. We show that this laser enables an approximate 4-fold decrease in fabrication times for protein-based microforms relative to the existing state-of-the-art microchip source and demonstrate its utility for creating complex 3D microarchitectures.

Morphologies and optical and electrical properties of InGaN/GaN micro-square array light-emitting diode chips.

PubMed

Han, Dan; Ma, Shufang; Jia, Zhigang; Liu, Peizhi; Jia, Wei; Shang, Lin; Zhai, Guangmei; Xu, Bingshe

2018-04-10

InGaN/GaN micro-square array light-emitting diode (LED) chips (micro-chips) have been prepared via the focused ion beam (FIB) etching technique, which can not only reduce ohmic contact degradation but also control the aspect ratio precisely in three-dimensional (3D) structure LED (3D-LED) device fabrication. The effects of FIB beam current and micro-square array depth on morphologies and optical and electrical properties of the micro-chips have been studied. Our results show that sidewall surface morphology and optical and electrical properties of the micro-chips degrade with increased beam current. After potassium hydroxide etching with different times, an optimal current-voltage and luminescence performance can be obtained. Combining the results of cathodoluminescence mappings and light output-current characteristics, the light extraction efficiency of the micro-chips is reduced as FIB etch depth increases. The mechanisms of micro-square depth on light extraction have been revealed by 3D finite difference time domain.

All-fiber pulse shortening of passively Q-switched microchip laser pulses down to sub-200 fs.

PubMed

Lehneis, R; Steinmetz, A; Limpert, J; Tünnermann, A

2014-10-15

We present an all-fiber concept that generates ultrashort pulses using a passively Q-switched microchip seed laser. A proof-of-principle configuration combines nonlinear pulse compression applying a chirped fiber-Bragg-grating, dispersion-free pulse shortening by means of a fiber-integrated spectral filtering, and a final hollow-core-fiber compression to reach the sub-200-fs pulse-duration region. In a compact all-fiber pulse-shortening unit, initial 100 ps long microchip pulses at 1064 nm wavelength have been shortened to 174 fs and shifted to 1034 nm while preserving a high temporal quality.

Wavelength-tunable, sub-picosecond pulses from a passively Q-switched microchip laser system.

PubMed

Lehneis, R; Steinmetz, A; Limpert, J; Tünnermann, A

2013-07-15

We present a novel concept to generate sub-picosecond pulses from a passively Q-switched Nd:YVO4 microchip laser system with an adjustable wavelength shift up to a few tens of nanometers around the original emission wavelength of 1064 nm. This concept comprises two stages: one that carries out a nonlinear compression of fiber-amplified microchip pulses and a subsequent stage in which the compressed pulses are coupled into a further waveguide structure followed by a bandpass filter. In a proof-of-principle experiment, pedestal-free 0.62 ps long pulses have been demonstrated with a wavelength shift to 1045 nm.

Direct generation of vector vortex beams with switchable radial and azimuthal polarizations in a monolithic Nd:YAG microchip laser

NASA Astrophysics Data System (ADS)

He, Hong-Sen; Chen, Zhen; Dong, Jun

2017-05-01

A hollow focus lens (HFL) has been designed to effectively produce a focused annular beam for high-intensity pumping. By applying the central-dark pump beam, a monolithic Nd:YAG microchip laser without any extra optical elements is demonstrated to generate vector vortex beams with switchable radially polarized (RP) and azimuthally polarized (AP) states by easily controlling the pump power. The order and handedness of the output vortex beam remain stable during the switching of the RP and AP states. The monolithic Nd:YAG microchip laser provides a new laser source for applications such as material processing and optical manipulation.

Efficient second to ninth harmonic generation using megawatt peak power microchip laser.

PubMed

Bhandari, R; Tsuji, N; Suzuki, T; Nishifuji, M; Taira, T

2013-11-18

We report the design and use of a megawatt peak power Nd:YAG/Cr4+:YAG microchip laser for efficient second to ninth harmonic generation. We show that the sub-nanosecond pulse width region, between 100 ps and 1 ns, is ideally suited for efficient wavelength conversion. Using this feature, we report 85% second harmonic generation efficiency using lithium triborate (LBO), 60% fourth harmonic generation efficiency usingß-barium borate, and 44% IR to UV third harmonic generation efficiency using Type I and Type II LBO. Finally, we report the first demonstration of 118 nm VUV generation in xenon gas using a microchip laser.

Correlative fluorescence and electron microscopy of quantum dot labeled proteins on whole cells in liquid.

PubMed

Peckys, Diana B; Dukes, Madeline J; de Jonge, Niels

2014-01-01

Correlative fluorescence microscopy and scanning transmission electron microscopy (STEM) of cells fully immersed in liquid is a new methodology with many application areas. Proteins, in live cells immobilized on microchips, are labeled with fluorescent quantum dot (QD) nanoparticles. In this protocol, the epidermal growth factor receptor (EGFR) is labeled. The cells are fixed after a selected labeling time, for example, 5 min as needed to form EGFR dimers. The microchip with cells is then imaged with fluorescence microscopy. Thereafter, the microchip with the labeled cells and one with a spacer are assembled in a special microfluidic device and imaged with STEM.

Triblock copolymer matrix-based capillary electrophoretic microdevice for high-resolution multiplex pathogen detection.

PubMed

Kim, Se Jin; Shin, Gi Won; Choi, Seok Jin; Hwang, Hee Sung; Jung, Gyoo Yeol; Seo, Tae Seok

2010-03-01

Rapid and simple analysis for the multiple target pathogens is critical for patient management. CE-SSCP analysis on a microchip provides high speed, high sensitivity, and a portable genetic analysis platform in molecular diagnostic fields. The capability of separating ssDNA molecules in a capillary electrophoretic microchannel with high resolution is a critical issue to perform the precise interpretation in the electropherogram. In this study, we explored the potential of poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) (PEO-PPO-PEO) triblock copolymer as a sieving matrix for CE-SSCP analysis on a microdevice. To demonstrate the superior resolving power of PEO-PPO-PEO copolymers, 255-bp PCR amplicons obtained from 16S ribosomal RNA genes of four bacterial species, namely Proteus mirabilis, Haemophilus ducreyi, Pseudomonas aeruginosa, and Neisseria meningitidis, were analyzed in the PEO-PPO-PEO matrix in comparison with 5% linear polyacrylamide and commercial GeneScan gel. Due to enhanced dynamic coating and sieving ability, PEO-PPO-PEO copolymer displayed fourfold enhancement of resolving power in the CE-SSCP to separate same-sized DNA molecules. Fivefold input of genomic DNA of P. aeruginosa and/or N. meningitidis produced proportionally increased corresponding amplicon peaks, enabling correct quantitative analysis in the pathogen detection. Besides the high-resolution sieving capability, a facile loading and replenishment of gel in the microchannel due to thermally reversible gelation property makes PEO-PPO-PEO triblock copolymer an excellent matrix in the CE-SSCP analysis on the microdevice.

Apparatus and method for performing electrodynamic focusing on a microchip

DOEpatents

Ramsey, John Michael; Jacobson, Stephen C.

1999-01-01

A microchip device includes a focusing channel, in which an electric field strength established in the focusing channel is controlled relative to an electric field strength established in a material transport channel segment to spatially focus the material traversing the material transport channel segment.

Apparatus and method for performing electrodynamic focusing on a microchip

DOEpatents

Ramsey, J.M.; Jacobson, S.C.

1999-01-12

A microchip device includes a focusing channel, in which an electric field strength established in the focusing channel is controlled relative to an electric field strength established in a material transport channel segment to spatially focus the material traversing the material transport channel segment. 22 figs.

Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in Border Collie dogs.

PubMed

Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

2012-01-01

P-glycoprotein, encoded by the MDR1 or ABCB1 gene, is an integral component of the blood-brain barrier as an efflux pump for xenobiotics crucial in limiting drug uptake into the central nervous system. Dogs homozygous for a 4-base pair deletion of the canine MDR1 gene show altered expression or function of P-glycoprotein, resulting in neurotoxicosis after administration of the substrate drugs. In the present study, the usefulness of microchip electrophoresis for genotyping assays detecting this deletion mutation was evaluated. Mutagenically separated polymerase chain reaction (MS-PCR) and real-time PCR assays were newly developed and evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies dogs in Japan to determine the allele frequency in this breed. Microchip electrophoresis showed advantages in detection sensitivity and time saving over other modes of electrophoresis. The MS-PCR assay clearly discriminated all genotypes. Real-time PCR assay was most suitable for a large-scale survey due to its high throughput and rapidity. The genotyping survey demonstrated that the carrier and mutant allele frequencies were 0.49% and 0.25%, respectively, suggesting that the mutant allele frequency in Border Collies is markedly low compared to that in the susceptible dog breeds such as rough and smooth Collies.

Measurement of monomolecular binding constants of neutral phenols into the beta-cyclodextrin by continuous frontal analysis in capillary and microchip electrophoresis via a competitive assay.

PubMed

Le Saux, Thomas; Hisamoto, Hideaki; Terabe, Shigeru

2006-02-03

Measurement of binding constant by chip electrophoresis is a very promising technique for the high throughput screening of non-covalent interactions. Among the different electrophoretic methods available that yield the binding parameters, continuous frontal analysis is the most appropriate for a transposition from capillary electrophoresis (CE) to microchip electrophoresis. Implementation of this methodology in microchip was exemplified by the measurement of inclusion constants of 2-naphtalenesulfonate and neutral phenols (phenol, 4-chlorophenol and 4-nitrophenol) into beta-cyclodextrin by competitive assays. The issue of competitor choice is discussed in relation to its appropriateness for proper monitoring of the interaction.

Design of anti-theft/cable cut real time alert system for copper cable using microcontroller and GSM technology

NASA Astrophysics Data System (ADS)

Lim, E. K.; Norizan, M. N.; Mohamad, I. S.; Yasin, M. N. M.; Murad, S. A. Z.; Baharum, N. A.; Jamalullail, N.

2017-09-01

This paper presents the design of anti-theft/cable cut real time alert system using microcontroller and GSM technology. The detection part is using the electrical circuit wire connection in detecting the voltage drop of the cable inside the microcontroller digital input port. The GSM wireless modem is used to send the location of cable cut directly to the authority mobile phone. Microcontroller SK40C with Microchip PIC16F887 is used as a controller to control the wireless modem and also the detection device. The device is able to detect and display the location of the cable cut on the LCD display besides of and sending out the location of the cable break to the authority mobile phone wirelessly via SMS.

In-band-pumped Ho:KLu(WO4)2 microchip laser with 84% slope efficiency.

PubMed

Loiko, Pavel; Serres, Josep Maria; Mateos, Xavier; Yumashev, Konstantin; Kuleshov, Nikolai; Petrov, Valentin; Griebner, Uwe; Aguiló, Magdalena; Díaz, Francesc

2015-02-01

We report on a continuous-wave Ho:KLu(WO4)2 (KLuW) microchip laser with a record slope efficiency of 84%, the highest value among the holmium inband-pumped lasers, delivering 201 mW output power at 2105 nm. The Ho laser operating at room temperature on the (5)I8→(5)I7 transition is in-band-pumped by a diode-pumped Tm:KLuW microchip laser at 1946 nm. Ho:KLuW laser operation at 2061 and 2079 nm is also demonstrated with a maximum slope efficiency of 79%. The microchip laser generates an almost diffraction-limited output beam with a Gaussian profile and a M2<1.1. The laser performance of the Ng-cut Ho:KLuW crystal is very similar for pump light polarizations ‖Nm and Np. The positive thermal lens plays a key role in the laser mode stabilization and proper mode-matching. The latter, together with the low quantum defect under in-band-pumping (∼0.08), is responsible for the extraordinary high slope efficiency.

Multi-watt passively Q-switched Yb:YAB/Cr:YAG microchip lasers

NASA Astrophysics Data System (ADS)

Serres, Josep Maria; Loiko, Pavel; Mateos, Xavier; Liu, Junhai; Zhang, Huaijing; Yumashev, Konstantin; Griebner, Uwe; Petrov, Valentin; Aguiló, Magdalena; Díaz, Francesc

2017-02-01

A trigonal 5.6 at.% Yb:YAl3(BO3)4 (Yb:YAB) crystal is employed in continuous-wave (CW) and passively Q-switched microchip lasers pumped by a diode at 978 nm. Using a 3 mm-thick, c-cut Yb:YAB crystal, which has a higher pump absorption efficiency, efficient CW microchip laser operation is demonstrated. This laser generated a maximum output power of 7.18 W at 1041-1044 nm with a slope efficiency η of 67% (with respect to the absorbed pump power) and an almost diffraction-limited beam, M2 x,y < 1.1. Inserting a Cr:YAG saturable absorber, stable passive Q-switching of the Yb:YAB microchip laser was obtained. The maximum average output power from the Yb:YAB/Cr:YAG laser reached 2.82 W at 1042 nm with η = 53% and a conversion efficiency with respect to the CW mode of 65% (when using a 0.7 mm-thick Cr:YAG). The latter corresponded to a pulse duration and energy of 7.1 ns / 47 μJ at a pulse repetition rate (PRR) of 60 kHz. Using a 1.3 mm-thick Cr:YAG, 2.02 W were achieved at 1041 nm corresponding to η = 38%. The pulse characteristics were 4.9 ns / 83 μJ at PRR = 24.3 kHz and the maximum peak power reached 17 kW. Yb:YAB crystals are very promising for compact sub-ns power-scalable microchip lasers.

Investigation of the mixing efficiency of a chaotic micromixer using thermal lens spectrometry.

PubMed

Ghaleb, Khalil Abbas; Stephan, Khaled; Pittet, Patrick; Ferrigno, Rosaria; Georges, Joseph

2006-05-01

This work investigates the efficiency of a chaotic micromixer using thermal lens spectrometry. The outlet of the mixing device was connected to a thermal lens detection head integrating the probe beam optical fibers and the sample capillary. The chaotic micromixer consisted of a Y-shaped poly(dimethylsiloxane) (PDMS) microchip in which ribbed herringbone microstructures were etched on the floor of the main channel. Due to the solvent composition dependence of the thermal lens response, the photothermal method was shown to be highly sensitive to nonhomogeneous mixing compared to fluorescence detection. The apparatus was applied to the determination of Fe2+ with 1,10-phenanthroline using flow injection analysis; a limit of detection of 11 microg L(-1) of iron was obtained.

Capillary electrophoresis-electrochemistry microfluidic system for the determination of organic peroxides

NASA Technical Reports Server (NTRS)

Wang, Joseph; Escarpa, Alberto; Pumera, Martin; Feldman, Jason; Svehla, D. (Principal Investigator)

2002-01-01

A microfluidic analytical system for the separation and detection of organic peroxides, based on a microchip capillary electrophoresis device with an integrated amperometric detector, was developed. The new microsystem relies on the reductive detection of both organic acid peroxides and hydroperoxides at -700 mV (vs. Ag wire/AgCl). Factors influencing the separation and detection processes were examined and optimized. The integrated microsystem offers rapid measurements (within 130 s) of these organic-peroxide compounds, down to micromolar levels. A highly stable response for repetitive injections (RSD 0.35-3.12%; n = 12) reflects the negligible electrode passivation. Such a "lab-on-a-chip" device should be attractive for on-site analysis of organic peroxides, as desired for environmental screening and industrial monitoring.

Recent advances in chemiluminescence detection coupled with capillary electrophoresis and microchip capillary electrophoresis.

PubMed

Liu, Yuxuan; Huang, Xiangyi; Ren, Jicun

2016-01-01

CE is an ideal analytical method for extremely volume-limited biological microenvironments. However, the small injection volume makes it a challenge to achieve highly sensitive detection. Chemiluminescence (CL) detection is characterized by providing low background with excellent sensitivity because of requiring no light source. The coupling of CL with CE and MCE has become a powerful analytical method. So far, this method has been widely applied to chemical analysis, bioassay, drug analysis, and environment analysis. In this review, we first introduce some developments for CE-CL and MCE-CL systems, and then put the emphasis on the applications in the last 10 years. Finally, we discuss the future prospects. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A dipole-assisted solid-phase extraction microchip combined with inductively coupled plasma-mass spectrometry for online determination of trace heavy metals in natural water.

PubMed

Shih, Tsung-Ting; Hsu, I-Hsiang; Chen, Shun-Niang; Chen, Ping-Hung; Deng, Ming-Jay; Chen, Yu; Lin, Yang-Wei; Sun, Yuh-Chang

2015-01-21

We employed a polymeric material, poly(methyl methacrylate) (PMMA), for fabricating a microdevice and then implanted the chlorine (Cl)-containing solid-phase extraction (SPE) functionality into the PMMA chip to develop an innovative on-chip dipole-assisted SPE technique. Instead of the ion-ion interactions utilized in on-chip SPE techniques, the dipole-ion interactions between the highly electronegative C-Cl moieties in the channel interior and the positively charged metal ions were employed to facilitate the on-chip SPE procedures. Furthermore, to avoid labor-intensive manual manipulation, a programmable valve manifold was designed as an interface combining the dipole-assisted SPE microchip and inductively coupled plasma-mass spectrometry (ICP-MS) to achieve the fully automated operation. Under the optimized operation conditions for the established system, the detection limits for each analyte ion were obtained based on three times the standard deviation of seven measurements of the blank eluent solution. The limits ranged from 3.48 to 20.68 ng L(-1), suggesting that this technique appears uniquely suited for determining the levels of heavy metal ions in natural water. Indeed, a series of validation procedures demonstrated that the developed method could be satisfactorily applied to the determination of trace heavy metals in natural water. Remarkably, the developed device was durable enough to be reused more than 160 times without any loss in its analytical performance. To the best of our knowledge, this is the first study reporting on the combination of a dipole-assisted SPE microchip and elemental analysis instrument for the online determination of trace heavy metal ions.

Optofluidic encapsulation and manipulation of silicon microchips using image processing based optofluidic maskless lithography and railed microfluidics.

PubMed

Chung, Su Eun; Lee, Seung Ah; Kim, Jiyun; Kwon, Sunghoon

2009-10-07

We demonstrate optofluidic encapsulation of silicon microchips using image processing based optofluidic maskless lithography and manipulation using railed microfluidics. Optofluidic maskless lithography is a dynamic photopolymerization technique of free-floating microstructures within a fluidic channel using spatial light modulator. Using optofluidic maskless lithography via computer-vision aided image processing, polymer encapsulants are fabricated for chip protection and guiding-fins for efficient chip conveying within a fluidic channel. Encapsulated silicon chips with guiding-fins are assembled using railed microfluidics, which is an efficient guiding and heterogeneous self-assembly system of microcomponents. With our technology, externally fabricated silicon microchips are encapsulated, fluidically guided and self-assembled potentially enabling low cost fluidic manipulation and assembly of integrated circuits.

Recent advances in enhancing the sensitivity of electrophoresis and electrochromatography in capillaries and microchips (2014-2016).

PubMed

Breadmore, Michael C; Wuethrich, Alain; Li, Feng; Phung, Sui Ching; Kalsoom, Umme; Cabot, Joan M; Tehranirokh, Masoomeh; Shallan, Aliaa I; Abdul Keyon, Aemi S; See, Hong Heng; Dawod, Mohamed; Quirino, Joselito P

2017-01-01

One of the most cited limitations of capillary (and microchip) electrophoresis is the poor sensitivity. This review continues to update this series of biennial reviews, first published in Electrophoresis in 2007, on developments in the field of on-line/in-line concentration methods in capillaries and microchips, covering the period July 2014-June 2016. It includes developments in the field of stacking, covering all methods from field amplified sample stacking and large volume sample stacking, through to isotachophoresis, dynamic pH junction, and sweeping. Attention is also given to on-line or in-line extraction methods that have been used for electrophoresis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High-efficiency microchip laser with self-injection seeding.

PubMed

Wang, Sha; Wang, Yan-biao; Yang, Xian-heng; Feng, Guo-ying; Zhou, Shou-huan

2015-12-10

In this paper, we use a small bandwidth 808 nm cw Ti:sapphire laser as a pump source to pump a picosecond microchip laser. Different focal length pump focus lenses have been tested to improve laser efficiency. A maximum slope efficiency of around 20% is obtained by a 30 mm focal length lens. The pump threshold is only 13 mW. In order to reduce the timing jitter, we explored the self-injection seeding method by adding a seeding cavity to the microchip laser. A reduction factor in the timing jitter of up to a factor of 23 relative to the unseeded laser is obtained. From the experiments, we also found that higher seeding pulse energy will help to reduce the jitter more.

High-pulse-energy passively Q-switched quasi-monolithic microchip lasers operating in the sub-100-ps pulse regime.

PubMed

Nodop, D; Limpert, J; Hohmuth, R; Richter, W; Guina, M; Tünnermann, A

2007-08-01

We present passively Q-switched microchip lasers with items bonded by spin-on-glass glue. Passive Q-switching is obtained by a semiconductor saturable absorber mirror. The laser medium is a Nd:YVO(4) crystal. These lasers generate pulse peak powers up to 20 kW at a pulse duration as short as 50 ps and pulse repetition rates of 166 kHz. At 1064 nm, a linear polarized transversal and longitudinal single-mode beam is emitted. To the best of our knowledge, these are the shortest pulses in the 1 microJ energy range ever obtained with passively Q-switched microchip lasers. The quasi-monolithic setup ensures stable and reliable performance.

A Monolithic Multisensor Microchip with Complete On-Chip RF Front-End

PubMed Central

Felini, Corrado; Della Corte, Francesco G.

2018-01-01

In this paper, a new wireless sensor, designed for a 0.35 µm CMOS technology, is presented. The microchip was designed to be placed on an object for the continuous remote monitoring of its temperature and illumination state. The temperature sensor is based on the temperature dependence of the I-V characteristics of bipolar transistors available in CMOS technology, while the illumination sensor is an integrated p-n junction photodiode. An on-chip 2.5 GHz transmitter, coupled to a mm-sized dipole radiating element fabricated on the same microchip and made in the top metal layer of the same die, sends the collected data wirelessly to a radio receiver using an On-Off Keying (OOK) modulation pattern. PMID:29301297

Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes.

PubMed

Fredlake, Christopher P; Hert, Daniel G; Kan, Cheuk-Wai; Chiesl, Thomas N; Root, Brian E; Forster, Ryan E; Barron, Annelise E

2008-01-15

To realize the immense potential of large-scale genomic sequencing after the completion of the second human genome (Venter's), the costs for the complete sequencing of additional genomes must be dramatically reduced. Among the technologies being developed to reduce sequencing costs, microchip electrophoresis is the only new technology ready to produce the long reads most suitable for the de novo sequencing and assembly of large and complex genomes. Compared with the current paradigm of capillary electrophoresis, microchip systems promise to reduce sequencing costs dramatically by increasing throughput, reducing reagent consumption, and integrating the many steps of the sequencing pipeline onto a single platform. Although capillary-based systems require approximately 70 min to deliver approximately 650 bases of contiguous sequence, we report sequencing up to 600 bases in just 6.5 min by microchip electrophoresis with a unique polymer matrix/adsorbed polymer wall coating combination. This represents a two-thirds reduction in sequencing time over any previously published chip sequencing result, with comparable read length and sequence quality. We hypothesize that these ultrafast long reads on chips can be achieved because the combined polymer system engenders a recently discovered "hybrid" mechanism of DNA electromigration, in which DNA molecules alternate rapidly between repeating through the intact polymer network and disrupting network entanglements to drag polymers through the solution, similar to dsDNA dynamics we observe in single-molecule DNA imaging studies. Most importantly, these results reveal the surprisingly powerful ability of microchip electrophoresis to provide ultrafast Sanger sequencing, which will translate to increased system throughput and reduced costs.

Ultrafast DNA sequencing on a microchip by a hybrid separation mechanism that gives 600 bases in 6.5 minutes

PubMed Central

Fredlake, Christopher P.; Hert, Daniel G.; Kan, Cheuk-Wai; Chiesl, Thomas N.; Root, Brian E.; Forster, Ryan E.; Barron, Annelise E.

2008-01-01

To realize the immense potential of large-scale genomic sequencing after the completion of the second human genome (Venter's), the costs for the complete sequencing of additional genomes must be dramatically reduced. Among the technologies being developed to reduce sequencing costs, microchip electrophoresis is the only new technology ready to produce the long reads most suitable for the de novo sequencing and assembly of large and complex genomes. Compared with the current paradigm of capillary electrophoresis, microchip systems promise to reduce sequencing costs dramatically by increasing throughput, reducing reagent consumption, and integrating the many steps of the sequencing pipeline onto a single platform. Although capillary-based systems require ≈70 min to deliver ≈650 bases of contiguous sequence, we report sequencing up to 600 bases in just 6.5 min by microchip electrophoresis with a unique polymer matrix/adsorbed polymer wall coating combination. This represents a two-thirds reduction in sequencing time over any previously published chip sequencing result, with comparable read length and sequence quality. We hypothesize that these ultrafast long reads on chips can be achieved because the combined polymer system engenders a recently discovered “hybrid” mechanism of DNA electromigration, in which DNA molecules alternate rapidly between reptating through the intact polymer network and disrupting network entanglements to drag polymers through the solution, similar to dsDNA dynamics we observe in single-molecule DNA imaging studies. Most importantly, these results reveal the surprisingly powerful ability of microchip electrophoresis to provide ultrafast Sanger sequencing, which will translate to increased system throughput and reduced costs. PMID:18184818

High-efficient Nd:YAG microchip laser for optical surface scanning

NASA Astrophysics Data System (ADS)

Šulc, Jan; Jelínková, Helena; Nejezchleb, Karel; Škoda, Václav

2017-12-01

A CW operating, compact, high-power, high-efficient diode pumped 1064nm laser, based on Nd:YAG active medium, was developed for optical surface scanning and mapping applications. To enhance the output beam quality, laser stability, and compactness, a microchip configuration was used. In this arrangement the resonator mirrors were deposited directly on to the laser crystal faces. The Nd-doping concentration was 1 at.% Nd/Y. The Nd:YAG crystal was 5mm long. The laser resonator without pumping radiation recuperation was investigated {the output coupler was transparent for pumping radiation. For the generated laser radiation the output coupler reflectivity was 95%@1064 nm. The diameter of the samples was 5 mm. For the laser pumping two arrangements were investigated. Firstly, a fibre coupled laser diode operating at wavelength 808nm was used in CW mode. The 400 ¹m fiber was delivering up to 14W of pump power amplitude to the microchip laser. The maximum CW output power of 7.2W @ 1064nm in close to TEM00 beam was obtained for incident pumping power 13.7W @ 808 nm. The differential efficiency in respect to the incident pump power reached 56 %. Secondly, a single-emitter, 1W laser diode operating at 808nm was used for Nd:YAG microchip pumping. The laser pumping was directly coupled into the microchip laser using free-space lens optics. Slope efficiency up to 70% was obtained in stable, high-quality, 1064nm laser beam with CW power up to 350mW. The system was successfully used for scanning of super-Gaussian laser mirrors reflectivity profile.

A comprehensive study of a new versatile microchip device based liquid phase microextraction for stopped-flow and double-flow conditions.

PubMed

Payán, María Ramos; Murillo, Elia Santigosa; Coello, Jordi; López, Miguel Ángel Bello

2018-06-29

A new geometry for a versatile microfluidic-chip device based liquid phase microextraction was developed in order to enhance the preconcentration in microfluidic chips and also to enable double-flow and stopped-flow working modes. The microchip device was combined with a HPLC procedure for the simultaneous determination of two different families as model analytes, which were parabens and non-steroidal anti-inflammatories (NSAIDs): Ethyl 4-hydroxybenzoate (Et-P), Propyl 4-hydroxybenzoate (Pr-P), Butyl 4-hydroxybenzoate (Bu-P), IsoButyl 4-hydroxybenzoate (iBu-P), salycilic acid (SAC), ketoprofen (KET), naproxen (NAX), diclofenac (DIC) and ibuprofen (IBU) in urine samples. The new miniaturized microchip proposed in this work allows not only the possibility of working in double-flow conditions, but also under stagnant conditions (stopped-flow) (SF-μLPME). The sample (pH 1.5) was delivered to the SF-μLPME at 20 μL min -1 while keeping the acceptor phase (pH 11.75) under stagnant conditions during 20 min. The highest enrichment factors (between 16 and 47) were obtained under stopped-flow conditions at 20 μL min -1 (sample flow rate) after 20 min extraction; whereas the extraction efficiencies were within the range of 27-81% for all compounds. The procedure provided very low detection limits between 0.7 and 8.5 μg L -1 with a sample volume consumption of 400 μL. Parabens and NSAIDs have successfully been extracted from urine samples with excellent clean up and recoveries over 90% for all compounds. In parallel, the new device was also tested under double flow conditions, obtaining good but lower enrichment factors (between 9 and 20) and higher extraction efficiencies (between 45 and 95) after 7 min extraction, consuming a volume sample of 140 μL. The versatile device offered very high extraction efficiencies and good enrichment factor for double flow and stopped-flow conditions, respectively. In addition, this new miniaturized SF-μLPME device significantly reduced costs compared to the existing analytical techniques for sample preparation since this microchip require few microliters of sample and reagents and it is reusable. Copyright © 2018 Elsevier B.V. All rights reserved.

Material transport method and apparatus

DOEpatents

Ramsey, J. Michael; Ramsey, Roswitha S.

2000-01-01

An electrospray apparatus uses a microchannel formed in a microchip. Fluid is pumped through the channel to an outlet orifice using either hydraulic or electrokinetic means. An electrospray is generated by establishing a sufficient potential difference between the fluid at the outlet orifice and a target electrode spaced from the outlet orifice. Electrokinetic pumping is also utilized to provide additional benefits to microchip devices.

Material transport method and apparatus

DOEpatents

Ramsey, J. Michael; Ramsey, Roswitha S.

2001-01-01

An electrospray apparatus uses a microchannel formed in a microchip. Fluid is pumped through the channel to an outlet orifice using either hydraulic or electrokinetic means. An electrospray is generated by establishing a sufficient potential difference between the fluid at the outlet orifice and a target electrode spaced from the outlet orifice. Electrokinetic pumping is also utilized to provide additional benefits to microchip devices.

From Bonding Wires to Banding Women. Proceedings of the International Consultation on Micro-Chips Technology (Manila, Philippines, October 1986).

ERIC Educational Resources Information Center

Center for Women's Resources, Quezon City (Philippines).

In October 1986, 40 women from 12 countries gathered in the Philippines for a 10-day meeting of organizers, educators, and workers affected by and confronting the international electronics industry in microchip plants and in automated offices. Participants were from Malaysia, Indonesia, Thailand, the Philippines, Hong Kong, Japan, the Netherlands,…

Particle-free microchip processing

DOEpatents

Geller, Anthony S.; Rader, Daniel J.

1996-01-01

Method and apparatus for reducing particulate contamination in microchip processing are disclosed. The method and apparatus comprise means to reduce particle velocity toward the wafer before the particles can be deposited on the wafer surface. A reactor using electric fields to reduce particle velocity and prevent particulate contamination is disclosed. A reactor using a porous showerhead to reduce particle velocities and prevent particulate contamination is disclosed.

Single-frequency Ince-Gaussian mode operations of laser-diode-pumped microchip solid-state lasers.

PubMed

Ohtomo, Takayuki; Kamikariya, Koji; Otsuka, Kenju; Chu, Shu-Chun

2007-08-20

Various single-frequency Ince-Gaussian mode oscillations have been achieved in laser-diode-pumped microchip solid-state lasers, including LiNdP(4)O(12) (LNP) and Nd:GdVO(4), by adjusting the azimuthal symmetry of the short laser resonator. Ince-Gaussian modes formed by astigmatic pumping have been reproduced by numerical simulation.

Microfluidic LC Device with Orthogonal Sample Extraction for On-Chip MALDI-MS Detection

PubMed Central

Lazar, Iulia M.; Kabulski, Jarod L.

2013-01-01

A microfluidic device that enables on-chip matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) detection for liquid chromatography (LC) separations is described. The device comprises an array of functional elements to carry out LC separations, integrates a novel microchip-MS interface to facilitate the orthogonal transposition of the microfluidic LC channel into an array of reservoirs, and enables sensitive MALDI-MS detection directly from the chip. Essentially, the device provides a snapshot MALDI-MS map of the content of the separation channel present on the chip. The detection of proteins with biomarker potential from MCF10A breast epithelial cell extracts, and detection limits in the low fmol range, are demonstrated. In addition, the design of the novel LC-MALDI-MS chip entices the promotion of a new concept for performing sample separations within the limited time-frame that accompanies the dead-volume of a separation channel. PMID:23592150

Multiplexed Western Blotting Using Microchip Electrophoresis.

PubMed

Jin, Shi; Furtaw, Michael D; Chen, Huaxian; Lamb, Don T; Ferguson, Stephen A; Arvin, Natalie E; Dawod, Mohamed; Kennedy, Robert T

2016-07-05

Western blotting is a commonly used protein assay that combines the selectivity of electrophoretic separation and immunoassay. The technique is limited by long time, manual operation with mediocre reproducibility, and large sample consumption, typically 10-20 μg per assay. Western blots are also usually used to measure only one protein per assay with an additional housekeeping protein for normalization. Measurement of multiple proteins is possible; however, it requires stripping membranes of antibody and then reprobing with a second antibody. Miniaturized alternatives to Western blot based on microfluidic or capillary electrophoresis have been developed that enable higher-throughput, automation, and greater mass sensitivity. In one approach, proteins are separated by electrophoresis on a microchip that is dragged along a polyvinylidene fluoride membrane so that as proteins exit the chip they are captured on the membrane for immunoassay. In this work, we improve this method to allow multiplexed protein detection. Multiple injections made from the same sample can be deposited in separate tracks so that each is probed with a different antibody. To further enhance multiplexing capability, the electrophoresis channel dimensions were optimized for resolution while keeping separation and blotting times to less than 8 min. Using a 15 μm deep × 50 μm wide × 8.6 cm long channel, it is possible to achieve baseline resolution of proteins that differ by 5% in molecular weight, e.g., ERK1 (44 kDa) from ERK2 (42 kDa). This resolution allows similar proteins detected by cross-reactive antibodies in a single track. We demonstrate detection of 11 proteins from 9 injections from a single Jurkat cell lysate sample consisting of 400 ng of total protein using this procedure. Thus, multiplexed Western blots are possible without cumbersome stripping and reprobing steps.

[Studies on a sequential injection renewable surface reflectance spectrophotometric system using a microchip flow cell].

PubMed

Wang, Jian-ya; Fang, Zhao-lun

2002-02-01

A microchip flow cell was developed for flow injection renewable surface assay by reflectance spectrophotometry. The flow cell was coupled to a sequential injection system and optical fiber photometric detection system. The flow cell featured a three-layer structure. The flow channel was cut into a silicone rubber membrance which formed the middle layer, and a porous filter was inlayed across a widened section of the channel to trap microbeads introduced into the flow cell. The area of the detection window of the flow cell was approximately 3.6 mm2, the volume of the bead trapped in the flow cell was 2.2 microL, the depth of the bead layer was 600 microns. A multistrand bifurcated optical fiber was coupled with incident light, detector and flow cell. The chromogenic reaction of Cr(VI) with 1,5-diphenylcarbohydrazide (DPC) which was adsorbed on trapped Polysorb C-18 beads was used as a model reaction to optimize the flow cell design and the experimental system. The reflectance of the renewable reaction surface was monitored at 540 nm. With 100 microL sample loaded and 1.0 mL.min-1 carrier flow rate, the linear response range was 0-0.6 microgram.mL-1 Cr(VI). A detection limit (3 sigma) of 6 ng.mL-1, precision of 1.5% RSD(n = 11), and a throughput of 64 samples per hour were achieved. Considerations in system and flow cell design, the influence of depth of the bead layer, weight of beads used, and the flow rates of carrier stream on the performance were discussed.

Integrated optical-fiber capillary electrophoresis microchips with novel spin-on-glass surface modification.

PubMed

Lin, Che-Hsin; Lee, Gwo-Bin; Fu, Lung-Ming; Chen, Shu-Hui

2004-07-30

This paper presents a novel micro-capillary electrophoresis (CE) chip with embedded optical fibers for the on-line detection of DNA samples. The optical fibers are pre-etched and then inserted directly into fiber channels incorporated within low-cost soda-lime glass substrates. The embedded optical fibers are precisely aligned with the microfluidic channels such that the induced fluorescence signals from labeled bio-samples can be detected. This arrangement avoids the requirement for delicate optical alignment procedures and equipment. Surface modification of the CE channels is accomplished by means of a simple and reliable organic-based spin-on-glass (SOG) method. The zeta potential distribution and the corresponding electroosmotic mobility of the fluid are simulated numerically for the modified and non-modified channel surfaces, and then both sets of results are verified experimentally. The present results indicate that the value of the zeta potential for a surface with an SOG coating is 19.3 times smaller than that of an untreated surface. A phiX-174 DNA marker fluid is used to evaluate the injection and separation performance of the developed micro-CE device. Furthermore, the long-term stability of the SOG-coated surface is also investigated. The experimental data reveal that the microchip device is capable of providing highly efficient separations of bio-molecules, and that the SOG layer retains its low zeta potential characteristics for at least 45 days. The present results confirm the effectiveness of the proposed micro-CE chip in performing the on-line detection of DNA samples, and indicate that the SOG process represents a simple and reliable solution for the surface modification of glass-based microchannels.

Electrokinetic gated injection-based microfluidic system for quantitative analysis of hydrogen peroxide in individual HepG2 cells.

PubMed

Zhang, Xinyuan; Li, Qingling; Chen, Zhenzhen; Li, Hongmin; Xu, Kehua; Zhang, Lisheng; Tang, Bo

2011-03-21

A microfluidic system to determine hydrogen peroxide (H(2)O(2)) in individual HepG2 cells based on the electrokinetic gated injection was developed for the first time. A home-synthesized fluorescent probe, bis(p-methylbenzenesulfonate)dichlorofluorescein (FS), was employed to label intracellular H(2)O(2) in the intact cells. On a simple cross microchip, multiple single-cell operations, including single cell injection, cytolysis, electrophoresis separation and detection of H(2)O(2), were automatically carried out within 60 s using the electrokinetic gated injection and laser-induced fluorescence detection (LIFD). The performance of the method was evaluated under the optimal conditions. The linear calibration curve was over a range of 4.39-610 amol (R(2)=0.9994). The detection limit was 0.55 amol or 9.0×10(-10) M (S/N=3). The relative standard deviations (RSDs, n=6) of migration time and peak area were 1.4% and 4.8%, respectively. With the use of this method, the average content of H(2)O(2) in single HepG2 cells was found to be 16.09±9.84 amol (n=15). Separation efficiencies in excess of 17,000 theoretical plates for the cells were achieved. These results demonstrated that the efficient integration and automation of these single-cell operations enabled the sensitive, reproducible, and quantitative examination of intracellular H(2)O(2) at single-cell level. Owing to the advantages of simple microchip structure, controllable single-cell manipulation and ease in building, this platform provides a universal way to automatically determine other intracellular constituents within single cells. This journal is © The Royal Society of Chemistry 2011

Simultaneous determination of superoxide and hydrogen peroxide in macrophage RAW 264.7 cell extracts by microchip electrophoresis with laser-induced fluorescence detection.

PubMed

Li, Hongmin; Li, Qingling; Wang, Xu; Xu, Kehua; Chen, Zhenzhen; Gong, Xiaocong; Liu, Xin; Tong, Lili; Tang, Bo

2009-03-15

A method for the first time to simultaneously determine superoxide and hydrogen peroxide in macrophage RAW 264.7 cell extracts by microchip electrophoresis with laser-induced fluorescence detection (MCE-LIF) was developed. 2-Chloro-1,3-dibenzothiazolinecyclohexene (DBZTC) and bis(p-methylbenzenesulfonyl) dichlorofluorescein (FS), two probes that can be specifically derivatized by superoxide and hydrogen peroxide, respectively, were synthesized and used. Parameters influencing the derivatization and on-chip separation were optimized. With the use of a HEPES (20 mM, pH 7.4) running buffer, a 50 mm long separation channel, and a separation voltage of 1800 V, baseline separation was achieved within 48 s for the two derivatization products, DBZTC-oxide (DBO) and 2,7-dichlorofluorescein (DCF). The linearity ranges of the method were 0.08-5.0 and 0.02-5.0 microM with detection limits (signal-to-noise ratio = 3) of 10 nM (1.36 amol) and 5.6 nM (0.76 amol) for superoxide and hydrogen peroxide, respectively. The relative standard deviations (RSDs) of migration time and peak area were less than 2.0% and 5.0%, respectively. The recoveries of the cell extract samples spiked with 1.0 microM standard solutions were 96.1% and 93.0% for superoxide and hydrogen peroxide, respectively. With the use of this method, superoxide and hydrogen peroxide in phorbol myristate acetate (PMA)-stimulated macrophage RAW 264.7 cell extracts were found to be 0.78 and 1.14 microM, respectively. The method has paved a way for simultaneously determining two or more reactive oxygen species (ROS) in a biological system with high resolution.

Sub-5-ps, multimegawatt peak-power pulses from a fiber-amplified and optically compressed passively Q-switched microchip laser.

PubMed

Steinmetz, A; Jansen, F; Stutzki, F; Lehneis, R; Limpert, J; Tünnermann, A

2012-07-01

We report on high-energy picosecond pulse generation from a passively Q-switched and fiber-amplified microchip laser system. Initially, the utilized microchip lasers produce pulses with durations of around 100 ps at 1064 nm central wavelength. These pulses are amplified to energies exceeding 100 μJ, simultaneously chirped and spectrally broadened by self-phase modulation using a double stage amplifier based on single-mode LMA photonic crystal fibers at repetition rates of up to 1 MHz. Subsequently, the pulse duration of chirped pulses is reduced by means of nonlinear pulse compression to durations of 2.7 ps employing a conventional grating compressor and 4.7 ps using a compact compressor based on a chirped volume Bragg grating.

Laser characteristics at 1535 nm and thermal effects of an Er:Yb phosphate glass microchip pumped by Ti:sapphire laser

NASA Astrophysics Data System (ADS)

Cai, Zhiping; Chardon, Alain; Xu, Huiying; Féron, Patrice; Michel Stéphan, Guy

2002-03-01

An Er:Yb codoped phosphate glass microchip laser has been studied under pumping with a Ti:sapphire laser ranging from 945 to 990 nm. The characteristics (threshold, slope efficiency) are first described for an optimized laser. The gain spectrum is calculated for the transition 4I13/2→ 4I15/2 around 1535 nm from fundamental spectroscopic data and from experimental results. Red-shift effect on the frequency of a single mode is experimentally observed when the pump power is increased, originating from thermal effects. Temperature inside the microchip cavity and thermal expansion coefficient were determined by employing the intensity ratio of two green upconversion emission line centered at 530 and 554 nm, respectively, which quantitatively explain this red shift.

Ultrasensitive microchip based on smart microgel for real-time online detection of trace threat analytes.

PubMed

Lin, Shuo; Wang, Wei; Ju, Xiao-Jie; Xie, Rui; Liu, Zhuang; Yu, Hai-Rong; Zhang, Chuan; Chu, Liang-Yin

2016-02-23

Real-time online detection of trace threat analytes is critical for global sustainability, whereas the key challenge is how to efficiently convert and amplify analyte signals into simple readouts. Here we report an ultrasensitive microfluidic platform incorporated with smart microgel for real-time online detection of trace threat analytes. The microgel can swell responding to specific stimulus in flowing solution, resulting in efficient conversion of the stimulus signal into significantly amplified signal of flow-rate change; thus highly sensitive, fast, and selective detection can be achieved. We demonstrate this by incorporating ion-recognizable microgel for detecting trace Pb(2+), and connecting our platform with pipelines of tap water and wastewater for real-time online Pb(2+) detection to achieve timely pollution warning and terminating. This work provides a generalizable platform for incorporating myriad stimuli-responsive microgels to achieve ever-better performance for real-time online detection of various trace threat molecules, and may expand the scope of applications of detection techniques.

A scalable correlator for multichannel diffuse correlation spectroscopy.

PubMed

Stapels, Christopher J; Kolodziejski, Noah J; McAdams, Daniel; Podolsky, Matthew J; Fernandez, Daniel E; Farkas, Dana; Christian, James F

2016-02-01

Diffuse correlation spectroscopy (DCS) is a technique which enables powerful and robust non-invasive optical studies of tissue micro-circulation and vascular blood flow. The technique amounts to autocorrelation analysis of coherent photons after their migration through moving scatterers and subsequent collection by single-mode optical fibers. A primary cost driver of DCS instruments are the commercial hardware-based correlators, limiting the proliferation of multi-channel instruments for validation of perfusion analysis as a clinical diagnostic metric. We present the development of a low-cost scalable correlator enabled by microchip-based time-tagging, and a software-based multi-tau data analysis method. We will discuss the capabilities of the instrument as well as the implementation and validation of 2- and 8-channel systems built for live animal and pre-clinical settings.

Low power integrated pumping and valving arrays for microfluidic systems

DOEpatents

Krulevitch, Peter A [Pleasanton, CA; Benett, William J [Livermore, CA; Rose, Klint A [Livermore, CA; Hamilton, Julie [Tracy, CA; Maghribi, Mariam [Davis, CA

2006-04-11

Low power integrated pumping and valving arrays which provide a revolutionary approach for performing pumping and valving approach for performing pumping and valving operations in microfabricated fluidic systems for applications such as medical diagnostic microchips. Traditional methods rely on external, large pressure sources that defeat the advantages of miniaturization. Previously demonstrated microfabrication devices are power and voltage intensive, only function at sufficient pressure to be broadly applicable. This approach integrates a lower power, high-pressure source with a polymer, ceramic, or metal plug enclosed within a microchannel, analogous to a microsyringe. When the pressure source is activated, the polymer plug slides within the microchannel, pumping the fluid on the opposite side of the plug without allowing fluid to leak around the plug. The plugs also can serve as microvalves.

Recent approaches for enhancing sensitivity in enantioseparations by CE.

PubMed

Sánchez-Hernández, Laura; García-Ruiz, Carmen; Luisa Marina, María; Luis Crego, Antonio

2010-01-01

This article reviews the latest methodological and instrumental improvements for enhancing sensitivity in chiral analysis by CE. The review covers literature from March 2007 until May 2009, that is, the works published after the appearance of the latest review article on the same topic by Sánchez-Hernández et al. [Electrophoresis 2008, 29, 237-251]. Off-line and on-line sample treatment techniques, on-line sample preconcentration strategies based on electrophoretic and chromatographic principles, and alternative detection systems to the widely employed UV/Vis detection in CE are the most relevant approaches discussed for improving sensitivity. Microchip technologies are also included since they can open up great possibilities to achieve sensitive and fast enantiomeric separations.

MACRO: a combined microchip-PCR and microarray system for high-throughput monitoring of genetically modified organisms.

PubMed

Shao, Ning; Jiang, Shi-Meng; Zhang, Miao; Wang, Jing; Guo, Shu-Juan; Li, Yang; Jiang, He-Wei; Liu, Cheng-Xi; Zhang, Da-Bing; Yang, Li-Tao; Tao, Sheng-Ce

2014-01-21

The monitoring of genetically modified organisms (GMOs) is a primary step of GMO regulation. However, there is presently a lack of effective and high-throughput methodologies for specifically and sensitively monitoring most of the commercialized GMOs. Herein, we developed a multiplex amplification on a chip with readout on an oligo microarray (MACRO) system specifically for convenient GMO monitoring. This system is composed of a microchip for multiplex amplification and an oligo microarray for the readout of multiple amplicons, containing a total of 91 targets (18 universal elements, 20 exogenous genes, 45 events, and 8 endogenous reference genes) that covers 97.1% of all GM events that have been commercialized up to 2012. We demonstrate that the specificity of MACRO is ~100%, with a limit of detection (LOD) that is suitable for real-world applications. Moreover, the results obtained of simulated complex samples and blind samples with MACRO were 100% consistent with expectations and the results of independently performed real-time PCRs, respectively. Thus, we believe MACRO is the first system that can be applied for effectively monitoring the majority of the commercialized GMOs in a single test.

Electrophoretic separations in poly(dimethylsiloxane) microchips using a mixture of ionic and zwitterionic surfactants

PubMed Central

Guan, Qian; Noblitt, Scott D.; Henry, Charles S.

2012-01-01

The use of mixtures of ionic and zwitterionic surfactants in poly(dimethylsiloxane) (PDMS) microchips is reported. The effect of surfactant concentration on EOF was studied for a single anionic surfactant (sodium dodecyl sulfate, SDS), a single zwitterionic surfactant (N-tetradecylammonium-N,N-dimethyl-3-ammonio-1-propanesulfonate, TDAPS), and a mixed SDS/TDAPS surfactant system. SDS increased the EOF as reported previously while TDAPS showed an initial increase in EOF followed by a reduction at higher concentrations. When TDAPS was added to a solution containing SDS, the EOF decreased in a concentration dependent manner. The EOF for all three surfactant systems followed expected pH trends, with increasing EOF at higher pH. The mixed surfactant system allowed tuning of the EOF across a range of pH and concentration conditions. After establishing the EOF behavior, the adsorption/desorption kinetics were measured and showed a slower adsorption/desorption rate for TDAPS than SDS. Finally, the separation and electrochemical detection of model catecholamines in buffer and reduced glutathione (GSH) in red blood cell lysate using the mixed surfactant system were explored. The mixed surfactant system provided shorter analysis times and/or improved resolution when compared to the single surfactant systems. PMID:22222982

Particle-free microchip processing

DOEpatents

Geller, A.S.; Rader, D.J.

1996-06-04

Method and apparatus for reducing particulate contamination in microchip processing are disclosed. The method and apparatus comprise means to reduce particle velocity toward the wafer before the particles can be deposited on the wafer surface. A reactor using electric fields to reduce particle velocity and prevent particulate contamination is disclosed. A reactor using a porous showerhead to reduce particle velocities and prevent particulate contamination is disclosed. 5 figs.

International Consultation on Micro-Chip Technology: Its Impact on the Lives of Women Workers. Summary of Proceedings (Manila, Philippines, October 5-15, 1986).

ERIC Educational Resources Information Center

Participatory Research Group, Toronto (Ontario).

An international consultation was attended by 40 women workers, educators, and organizers who work directly with women affected by the new "global assembly line" that has developed as a part of the microchip technology industry. The women, who represented 12 countries, shared information and organizing experiences and worked to…

Additive manufacturing and analysis of high frequency interconnects for microwave devices

NASA Astrophysics Data System (ADS)

Harper, Elicia K.

Wire bond interconnects have been the main approach to interconnecting microelectronic devices within a package. Conventional wirebonding however offers little control of the impedance of the interconnect and also introduces parasitic inductance that can degrade performance at microwave frequencies. The size and compactness of microchips is often an issue when it comes to attaching wirebonds to the microchip or other components within a microwave module. This work demonstrates the use of additive manufacturing for printing interconnects directly between bare die microchips and other components within a microwave module. A test structure was developed consisting of a GaAs microchip sandwiched between two alumina blocks patterned with coplanar waveguides (CPW). A printed dielectric ink is used to fill the gap between the alumina CPW blocks and the GaAs chip. Conductive interconnects are printed on top of the dielectric bridge material to connect the CPW traces to the bonding pads on the GaAs microchip. Simulations of these structures were modeled in the electromagnetics simulation tool by ANSYS, high frequency structure simulation (HFSS), to optimize the printed interconnects at 1-40 GHz (ANSYS Inc., Canonsburg, PA). The dielectric constant and loss tangent of the simulated dielectric was varied along with the dimensions of the conductive interconnects. The best combination of dielectric properties and interconnect dimensions was chosen for impedance matching by analyzing the insertion losses and return losses. A dielectric ink, which was chosen based on the simulated results, was experimentally printed between the two CPW blocks and the GaAs chip and subsequently cured. The conductive interconnects were then printed with an aerosol jet printer, connecting the CPW traces to the bonding pads on the GaAs microchip. The experimental prototype was then measured with a network analyzer and the measured data were compared to simulations. Results show good agreement between the simulated and measured S-parameters. This work demonstrates the potential for using additive manufacturing technology to create impedance- matched interconnects between high frequency ICs and other module components such as high frequency CPW transmission lines.

Photometric flow injection determination of phosphate on a PDMS microchip using an optical detection system assembled with an organic light emitting diode and an organic photodiode.

PubMed

Liu, Rong; Ishimatsu, Ryoichi; Yahiro, Masayuki; Adachi, Chihaya; Nakano, Koji; Imato, Toshihiko

2015-01-01

A compact photometric detector was constructed from an organic light emitting diode (OLED) based on a europium complex, europium(diben-zoylmethanato)3(bathophenanthroline) (Eu(DBM)3bath), as the light source and an organic photodiode (OPD) fabricated from a hetero-junction of two layers of copper phthalocyanine (CuPc)/fullerene (C60) as the photo-detector on a microchip prepared from poly(dimethylsiloxan) (PDMS) and was applied to the determination of phosphate. The OLED and the OPD were fabricated by a vapor deposition method on an indium tin oxide (ITO) coated glass substrate with the following layered structure; Glass (0.7 mm)/ITO (110 nm)/4,4'-bis[N-(1-naphthyl)-N-phenyl amino]-biphenyl (α-NPD) (30 nm)/4,4'-di(N-carbazolyl)biphenyl (CBP): Eu(3+) (8 wt%, 30 nm)/bathocuproine (BCP) (30 nm)/aluminum tris(8-hydroxyquinoline) (Alq3) (25 nm)/magnesium and silver (MgAg) (100 nm)/Ag (10nm) and Glass (0.7 mm)/ITO (110 nm)/CuPc (35 nm)/C60 (50 nm)/BCP (10 nm)/Ag (50 nm), respectively. The OLED based on the europium complex emitted a sharp light at the wavelength of 612 nm with a full width at half maximum (FWHM) of 8 nm. The performance of the photometric detector assembled was evaluated based on measurements of the absorbance of different concentrations of malachite green (MG) solutions for a batch system with 1cm long path length. The molar absorptive coefficient of the MG solution, calculated from the photocurrent of the OPD, was in good agreement with the value reported in the literature. A microchip with two inlets and one outlet U-shaped channel was prepared by a conventional photolithograph method. The OLED and the OPD were configured so as to face each other through the PDMS microchip in parallel in order to align the light axis of the OLED and the OPD with the flow cell (optical path length of 5mm), which was located at the end of outlet. For the determination of phosphate, an ion-association reaction between MG and a molybdenum-phosphate complex was utilized and a good linear relationship between the concentration and absorbance was observed in the concentration range 0-0.2 ppm, with a detection limit (S/N=3) of 0.02 ppm. The assembled photometric detector was also applied to the determination of phosphate by the flow injection of river water samples using the reagent solution containing MG and molybdenum ammonium in sulfuric acid. A good recovery (97-99%) for the river water samples, which had been spiked with the standard 0.08 ppm, with an RSD of ca 5% (n=5) was obtained using the constructed system. Copyright © 2014 Elsevier B.V. All rights reserved.

Integration of continuous-flow sampling with microchip electrophoresis using poly(dimethylsiloxane)-based valves in a reversibly sealed device.

PubMed

Li, Michelle W; Martin, R Scott

2007-07-01

Here we describe a reversibly sealed microchip device that incorporates poly(dimethylsiloxane) (PDMS)-based valves for the rapid injection of analytes from a continuously flowing stream into a channel network for analysis with microchip electrophoresis. The microchip was reversibly sealed to a PDMS-coated glass substrate and microbore tubing was used for the introduction of gas and fluids to the microchip device. Two pneumatic valves were incorporated into the design and actuated on the order of hundreds of milliseconds, allowing analyte from a continuously flowing sampling stream to be injected into an electrophoresis separation channel. The device was characterized in terms of the valve actuation time and pushback voltage. It was also found that the addition of sodium dodecyl sulfate (SDS) to the buffer system greatly increased the reproducibility of the injection scheme and enabled the analysis of amino acids derivatized with naphthalene-2,3-dicarboxaldehyde/cyanide. Results from continuous injections of a 0.39 nL fluorescein plug into the optimized system showed that the injection process was reproducible (RSD of 0.7%, n = 10). Studies also showed that the device was capable of monitoring off-chip changes in concentration with a device lag time of 90 s. Finally, the ability of the device to rapidly monitor on-chip concentration changes was demonstrated by continually sampling from an analyte plug that was derivatized upstream from the electrophoresis/continuous flow interface. A reversibly sealed device of this type will be useful for the continuous monitoring and analysis of processes that occur either off-chip (such as microdialysis sampling) or on-chip from other integrated functions.

Monodisperse microdroplet generation and stopping without coalescence

DOEpatents

Beer, Neil Reginald

2015-04-21

A system for monodispersed microdroplet generation and trapping including providing a flow channel in a microchip; producing microdroplets in the flow channel, the microdroplets movable in the flow channel; providing carrier fluid in the flow channel using a pump or pressure source; controlling movement of the microdroplets in the flow channel and trapping the microdroplets in a desired location in the flow channel. The system includes a microchip; a flow channel in the microchip; a droplet maker that generates microdroplets, the droplet maker connected to the flow channel; a carrier fluid in the flow channel, the carrier fluid introduced to the flow channel by a source of carrier fluid, the source of carrier fluid including a pump or pressure source; a valve connected to the carrier fluid that controls flow of the carrier fluid and enables trapping of the microdroplets.

Monodisperse microdroplet generation and stopping without coalescence

DOEpatents

Beer, Neil Reginald

2016-02-23

A system for monodispersed microdroplet generation and trapping including providing a flow channel in a microchip; producing microdroplets in the flow channel, the microdroplets movable in the flow channel; providing carrier fluid in the flow channel using a pump or pressure source; controlling movement of the microdroplets in the flow channel and trapping the microdroplets in a desired location in the flow channel. The system includes a microchip; a flow channel in the microchip; a droplet maker that generates microdroplets, the droplet maker connected to the flow channel; a carrier fluid in the flow channel, the carrier fluid introduced to the flow channel by a source of carrier fluid, the source of carrier fluid including a pump or pressure source; a valve connected to the carrier fluid that controls flow of the carrier fluid and enables trapping of the microdroplets.

Single-longitudinal-mode Er:GGG microchip laser operating at 2.7  μm.

PubMed

You, Zhenyu; Wang, Yan; Xu, Jinlong; Zhu, Zhaojie; Li, Jianfu; Wang, Hongyan; Tu, Chaoyang

2015-08-15

We reported on a diode-end-pumped single-longitudinal-mode microchip laser using a 600-μm-thick Er:GGG crystal at ∼2.7  μm, generating a maximum output power of 50.8 mW and the maximum pulsed energy of 0.306 mJ, with repetition rates of pumping light of 300, 200, and 100 Hz, respectively. The maximum slope efficiency of the laser was 20.1%. The laser was operated in a single-longitudinal mode centered at about 2704 nm with a FWHM of 0.42 nm. The laser had a fundamental beam profile and the beam quality parameter M(2) was measured as 1.46. These results indicate that the Er:GGG microchip laser is a potential compact mid-infrared laser source.

Separation of large DNA molecules by applying pulsed electric field to size exclusion chromatography-based microchip

NASA Astrophysics Data System (ADS)

Azuma, Naoki; Itoh, Shintaro; Fukuzawa, Kenji; Zhang, Hedong

2018-02-01

Through electrophoresis driven by a pulsed electric field, we succeeded in separating large DNA molecules with an electrophoretic microchip based on size exclusion chromatography (SEC), which was proposed in our previous study. The conditions of the pulsed electric field required to achieve the separation were determined by numerical analyses using our originally proposed separation model. From the numerical results, we succeeded in separating large DNA molecules (λ DNA and T4 DNA) within 1600 s, which was approximately half of that achieved under a direct electric field in our previous study. Our SEC-based electrophoresis microchip will be one of the effective tools to meet the growing demand of faster and more convenient separation of large DNA molecules, especially in the field of epidemiological research of infectious diseases.

1.6 μm microchip laser

NASA Astrophysics Data System (ADS)

Šulc, J.; Jelínková, H.; Ryba-Romanowski, W.; Lukasiewicz, T.

2009-03-01

Properties of new pulsed-diode-pumped Er:YVO4 and Er:YVO4+CaO microchip lasers working in an ``eye-safe'' spectral region were investigated. As a pumping source, a fiber coupled (core diameter-200 μm) laser diode emitting radiation at wavelength 976 nm was used. The laser diode was operating in pulsed regime with 3 ms pulse width, and 20 Hz repetition rate. The result obtained was 175 mW and 152 mW output peak power for the Er:YVO4 and Er:YVO4+CaO lasers, respectively. The maximal efficiency with respect to the absorbed power was ~ 5%. The laser emission for Er:YVO4 microchip was observed in detail in the range 1593 nm to 1604 nm with respect to pumping. However, for Er:YVO4+CaO crystal only 1604 nm was generated.

Microchip-based electrochemical detection using a 3-D printed wall-jet electrode device.

PubMed

Munshi, Akash S; Martin, R Scott

2016-02-07

Three dimensional (3-D) printing technology has evolved dramatically in the last few years, offering the capability of printing objects with a variety of materials. Printing microfluidic devices using this technology offers various advantages such as ease and uniformity of fabrication, file sharing between laboratories, and increased device-to-device reproducibility. One unique aspect of this technology, when used with electrochemical detection, is the ability to produce a microfluidic device as one unit while also allowing the reuse of the device and electrode for multiple analyses. Here we present an alternate electrode configuration for microfluidic devices, a wall-jet electrode (WJE) approach, created by 3-D printing. Using microchip-based flow injection analysis, we compared the WJE design with the conventionally used thin-layer electrode (TLE) design. It was found that the optimized WJE system enhances analytical performance (as compared to the TLE design), with improvements in sensitivity and the limit of detection. Experiments were conducted using two working electrodes - 500 μm platinum and 1 mm glassy carbon. Using the 500 μm platinum electrode the calibration sensitivity was 16 times higher for the WJE device (as compared to the TLE design). In addition, use of the 1 mm glassy carbon electrode led to limit of detection of 500 nM for catechol, as compared to 6 μM for the TLE device. Finally, to demonstrate the versatility and applicability of the 3-D printed WJE approach, the device was used as an inexpensive electrochemical detector for HPLC. The number of theoretical plates was comparable to the use of commercially available UV and MS detectors, with the WJE device being inexpensive to utilize. These results show that 3-D-printing can be a powerful tool to fabricate reusable and integrated microfluidic detectors in configurations that are not easily achieved with more traditional lithographic methods.

Efficient diode-pumped Tm:KYW 1.9-μm microchip laser with 1 W cw output power.

PubMed

Gaponenko, Maxim; Kuleshov, Nikolay; Südmeyer, Thomas

2014-05-19

We report on a diode-pumped Tm:KYW microchip laser generating 1 W continuous-wave output power. The laser operates at a wavelength of 1.94 μm in the fundamental TEM(00) mode with 71% slope efficiency relative to the absorbed pump radiation and 59% slope efficiency relative to the incident pump radiation. The optical-to-optical laser efficiency is 43%.

High-gain mid-infrared optical-parametric generation pumped by microchip laser.

PubMed

Ishizuki, Hideki; Taira, Takunori

2016-01-25

High-gain mid-infrared optical-parametric generation was demonstrated by simple single-pass configuration using PPMgLN devices pumped by giant-pulse microchip laser. Effective mid-infrared wavelength conversion with 1 mJ output energy from 2.4 mJ pumping using conventional PPMgLN could be realized. Broadband optical-parametric generation from 1.7 to 2.6 µm could be also measured using chirped PPMgLN.

Liquid biopsy on chip: a paradigm shift towards the understanding of cancer metastasis.

PubMed

Tadimety, Amogha; Syed, Abeer; Nie, Yuan; Long, Christina R; Kready, Kasia M; Zhang, John X J

2017-01-23

This comprehensive review serves as a guide for developing scalable and robust liquid biopsies on chip for capture, detection, and analysis of circulating tumor cells (CTCs). Liquid biopsy, the detection of biomarkers from body fluids, has proven challenging because of CTC rarity and the heterogeneity of CTCs shed from tumors. The review starts with the underlying biological mechanisms that make liquid biopsy a challenge before moving into an evaluation of current technological progress. Then, a framework for evaluation of the technologies is presented with special attention to throughput, capture rate, and cell viability for analysis. Technologies for CTC capture, detection, and analysis will be evaluated based on these criteria, with a focus on current approaches, limitations and future directions. The paper provides a critical review for microchip developers as well as clinical investigators to build upon the existing progress towards the goal of designing CTC capture, detection, and analysis platforms.

Geo-material surface modification of microchips using layer-by-layer (LbL) assembly for subsurface energy and environmental applications.

PubMed

Zhang, Y Q; Sanati-Nezhad, A; Hejazi, S H

2018-01-16

A key constraint in the application of microfluidic technology to subsurface flow and transport processes is the surface discrepancy between microchips and the actual rocks/soils. This research employs a novel layer-by-layer (LbL) assembly technology to produce rock-forming mineral coatings on microchip surfaces. The outcome of the work is a series of 'surface-mimetic micro-reservoirs (SMMR)' that represent multi-scales and multi-types of natural rocks/soils. For demonstration, the clay pores of sandstones and mudrocks are reconstructed by representatively coating montmorillonite and kaolinite in polydimethylsiloxane (PDMS) microchips in a wide range of channel sizes (width of 10-250 μm, depth of 40-100 μm) and on glass substrates. The morphological and structural properties of mineral coatings are characterized using a scanning electron microscope (SEM), optical microscope and profilometer. The coating stability is tested by dynamic flooding experiments. The surface wettability is characterized by measuring mineral oil-water contact angles. The results demonstrate the formation of nano- to micro-scale, fully-covered and stable mineral surfaces with varying wetting properties. There is an opportunity to use this work in the development of microfluidic technology-based applications for subsurface energy and environmental research.

Linearly polarized pumped passively Q-switched Nd:YVO4 microchip laser for Ince-Gaussian laser modes with controllable orientations

NASA Astrophysics Data System (ADS)

He, Hong-Sen; Zhang, Ming-Ming; Dong, Jun; Ueda, Ken-Ichi

2016-12-01

A tilted, linearly polarized laser diode end-pumped Cr4+:YAG passively Q-switched a-cut Nd:YVO4 microchip laser for generating numerous Ince-Gaussian (IG) laser modes with controllable orientations has been demonstrated by selecting the crystalline orientation of an a-cut Nd:YVO4 crystal. The same IG laser mode with different orientations has been achieved with the same absorbed pump power in a passively Q-switched Nd:YVO4 microchip laser under linearly polarized pumping when the incident pump power and the crystalline orientation of an a-cut Nd:YVO4 crystal are both properly selected. The significant improvement of pulsed laser performance of controllable IG modes has been achieved by selecting the crystalline orientation of an a-cut Nd:YVO4 crystal. The maximum pulse energy is obtained along the a-axis of an a-cut Nd:YVO4 crystal and the highest peak power is achieved along the c-axis of an a-cut Nd:YVO4 crystal, respectively, which has potential applications on quantum computation and optical manipulation. The generation of controllable IG laser modes in microchip lasers under linearly polarized pumping provides a convenient and universal way to control IG laser mode numbers with anisotropic crystal as a gain medium.

940  mW 1564  nm multi-longitudinal-mode and 440  mW 1537  nm single-longitudinal-mode continuous-wave Er:Yb:Lu2Si2O7 microchip lasers.

PubMed

Huang, Jianhua; Chen, Yujin; Lin, Yanfu; Gong, Xinghong; Luo, Zundu; Huang, Yidong

2018-04-15

An Er:Yb:Lu 2 Si 2 O 7 microchip laser was constructed by placing a 1.2 mm thick, Y-cut Er:Yb:Lu 2 Si 2 O 7 microchip between two 1.2 mm thick sapphire crystals, in which input and output mirrors were directly deposited onto one face of each crystal. End-pumped by a continuous-wave 975.4 nm diode laser, a 1564 nm multi-longitudinal-mode laser with a maximum output power of 940 mW and slope efficiency of 20% was realized at an absorbed pump power of 5.5 W when the transmission of output mirror was 2.2%. When the transmission of the output mirror was increased to 6%, a 1537 nm single-longitudinal-mode laser with a maximum output power of 440 mW and slope efficiency of 12% was realized at an absorbed pump power of 4.3 W. The results indicate that the Er:Yb:Lu 2 Si 2 O 7 crystal is a promising microchip gain medium to realize a single-longitudinal-mode laser.

Fabrication and characterization of semicircular detection electrodes for contactless conductivity detector - CE microchips.

PubMed

Lee, Chia-Yen; Chen, C M; Chang, Guan-Liang; Lin, Che-Hsin; Fu, Lung-Ming

2006-12-01

This study uses simple and reliable microfabrication techniques to fabricate CE biochips, integrating a novel contactless conductivity detector in a miniaturized detection system in a microfluidic biochip. The off-channel electrodes are deposited around side channels by Au sputtering and patterned using a standard "lift-off" process. A vacuum fusion bonding process is employed to seal the lower substrate containing the microchannels and the electrodes to an upper glass cover plate. The variations in the capacitance between the semicircular detection electrodes in the side channels are measured as different samples and ions pass through the detection region of the CE separation channel. Samples of Rhodamine B, commercial sports drinks, mineral waters, and a red wine, respectively, are mixed in different buffer solutions, separated, and successfully detected using the developed device. The semicircular detection electrodes for the contactless conductivity detector have microscale dimensions and provide a valuable contribution to the realization of the lab-on-a-chip concept.

Micro-Detection System for Determination of the Biotic or Abiotic Origin of Amino Acids

NASA Technical Reports Server (NTRS)

Bada, Jeffrey L.; Betts, Bruce (Technical Monitor)

2002-01-01

The research involved the development of a breadboard version of a spacecraft based system for the detection of amino acid chirality (handedness) on solar system bodies. The design concept has three distinct components: a sublimation chamber for the release of amino acids from an acquired sample; a microchip based capillary electrophoresis (CE) chip for the separation of amino acids and their enantiomers; and a fluorescent based detection system. In addition, we have investigated the use of a microfluidics system for the extraction of amino acids in samples in which sublimation has proven to be problematic. This is a joint project carried out at the Scripps Institution of Oceanography (SIO), University of California at San Diego; the Jet Propulsion Laboratory (JPL), Pasadena; and the Department of Chemistry, University of California, Berkeley.

Linearly Polarized Single-Frequency Oscillations of Laser-Diode-Pumped Microchip Ceramic Nd:YAG Lasers with Forced Ince-Gaussian Mode Operations

NASA Astrophysics Data System (ADS)

Otsuka, Kenju; Nemoto, Kana; Kamikariya, Koji; Miyasaka, Yoshihiko; Chu, Shu-Chun

2007-09-01

Detailed oscillation spectra and polarization properties have been examined in laser-diode-pumped (LD-pumped) microchip ceramic (i.e., polycrystalline) Nd:YAG lasers and the inherent segregation of lasing patterns into local modes possessing different polarization states was observed. Single-frequency linearly-polarized stable oscillations were realized by forcing the laser to Ince-Gaussian mode operations by adjusting azimuthal cavity symmetry.

Capillary electrochromatography and preconcentration of neutral compounds on poly(dimethylsiloxane) microchips.

PubMed

Ro, Kyung Won; Chang, Woo-Jin; Kim, Ho; Koo, Yoon-Mo; Hahn, Jong Hoon

2003-09-01

Capillary electrochromatography (CEC) and preconcentration of neutral compounds have been realized on poly(dimethylsiloxane) (PDMS) microchips. The channels are coated with polyelectrolyte multilayers to avoid absorption of hydrophobic analytes into PDMS. The structures of a microchip include an injector and a bead chamber with integrated frits, where the particles of the stationary phase are completely retained. Dimensions of the frit structures are 25 micro mx20 micro m, and the space between the structures is 3 micro m. A neutral compound, BODIPY, that is strongly absorbed into native PDMS, is successfully and selectively retained on octadecylsilane-coated silica beads in the bead chamber with a concentration enhancement of up to 100 times and eluted with elution buffer solution containing 70% acetonitrile. Preconcentrations and CEC separations of coumarins have been conducted with the same device and achieved complete separations in less than 50 s.

Diode-pumped 1.5-1.6 μm laser operation in Er³⁺ doped YbAl₃(BO₃)₄ microchip.

PubMed

Chen, Yujin; Lin, Yanfu; Zou, Yuqi; Huang, Jianhua; Gong, Xinghong; Luo, Zundu; Huang, Yidong

2014-06-02

Er3+ doped YbAl3(BO3)4 crystal with large absorption coefficient of 184 cm(-1) at pump wavelength of 976 nm is a promising microchip gain medium of 1.5-1.6 μm laser. End-pumped by a 976 nm diode laser, 1.5-1.6 μm continuous-wave laser with maximum output power of 220 mW and slope efficiency of 8.1% was obtained at incident pump power of 4.54 W in a c-cut 200-μm-thick Er:YbAl3(BO3)4 microchip. When a Co2+:Mg0.4Al2.4O4 crystal was used as the saturable absorber, 1521 nm passively Q-switched pulse laser with about 0.19 μJ energy, 265 ns duration, and 96 kHz repetition rate was realized.

Diode-pumped microchip Tm:KLu(WO₄)₂ laser with more than 3 W of output power.

PubMed

Serres, Josep Maria; Mateos, Xavier; Loiko, Pavel; Yumashev, Konstantin; Kuleshov, Nikolai; Petrov, Valentin; Griebner, Uwe; Aguiló, Magdalena; Díaz, Francesc

2014-07-15

A diode-pumped microchip laser containing a quasi-monolithic plano-plano cavity is realized on the basis of a Tm:KLu(WO₄)₂ crystal. The maximum CW output power is 3.2 W (at an absorbed pump power of 6.8 W) and the slope efficiency as high as 50.4%. The laser is operating at 1946 nm in the TEM₀₀ mode with a M²<1.05. Microchip operation with Tm:KLu(WO₄)₂ is, in principle, due to a special crystal cut along the N(g) optical indicatrix axis. This crystal cut possesses positive near-spherical thermal lens that provides the required mode stabilization in the plano-plano cavity. Sensitivity factors of the thermal lens, "generalized" thermo-optic coefficients and constants describing the photoelastic effect are determined for the monolithic Tm:KLu(WO₄)₂ crystal.

Single-longitudinal mode Nd:YVO4 microchip laser with orthogonal-polarization bidirectional traveling-waves mode.

PubMed

Ma, Yingjun; Wu, Li; Wu, Hehui; Chen, Weimin; Wang, Yanli; Gu, Shijie

2008-11-10

We present a single longitudinal mode, diode pumped Nd:YVO(4) microchip laser where a pair of quarter-wave plates (QWPs) sandwich Nd:YVO(4) and the principle axes of QWPs are oriented at 45 degrees to the c-axis of Nd:YVO(4). Three pieces of crystals were optically bonded together as a microchip without adhesive. Owing to large birefringence of Nd:YVO(4), two standing waves with orthogonal polarizations compensate their hole-burning effects with each other, which diminish total spatial hole-burning effects in Nd:YVO(4). The maximum pump power of greater than 25 times the threshold for single longitudinal mode operation has been theoretically shown and experimentally demonstrated. The power of output, slope efficiencies and temperature range of single longitudinal mode operation are greater than 730 mw (at 1.25 W pump), 60% and 30 degrees C, respectively.

Microfluidic devices for the controlled manipulation of small volumes

DOEpatents

Ramsey, Michael J; Jacobson, Stephen C

2012-09-18

A method for conducting a broad range of biochemical analyses or manipulations on a series of nano- to subnanoliter reaction volumes and an apparatus for carrying out the same are disclosed. The invention is implemented on a fluidic microchip to provide high serial throughput. In particular, the disclosed device is a microfabricated channel device that can manipulate nanoliter or subnanoliter reaction volumes in a controlled manner to produce results at rates of 1 to 10 Hz per channel. The reaction volumes are manipulated in serial fashion analogous to a digital shift register. The invention has application to such problems as screening molecular or cellular targets using single beads from split-synthesis combinatorial libraries, screening single cells for RNA or protein expression, genetic diagnostic screening at the single cell level, or performing single cell signal transduction studies.

Microfluidic devices for the controlled manipulation of small volumes

DOEpatents

Ramsey, J Michael [Knoxville, TN; Jacobson, Stephen C [Knoxville, TN

2007-07-03

A method for conducting a broad range of biochemical analyses or manipulations on a series of nano- to subnanoliter reaction volumes and an apparatus for carrying out the same are disclosed. The invention is implemented on a fluidic microchip to provide high serial throughput. In particular, the disclosed device is a microfabricated channel device that can manipulate nanoliter or subnanoliter reaction volumes in a controlled manner to produce results at rates of 1 to 10 Hz per channel. The reaction volumes are manipulated in serial fashion analogous to a digital shift register. The invention has application to such problems as screening molecular or cellular targets using single beads from split-synthesis combinatorial libraries, screening single cells for RNA or protein expression, genetic diagnostic screening at the single cell level, or performing single cell signal transduction studies.

Continuous two-wave lasing in microchip Nd : YAG lasers

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

Ievlev, Ivan V; Koryukin, Igor' V; Lebedeva, Yu S

2011-08-31

Simultaneous two-wave lasing was obtained in microchip end-pumped Nd:YAG lasers at the wavelengths of 1061.5 and 1064.17 nm at room temperature. Laser wave intensities were studied as functions of crystal temperature and pump power. The ranges of parameters were determined in which the two-wave lasing occurs and the reasons for such lasing were established. A model is suggested, which adequately describes the experimental results obtained. (control of radiation parameters)

Miniaturization of flight deflection measurement system

NASA Technical Reports Server (NTRS)

Fodale, Robert (Inventor); Hampton, Herbert R. (Inventor)

1990-01-01

A flight deflection measurement system is disclosed including a hybrid microchip of a receiver/decoder. The hybrid microchip decoder is mounted piggy back on the miniaturized receiver and forms an integral unit therewith. The flight deflection measurement system employing the miniaturized receiver/decoder can be used in a wind tunnel. In particular, the miniaturized receiver/decoder can be employed in a spin measurement system due to its small size and can retain already established control surface actuation functions.

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

Multi-wavelength Yb:YAG/Nd³⁺:YVO₄ continuous-wave microchip Raman laser.

PubMed

Wang, Xiao-Lei; Dong, Jun; Wang, Xiao-Jie; Xu, Jie; Ueda, Ken-Ichi; Kaminskii, Alexander A

2016-08-01

Multi-wavelength continuous-wave (CW) Raman lasers in a laser diode pumped Yb:YAG/Nd³⁺:YVO₄ microchip Raman laser have been demonstrated for the first time to our best knowledge. The multi-wavelength laser of the first Stokes radiation around 1.08 μm has been achieved with a Raman shift of 261  cm^-1 for a-cut Nd:YVO₄ crystal corresponding to the fundamental wavelength at 1.05 μm. Multi-wavelength laser operation simultaneously around 1.05 and 1.08 μm has been achieved under the incident pump power between 1.5 and 1.7 W. Multi-wavelength Raman laser with frequency separation of 1 THz around 1.08 μm has been obtained when the incident pump power is higher than 1.7 W. The maximum Raman laser output power of 260 mW at 1.08 μm is obtained and the corresponding optical-to-optical conversion efficiency is 4.2%. Elliptically polarized fundamental laser and linearly polarized Raman laser were observed in an Yb:YAG/Nd:YVO₄ CW microchip Raman laser. The experimental results of linearly polarized, multi-wavelength Yb:YAG/Nd:YVO₄ CW microchip Raman laser with adjustable frequency separation provide a novel approach for developing potential compact laser sources for Terahertz generation.

An integrated microfludic device for culturing and screening of Giardia lamblia.

PubMed

Zheng, Guo-Xia; Zhang, Xue-Mei; Yang, Yu-Suo; Zeng, Shu-Rui; Wei, Jun-Feng; Wang, Yun-Hua; Li, Ya-Jie

2014-02-01

In vitro culturing of trophozoites was important for research of Giardia lamblia (G. lamblia), especially in discovery of anti-Giardia agents. The current culture methods mainly suffer from lab-intension or the obstacle in standardizing the gas condition. Thus, it could benefit from a more streamlined and integrated approach. Microfluidics offers a way to accomplish this goal. Here we presented an integrated microfluidic device for culturing and screening of G. lamblia. The device consisted of a polydimethylsiloxane (PDMS) microchip with an aerobic culture system. In the microchip, the functionality of integrated concentration gradient generator (CGG) with micro-scale cell culture enables dose-response experiment to be performed in a simple and reagent-saving way. The diffusion-based culture chambers allowed growing G. lamblia at the in vivo like environment. It notable that the highly air permeable material of parallel chambers maintain uniform anaerobic environment in different chambers easily. Using this device, G. lamblia were successfully cultured and stressed on-chip. In all cases, a dose-related inhibitory response was detected. The application of this device for these purposes represents the first step in developing a completely integrated microfluidic platform for high-throughput screening and might be expanded to other assays based on in vitro culture of G. lamblia with further tests. Copyright © 2013 Elsevier Inc. All rights reserved.

Direct coupling of polymer-based microchip electrophoresis to online MALDI-MS using a rotating ball inlet.

PubMed

Musyimi, Harrison K; Guy, Jason; Narcisse, Damien A; Soper, Steven A; Murray, Kermit K

2005-12-01

We report on the coupling of a polymer-based microfluidic chip to a MALDI-TOF MS using a rotating ball interface. The microfluidic chips were fabricated by micromilling a mold insert into a brass plate, which was then used for replicating polymer microparts via hot embossing. Assembly of the chip was accomplished by thermally annealing a cover slip to the embossed substrate to enclose the channels. The linear separation channel was 50 microm wide, 100 microm deep, and possessed an 8 cm effective length separation channel with a double-T injector (V(inj) = 10 nL). The exit of the separation channel was machined to allow direct contact deposition of effluent onto a specially constructed rotating ball inlet to the mass spectrometer. Matrix addition was accomplished in-line on the surface of the ball. The coupling utilized the ball as the cathode transfer electrode to transport sample into the vacuum for desorption with a 355 nm Nd:YAG laser and analyzed on a TOF mass spectrometer. The ball was cleaned online after every rotation. The ability to couple poly(methylmethacrylate) microchip electrophoresis devices for the separation of peptides and peptide fragments produced from a protein digest with subsequent online MALDI MS detection was demonstrated.

Rapid separation and sensitive determination of banned aromatic amines with plastic microchip electrophoresis.

PubMed

Li, Ruina; Wang, Lili; Gao, Xiaotong; Du, Gangfeng; Zhai, Honglin; Wang, Xiayan; Guo, Guangsheng; Pu, Qiaosheng

2013-03-15

Rapid analysis of trace amount of aromatic amines in environmental samples and daily necessities has attracted considerable attentions because some of them are strongly toxic and carcinogenic. In this study, fast and efficient electrophoretic separation and sensitive determination of 5 banned aromatic amines were explored for practical analysis using disposable plastic microchips combined with a low-cost laser-induced fluorescence detector. The effect of running buffer and its additive was systematically investigated. Under the selected condition, 5 fluorescein isothiocyanate labeled aromatic amines could be baseline separated within 90s by using a 10mmol/L borate buffer containing 2% (w/v) hydroxypropyl cellulose. Calibration curves of peak areas vs. concentrations were linear up to 40 or 120μmol/L for different analytes and limits of detection were in a range of 1-3nmol/L. Theoretical plate numbers of 6.8-8.5×10(5)/m were readily achieved. The method exhibited good repeatability, relative standard deviations (n=5) of peak areas and migration times were no more than 4.6% and 0.9%, respectively. The established method was successfully applied in the quantitative analysis of these banned aromatic amines in real samples of waste water and textile, recoveries of added standards were 85-110%. Copyright © 2013 Elsevier B.V. All rights reserved.

Sensitive, microliter PCR with consensus degenerate primers for Epstein Barr virus amplification

PubMed Central

Oh, Kyudam; Pak, Nikita; Saunders, D. Curtis; Conrardy, Christina; Landers, James P.; Tong, Suxiang; Forest, Craig R.

2016-01-01

Sensitive identification of the etiology of viral diseases is key to implementing appropriate prevention and treatment. The gold standard for virus identification is the polymerase chain reaction (PCR), a technique that allows for highly specific and sensitive detection of pathogens by exponentially amplifying a specific region of DNA from as little as a single copy through thermocycling a biochemical cocktail. Today, molecular biology laboratories use commercial instruments that operate in 0.5–2 h/analysis using reaction volumes of 5–50 μL contained within polymer tubes or chambers. Towards reducing this volume and maintaining performance, we present a semi-quantitative, systematic experimental study of how PCR yield is affected by tube/chamber substrate, surface-area-to-volume ratio (SA:V), and passivation methods. We perform PCR experiments using traditional PCR tubes as well as using disposable polymer microchips with 1 μL reaction volumes thermocycled using water baths. We report the first oil encapsulation microfluidic PCR method without fluid flow and its application to the first microfluidic amplification of Epstein Barr virus using consensus degenerate primers, a powerful and broad PCR method to screen for both known and novel members of a viral family. The limit of detection is measured as 140 starting copies of DNA from a starting concentration of 3×105 copies/mL, regarded as an accepted sensitivity threshold for diagnostic purposes, and reaction specificity was improved as compared to conventional methods. Also notable, these experiments were conducted with conventional reagent concentrations, rather than commonly spiked enzyme and/or template mixtures. This experimental study of the effects of substrate, SA:V, and passivation, together with sensitive and specific microfluidic PCR with consensus degenerate primers represent advances towards lower cost and higher throughput pathogen screening. PMID:23080522

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.

Electro-optically tunable microwave source based on composite-cavity microchip laser.

PubMed

Qiao, Yunfei; Zheng, Shilie; Chi, Hao; Jin, Xiaofeng; Zhang, Xianmin

2012-12-17

A compact and electric tuning microwave source based on a diode-pumped composite Nd:YAG-LiNbO(3) cavity microchip laser is demonstrated. The electro-optical element introduces an electric tuning intra-cavity birefringence which causes a tunable frequency difference between two spilt orthogonal polarization states of a longitude mode. Thus a continuously tunable microwave signal with frequency up to 14.12 GHz can be easily generated by beating the two polarization modes on a high speed photodetector.

Tm:KLu(WO(4))(2) microchip laser Q-switched by a graphene-based saturable absorber.

PubMed

Serres, Josep Maria; Loiko, Pavel; Mateos, Xavier; Yumashev, Konstantin; Griebner, Uwe; Petrov, Valentin; Aguiló, Magdalena; Díaz, Francesc

2015-06-01

We report on the first Tm-doped double tungstate microchip laser Q-switched with graphene using a Tm:KLu(WO₄)₂ crystal cut along the N_g dielectric axis. This laser generates a maximum average output power of 310 mW with a slope efficiency of 13%. At a repetition rate of 190 kHz the shortest pulses with 285 ns duration and 1.6 µJ energy are achieved.

Generation of Hermite-Gaussian modes and vortex arrays based on two-dimensional gain distribution controlled microchip laser.

PubMed

Kong, Weipeng; Sugita, Atsushi; Taira, Takunori

2012-07-01

We have demonstrated high-order Hermite-Gaussian (HG) mode generation based on 2D gain distribution control edge-pumped, composite all-ceramic Yb:YAG/YAG microchip lasers using a V-type cavity. Several hundred milliwatts to several watts HG(mn) modes are achieved. We also generated different kinds of vortex arrays directly from the oscillator with the same power level. In addition, a more than 7 W doughnut-shape mode can be generated in the same cavity.

Development of a conductivity-based photothermal absorbance detection microchip using polyelectrolytic gel electrodes.

PubMed

Chun, Honggu; Dennis, Patty J; Ferguson Welch, Erin R; Alarie, Jean Pierre; Jorgenson, James W; Ramsey, J Michael

2017-11-10

The development and application of polyelectrolytic gel electrodes (PGEs) for a microfluidic photothermal absorbance detection system is described. The PGEs are used to measure changes in conductivity based on heat generation by analytes absorbing light and changing the solution viscosity. The PGEs are suitable for direct contact conductivity measurements since they do not degrade with exposure to high electric fields. Both a 2-electrode system with DC voltages and a 3-electrode system with AC voltages were investigated. Experimental factors including excitation voltage, excitation frequency, laser modulation frequency, laser power, and path length were tested. The limits of detection for the 3-electrode and 2-electrode systems are 500nM and 0.55nM for DABSYL-tagged glucosamine, respectively. In addition, an electrokinetic separation of a potassium, DABSYL-tagged glucosamine, Rhodamine 6G, and Rhodamine B mixture was demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

Separation of three water-soluble vitamins by poly(dimethylsiloxane) microchannel electrophoresis with electrochemical detection.

PubMed

Li, Xiang-Yun; Zhang, Qian-Li; Lian, Hong-Zhen; Xu, Jing-Juan; Chen, Hong-Yuan

2007-09-01

A method for rapid separation and sensitive determination of three water-soluble vitamins, pyridoxine, ascorbic acid (VC), and p-aminobenzoic acid (PABA) has been developed by PDMS microchannel electrophoresis integrated with amperometric detection. After treatment of the microchip with oxygen plasma, the peak shapes of the three analytes were essentially improved. Pyridoxine, VC, and PABA were well separated within only 80 s in a running buffer of 20 mM borate solution (pH 8.5). Good linearity was obtained within the concentration range of 2-200 microM for the three water-soluble vitamins. The detection limits were 1.0 microM for pyridoxine and VC, and 1.5 microM for PABA. The proposed method has been successfully applied to real human urine sample, without solid phase extraction, with recoveries of 80-122% for the three water-soluble vitamins.

When microchip implants do more than drug delivery: blending, blurring, and bundling of protected health information and patient monitoring.

PubMed

Bramstedt, Katrina A

2005-01-01

Although currently in the research stage, scientists argue that drug-releasing microchip implants are on the horizon for future patients. This paper presents ethical reflection on these implants and identifies specific areas of concern; namely, patient monitoring and tracking, and patient privacy and confidentiality. It is foreseeable that drug delivery chips could be multifunctional with the overt or covert addition of sensors that monitor more than just the bloodstream concentrations of prescribed drugs (e.g., cotinine and alcohol in non-compliant patients, patient location via radio frequency or global positioning satellite). Similarly, it is foreseeable that these chips could be embedded with a patient's protected health information that could potentially be accessed and used by unauthorized persons. While drug delivery microchips are theoretically convenient and accurate for dosing, and might offer faster drug delivery with fewer side effects, ethical issues loom and should be contemplated now, while the technology is still under development.

Multi-pulse drug delivery from a resorbable polymeric microchip device

NASA Astrophysics Data System (ADS)

Grayson, Amy C. Richards; Choi, Insung S.; Tyler, Betty M.; Wang, Paul P.; Brem, Henry; Cima, Michael J.; Langer, Robert

2003-11-01

Controlled-release drug delivery systems have many applications, including treatments for hormone deficiencies and chronic pain. A biodegradable device that could provide multi-dose drug delivery would be advantageous for long-term treatment of conditions requiring pulsatile drug release. In this work, biodegradable polymeric microchips were fabricated that released four pulses of radiolabelled dextran, human growth hormone or heparin in vitro. Heparin that was released over 142 days retained on average 96 +/- 12% of its bioactivity. The microchips were 1.2 cm in diameter, 480-560 μm thick and had 36 reservoirs that could each be filled with a different chemical. The devices were fabricated from poly(L-lactic acid) and had poly(D,L-lactic-co-glycolic acid) membranes of different molecular masses covering the reservoirs. A drug delivery system can be designed with the potential to release pulses of different drugs at intervals after implantation in a patient by using different molecular masses or materials for the membrane.

Electrospray micromixer chip for on-line derivatization and kinetic studies.

PubMed

Abonnenc, Mélanie; Dayon, Loïc; Perruche, Brice; Lion, Niels; Girault, Hubert H

2008-05-01

An electrospray microchip for mass spectrometry comprising an integrated passive mixer to carry out on-chip chemical derivatizations is described. The microchip fabricated using UV-photoablation is composed of two microchannels linked together by a liquid junction. Downstream of this liquid junction, a mixing unit made of parallel oblique grooves is integrated to the microchannel in order to create flow perturbations. Several mixer designs are evaluated. The mixer efficiency is investigated both by fluorescence study and mass spectrometric monitoring of the tagging reaction of cysteinyl peptides with 1,4-benzoquinone. The comparisons with a microchip without a mixing unit and a kinetic model are used to assess the efficiency of the mixer showing tagging kinetics close to that of bulk reactions in an ideally mixed reactor. As an ultimate application, the electrospray micromixer is implemented in a LC-MS workflow. On-line derivatization of albumin tryptic peptides after a reversed-phase separation and counting of their cysteines drastically enhance the protein identification.

A micro surface tension pump (MISPU) in a glass microchip.

PubMed

Peng, Xing Yue Larry

2011-01-07

A non-membrane micro surface tension pump (MISPU) was fabricated on a glass microchip by one-step glass etching. It needs no material other than glass and is driven by digital gas pressure. The MISPU can be seen working like a piston pump inside the glass microchip under a microscope. The design of the valves (MISVA) and pistons (MISTON) was based on the surface tension theory of the micro surface tension alveolus (MISTA). The digital gas pressure controls the moving gas-liquid interface to open or close the input and output MISVAs to refill or drive the MISTON for pumping a liquid. Without any moving parts, a MISPU is a kind of long-lasting micro pump for micro chips that does not lose its water pumping efficiency over a 20-day period. The volumetric pump output varied from 0 to 10 nl s(-1) when the pump cycle time decreased from 5 min to 15 s. The pump head pressure was 1 kPa.

Fully packed capillary electrochromatographic microchip with self-assembly colloidal silica beads.

PubMed

Park, Jongman; Lee, Dami; Kim, Won; Horiike, Shigeyoshi; Nishimoto, Takahiro; Lee, Se Hwan; Ahn, Chong H

2007-04-15

A fully packed capillary electrochromatographic (CEC) microchip showing improved solution and chip handling was developed. Microchannels for the CEC microchip were patterned on a cyclic olefin copolymer substrate by injection molding and packed fully with 0.8-microm monodisperse colloidal silica beads utilizing a self-assembly packing technique. The silica packed chip substrate was covered and thermally press-bonded. After fabrication, the chip was filled with buffer solution by self-priming capillary action. The self-assembly packing at each channel served as a built-in nanofilter allowing quick loading of samples and running buffer solution without filtration. Because of a large surface area-to-volume ratio of the silica packing, reproducible control of electroosmotic flow was possible without leveling of the solutions in the reservoirs resulting 1.3% rsd in migration rate. The capillary electrophoretic separation characteristics of the chip were studied using fluorescein isothiocyanate (FITC)-derivatized amino acids as probe molecules. A mixture of FITC and four FITC-derivatized amino acids was successfully separated with 2-mm separation channel length.

Plate-shaped Yb:LuPO4 crystal for efficient CW and passively Q-switched microchip lasers

NASA Astrophysics Data System (ADS)

Liu, Junhai; Wang, Lisha; Han, Wenjuan; Xu, Honghao; Zhong, Degao; Teng, Bing

2016-10-01

It is demonstrated that plate-shaped crystals of Yb:LuPO4, which are grown from spontaneous nucleation by high-temperature solution method, can be utilized to make microchip lasers operating in continuous-wave (CW) or passively Q-switched mode. Efficient operation of such a microchip laser, which is built with a 0.3 mm thick crystal plate in a 2 mm long plane-parallel cavity, is realized at room temperature. With 2.37 W of pump power absorbed, 1.45 W of CW output power is generated with a slope efficiency of 73%. When passively Q-switched with a Cr4+:YAG crystal plate as saturable absorber, the laser produces a maximum pulsed output power of 0.53 W at 1013.3 nm, at a pulse repetition rate of 23.8 kHz, the resulting pulse energy, duration, and peak power are 22.3 μJ, 4.0 ns, and 5.6 kW, respectively.

Pump beam waist-dependent pulse energy generation in Nd:YAG/Cr4+:YAG passively Q-switched microchip laser

NASA Astrophysics Data System (ADS)

Li, Chao-yu; Dong, Jun

2016-08-01

The incident pump beam waist-dependent pulse energy generation in Nd:YAG/Cr4+:YAG composite crystal passively Q-switched microchip laser has been investigated experimentally and theoretically by moving the Nd:YAG/Cr4+:YAG composite crystal along the pump beam direction. Highest pulse energy of 0.4 mJ has been generated when the Nd:YAG/Cr4+:YAG composite crystal is moved about 6 mm away from the focused pump beam waist. Laser pulses with pulse width of 1.7 ns and peak power of over 235 kW have been achieved. The theoretically calculated effective laser beam area at different positions of Nd:YAG/Cr4+:YAG composite crystal along the pump beam direction is in good agreement with the experimental results. The highest peak power can be generated by adjusting the pump beam waist incident on the Nd:YAG/Cr4+:YAG composite crystal to optimize the effective laser beam area in passively Q-switched microchip laser.

Fabrication of a Dipole-assisted Solid Phase Extraction Microchip for Trace Metal Analysis in Water Samples

PubMed Central

Chen, Ping-Hung; Chen, Shun-Niang; Tseng, Sheng-Hao; Deng, Ming-Jay; Lin, Yang-Wei; Sun, Yuh-Chang

2016-01-01

This paper describes a fabrication protocol for a dipole-assisted solid phase extraction (SPE) microchip available for trace metal analysis in water samples. A brief overview of the evolution of chip-based SPE techniques is provided. This is followed by an introduction to specific polymeric materials and their role in SPE. To develop an innovative dipole-assisted SPE technique, a chlorine (Cl)-containing SPE functionality was implanted into a poly(methyl methacrylate) (PMMA) microchip. Herein, diverse analytical techniques including contact angle analysis, Raman spectroscopic analysis, and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis were employed to validate the utility of the implantation protocol of the C-Cl moieties on the PMMA. The analytical results of the X-ray absorption near-edge structure (XANES) analysis also demonstrated the feasibility of the Cl-containing PMMA used as an extraction medium by virtue of the dipole-ion interactions between the highly electronegative C-Cl moieties and the positively charged metal ions. PMID:27584954

Microchip laser operation of Tm,Ho:KLu(WO₄)₂ crystal.

PubMed

Loiko, Pavel; Serres, Josep Maria; Mateos, Xavier; Yumashev, Konstantin; Kuleshov, Nikolai; Petrov, Valentin; Griebner, Uwe; Aguiló, Magdalena; Díaz, Francesc

2014-11-17

A microchip laser is realized on the basis of a monoclinic Tm,Ho-codoped KLu(WO₄)₂crystal cut for light propagation along the Ng optical indicatrix axis. This crystal cut provides positive thermal lens with extremely weak astigmatism, S/M = 4%. High sensitivity factors, M = dD/dP(abs), of 24.9 and 24.1 m(-1)/W for the mg- and pg- tangential planes are calculated with respect to the absorbed pump power. Such thermo-optic behavior is responsible for mode stabilization in the plano-plano microchip laser cavity, as well as the demonstrated perfect circular beam profile (M(2) < 1.1). Maximum continuous-wave output power of 450 mW is obtained with a slope efficiency of 31%. A set of output couplers is employed to achieve lasing in the spectral range of 2060-2096 nm. The increase of output coupler transmission results in deterioration of the laser performance attributed to the increased up-conversion losses.

Microchip-Based Single-Cell Functional Proteomics for Biomedical Applications

PubMed Central

Lu, Yao; Yang, Liu; Wei, Wei; Shi, Qihui

2017-01-01

Cellular heterogeneity has been widely recognized but only recently have single cell tools become available that allow characterizing heterogeneity at the genomic and proteomic levels. We review the technological advances in microchip-based toolkits for single-cell functional proteomics. Each of these tools has distinct advantages and limitations, and a few have advanced toward being applied to address biological or clinical problems that fail to be addressed by traditional population-based methods. High-throughput single-cell proteomic assays generate high-dimensional data sets that contain new information and thus require developing new analytical framework to extract new biology. In this review article, we highlight a few biological and clinical applications in which the microchip-based single-cell proteomic tools provide unique advantages. The examples include resolving functional heterogeneity and dynamics of immune cells, dissecting cell-cell interaction by creating well-contolled on-chip microenvironment, capturing high-resolution snapshots of immune system functions in patients for better immunotherapy and elucidating phosphoprotein signaling networks in cancer cells for guiding effective molecularly targeted therapies. PMID:28280819

Tm:GdVO4 microchip laser Q-switched by a Sb2Te3 topological insulator

NASA Astrophysics Data System (ADS)

Loiko, Pavel; Bogusławski, Jakub; Serres, Josep Maria; Kifle, Esrom; Kowalczyk, Maciej; Mateos, Xavier; Sotor, Jarosław; Zybała, Rafał; Mars, Krzysztof; Mikuła, Andrzej; Aguiló, Magdalena; Díaz, Francesc; Griebner, Uwe; Petrov, Valentin

2018-02-01

We report on the first application of a topological insulator based on antimony telluride (Sb2Te3) as a saturable absorber (SA) in a bulk microchip laser. The transmission-type SA consisted of a thin film of Sb2Te3 (thickness: 3 nm) deposited on a glass substrate by pulsed magnetron sputtering. The saturable absorption of the Sb2Te3 film was confirmed for ns-long pulses. The microchip laser was based on a Tm:GdVO4 crystal diode-pumped at 802 nm. In the continuous-wave regime, this laser generated 3.54 W at 1905-1921 nm with a slope efficiency η of 37%. The Q-switched laser generated a maximum average output power of 0.70 W at 1913 nm. The pulse energy and duration were 3.5 μJ and 223 ns, respectively, at a repetition rate of 200 kHz. The Sb2Te3 SAs are promising for passively Q-switched waveguide lasers at 2 μm.

Indirect detection of superoxide in RAW 264.7 macrophage cells using microchip electrophoresis coupled to laser-induced fluorescence.

PubMed

de Campos, Richard P S; Siegel, Joseph M; Fresta, Claudia G; Caruso, Giuseppe; da Silva, José A F; Lunte, Susan M

2015-09-01

Superoxide, a naturally produced reactive oxygen species (ROS) in the human body, is involved in many pathological and physiological signaling processes. However, if superoxide formation is left unregulated, overproduction can lead to oxidative damage to important biomolecules, such as DNA, lipids, and proteins. Superoxide can also lead to the formation of peroxynitrite, an extremely hazardous substance, through its reaction with endogenously produced nitric oxide. Despite its importance, quantitative information regarding superoxide production is difficult to obtain due to its high reactivity and low concentrations in vivo. MitoHE, a fluorescent probe that specifically reacts with superoxide, was used in conjunction with microchip electrophoresis (ME) and laser-induced fluorescence (LIF) detection to investigate changes in superoxide production by RAW 264.7 macrophage cells following stimulation with phorbol 12-myristate 13-acetate (PMA). Stimulation was performed in the presence and absence of the superoxide dismutase (SOD) inhibitors, diethyldithiocarbamate (DDC) and 2-metoxyestradiol (2-ME). The addition of these inhibitors resulted in an increase in the amount of superoxide specific product (2-OH-MitoE(+)) from 0.08 ± 0.01 fmol (0.17 ± 0.03 mM) in native cells to 1.26 ± 0.06 fmol (2.5 ± 0.1 mM) after PMA treatment. This corresponds to an approximately 15-fold increase in intracellular concentration per cell. Furthermore, the addition of 3-morpholino-sydnonimine (SIN-1) to the cells during incubation resulted in the production of 0.061 ± 0.006 fmol (0.12 ± 0.01 mM) of 2-OH-MitoE(+) per cell on average. These results demonstrate that indirect superoxide detection coupled with the use of SOD inhibitors and a separation method is a viable method to discriminate the 2-OH-MitoE(+) signal from possible interferences.

Dual fluorescence/contactless conductivity detection for microfluidic chip.

PubMed

Liu, Cui; Mo, Yun-yan; Chen, Zuan-guang; Li, Xiang; Li, Ou-lian; Zhou, Xie

2008-07-28

A new dual detection system for microchip is reported. Both fluorescence detector (FD) and contactless conductivity detector (CCD) were combined together and integrated on a microfluidic chip. They shared a common detection position and responded simultaneously. A blue light-emitting diode was used as excitation source and a small planar photodiode was used to collect the emitted fluorescence in fluorescence detection, which made the device more compact and portable. The coupling of the fluorescence and contactless conductivity modes at the same position of a single separation channel enhanced the detection characterization of sample and offered simultaneous detection information of both fluorescent and charged specimen. The detection conditions of the system were optimized. K(+), Na(+), fluorescein sodium, fluorescein isothiocyanate (FITC) and FITC-labeled amino acids were used to evaluate the performance of the dual detection system. The limits of detection (LOD) of FD for fluorescein Na(+), FITC, FITC-labeled arginine (Arg), glycine (Gly) and phenylalanine (Phe) were 0.02micromolL(-1), 0.05micromolL(-1), 0.16micromolL(-1), 0.15micromolL(-1), 0.12micromolL(-1) respectively, and the limits of detection (LOD) of CCD achieved 0.58micromolL(-1) and 0.39micromolL(-1) for K(+) and Na(+) respectively.

Comparison of three methods of temperature measurement in hypothermic, euthermic, and hyperthermic dogs.

PubMed

Greer, Rebecca J; Cohn, Leah A; Dodam, John R; Wagner-Mann, Colette C; Mann, F A

2007-06-15

To assess the reliability and accuracy of a predictive rectal thermometer, an infrared auricular thermometer designed for veterinary use, and a subcutaneous temperature-sensing microchip for measurement of core body temperature over various temperature conditions in dogs. Prospective study. 8 purpose-bred dogs. A minimum of 7 days prior to study commencement, a subcutaneous temperature-sensing microchip was implanted in 1 of 3 locations (interscapular, lateral aspect of shoulder, or sacral region) in each dog. For comparison with temperatures measured via rectal thermometer, infrared auricular thermometer, and microchip, core body temperature was measured via a thermistor-tipped pulmonary artery (TTPA) catheter. Hypothermia was induced during anesthesia at the time of TTPA catheter placement; on 3 occasions after placement of the catheter, hyperthermia was induced via administration of a low dose of endotoxin. Near-simultaneous duplicate temperature measurements were recorded from the TTPA catheter, the rectal thermometer, auricular thermometer, and subcutaneous microchips during hypothermia, euthermia, and hyperthermia. Reliability (variability) of temperature measurement for each device and agreement between each device measurement and core body temperature were assessed. Variability between duplicate near-simultaneous temperature measurements was greatest for the auricular thermometer and least for the TTPA catheter. Measurements obtained by use of the rectal thermometer were in closest agreement with core body temperature; for all other devices, temperature readings typically underestimated core body temperature. Among the 3 methods of temperature measurement, rectal thermometry provided the most accurate estimation of core body temperature in dogs.

Integrating Internal Standards into Disposable Capillary Electrophoresis Devices To Improve Quantification

PubMed Central

2017-01-01

To improve point-of-care quantification using microchip capillary electrophoresis (MCE), the chip-to-chip variabilities inherent in disposable, single-use devices must be addressed. This work proposes to integrate an internal standard (ISTD) into the microchip by adding it to the background electrolyte (BGE) instead of the sample—thus eliminating the need for additional sample manipulation, microchip redesigns, and/or system expansions required for traditional ISTD usage. Cs and Li ions were added as integrated ISTDs to the BGE, and their effects on the reproducibility of Na quantification were explored. Results were then compared to the conclusions of our previous publication which used Cs and Li as traditional ISTDs. The in-house fabricated microchips, electrophoretic protocols, and solution matrixes were kept constant, allowing the proposed method to be reliably compared to the traditional method. Using the integrated ISTDs, both Cs and Li improved the Na peak area reproducibility approximately 2-fold, to final RSD values of 2.2–4.7% (n = 900). In contrast (to previous work), Cs as a traditional ISTD resulted in final RSDs of 2.5–8.8%, while the traditional Li ISTD performed poorly with RSDs of 6.3–14.2%. These findings suggest integrated ISTDs are a viable method to improve the precision of disposable MCE devices—giving matched or superior results to the traditional method in this study while neither increasing system cost nor complexity. PMID:28192985

Microchip laser based on Yb:YAG/V:YAG monolith crystal

NASA Astrophysics Data System (ADS)

Nejezchleb, Karel; Šulc, Jan; Jelínková, Helena; Škoda, Václav

2016-03-01

V:YAG crystal was investigated as a passive Q-switch of longitudinally diode-pumped microchip laser, emitting radiation at wavelength 1030.5 nm. This laser was based on diffusion bonded monolith crystal (diameter 3 mm) which combines in one piece an active laser part (Yb:YAG crystal, 10 at.% Yb/Y, 3 mm long) and saturable absorber (V:YAG crystal, 2 mm long, initial transmission 86 % @ 1031 nm). The microchip resonator consisted of dielectric mirrors directly deposited on the monolith surfaces (pump mirror HT @ 968 nm and HR @ 1031 nm on Yb:YAG part, output coupler with reflection 55 % @ 1031 nm on the V:YAG part). For longitudinal CW pumping of Yb:YAG part, a fibre coupled (core diameter 100 μm, NA = 0.22, emission @ 968 nm) laser diode was used. The laser threshold was 3.8W. The laser slope efficiency for output mean in respect to incident pumping was 16 %. The linearly polarized generated transversal intensity beam profile was close to the fundamental Gaussian mode. The generated pulse length, stable and mostly independent on pumping power, was equal to 1.3 ns (FWHM). The single pulse energy was increasing with the pumping power and for the maximum pumping 9.7W it was 78 μJ which corresponds to the pulse peak-power 56 kW. The maximum Yb:YAG/V:YAG microchip laser mean output power of 1W was reached without observable thermal roll-over. The corresponding Q-switched pulses repetition rate was 13.1 kHz.

Spontaneous Packaging and Hypothermic Storage of Mammalian Cells with a Cell-Membrane-Mimetic Polymer Hydrogel in a Microchip.

PubMed

Xu, Yan; Mawatari, Kazuma; Konno, Tomohiro; Kitamori, Takehiko; Ishihara, Kazuhiko

2015-10-21

Currently, continuous culture/passage and cryopreservation are two major, well-established methods to provide cultivated mammalian cells for experiments in laboratories. Due to the lack of flexibility, however, both laboratory-oriented methods are unable to meet the need for rapidly growing cell-based applications, which require cell supply in a variety of occasions outside of laboratories. Herein, we report spontaneous packaging and hypothermic storage of mammalian cells under refrigerated (4 °C) and ambient conditions (25 °C) using a cell-membrane-mimetic methacryloyloxyethyl phosphorylcholine (MPC) polymer hydrogel incorporated within a glass microchip. Its capability for hypothermic storage of cells was comparatively evaluated over 16 days. The results reveal that the cytocompatible MPC polymer hydrogel, in combination with the microchip structure, enabled hypothermic storage of cells with quite high viability, high intracellular esterase activity, maintained cell membrane integrity, and small morphological change for more than 1 week at 4 °C and at least 4 days at 25 °C. Furthermore, the stored cells could be released from the hydrogel and exhibited the ability to adhere to a surface and achieve confluence under standard cell culture conditions. Both hypothermic storage conditions are ordinary flexible conditions which can be easily established in places outside of laboratories. Therefore, cell packaging and storage using the hydrogel incorporated within the microchip would be a promising miniature and portable solution for flexible supply and delivery of small amounts of cells from bench to bedside.

Recent approaches in sensitive enantioseparations by CE.

PubMed

Sánchez-Hernández, Laura; Castro-Puyana, María; Marina, María Luisa; Crego, Antonio L

2012-01-01

The latest strategies and instrumental improvements for enhancing the detection sensitivity in chiral analysis by CE are reviewed in this work. Following the previous reviews by García-Ruiz et al. (Electrophoresis 2006, 27, 195-212) and Sánchez-Hernández et al. (Electrophoresis 2008, 29, 237-251; Electrophoresis 2010, 31, 28-43), this review includes those papers that were published during the period from June 2009 to May 2011. These works describe the use of offline and online sample treatment techniques, online sample preconcentration techniques based on electrophoretic principles, and alternative detection systems to UV-Vis to increase the detection sensitivity. The application of the above-mentioned strategies, either alone or combined, to improve the sensitivity in the enantiomeric analysis of a broad range of samples, such as pharmaceutical, biological, food and environmental samples, enables to decrease the limits of detection up to 10⁻¹² M. The use of microchips to achieve sensitive chiral separations is also discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of beta cell dysfunction at the pre-symptomatic stage of diabetes mellitus by novel analytical system: liquid biopsy measurements in femtograms.

PubMed

Krapfenbauer, Kurt

2017-12-01

Diabetes mellitus is produced and progresses as a consequence of complex and gradual processes, in which a variety of alterations of the endocrine pancreas, are involved and which mainly result in beta cell failure. Those molecular alterations can be found in the bloodstream, which suggests that we could quantify specific biomarkers in plasma or serum by very sensitive methods before the onset diabetes mellitus is diagnosed. However, classical methods of protein analysis such as electrophoresis, Western blot, ELISA, and liquid chromatography are generally time-consuming, lab-intensive, and not sensitive enough to detect such alteration in a pre-symptomatic state of the disease. A very sensitive and novel analytical detection conjugate system by using the combination of polyfluorophor technology with protein microchip method was developed. This innovative system facilitates the use of a very sensitive microchip assays that measure selected biomarkers in a small sample volume (10 μL) with a much higher sensitivity (92%) compare to common immune assay systems. Further advances of the application of this technology combine the power of miniaturization and faster quantification (around 10 min). The power of this technology offers great promise for point-of-care clinical testing and monitoring of specific biomarkers for diabetes in femtogram level in serum or plasma. In conclusion, the results indicate that the technical performance of this new technology is valid and that the assay is able to quantified PPY-specific antigens in plasma at femtogram levels which can be used for identification of beta cell dysfunction at the pre-symptomatic stage of diabetes mellitus.

Simultaneous determination of reactive oxygen and nitrogen species in mitochondrial compartments of apoptotic HepG2 cells and PC12 cells based on microchip electrophoresis-laser-induced fluorescence.

PubMed

Chen, Zhenzhen; Li, Qingling; Sun, Qianqian; Chen, Hao; Wang, Xu; Li, Na; Yin, Miao; Xie, Yanxia; Li, Hongmin; Tang, Bo

2012-06-05

Determination of intracellular bioactive species will afford beneficial information related to cell metabolism, signal transduction, cell function, and disease treatment. In this study, the first application of a microchip electrophoresis-laser-induced fluorescence (MCE-LIF) method for concurrent determination of reactive oxygen species (ROS) and reactive nitrogen species (RNS), i.e., superoxide (O(2)(-•)) and nitric oxide (NO) in mitochondria, was developed using fluorescent probes 2-chloro-1,3-dibenzothiazolinecyclohexene (DBZTC) and 3-amino,4-aminomethyl-2',7'-difluorescein (DAF-FM), respectively. Potential interference of intracellular dehydroascorbic acid (DHA) and ascorbic acid (AA) for NO detection with DAF-FM was eliminated through oxidation of AA with the addition of ascorbate oxidase, followed by subsequent MCE separation. Fluorescent products of O(2)(-•) and NO, DBZTC oxide (DBO), and DAF-FM triazole (DAF-FMT) showed excellent baseline separation within 1 min with a running buffer of 40 mM Tris solution (pH 7.4) and a separating electric field of 500 V/cm. The levels of DBO and DAF-FMT in mitochondria isolated from normal HepG2 cells and PC12 cells were evaluated using this method. Furthermore, the changes of DBO and DAF-FMT levels in mitochondria isolated from apoptotic HepG2 cells and PC12 cells could also be detected. The current approach was proved to be simple, fast, reproducible, and efficient. Measurement of the two species with the method will be beneficial to understand ROS/RNS distinctive functions. In addition, it will provide new insights into the role that both species play in biological systems.

Novel immunoassay formats for integrated microfluidic circuits: diffusion immunoassays (DIA)

NASA Astrophysics Data System (ADS)

Weigl, Bernhard H.; Hatch, Anson; Kamholz, Andrew E.; Yager, Paul

2000-03-01

Novel designs of integrated fluidic microchips allow separations, chemical reactions, and calibration-free analytical measurements to be performed directly in very small quantities of complex samples such as whole blood and contaminated environmental samples. This technology lends itself to applications such as clinical diagnostics, including tumor marker screening, and environmental sensing in remote locations. Lab-on-a-Chip based systems offer many *advantages over traditional analytical devices: They consume extremely low volumes of both samples and reagents. Each chip is inexpensive and small. The sampling-to-result time is extremely short. They perform all analytical functions, including sampling, sample pretreatment, separation, dilution, and mixing steps, chemical reactions, and detection in an integrated microfluidic circuit. Lab-on-a-Chip systems enable the design of small, portable, rugged, low-cost, easy to use, yet extremely versatile and capable diagnostic instruments. In addition, fluids flowing in microchannels exhibit unique characteristics ('microfluidics'), which allow the design of analytical devices and assay formats that would not function on a macroscale. Existing Lab-on-a-chip technologies work very well for highly predictable and homogeneous samples common in genetic testing and drug discovery processes. One of the biggest challenges for current Labs-on-a-chip, however, is to perform analysis in the presence of the complexity and heterogeneity of actual samples such as whole blood or contaminated environmental samples. Micronics has developed a variety of Lab-on-a-Chip assays that can overcome those shortcomings. We will now present various types of novel Lab- on-a-Chip-based immunoassays, including the so-called Diffusion Immunoassays (DIA) that are based on the competitive laminar diffusion of analyte molecules and tracer molecules into a region of the chip containing antibodies that target the analyte molecules. Advantages of this technique are a reduction in reagents, higher sensitivity, minimal preparation of complex samples such as blood, real-time calibration, and extremely rapid analysis.

A microchip CD4 counting method for HIV monitoring in resource-poor settings.

PubMed

Rodriguez, William R; Christodoulides, Nicolaos; Floriano, Pierre N; Graham, Susan; Mohanty, Sanghamitra; Dixon, Meredith; Hsiang, Mina; Peter, Trevor; Zavahir, Shabnam; Thior, Ibou; Romanovicz, Dwight; Bernard, Bruce; Goodey, Adrian P; Walker, Bruce D; McDevitt, John T

2005-07-01

More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.

Nanobiotechnology advanced antifouling surfaces for the continuous electrochemical monitoring of glucose in whole blood using a lab-on-a-chip.

PubMed

Picher, Maria M; Küpcü, Seta; Huang, Chun-Jen; Dostalek, Jakub; Pum, Dietmar; Sleytr, Uwe B; Ertl, Peter

2013-05-07

In the current work we have developed a lab-on-a-chip containing embedded amperometric sensors in four microreactors that can be addressed individually and that are coated with crystalline surface protein monolayers to provide a continuous, stable, reliable and accurate detection of blood glucose. It is envisioned that the microfluidic device will be used in a feedback loop mechanism to assess natural variations in blood glucose levels during hemodialysis to allow the individual adjustment of glucose. Reliable and accurate detection of blood glucose is accomplished by simultaneously performing (a) blood glucose measurements, (b) autocalibration routines, (c) mediator-interferences detection, and (d) background subtractions. The electrochemical detection of blood glucose variations in the absence of electrode fouling events is performed by integrating crystalline surface layer proteins (S-layer) that function as an efficient antifouling coating, a highly-oriented immobilization matrix for biomolecules and an effective molecular sieve with pore sizes of 4 to 5 nm. We demonstrate that the S-layer protein SbpA (from Lysinibacillus sphaericus CCM 2177) readily forms monomolecular lattice structures at the various microchip surfaces (e.g. glass, PDMS, platinum and gold) within 60 min, eliminating unspecific adsorption events in the presence of human serum albumin, human plasma and freshly-drawn blood samples. The highly isoporous SbpA-coating allows undisturbed diffusion of the mediator between the electrode surface, thus enabling bioelectrochemical measurements of glucose concentrations between 500 μM to 50 mM (calibration slope δI/δc of 8.7 nA mM(-1)). Final proof-of-concept implementing the four microfluidic microreactor design is demonstrated using freshly drawn blood. Accurate and drift-free assessment of blood glucose concentrations (6. 4 mM) is accomplished over 130 min at 37 °C using immobilized enzyme glucose oxidase by calculating the difference between autocalibration (10 mM glc) and background measurements. The novel combination of biologically-derived nanostructured surfaces with microchip technology constitutes a powerful new tool for multiplexed analysis of complex samples.

Microchip dual-frequency laser with well-balanced intensity utilizing temperature control.

PubMed

Hu, Miao; Zhang, Yu; Wei, Mian; Zeng, Ran; Li, Qiliang; Lu, Yang; Wei, Yizhen

2016-10-03

A continuous-wave microchip dual-frequency laser (DFL) with well balanced intensity was presented. In order to obtain such a balanced intensity distribution of the two frequency components, the DFL wavelengths were precisely tuned and spectrally matched with the emission cross section (ECS) spectrum of the gain medium by employing a temperature controller. Finally, when the heat sink temperature was controlled at -5.6°C, a 264 mW DFL signal was achieved with frequency separation at 67.52 GHz and intensity balance ratio (IBR) at 0.991.

Profiling a multiplex short tandem repeat loci from human urine with use of low cost on-site technology for verification of sample authenticity.

PubMed

Pires, Nuno M M; Tao Dong; Berntzen, Lasse; Lonningdal, Torill

2017-07-01

This work focuses on the development of a sophisticated technique via STR typing to unequivocally verify the authenticity of urine samples before sent to laboratories. STR profiling was conducted with the CSF1PO, TPOX, TH01 Multiplex System coupled with a smartphone-based detection method. The promising capability of the method to identify distinct STR profiles from urine of different persons opens the possibility to conduct sample authenticity tests. On-site STR profiling could be realized with a self-contained autonomous device with an integrated PCR microchip shown hereby.

High-power, single-longitudinal-mode terahertz-wave generation pumped by a microchip Nd:YAG laser [Invited].

PubMed

Hayashi, Shin'ichiro; Nawata, Koji; Sakai, Hiroshi; Taira, Takunori; Minamide, Hiroaki; Kawase, Kodo

2012-01-30

We report on the development of a high-peak-power, single-longitudinal-mode and tunable injection-seeded terahertz-wave parametric generator using MgO:LiNbO3, which operates at room temperature. The high peak power (> 120 W) is enough to allow easy detection by commercial and calibrated pyroelectric detectors, and the spectral resolution (< 10 GHz) is the Fourier transform limit of the sub-nanosecond terahertz-wave pulse. The tunability (1.2-2.8 THz) and the small footprint size (A3 paper, 29.7 × 42 cm) are suitable for a variety of applications.

Sensitive Amino Acid Composition and Chirality Analysis with the Mars Organic Analyzer (MOA)

NASA Technical Reports Server (NTRS)

Skelley, Alison M.; Scherer, James R.; Aubrey, Andrew D.; Grover, William H.; Ivester, Robin H. C.; Ehrenfreund, Pascale; Grunthaner, Frank J.; Bada, Jeffrey L.; Mathies, Richard A.

2005-01-01

Detection of life on Mars requires definition of a suitable biomarker and development of sensitive yet compact instrumentation capable of performing in situ analyses. Our studies are focused on amino acid analysis because amino acids are more resistant to decomposition than other biomolecules, and because amino acid chirality is a well-defined biomarker. Amino acid composition and chirality analysis has been previously demonstrated in the lab using microfabricated capillary electrophoresis (CE) chips. To analyze amino acids in the field, we have developed the Mars Organic Analyzer (MOA), a portable analysis system that consists of a compact instrument and a novel multi-layer CE microchip.

Influence of temperature on Yb:YAG/Cr:YAG microchip laser operation

NASA Astrophysics Data System (ADS)

Šulc, Jan; Eisenschreiber, Jan; Jelínková, Helena; Nejezchleb, Karel; Å koda, Václav

2017-02-01

The goal of this work was an investigation of the temperature influence (in range from 80 up to 320 K) on the laser properties of Yb:YAG/Cr:YAG Q-switched diode-pumped microchip laser. This laser was based on monolith crystal (diameter 3mm) which combines in one piece an active laser part (Yb:YAG crystal, 10 at.% Yb/Y, 3mm long) and saturable absorber (Cr:YAG crystal, 1.36mm long, initial transmission 90% @ 1031 nm). The laser resonator pump mirror (HT for pump radiation, HR for generated radiation) was directly deposited on the Yb:YAG monolith part. The output coupler with reflection 55% for the generated wavelength was placed on the Cr:YAG part. The microchip laser was placed in the temperature controlled cupreous holder inside vacuum chamber of the liquid nitrogen cryostat. For Yb:YAG part longitudinal pulsed pumping (pumping pulse length 2.5 ms, rep-rate 20 Hz, power amplitude 21W) a fibre coupled (core diameter 400 μm, NA= 0:22) laser diode, operating at wavelength 933 nm, was used. The microchip laser mean output power, pulse duration, repetition rate, emission wavelength, and laser beam profile were measured in dependence on temperature. The generated pulse length was in range from 2.2 ns to 1.1 ns (FWHM) with the minimum at 230 K. The single pulse energy was peaking (0.4 mJ) at 180 K. The highest peak power (325 kW) was obtained at 220 K. The highest pulse repetition rate (38 kHz) and output mean power (370mW) was reached for temperature 80 K.

Native and sodium dodecyl sulfate-capillary gel electrophoresis of proteins on a single microchip.

PubMed

Tsai, Shuo-Wen; Loughran, Michael; Suzuki, Hiroaki; Karube, Isao

2004-02-01

Simultaneous electrophoresis of both native and Sodium dodecyl sulfate (SDS) proteins was observed on a single microchip within 20 min. The capillary array prevented lateral diffusion of SDS components and avoided cross contamination of native protein samples. The planar sputtered electrode format provided a more uniform distribution of separation voltage into each of the 36 parallel microchannel capillaries than platinum wire electrodes commonly used in conventional electrophoresis. The customized geometry of the stacking capillary machined into the cover plate of the microchip facilitated reproducible sample injection without the requirement for stacking gel. Polyimide served as a mask and facilitated insulation of the anode and cathode to prevent electrode lift off and deterioration during continuous electrophoresis, even at a constant current of 8 mA. Improved protein separation was observed during capillary electrophoresis at lower currents. Ferguson plot analysis confirmed the electrophoretic mobility of native globular proteins in accordance with their charge and size. Corresponding Ferguson plot analysis of SDS-associated proteins on the same chip confirmed separation of marker proteins according to their molecular weight.

MicrofluIdic circuit designs for performing electrokinetic manipulations that reduce the number of voltage sources and fluid reservoirs

DOEpatents

Jacobson, Stephen C.; Ramsey, J. Michael

2000-01-01

A microfabricated device and method for proportioning and mixing electrokinetically manipulated biological or chemical materials is disclosed. The microfabricated device mixes a plurality of materials in volumetric proportions controlled by the electrical resistances of tributary reagent channels through which the materials are transported. The microchip includes two or more tributary reagent channels combining at one or more junctions to form one or more mixing channels. By varying the geometries of the channels (length, cross section, etc.), a plurality of reagent materials can be mixed at a junction such that the proportions of the reagent materials in the mixing channel depend on a ratio of the channel geometries and material properties. Such an approach facilitates voltage division on the microchip without relying on external wiring schemes and voltage division techniques external to the microchip. Microchannel designs that provide the necessary voltage division to accomplish electrokinetic valving operations using a single voltage source and a switch are also described. In addition, microchannel designs that accomplish fluidic operation utilizing a minimal number of fluidic reservoirs are disclosed.

Microfluidic circuit designs for performing fluidic manipulations that reduce the number of pumping sources and fluid reservoirs

DOEpatents

Jacobson, Stephen C [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

2001-01-01

A microfabricated device and method for proportioning and mixing biological or chemical materials by pressure- or vacuum-driven flow is disclosed. The microfabricated device mixes a plurality of materials in volumetric proportions controlled by the flow resistances of tributary reagent channels through which the materials are transported. The microchip includes two or more tributary reagent channels combining at one or more junctions to form one or more mixing channels. By varying the geometries of the channels (length, cross section, etc.), a plurality of reagent materials can be mixed at a junction such that the proportions of the reagent materials in the mixing channel depend on a ratio of the channel geometries and material properties. Such an approach facilitates flow division on the microchip without relying on techniques external to the microchip. Microchannel designs that provide the necessary flow division to accomplish valving operations using a minimum of pressure or vacuum sources are also described. In addition, microchannel designs that accomplish fluidic operation utilizing a minimal number of fluidic reservoirs are disclosed.

Microchip electrospray: improvements in spray and signal stability during gradient elution by an inverted postcolumn makeup flow.

PubMed

Jung, Stephanie; Effelsberg, Uwe; Tallarek, Ulrich

2011-12-01

Dynamic changes in mobile phase composition during high-performance liquid chromatography (HPLC) gradient elution coupled to mass spectrometry (MS) sensitively affect electrospray modes. We investigate the impact of the eluent composition on spray stability and MS response by infusion and injection experiments with a small tetrapeptide in water-acetonitrile mixtures. The employed HPLC/electrospray (ESI)-MS configuration uses a microchip equipped with an enrichment column, a separation column, and a makeup flow (MUF) channel. One nano pump is connected to the separation column, while a second one delivers solvent of exactly inverted composition to the MUF channel. Both solvent streams are united behind the separation column, before the ESI tip, such that the resulting electrosprayed solution always has identical composition during a gradient elution. Analyte peak parameters without and with MUF compensation are determined and discussed with respect to the electrospray mode and eluent composition. The postcolumn MUF significantly improves spray and signal stability over the entire solvent gradient, without compromising the performance of the HPLC separation column. It can also be conveniently implemented on microchip platforms.

Low-power microwave-mediated heating for microchip-based PCR.

PubMed

Marchiarullo, Daniel J; Sklavounos, Angelique H; Oh, Kyudam; Poe, Brian L; Barker, N Scott; Landers, James P

2013-09-07

Microwave energy has been used to rapidly heat food and drinks for decades, in addition to assisting other chemical reactions. However, only recently has microwave energy been applied in microfluidic systems to heat solution in reaction chambers, in particular, the polymerase chain reaction (PCR). One of the difficulties in developing microwave-mediated heating on a microchip is the construction of the appropriate architecture for delivery of the energy to specific micro-areas on the microchip. This work employs commercially-available microwave components commonly used in the wireless communications industry to generate a microwave signal, and a microstrip transmission line to deliver the energy to a 1 μL reaction chamber fabricated in plastic microdevices. A model was developed to create transmission lines that would optimally transmit energy to the reaction chamber at a given frequency, minimizing energy usage while focusing microwave delivery to the target chamber. Two different temperature control methods were demonstrated, varying microwave power or frequency. This system was used to amplify a fragment of the lambda-phage genome, thereby demonstrating its potential for integration into a portable PCR system.

Effect of Compressive Stresses on Leakage Currents in Microchip Tantalum Capacitors

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander

2012-01-01

Microchip tantalum capacitors are manufactured using new technologies that allow for production of small size capacitors (down to EIA case size 0402) with volumetric efficiency much greater than for regular chip capacitors. Due to a small size of the parts and leadless design they might be more sensitive to mechanical stresses that develop after soldering onto printed wiring boards (PWB) compared to standard chip capacitors. In this work, the effect of compressive stresses on leakage currents in capacitors has been investigated in the range of stresses up to 200 MPa. Significant, up to three orders of magnitude, variations of currents were observed after the stress exceeds a certain critical level that varied from 10 MPa to 180 MPa for capacitors used in this study. A stress-induced generation of electron traps in tantalum pentoxide dielectric is suggested to explain reversible variations of leakage currents in tantalum capacitors. Thermo-mechanical characteristics of microchip capacitors have been studied to estimate the level of stresses caused by assembly onto PWB and assess the risk of stress-related degradation and failures. Keywords: tantalum capacitors, leakage current, soldering, reliability, mechanical stress.

Solvent-programmed microchip open-channel electrochromatography.

PubMed

Kutter, J P; Jacobson, S C; Matsubara, N; Ramsey, J M

1998-08-01

Open-channel electrochromatography in combination with solvent programming is demonstrated using a microchip device. Channel walls were coated with octadecylsilanes at ambient temperatures, yielding stationary phases for chromatographic separations of neutral dyes. The electroosmotic flow after coating was sufficient to ensure transport of all species and on-chip mixing of isocratic and gradient elution conditions with acetonitrile-buffer mixtures. Chips having different channel depths between 10.2 and 2.9 μm were evaluated for performance, and van Deemter plots were established. Channel depths of about 5 μm were found to be a good compromise between efficiency and ease of operation. Isocratic and gradient elution conditions were easily established and manipulated by computer-controlled application of voltages to the terminals of the microchip. Linear gradients with different slopes, start times, duration times, and start percentages of organic modifier proved to be powerful tools to tune selectivity and analysis time for the separation of a test mixture. Even very steep gradients still produced excellent efficiencies. Together with fast reconditioning times, complete runs could be finished in under 60 s.

Optically pumped quantum-dot Cd(Zn)Se/ZnSe laser and microchip converter for yellow-green spectral region

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

Lutsenko, E V; Voinilovich, A G; Rzheutskii, N V

2013-05-31

The room temperature laser generation in the yellow-green ({lambda} = 558.5-566.7 nm) spectral range has been demonstrated under optical pumping by a pulsed nitrogen laser of Cd(Zn)Se/ZnSe quantum dot heterostructures. The maximum achieved laser wavelength was as high as {lambda} = 566.7 nm at a laser cavity length of 945 {mu}m. High values of both the output pulsed power (up to 50 W) and the external differential quantum efficiency ({approx}60%) were obtained at a cavity length of 435 {mu}m. Both a high quality of the laser heterostructure and a low lasing threshold ({approx}2 kW cm{sup -2}) make it possible tomore » use a pulsed InGaN laser diode as a pump source. A laser microchip converter based on this heterostructure has demonstrated a maximum output pulse power of {approx}90 mW at {lambda} = 560 nm. The microchip converter was placed in a standard TO-18 (5.6 mm in diameter) laser diode package. (semiconductor lasers. physics and technology)« less

Enhanced performance of Cr,Yb:YAG microchip laser by bonding Yb:YAG crystal.

PubMed

Cheng, Ying; Dong, Jun; Ren, Yingying

2012-10-22

Highly efficient, laser-diode pumped Yb:YAG/Cr,Yb:YAG self-Q-switched microchip lasers by bonding Yb:YAG crystal have been demonstrated for the first time to our best knowledge. The effect of transmission of output coupler (T(oc)) on the enhanced performance of Yb:YAG/Cr,Yb:YAG microchip lasers has been investigated and found that the best laser performance was achieved with T(oc) = 50%. Slope efficiency of over 38% was achieved. Average output power of 0.8 W was obtained at absorbed pump power of 2.5 W; corresponding optical-to-optical efficiency of 32% was obtained. Laser pulses with pulse width of 1.68 ns, pulse energy of 12.4 μJ, and peak power of 7.4 kW were obtained. The lasers oscillated in multi-longitudinal modes. The wide separation of longitudinal modes was attributed to the mode selection by combined etalon effect of Cr,Yb:YAG, Yb:YAG thin plates and output coupler. Stable periodical pulse trains at different pump power levels have been observed owing to the longitudinal modes coupling and competition.

Structured optical vortices with broadband comb-like optical spectra in Yb:Y3Al5O12/YVO4 Raman microchip laser

NASA Astrophysics Data System (ADS)

Dong, Jun; Wang, Xiaolei; Zhang, Mingming; Wang, Xiaojie; He, Hongsen

2018-04-01

Structured optical vortices with 4 phase singularities have been generated in a laser diode pumped continuous-wave Yb:Y3Al5O12/YVO4 (Yb:YAG/YVO4) Raman microchip laser. The broadband comb-like first order Stokes laser emitting spectrum including 30 longitudinal modes covers from 1072.49 nm to 1080.13 nm with a bandwidth of 7.64 nm, which is generated with the Raman shift 259 cm-1 of the c-cut YVO4 crystal converted from the fundamental laser around 1.05 μm. Pump power dependent optical vortex beams are attributed to overlap of the Stokes laser field with the fundamental laser field caused by dynamically changing the coupling losses of the fundamental laser field. The maximum output power is 1.16 W, and the optical-to-optical efficiency is 18.4%. This work provides a method for generating structured optical vortices with an optical frequency comb in solid-state Raman microchip lasers, which have potential applications in quantum computations, micro-machining, and information processing.

From Bell Labs to Silicon Valley: A Saga of Technology Transfer, 1954-1961

NASA Astrophysics Data System (ADS)

Riordan, Michael

2009-03-01

Although Bell Telephone Laboratories invented the transistor and developed most of the associated semiconductor technology, the integrated circuit or microchip emerged elsewhere--at Texas Instruments and Fairchild Semiconductor Company. I recount how the silicon technology required to make microchips possible was first developed at Bell Labs in the mid-1950s. Much of it reached the San Francisco Bay Area when transistor pioneer William Shockley left Bell Labs in 1955 to establish the Shockley Semiconductor Laboratory in Mountain View, hiring a team of engineers and scientists to develop and manufacture transistors and related semiconductor devices. But eight of them--including Gordon Moore and Robert Noyce, eventually the co-founders of Intel--resigned en masse in September 1957 to start Fairchild, bringing with them the scientific and technological expertise they had acquired and further developed at Shockley's firm. This event marked the birth of Silicon Valley, both technologically and culturally. By March 1961 the company was marketing its Micrologic integrated circuits, the first commercial silicon microchips, based on the planar processing technique developed at Fairchild by Jean Hoerni.

Chip-based sequencing nucleic acids

DOEpatents

Beer, Neil Reginald

2014-08-26

A system for fast DNA sequencing by amplification of genetic material within microreactors, denaturing, demulsifying, and then sequencing the material, while retaining it in a PCR/sequencing zone by a magnetic field. One embodiment includes sequencing nucleic acids on a microchip that includes a microchannel flow channel in the microchip. The nucleic acids are isolated and hybridized to magnetic nanoparticles or to magnetic polystyrene-coated beads. Microreactor droplets are formed in the microchannel flow channel. The microreactor droplets containing the nucleic acids and the magnetic nanoparticles are retained in a magnetic trap in the microchannel flow channel and sequenced.

View northeast of a microchip based computer control system installed ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View northeast of a microchip based computer control system installed in the early 1980's to replace Lamokin Tower, at center of photograph; panels 1 and 2 at right of photograph are part of main supervisory board; panel 1 controlled Allen Lane sub-station #7; responsiblity for this portion of the system was transferred to southeast Pennsylvania transit authority (septa) in 1985; panel 2 at extreme right controls catenary switches in a coach storage yard adjacent to the station - Thirtieth Street Station, Power Director Center, Thirtieth & Market Streets in Amtrak Railroad Station, Philadelphia, Philadelphia County, PA

Generation of supercontinuum light in micro-structured fiber and polarization study at different wavelengths

NASA Astrophysics Data System (ADS)

Valle-Atilano, F. J.; Estudillo-Ayala, J. M.; Filoteo-Razo, J. D.; Hernández-García, J. C.; Jáuregui-Vázquez, D.; Sierra-Hernández, J. M.; Rojas-Laguna, R.; Mata-Chavez, R. I.; Samano-Aguilar, L. F.

2016-09-01

In this work, we study the changes of polarization at different wavelengths in a supercontinuum source generated through a microchip laser in the IR spectrum. We use a microchip laser pulsed as pumped source, 1064 nm of wavelength, and a photonic crystal fiber by generated a supercontinuum spectrum. We twist the fiber to the purpose to induce birefringence and study the changes of the state of polarization, and through bandpass filters we observe a single wavelength of the broad spectrum obtained. Besides, ellipticity study for different filters and its relation with the supercontinuum results is discussed.

Frequency-doubled passively Q-switched microchip laser producing 225  ps pulses at 671  nm.

PubMed

Nikkinen, Jari; Korpijärvi, Ville-Markus; Leino, Iiro; Härkönen, Antti; Guina, Mircea

2016-11-15

We report a 671 nm laser source emitting 225 ps pulses with an average power of 55 mW and a repetition rate of 444 kHz. The system consists of a 1342 nm SESAM Q-switched Nd:YVO₄ microchip master oscillator and a dual-stage Nd:YVO₄ power amplifier. The 1342 nm signal was frequency-doubled to 671 nm using a periodically poled lithium niobate crystal. This laser source provides a practical alternative for applications requiring high energy picosecond pulses, such as time-gated Raman spectroscopy.

Efficient blue conversion from a 1064 nm microchip laser in long photonic crystal fiber tapers for fluorescence microscopy.

PubMed

Kudlinski, A; Lelek, M; Barviau, B; Audry, L; Mussot, A

2010-08-02

Using a low-cost microchip laser and a long photonic crystal fiber taper, we report a supercontinuum source with a very efficient visible conversion, especially in the blue region (around 420 nm). About 30 % of the total average output power is located in the 350-600 nm band, which is of primary importance in a number of biophotonics applications such as flow cytometry or fluorescence imaging microscopy for instance. We successfully demonstrate the use of this visible-enhanced source for a three-color imaging of HeLa cells in wide-field microscopy.

Effect of pump polarization direction on power characteristics in monolithic microchip Nd:YAG dual-frequency laser.

PubMed

Chen, Hao; Zhang, Shulian; Tan, Yidong

2016-04-10

The pump polarization direction can greatly influence the characteristics of the laser diode end-pumped monolithic microchip Nd:YAG dual-frequency laser. We experimentally observe the lasing thresholds and the optical powers of two splitting modes versus the pump polarization direction. The effect of the pump-induced gain anisotropy on the mode oscillation sequence is analyzed. And the effect on the intensities of these modes is also proved with a rate equation model. This study contributes to the improvement of the stability and the reliability of the Nd:YAG dual-frequency laser.

Microchip solid-state cylindrical vector lasers with orthogonally polarized dual laser-diode end pumping.

PubMed

Otsuka, Kenju; Chu, Shu-Chun

2013-05-01

We report a simple method for generating cylindrical vector beams directly from laser-diode (LD)-pumped microchip solid-state lasers by using dual end-pumping beams. Radially as well as azimuthally polarized vector field emissions have been generated from the common c-cut Nd:GdVO4 laser cavity merely by controlling the focus positions of orthogonally polarized LD off-axis pump beams. Hyperbolically polarized vector fields have also been observed, in which the cylindrical symmetry of vector fields is broken. Experimental results have been well reproduced by numerical simulations.

The Role of Aerospace Power in U.S. National Security in the Next Quarter Century: Conference Proceedings Held in Arlington, Virginia on 16 March 1993

DTIC Science & Technology

1993-04-16

Kentucky long rifle is an F-15E Strike Eagle with laser -guided munitions). Aerospace power offers the ability for the United States to intervene with...glowing vacuum tubes might overshadow a single, cool microchip in their mids The Gulf War ushered in the era of the very small, very important target...precision, on making it better and better. Use the microchip as the role model. -Focus on forces and ideas which can execute rapidly, and with the minimum of

A Microchip-based Endothelium Mimic Utilizing Open Reservoirs for Cell Immobilization and Integrated Carbon Ink Microelectrodes for Detection

PubMed Central

Hulvey, Matthew K; Martin, R. Scott

2010-01-01

This paper describes the fabrication and characterization of a microfluidic device that utilizes a reservoir-based approach for endothelial cell immobilization and integrated embedded carbon ink microelectrodes for the amperometric detection of extracellular nitric oxide (NO) release. The design utilizes a buffer channel to continuously introduce buffer or a plug of stimulant to the reservoir as well as a separate sampling channel that constantly withdraws buffer from the reservoir and over the microelectrode. A steel pin is used for both the fluidic connection to the sampling channel and to provide a quasi-reference electrode for the carbon ink microelectrode. Characterization of the device was performed using NO standards produced from a NONOate salt. Finally, NO release from a layer of immobilized endothelial cells was monitored and quantified using the system. This system holds promise as a means to electrochemically detect extracellular NO release from endothelial cells in either an array of reservoirs or concurrently with fluorescence-based intracellular NO measurements. PMID:18989663

Hollow-fiber liquid-phase microextraction coupled with miniature capillary electrophoresis for the trace analysis of four aliphatic aldehydes in water samples.

PubMed

Li, Ying; Yi, Fan; Zheng, Yiliang; Wang, Yu; Ye, Jiannong; Chu, Qingcui

2015-08-01

An environmentally friendly method for the trace analysis of four aliphatic aldehydes as water disinfection byproducts has been developed based on hollow-fiber liquid-phase microextraction followed by miniature capillary electrophoresis with amperometric detection. After derivatization with 2-thiobarbituric acid, four aliphatic aldehydes (formaldehyde, acetaldehyde, propylaldehyde, and butyraldehyde) became detectable by the amperometric detector. Under the optimum conditions, four aliphatic aldehydes can be well separated from the coexisting interferents as well as their homologs (pentanal, glyoxal, and methyl-glyoxal), and the limits of detection (S/N = 3) could reach sub-nanogram-per-milliliter level based on hollow-fiber liquid-phase microextraction. The proposed method has been applied for the analyses of above four aliphatic aldehydes in different water samples such as drinking water, tap water, and river water, and the average recoveries were in the range of 90-113%, providing an alternative to conventional and microchip capillary electrophoresis approaches. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The impact of neurotechnology on rehabilitation.

PubMed

Berger, Theodore W; Gerhardt, Greg; Liker, Mark A; Soussou, Walid

2008-01-01

This paper present results of a multi-disciplinary project that is developing a microchip-based neural prosthesis for the hippocampus, a region of the brain responsible for the formation of long-term memories. Damage to the hippocampus is frequently associated with epilepsy, stroke, and dementia (Alzheimer's disease) and is considered to underlie the memory deficits related to these neurological conditions. The essential goals of the multi-laboratory effort include: (1) experimental study of neuron and neural network function--how does the hippocampus encode information? (2) formulation of biologically realistic models of neural system dynamics--can that encoding process be described mathematically to realize a predictive model of how the hippocampus responds to any event? (3) microchip implementation of neural system models--can the mathematical model be realized as a set of electronic circuits to achieve parallel processing, rapid computational speed, and miniaturization? and (4) creation of hybrid neuron-silicon interfaces-can structural and functional connections between electronic devices and neural tissue be achieved for long-term, bi-directional communication with the brain? By integrating solutions to these component problems, we are realizing a microchip-based model of hippocampal nonlinear dynamics that can perform the same function as part of the hippocampus. Through bi-directional communication with other neural tissue that normally provides the inputs and outputs to/from a damaged hippocampal area, the biomimetic model could serve as a neural prosthesis. A proof-of-concept will be presented in which the CA3 region of the hippocampal slice is surgically removed and is replaced by a microchip model of CA3 nonlinear dynamics--the "hybrid" hippocampal circuit displays normal physiological properties. How the work in brain slices is being extended to behaving animals also will be described.

In vitro and in vivo evaluation of ultrananocrystalline diamond as an encapsulation layer for implantable microchips.

PubMed

Chen, Ying-Chieh; Tsai, Che-Yao; Lee, Chi-Young; Lin, I-Nan

2014-05-01

Thin ultrananocrystalline diamond (UNCD) films were evaluated for use as hermetic and bioinert encapsulating coatings for implantable microchips, where the reaction to UNCD in vitro and in vivo tissue was investigated. Leakage current tests showed that depositing UNCD coatings, which were conformally grown in (1% H2) Ar/CH4 plasma, on microchips rendered the surface electrochemically inactive, i.e. with a very low leakage current density (2.8×10(-5)Acm(-2) at -1V and 1.9×10(-3)Acm(-2) at ±5V) ex vivo. The impact of UNCD with different surface modifications on the growth and activation of macrophages was compared to that of standard-grade polystyrene. Macrophages attached to oxygen-terminated UNCD films down-regulated their production of cytokines and chemokines. Moreover, with UNCD-coated microchips, which were implanted subcutaneously into BALB/c mice for up to 3months, the tissue reaction and capsule formation was significantly decreased compared to the medical-grade titanium alloy Ti-6Al-4V and bare silicon. Additionally, the leakage current density, elicited by electrochemical activity, on silicon chips encapsulated in oxygen-terminated UNCD coatings remained at the low level of 2.5×10(-3)Acm(-2) at 5V for up to 3months in vivo, which is half the level of those encapsulated in hydrogen-terminated UNCD coatings. Thus, controlling the surface properties of UNCDs makes it possible to manipulate the in vivo functionality and stability of implantable devices so as to reduce the host inflammatory response following implantation. These observations suggest that oxygen-terminated UNCDs are promising candidates for use as encapsulating coatings for implantable microelectronic devices. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Simple ps microchip Nd:YVO4 laser with 3.3-ps pulses at 0.2 to 1.4 MHz and single-stage amplification to the microjoule level

NASA Astrophysics Data System (ADS)

Türkyilmaz, Erdal; Lohbreier, Jan; Günther, Christian; Mehner, Eva; Kopf, Daniel; Giessen, Harald; Braun, Bernd

2016-06-01

Commercial picosecond sources have found widespread applications. Typical system parameters are pulse widths below 20 ps, repetition rates between 0.1 and 2 MHz, and microjoule level pulse energies. Most systems are based on short pulse mode-locked oscillators, regenerative amplifiers, and pockel cells as active beam switches. In contrast, we present a completely passive system, consisting of a passively Q-switched microchip laser, a single-stage amplifier, and a pulse compressor. The Q-switched microchip laser has a 50-μm-long Nd:YVO4 gain material optically bonded to a 4.6-mm-thick undoped YVO4 crystal. It delivers pulse widths of 40 ps and repetition rates of 0.2 to 1.4 MHz at a wavelength of 1.064 μm. The pulse energy is a few nanojoule. These 40-ps pulses are spectrally broadened in a standard single-mode fiber and then compressed in a 24-mm-long chirped Bragg grating to as low as 3.3 ps. The repetition rate can be tuned from ˜0.2 to 1.4 MHz by changing the pump power, while the pulse width and the pulse energy from the microchip laser are unchanged. The spectral broadening in the fiber is observed throughout the pulse repetition rate, supporting sub-10-ps pulses. Finally, the pulses are amplified in a single-stage Nd:YVO4 amplifier up to the microjoule level (up to 4 μJ pulse energy). As a result, the system delivers sub-10-ps pulses at a microjoule level with about 1 MHz repetition rate, and thus fulfills the requirements for ps-micromachining. It does not contain any active switching elements and can be integrated in a very compact setup.

Simple ps microchip Nd:YVO4 laser with 3.3 ps pulses at 0.2 - 1.4 MHz and single-stage amplification to the microjoule level

NASA Astrophysics Data System (ADS)

Türkyilmaz, Erdal; Lohbreier, Jan; Günther, Christian; Mehner, Eva; Kopf, Daniel; Giessen, Harald; Braun, Bernd

2016-03-01

Commercial picosecond sources have found widespread applications. Typical system parameters are pulse widths below 20 ps, repetition rates between 0.1 to 2 MHz, and micro Joule level pulse energies. Most systems are based on short pulse modelocked oscillators, regenerative amplifiers, and pockel cells as active beam switches. In contrast we present a completely passive system, consisting of a passively Q-switched microchip laser, a single-stage amplifier, and a pulse compressor. The Q-switched microchip laser has a 50 μm long Nd:YVO4-gain material optically bonded to a 4.6 mm thick undoped YVO4-crystal. It delivers pulse widths of 40 ps and repetition rates of 0.2 - 1.4 MHz at a wavelength of 1.064 μm. The pulse energy is a few nJ. These 40-ps pulses are spectrally broadened in a standard single mode fibre and then compressed in a 24 mm long chirped Bragg grating to as low as 3.3 ps. The repetition rate can be tuned from app. 0.2 to 1.4 MHz by changing the pump power while the pulse width and the pulse energy from the microchip laser are unchanged. The spectral broadening in the fibre is observed throughout the pulse repetition rate, supporting sub-10- ps pulses. Finally, the pulses are amplified in a single-stage Nd:YVO4-amplifier up to the microjoule level (up to 4 μJ pulse energy). As a result the system delivers sub-10-ps pulses at a microjoule level with about 1 MHz repetition rate, and thus fulfills the requirements for ps-micromachining. It does not contain any active switching elements and can be integrated in a very compact setup.

Performance of an organic photodiode as an optical detector and its application to fluorometric flow-immunoassay for IgA.

PubMed

Miyake, Mayo; Nakajima, Hizuru; Hemmi, Akihide; Yahiro, Masayuki; Adachi, Chihaya; Soh, Nobuaki; Ishimatsu, Ryoichi; Nakano, Koji; Uchiyama, Katsumi; Imato, Toshihiko

2012-07-15

The performance of an organic thin film photodiode (OPD), fabricated from a hetero-junction comprised of two layers of C(60) and a phthalocyanine-Cu(II) complex was evaluated by detecting the chemiluminescence generated from the reaction of luminol with horseradish peroxidase in the presence of H(2)O(2), and the fluorescence from resorufin, as an optical detector. The photocurrent of the OPD was linear with respect to the power of light from a commercial LED. The sensitivity of the OPD was sufficient for detecting chemiluminescence with a power 0.1μW/cm(2). The OPD was successfully used in a flow-immunoassay for IgA, a marker of human stress, in which a sandwich immunoassay was carried out on the microchip and the fluorescence from resorufin, produced by the enzymatic reaction, was detected. The detection limits for resorufin and IgA were 5.0μM and 16ng/mL, respectively. The photosensitivity of the OPD remained relatively constant for a minimum of one year. Copyright © 2012 Elsevier B.V. All rights reserved.

A portable explosive detector based on fluorescence quenching of pyrene deposited on coloured wax-printed μPADs.

PubMed

Taudte, Regina Verena; Beavis, Alison; Wilson-Wilde, Linzi; Roux, Claude; Doble, Philip; Blanes, Lucas

2013-11-07

A new technique for the detection of explosives has been developed based on fluorescence quenching of pyrene on paper-based analytical devices (μPADs). Wax barriers were generated (150 °C, 5 min) using ten different colours. Magenta was found as the most suitable wax colour for the generation of the hydrophobic barriers with a nominal width of 120 μm resulting in fully functioning hydrophobic barriers. One microliter of 0.5 mg mL(-1) pyrene dissolved in an 80:20 methanol-water solution was deposited on the hydrophobic circle (5 mm diameter) to produce the active microchip device. Under ultra-violet (UV) illumination, ten different organic explosives were detected using the μPAD, with limits of detection ranging from 100-600 ppm. A prototype of a portable battery operated instrument using a 3 W power UV light-emitting-diode (LED) (365 nm) and a photodiode sensor was also built and evaluated for the successful automatic detection of explosives and potential application for field-based screening.

Ceramic capillary electrophoresis chip for the measurement of inorganic ions in water samples.

PubMed

Fercher, Georg; Haller, Anna; Smetana, Walter; Vellekoop, Michael J

2010-05-01

We present a microchip capillary electrophoresis (CE) device build-up in low temperature co-fired ceramics (LTCC) multilayer technology for the analysis of major inorganic ions in water samples in less than 80 s. Contactless conductivity measurement is employed as a robust alternative to direct-contact conductivity detection schemes. The measurement electrodes are placed in a planar way at the top side of the CE chip and are realized by screen printing. Laser-cutting of channel and double-T injector structures is used to minimize irregularities and wall defects, elevating plate numbers per meter up to values of 110,000. Lowest limit of detection is 6 microM. The cost efficient LTCC module is attractive particularly for portable instruments in environmental applications because of its chemical inertness, hermeticity and easy three-dimensional integration capabilities of fluidic, electrical and mechanical components.

Photoacoustic detection of blood in dental pulp by using short-time Fourier transform

NASA Astrophysics Data System (ADS)

Yamada, Azusa; Kakino, Satoko; Matsuura, Yuji

2016-03-01

A method based on photoacoustic analysis is proposed to diagnose dental pulp vitality. Photoacoustic analysis enables to get signal from deeper tissues than other optical analyses and therefore, signal detection from root canal of thick dental tissues such as molar teeth is expected. As a light source for excitation of photoacoustic waves, a microchip Q-switched YAG laser with a wavelength of 1064 nm was used and owing to large penetration depth of the near infrared laser, photoacoustic signals from dental root were successfully obtained. It was found that the photoacoustic signals from the teeth containing hemoglobin solution in the pulp cavity provide vibration in high frequency region. It was also shown that the intensities of the high frequency component have correlation with the hemoglobin concentration of solution. We applied short-time Fourier transform for evaluation of photoacoustic signals and this analysis clearly showed photoacoustic signals from dental root.

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

Zhang, Xing; Ibrahim, Yehia M.; Chen, Tsung-Chi

We report the first evaluation of a platform coupling a high speed field asymmetric ion mobility spectrometry microchip (µFAIMS) with drift tube ion mobility and mass spectrometry (IMS-MS). The µFAIMS/IMS-MS platform was used to analyze biological samples and simultaneously acquire multidimensional information of detected features from the measured FAIMS compensation fields and IMS drift times, while also obtaining accurate ion masses. These separations thereby increase the overall separation power, resulting increased information content, and provide more complete characterization of more complex samples. The separation conditions were optimized for sensitivity and resolving power by the selection of gas compositions and pressuresmore » in the FAIMS and IMS separation stages. The resulting performance provided three dimensional separations, benefitting both broad complex mixture studies and targeted analyses by e.g. improving isomeric separations and allowing detection of species obscured by “chemical noise” and other interfering peaks.« less

Portable biochip scanner device

DOEpatents

Perov, Alexander; Sharonov, Alexei; Mirzabekov, Andrei D.

2002-01-01

A portable biochip scanner device used to detect and acquire fluorescence signal data from biological microchips (biochips) is provided. The portable biochip scanner device employs a laser for emitting an excitation beam. An optical fiber delivers the laser beam to a portable biochip scanner. A lens collimates the laser beam, the collimated laser beam is deflected by a dichroic mirror and focused by an objective lens onto a biochip. The fluorescence light from the biochip is collected and collimated by the objective lens. The fluorescence light is delivered to a photomultiplier tube (PMT) via an emission filter and a focusing lens. The focusing lens focuses the fluorescence light into a pinhole. A signal output of the PMT is processed and displayed.

Large scale DNA microsequencing device

DOEpatents

Foote, Robert S.

1997-01-01

A microminiature sequencing apparatus and method provide means for simultaneously obtaining sequences of plural polynucleotide strands. The apparatus comprises a microchip into which plural channels have been etched using standard lithographic procedures and chemical wet etching. The channels include a reaction well and a separating section. Enclosing the channels is accomplished by bonding a transparent cover plate over the apparatus. A first oligonucleotide strand is chemically affixed to the apparatus through an alkyl chain. Subsequent nucleotides are selected by complementary base pair bonding. A target nucleotide strand is used to produce a family of labelled sequencing strands in each channel which are separated in the separating section. During or following separation the sequences are determined using appropriate detection means.

Large scale DNA microsequencing device

DOEpatents

Foote, Robert S.

1999-01-01

A microminiature sequencing apparatus and method provide means for simultaneously obtaining sequences of plural polynucleotide strands. The apparatus comprises a microchip into which plural channels have been etched using standard lithographic procedures and chemical wet etching. The channels include a reaction well and a separating section. Enclosing the channels is accomplished by bonding a transparent cover plate over the apparatus. A first oligonucleotide strand is chemically affixed to the apparatus through an alkyl chain. Subsequent nucleotides are selected by complementary base pair bonding. A target nucleotide strand is used to produce a family of labelled sequencing strands in each channel which are separated in the separating section. During or following separation the sequences are determined using appropriate detection means.

Large scale DNA microsequencing device

DOEpatents

Foote, R.S.

1999-08-31

A microminiature sequencing apparatus and method provide means for simultaneously obtaining sequences of plural polynucleotide strands. The apparatus comprises a microchip into which plural channels have been etched using standard lithographic procedures and chemical wet etching. The channels include a reaction well and a separating section. Enclosing the channels is accomplished by bonding a transparent cover plate over the apparatus. A first oligonucleotide strand is chemically affixed to the apparatus through an alkyl chain. Subsequent nucleotides are selected by complementary base pair bonding. A target nucleotide strand is used to produce a family of labelled sequencing strands in each channel which are separated in the separating section. During or following separation the sequences are determined using appropriate detection means. 11 figs.

Compressed 6 ps pulse in nonlinear amplification of a Q-switched microchip laser

NASA Astrophysics Data System (ADS)

Diao, Ruxin; Liu, Zuosheng; Niu, Fuzeng; Wang, Aimin; Taira, Takunori; Zhang, Zhigang

2017-02-01

We present a passively Q-switched Nd:YVO4 crystal microchip laser with a 6 ps pulse width, which is based on SPM-induced spectral broadening and pulse compression. The passive Q-switching is obtained by a semiconductor saturable absorber mirror. The laser’s seed source centered at 1064 nm pulses with a duration of 80 ps, at a repetition rate of 600 kHz corresponding to an average output power of 10 mW. After amplification and compression, the pulses were compressed to 6 ps with a maximum pulse energy of 0.5 µJ.

Passively Q-switched microchip Er, Yb:YAl3(BO3)4 diode-pumped laser.

PubMed

Kisel, V E; Gorbachenya, K N; Yasukevich, A S; Ivashko, A M; Kuleshov, N V; Maltsev, V V; Leonyuk, N I

2012-07-01

We report, for the first time to our knowledge, a diode-pumped cw and passively Q-switched microchip Er, Yb:YAl(3)(BO(3))(4) laser. A maximal output power of 800 mW at 1602 nm in the cw regime was obtained at an absorbed pump power of 7.7 W. By using Co(2+):MgAl(2)O(4) as a saturable absorber, a TEM(00)-mode Q-switched average output power of 315 mW was demonstrated at 1522 nm, with pulse duration of 5 ns and pulse energy of 5.25 μJ at a repetition rate of 60 kHz.

Laser micromachined isoelectric focusing devices on polymer substrate for electrospray mass spectrometry

NASA Astrophysics Data System (ADS)

Lin, Yuehe; Wen, Jenny; Fan, Xiang; Matson, Dean W.; Smith, Richard D.

1999-08-01

A microfabricated device for isoelectric focusing (IEF) incorporating an optimized electrospray ionization (ESI) tip was constructed on polycarbonate plates using a laser micromachining technique. The separation channels on an IEF chip were 16 cm long, 50 micrometers wide and 30 micrometers deep. Electrical potentials used for IEF focusing and electrospray were applied through platinum electrodes placed in the buffer reservoirs, and which were isolated from the separation channel by molecular porous membranes. On-line ESI produced directly from a sharp `tip' on the microchip was evaluated. The results indicate that this design can produce a stable electrospray that is further improved and made more flexible with the assistance of sheath gas and sheath liquid. Error analysis of the spectral data shows that the standard deviation in signal intensity for an analyte peak was less than approximately 5% over 3 hours. The production of stable electrosprays directly from microchip IEF devices represents a step towards easily- fabricated microanalytical devices. IEF separations of protein mixtures were demonstrated for uncoated polycarbonate microchips. On-line IEF/ESI-MS was demonstrated using the microfabricated chip with an ion-trap ESI mass spectrometer for characterization of protein mixtures.

3D printing of biomimetic microstructures for cancer cell migration.

PubMed

Huang, Tina Qing; Qu, Xin; Liu, Justin; Chen, Shaochen

2014-02-01

To understand the physical behavior and migration of cancer cells, a 3D in vitro micro-chip in hydrogel was created using 3D projection printing. The micro-chip has a honeycomb branched structure, aiming to mimic 3D vascular morphology to test, monitor, and analyze differences in the behavior of cancer cells (i.e. HeLa) vs. non-cancerous cell lines (i.e. 10 T1/2). The 3D Projection Printing system can fabricate complex structures in seconds from user-created designs. The fabricated microstructures have three different channel widths of 25, 45, and 120 microns wide to reflect a range of blood vessel diameters. HeLa and 10 T1/2 cells seeded within the micro-chip were then analyzed for morphology and cell migration speed. 10 T1/2 cells exhibited greater changes in morphology due to channel size width than HeLa cells; however, channel width had a limited effect on 10 T1/2 cell migration while HeLa cancer cell migration increased as channel width decreased. This physiologically relevant 3D cancer tissue model has the potential to be a powerful tool for future drug discoveries and cancer migration studies.

Measurement of blood coagulation with considering RBC aggregation through a microchip-based light transmission aggregometer.

PubMed

Lim, Hyunjung; Nam, Jeonghun; Xue, Shubin; Shin, Sehyun

2011-01-01

Even though blood coagulation can be tested by various methods and techniques, the effect of RBC aggregation on blood coagulation is not fully understood. The present study monitored clot formation in a microchip-based light transmission aggregometer. Citrated blood samples with and without the addition of calcium ion solution were initially disaggregated by rotating a stirrer in the microchip. After abrupt stop of the rotating stirrer, the transmitted light intensity over time was recorded. The syllectogram (light intensity vs. time graph) manifested a rapid increase that is associated with RBC aggregation followed by a decrease that is associated with blood coagulation. The time to reach the peak point was used as a new index of coagulation time (CT) and ranged from 200 to 500 seconds in the present measurements. The CT was inversely proportional to the concentration of fibrinogen, which enhances RBC aggregation. In addition, the CT was inversely proportional to the hematocrit, which is similar to the case of the prothrombin time (PT), as measured by a commercial coagulometer. Thus, we carefully concluded that RBC aggregation should be considered in tests of blood coagulation.

Manufacturing and application of a fully polymeric electrophoresis chip with integrated polyaniline electrodes.

PubMed

Henderson, Rowan D; Guijt, Rosanne M; Haddad, Paul R; Hilder, Emily F; Lewis, Trevor W; Breadmore, Michael C

2010-07-21

This work describes the development of a fully polymeric microchip with integrated polymeric electrodes suitable for performing microchip electrophoresis. The polymer electrodes were fabricated in a thin film of the conducting polymer, polyaniline (PANI), by flash lithography using a studio camera flash and a transparency mask. During flash welding, exposed regions welded into non-conducting regions forming a conducting polymer circuit in the non-exposed regions. Using a structured layer of dry film photoresist for sealing, a polydimethylsiloxane (PDMS) substrate containing channels and reservoirs was bound to the PANI film to form an integrated microfluidic device. The conducting regions of the PANI film were shown to be capable of carrying the high voltages of up to 2000 V required for chip electrophoresis, and were stable for up to 30 minutes under these conditions. The PANI electrodes were used for the electrophoretic separation of three sugars labelled with 8-amino-1,3,6-pyrenetrisulfonic acid (APTS) in the dry film resist-PDMS hybrid device. Highly efficient separations comparable to those achieved in similar microchips using platinum electrodes confirm the potential of polyaniline as a new material suitable for high voltage electrodes in Lab-on-a-chip devices.

Study on mechanism of amplitude fluctuation of dual-frequency beat in microchip Nd:YAG laser

NASA Astrophysics Data System (ADS)

Chen, Hao; Tan, Yidong; Zhang, Shulian; Sun, Liqun

2017-01-01

In the laser heterodyne interferometry based on the microchip Nd:YAG dual-frequency laser, the amplitude of the beat note periodically fluctuates in time domain, which leads to the instability of the measurement. On the frequency spectrums of the two mono-frequency components of the laser and their beat note, several weak sideband signals are observed on both sides of the beat note. It is proved that the sideband frequencies are associated with the relaxation oscillation frequencies of the laser. The mechanism for the relaxation oscillations inducing the occurrence of the sideband signals is theoretically analyzed, and the quantitative relationship between the intensity ratio of the beat note to the sideband signal and the level of the amplitude fluctuation is simulated with the derived mathematical model. The results demonstrate that the periodical amplitude fluctuation of the beat note is actually induced by the relaxation oscillation. And the level of the amplitude fluctuation is lower than 10% when the intensity ratio is greater than 32 dB. These conclusions are beneficial to reduce the amplitude fluctuation of the microchip Nd:YAG dual-frequency laser and improve the stability of the heterodyne interferometry.

Passive Q-switching of microchip lasers based on Ho:YAG ceramics.

PubMed

Lan, R; Loiko, P; Mateos, X; Wang, Y; Li, J; Pan, Y; Choi, S Y; Kim, M H; Rotermund, F; Yasukevich, A; Yumashev, K; Griebner, U; Petrov, V

2016-06-20

A Ho:YAG ceramic microchip laser pumped by a Tm fiber laser at 1910 nm is passively Q-switched by single- and multi-layer graphene, single-walled carbon nanotubes (SWCNTs), and Cr²⁺:ZnSe saturable absorbers (SAs). Employing SWCNTs, this laser generated an average power of 810 mW at 2090 nm with a slope efficiency of 68% and continuous wave to Q-switching conversion efficiency of 70%. The shortest pulse duration was 85 ns at a repetition rate of 165 kHz, and the pulse energy reached 4.9 μJ. The laser performance and pulse stability were superior compared to graphene SAs even for a different number of graphene layers (n=1 to 4). A model for the description of the Ho:YAG laser Q-switched by carbon nanostructures is presented. This modeling allowed us to estimate the saturation intensity for multi-layered graphene and SWCNT SAs to be 1.2±0.2 and 7±1  MW/cm², respectively. When using Cr²⁺:ZnSe, the Ho:YAG microchip laser generated 11 ns/25 μJ pulses at a repetition rate of 14.8 kHz.

Temperature-dependent spectroscopy and microchip laser operation of Nd:KGd(WO4)2

NASA Astrophysics Data System (ADS)

Loiko, P.; Yoon, S. J.; Serres, J. M.; Mateos, X.; Beecher, S. J.; Birch, R. B.; Savitski, V. G.; Kemp, A. J.; Yumashev, K.; Griebner, U.; Petrov, V.; Aguiló, M.; Díaz, F.; Mackenzie, J. I.

2016-08-01

High-resolution absorption and stimulated-emission cross-section spectra are presented for monoclinic Nd:KGd(WO4)2 (Nd:KGW) laser crystals in the temperature range 77-450 K. At room-temperature, the maximum stimulated emission cross-section is σSE = 21.4 × 10-20 cm2 at 1067.3 nm, for light polarization E || Nm. The lifetime of the 4F3/2 state of Nd3+ in KGW is practically temperature independent at 115 ± 5 μs. Measurement of the energy transfer upconversion parameter for a 3 at.% Nd:KGW crystal proved that this was significantly smaller than for alternative hosts, ∼2.5 × 10-17 cm3/s. When cut along the Ng optical indicatrix axis, the Nd:KGW crystal was configured as a microchip laser, generating ∼4 W of continuous-wave output at 1067 nm with a slope efficiency of 61% under diode-pumping. Using a highly-doped (10 at.%) Nd:KGW crystal, the slope efficiency reached 71% and 74% when pumped with a laser diode and a Ti:Sapphire laser, respectively. The concept of an ultrathin (250 μm) Nd:KGW microchip laser sandwiched between two synthetic diamond heat-spreaders is demonstrated.

A strategy to modulate the electrophoretic behavior in plastic microchips using sodium polystyrene sulfonate.

PubMed

Guo, Jinxiu; Chen, Yu; Zhao, Lizhi; Sun, Ping; Li, Hongli; Zhou, Lei; Wang, Xiayan; Pu, Qiaosheng

2016-12-16

Plastic microchips have been broadly used as disposable microfluidic devices, but the poorly defined surface properties limit their application. Herein, we proved that an anionic polymer could be used as the background electrolyte (BGE) to provide a strong and stable cathodic electroosmotic flow (EOF) and modulate the electrophoretic behavior for efficient separation in relative thicker microchannels (∼75μm id). A cathodic EOF of ∼3.3×10 -4 cm 2 V -1 s -1 was maintained using sodium polystyrene sulfonate (PSSNa) with a molecular weight of 5×10 5 as the BGE, which ensured fluorescein isothiocyanate labeled biogenic amines (BAs) appeared ahead of other components in the electropherograms obtained with microchips of cyclic olefin copolymer. Four selected BAs appeared within 50s and theoretical plate numbers of 8.0×10 5 /m were achieved. The role of PSSNa was evaluated with streaming potential, dynamic light scattering, contact angle and atomic force microscopy. Its functionalities as surface modifier, viscosity regulator and pseudostationary phase were also confirmed. The proposed electrophoretic method was applied in the fast determination of BAs in fish meat samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Microchip capillary electrophoresis instrumentation for in situ analysis in the search for extraterrestrial life.

PubMed

Mora, Maria F; Stockton, Amanda M; Willis, Peter A

2012-09-01

The search for signs of life on extraterrestrial planetary bodies is among NASA's top priorities in Solar System exploration. The associated pursuit of organics and biomolecules as evidence of past or present life demands in situ investigations of planetary bodies for which sample return missions are neither practical nor affordable. These in situ studies require instrumentation capable of sensitive chemical analyses of complex mixtures including a broad range of organic molecules. Instrumentation must also be capable of autonomous operation aboard a robotically controlled vehicle that collects data and transmits it back to Earth. Microchip capillary electrophoresis (μCE) coupled to laser-induced fluorescence (LIF) detection provides this required sensitivity and targets a wide range of relevant organics while offering low mass, volume, and power requirements. Thus, this technology would be ideally suited for in situ studies of astrobiology targets, such as Mars, Europa, Enceladus, and Titan. In this review, we introduce the characteristics of these planetary bodies that make them compelling destinations for extraterrestrial astrobiological studies, and the principal groups of organics of interest associated with each. And although the technology we describe here was first developed specifically for proposed studies of Mars, by summarizing its evolution over the past decade, we demonstrate how μCE-LIF instrumentation has become an ideal candidate for missions of exploration to all of these nearby worlds in our Solar System. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fabrication of a microfluidic Ag/AgCl reference electrode and its application for portable and disposable electrochemical microchips.

PubMed

Zhou, Jianhua; Ren, Kangning; Zheng, Yizhe; Su, Jing; Zhao, Yihua; Ryan, Declan; Wu, Hongkai

2010-09-01

This report describes a convenient method for the fabrication of a miniaturized, reliable Ag/AgCl reference electrode with nanofluidic channels acting as a salt bridge that can be easily integrated into microfluidic chips. The Ag/AgCl reference electrode shows high stability with millivolt variations. We demonstrated the application of this reference electrode in a portable microfluidic chip that is connected to a USB-port microelectrochemical station and to a computer for data collection and analysis. The low fabrication cost of the chip with the potential for mass production makes it disposable and an excellent candidate for real-world analysis and measurement. We used the chip to quantitatively analyze the concentrations of heavy metal ions (Cd(2+) and Pb(2+)) in sea water. We believe that the Ag/AgCl reference microelectrode and the portable electrochemical system will be of interest to people in microfluidics, environmental science, clinical diagnostics, and food research.

Microfluidic devices for the controlled manipulation of small volumes

DOEpatents

Ramsey, J Michael [Knoxville, TN; Jacobson, Stephen C [Knoxville, TN

2003-02-25

A method for conducting a broad range of biochemical analyses or manipulations on a series of nano- to subnanoliter reaction volumes and an apparatus for carrying out the same are disclosed. The method and apparatus are implemented on a fluidic microchip to provide high serial throughput. The method and device of the invention also lend themselves to multiple parallel analyses and manipulation to provide greater throughput for the generation of biochemical information. In particular, the disclosed device is a microfabricated channel device that can manipulate nanoliter or subnanoliter biochemical reaction volumes in a controlled manner to produce results at rates of 1 to 10 Hz per channel. The individual reaction volumes are manipulated in serial fashion analogous to a digital shift register. The method and apparatus according to this invention have application to such problems as screening molecular or cellular targets using single beads from split-synthesis combinatorial libraries, screening single cells for RNA or protein expression, genetic diagnostic screening at the single cell level, or performing single cell signal transduction studies.

Oil-encapsulated nanodroplet array for bio-molecular detection.

PubMed

Qiao, Wen; Zhang, Tiantian; Yen, Tony; Ku, Ti-Hsuan; Song, Junlan; Lian, Ian; Lo, Yu-Hwa

2014-09-01

Detection of low abundance biomolecules is challenging for biosensors that rely on surface chemical reactions. For surface reaction based biosensors, it require to take hours or even days for biomolecules of diffusivities in the order of 10(-10-11) m2/s to reach the surface of the sensors by Brownian motion. In addition, often times the repelling Coulomb interactions between the molecules and the probes further defer the binding process, leading to undesirably long detection time for applications such as point-of-care in vitro diagnosis. In this work, we designed an oil encapsulated nanodroplet array microchip utilizing evaporation for pre-concentration of the targets to greatly shorten the reaction time and enhance the detection sensitivity. The evaporation process of the droplets is facilitated by the superhydrophilic surface and resulting nanodroplets are encapsulated by oil drops to form stable reaction chamber. Using this method, desirable droplet volumes, concentrations of target molecules, and reaction conditions (salt concentrations, reaction temperature, etc.) in favour of fast and sensitive detection are obtained. A linear response over 2 orders of magnitude in target concentration was achieved at 10 fM for protein targets and 100 fM for miRNA mimic oligonucleotides.

A microchip electrophoresis-mass spectrometric platform with double cell lysis nano-electrodes for automated single cell analysis.

PubMed

Li, Xiangtang; Zhao, Shulin; Hu, Hankun; Liu, Yi-Ming

2016-06-17

Capillary electrophoresis-based single cell analysis has become an essential approach in researches at the cellular level. However, automation of single cell analysis has been a challenge due to the difficulty to control the number of cells injected and the irreproducibility associated with cell aggregation. Herein we report the development of a new microfluidic platform deploying the double nano-electrode cell lysis technique for automated analysis of single cells with mass spectrometric detection. The proposed microfluidic chip features integration of a cell-sized high voltage zone for quick single cell lysis, a microfluidic channel for electrophoretic separation, and a nanoelectrospray emitter for ionization in MS detection. Built upon this platform, a microchip electrophoresis-mass spectrometric method (MCE-MS) has been developed for automated single cell analysis. In the method, cell introduction, cell lysis, and MCE-MS separation are computer controlled and integrated as a cycle into consecutive assays. Analysis of large numbers of individual PC-12 neuronal cells (both intact and exposed to 25mM KCl) was carried out to determine intracellular levels of dopamine (DA) and glutamic acid (Glu). It was found that DA content in PC-12 cells was higher than Glu content, and both varied from cell to cell. The ratio of intracellular DA to Glu was 4.20±0.8 (n=150). Interestingly, the ratio drastically decreased to 0.38±0.20 (n=150) after the cells are exposed to 25mM KCl for 8min, suggesting the cells released DA promptly and heavily while they released Glu at a much slower pace in response to KCl-induced depolarization. These results indicate that the proposed MCE-MS analytical platform may have a great potential in researches at the cellular level. Copyright © 2016 Elsevier B.V. All rights reserved.

Potent method for the simultaneous determination of glutathione and hydrogen peroxide in mitochondrial compartments of apoptotic cells with microchip electrophoresis-laser induced fluorescence.

PubMed

Chen, Zhenzhen; Li, Qingling; Wang, Xu; Wang, Zhiyuan; Zhang, Ruirui; Yin, Miao; Yin, Lingling; Xu, Kehua; Tang, Bo

2010-03-01

The first application of microchip electrophoresis with laser-induced fluorescence (MCE-LIF) detection to simultaneously determine glutathione (GSH) and hydrogen peroxide (H(2)O(2)) in mitochondria was described. Organoselenium probe Rh-Se-2 and bis(p-methylbenzenesulfonate)dichlorofluorescein (FS) synthesized in our laboratory were utilized as fluorescent probes for GSH and H(2)O(2), respectively. Rh-Se-2, which is nonfluorescent, reacts with GSH to produce rhodamine 110 (Rh110) with high quantum yield. Similarly, nonfluorescent FS reacts with H(2)O(2) and produces dichlorofluorescein (DCF) accompanied by drastic fluorescence enhancement. Both probes exhibit good sensitivity toward their respective target molecule determination. Fast, simple, and sensitive determination of GSH and H(2)O(2) was realized within 37 s using a running buffer of 50 mM mannitol, 40 mM HEPES (pH 7.4), and an electric field of 360 V/cm for separation. The linear ranges of the method were 3.3 x 10(-9)-1.0 x 10(-7) M/2.9 x 10(-7)-1.0 x 10(-4) M and 2.7 x 10(-9)-4.0 x 10(-7) M with detection limits (signal-to-noise ratio = 3) of 1.3 nM (0.16 amol) and 1.0 nM (0.12 amol) for GSH and H(2)O(2), respectively. The relative standard deviations (RSDs) of migration time and peak area were less than 1.0% and 4.0%, respectively. The MCE-LIF assay was utilized to investigate the levels of GSH and H(2)O(2) in mitochondria isolated from HepG2 cells and were found to be 2.01 +/- 0.21 mM and 5.36 +/- 0.45 microM, respectively. The method was further extended to observe situations of the two species in mitochondria of HepG2 cells experiencing cell apoptosis that were induced by doxorubicin and photodynamic therapy (PDT).

Electric field effects on current–voltage relationships in microfluidic channels presenting multiple working electrodes in the weak-coupling limit

DOE PAGES

Contento, Nicholas M.; Bohn, Paul W.

2014-05-23

While electrochemical methods are well suited for lab-on-a-chip applications, reliably coupling multiple, electrode-controlled processes in a single microfluidic channel remains a considerable challenge, because the electric fields driving electrokinetic flow make it difficult to establish a precisely known potential at the working electrode(s). The challenge of coupling electrochemical detection with microchip electrophoresis is well known; however, the problem is general, arising in other multielectrode arrangements with applications in enhanced detection and chemical processing. Here, we study the effects of induced electric fields on voltammetric behavior in a microchannel containing multiple in-channel electrodes, using a Fe(CN) 6 3/4- model system. Whenmore » an electric field is induced by applying a cathodic potential at one inchannel electrode, the half-wave potential (E 1/2) for the oxidation of ferrocyanide at an adjacent electrode shifts to more negative potentials. The E 1/2 value depends linearly on the electric field current at a separate in-channel electrode. The observed shift in E 1/2 is quantitatively described by a model, which accounts for the change in solution potential caused by the iR drop along the length of the microchannel. The model, which reliably captures changes in electrode location and solution conductivity, apportions the electric field potential between iR drop and electrochemical potential components, enabling the study of microchannel electric field magnitudes at low applied potentials. In the system studied, the iR component of the electric field potential increases exponentially with applied current before reaching an asymptotic value near 80 % of the total applied potential. The methods described will aid in the development and interpretation of future microchip electrochemistry methods, particularly those that benefit from the coupling of electrokinetic and electrochemical phenomena at low voltages.« less

Multiscale free-space optical interconnects for intrachip global communication: motivation, analysis, and experimental validation.

PubMed

McFadden, Michael J; Iqbal, Muzammil; Dillon, Thomas; Nair, Rohit; Gu, Tian; Prather, Dennis W; Haney, Michael W

2006-09-01

The use of optical interconnects for communication between points on a microchip is motivated by system-level interconnect modeling showing the saturation of metal wire capacity at the global layer. Free-space optical solutions are analyzed for intrachip communication at the global layer. A multiscale solution comprising microlenses, etched compound slope microprisms, and a curved mirror is shown to outperform a single-scale alternative. Microprisms are designed and fabricated and inserted into an optical setup apparatus to experimentally validate the concept. The multiscale free-space system is shown to have the potential to provide the bandwidth density and configuration flexibility required for global communication in future generations of microchips.

Laser heating of aqueous samples on a micro-optical-electro-mechanical system

DOEpatents

Beer, Neil Reginald; Kennedy, Ian

2013-12-17

A system of heating a sample on a microchip includes the steps of providing a microchannel flow channel in the microchip; positioning the sample within the microchannel flow channel, providing a laser that directs a laser beam onto the sample for heating the sample; providing the microchannel flow channel with a wall section that receives the laser beam and enables the laser beam to pass through wall section of the microchannel flow channel without being appreciably heated by the laser beam; and providing a carrier fluid in the microchannel flow channel that moves the sample in the microchannel flow channel wherein the carrier fluid is not appreciably heated by the laser beam.

Laser heating of aqueous samples on a micro-optical-electro-mechanical system

DOEpatents

Beer, Neil Reginald; Kennedy, Ian

2013-02-05

A system of heating a sample on a microchip includes the steps of providing a microchannel flow channel in the microchip; positioning the sample within the microchannel flow channel, providing a laser that directs a laser beam onto the sample for heating the sample; providing the microchannel flow channel with a wall section that receives the laser beam and enables the laser beam to pass through wall section of the microchannel flow channel without being appreciably heated by the laser beam; and providing a carrier fluid in the microchannel flow channel that moves the sample in the microchannel flow channel wherein the carrier fluid is not appreciably heated by the laser beam.

Giant-pulse Nd:YVO4 microchip laser with MW-level peak power by emission cross-sectional control.

PubMed

Kausas, Arvydas; Taira, Takunori

2016-02-22

We present a giant-pulse generation laser realized by the emission cross-section control of a gain medium in a passively Q-switched Nd:YVO4 microchip laser with a Cr4+:YAG saturable absorber. Up to 1.17 MW peak power and 1.03 mJ pulse energy were obtained with a 100 Hz repetition rate. By combining the Nd:YVO4 crystal with a Sapphire plate, lower temperature difference between a pump region in the gain crystal and a crystal holder was obtained which helped to keep the cavity in stability zone at elevated temperatures and allowed the achievement of the high peak power for this laser system.

Response of microchip solid-state laser to external frequency-shifted feedback and its applications

PubMed Central

Tan, Yidong; Zhang, Shulian; Zhang, Song; Zhang, Yongqing; Liu, Ning

2013-01-01

The response of the microchip solid-state Nd:YAG laser, which is subjected to external frequency-shifted feedback, is experimentally and theoretically analysed. The continuous weak response of the laser to the phase and amplitude of the feedback light is achieved by controlling the feedback power level, and this system can be used to achieve contact-free measurement of displacement, vibration, liquid evaporation and thermal expansion with nanometre accuracy in common room conditions without precise environmental control. Furthermore, a strong response, including chaotic harmonic and parametric oscillation, is observed, and the spectrum of this response, as examined by a frequency-stabilised Nd:YAG laser, indicates laser spectral linewidth broadening. PMID:24105389

Subnanosecond Tm:KLuW microchip laser Q-switched by a Cr:ZnS saturable absorber.

PubMed

Loiko, Pavel; Serres, Josep Maria; Mateos, Xavier; Yumashev, Konstantin; Yasukevich, Anatoly; Petrov, Valentin; Griebner, Uwe; Aguiló, Magdalena; Díaz, Francesc

2015-11-15

Passive Q-switching of a compact Tm:KLu(WO(4))(2) microchip laser diode pumped at 805 nm is demonstrated with a polycrystalline Cr(2+):ZnS saturable absorber. This laser generates subnanosecond (780 ps) pulses with a pulse repetition frequency of 5.6 kHz at 1846.6 nm, the shortest pulse duration ever achieved by Q-switching of ~2 μm lasers. The maximum average output power is 146 mW with a slope efficiency of 21% with respect to the absorbed power. This corresponds to a pulse energy of 25.6 μJ and a peak power of 32.8 kW.

Response of microchip solid-state laser to external frequency-shifted feedback and its applications.

PubMed

Tan, Yidong; Zhang, Shulian; Zhang, Song; Zhang, Yongqing; Liu, Ning

2013-10-09

The response of the microchip solid-state Nd:YAG laser, which is subjected to external frequency-shifted feedback, is experimentally and theoretically analysed. The continuous weak response of the laser to the phase and amplitude of the feedback light is achieved by controlling the feedback power level, and this system can be used to achieve contact-free measurement of displacement, vibration, liquid evaporation and thermal expansion with nanometre accuracy in common room conditions without precise environmental control. Furthermore, a strong response, including chaotic harmonic and parametric oscillation, is observed, and the spectrum of this response, as examined by a frequency-stabilised Nd:YAG laser, indicates laser spectral linewidth broadening.

Thermal analysis of a diffusion bonded Er3+,Yb3+:glass/Co2+: MgAl2O4 microchip lasers

NASA Astrophysics Data System (ADS)

Belghachem, Nabil; Mlynczak, Jaroslaw; Kopczynski, krzysztof; Mierczyk, Zygmunt; Gawron, Michal

2016-10-01

The analysis of thermal effects in a diffusion bonded Er3+,Yb3+:glass/Co2+:MgAl2O4 microchip laser is presented. The analysis is performed for both wavelengths at 940 nm and at 975 nm as well as for two different sides of pumping, glass side and saturable absorber side. The heat sink effect of Co2+:MgAl2O4, as well as the impact of the thermal expansion and induced stress on the diffusion bonding are emphasised. The best configurations for reducing the temperature peaks, the Von Mises stresses on the diffusion bonding, and the thermal lensing are determined.

Recent Developments in Instrumentation for Capillary Electrophoresis and Microchip-Capillary Electrophoresis

PubMed Central

Felhofer, Jessica L.; Blanes, Lucas; Garcia, Carlos D.

2010-01-01

Over the last years there has been an explosion in the number of developments and applications of capillary electrophoresis (CE) and microchip-CE. In part, this growth has been the direct consequence of recent developments in instrumentation associated with CE. This review, which is focused on contributions published in the last five years, is intended to complement the papers presented in this special issue dedicated to Instrumentation and to provide an overview on the general trend and some of the most remarkable developments published in the areas of high voltage power supplies, detectors, auxiliary components, and compact systems. It also includes few examples of alternative uses of and modifications to traditional CE instruments. PMID:20665910

Automated microfluidic devices integrating solid-phase extraction, fluorescent labeling, and microchip electrophoresis for preterm birth biomarker analysis.

PubMed

Sahore, Vishal; Sonker, Mukul; Nielsen, Anna V; Knob, Radim; Kumar, Suresh; Woolley, Adam T

2018-01-01

We have developed multichannel integrated microfluidic devices for automated preconcentration, labeling, purification, and separation of preterm birth (PTB) biomarkers. We fabricated multilayer poly(dimethylsiloxane)-cyclic olefin copolymer (PDMS-COC) devices that perform solid-phase extraction (SPE) and microchip electrophoresis (μCE) for automated PTB biomarker analysis. The PDMS control layer had a peristaltic pump and pneumatic valves for flow control, while the PDMS fluidic layer had five input reservoirs connected to microchannels and a μCE system. The COC layers had a reversed-phase octyl methacrylate porous polymer monolith for SPE and fluorescent labeling of PTB biomarkers. We determined μCE conditions for two PTB biomarkers, ferritin (Fer) and corticotropin-releasing factor (CRF). We used these integrated microfluidic devices to preconcentrate and purify off-chip-labeled Fer and CRF in an automated fashion. Finally, we performed a fully automated on-chip analysis of unlabeled PTB biomarkers, involving SPE, labeling, and μCE separation with 1 h total analysis time. These integrated systems have strong potential to be combined with upstream immunoaffinity extraction, offering a compact sample-to-answer biomarker analysis platform. Graphical abstract Pressure-actuated integrated microfluidic devices have been developed for automated solid-phase extraction, fluorescent labeling, and microchip electrophoresis of preterm birth biomarkers.

Second Names Chip is Placed on InSight

NASA Image and Video Library

2018-01-24

An engineer in the clean room at Lockheed Martin Space in Littleton, Colorado, affixes a dime-size chip onto the lander deck of NASA's InSight spacecraft. This second microchip, contains 1.6 million names submitted by the public to ride along with InSight to Mars. The chip was installed on Jan. 23, 2018. This joins another microchip that was previously installed that included 800,000 names for a grand total of 2.4 million names going to Mars as early as May 5, 2018. Engineers at NASA's Jet Propulsion Laboratory, Pasadena, California, put the names onto this tiny 0.3 square inches (8 millimeter-square) silicon wafer microchip using an electron beam to write extremely tiny letters with lines smaller than one one-thousandth the width of a human hair. The dime-size chip is affixed to the InSight lander deck and will remain on Mars forever. Normally used to make high-precision nanometer-scale devices, this technique was also used to write millions of names that were transported on NASA Mars rovers and Orion's first test flight. InSight is the first Mars mission dedicated to study the deep interior of Mars. Its findings will advance understanding of the early history of all rocky planets, including Earth. https://photojournal.jpl.nasa.gov/catalog/PIA22236

Simultaneous Identification and Antimicrobial Susceptibility Testing of Multiple Uropathogens on a Microfluidic Chip with Paper-Supported Cell Culture Arrays.

PubMed

Xu, Banglao; Du, Yan; Lin, Jinqiong; Qi, Mingyue; Shu, Bowen; Wen, Xiaoxia; Liang, Guangtie; Chen, Bin; Liu, Dayu

2016-12-06

A microfluidic chip was developed for one-step identification and antimicrobial susceptibility testing (AST) of multiple uropathogens. The polydimethylsiloxane (PDMS) microchip used had features of cell culture chamber arrays connected through a sample introduction channel. At the bottom of each chamber, a paper substrate preloaded with chromogenic media and antimicrobial agents was embedded. By integrating a hydrophobic membrane valve on the microchip, the urine sample can be equally distributed into and confined in individual chambers. The identification and AST assays on multiple uropathogens were performed by combining the spatial resolution of the cell culture arrays and the color resolution from the chromogenic reaction. The composite microbial testing assay was based on dynamic changes in color in a serial of chambers. The bacterial antimicrobial susceptibility was determined by the lowest concentration of an antimicrobial agent that is capable of inhibiting the chromogenic reaction. Using three common uropathogenic bacteria as test models, the developed microfluidic approach was demonstrated to be able to complete the multiple colorimetric assays in 15 h. The accuracy of the microchip method, in comparison with that of the conventional approach, showed a coincidence of 94.1%. Our data suggest this microfluidic approach will be a promising tool for simple and fast uropathogen testing in resource-limited settings.

Simple and Rapid Immobilization of Coating Polymers on Poly(dimethyl siloxane)-glass Hybrid Microchips by a Vacuum-drying Method.

PubMed

Kitagawa, Fumihiko; Nakagawara, Syo; Nukatsuka, Isoshi; Hori, Yusuke; Sueyoshi, Kenji; Otsuka, Koji

2015-01-01

A simple and rapid vacuum-drying modification method was applied to several neutral and charged polymers to obtain coating layers for controlling electroosmotic flow (EOF) and suppressing sample adsorption on poly(dimethyl siloxane) (PDMS)-glass hybrid microchips. In the vacuum-dried poly(vinylpyrrolidone) coating, the electroosmotic mobility (μeo) was suppressed from +2.1 to +0.88 × 10(-4) cm(2)/V·s, and the relative standard deviation (RSD) of μeo was improved from 10.2 to 2.5% relative to the bare microchannel. Among several neutral polymers, poly(vinylalcohol) (PVA) and poly(dimethylacrylamide) coatings gave more suppressed and repeatable EOF with RSDs of less than 2.3%. The vacuum-drying method was also applicable to polyanions and polycations to provide accelerated and inversed EOF, respectively, with acceptable RSDs of less than 4.9%. In the microchip electrophoresis (MCE) analysis of bovine serum albumin (BSA) in the vacuum-dried and thermally-treated PVA coating channel, an almost symmetric peak of BSA was obtained, while in the native microchannel a significantly skewed peak was observed. The results demonstrated that the vacuum-dried polymer coatings were effective to control the EOF, and reduced the surface adsorption of proteins in MCE.

A Continuous-Flow Polymerase Chain Reaction Microchip With Regional Velocity Control

PubMed Central

Li, Shifeng; Fozdar, David Y.; Ali, Mehnaaz F.; Li, Hao; Shao, Dongbing; Vykoukal, Daynene M.; Vykoukal, Jody; Floriano, Pierre N.; Olsen, Michael; McDevitt, John T.; Gascoyne, Peter R.C.; Chen, Shaochen

2009-01-01

This paper presents a continuous-flow polymerase chain reaction (PCR) microchip with a serpentine microchannel of varying width for “regional velocity control.” Varying the channel width by incorporating expanding and contracting conduits made it possible to control DNA sample velocities for the optimization of the exposure times of the sample to each temperature phase while minimizing the transitional periods during temperature transitions. A finite element analysis (FEA) and semi-analytical heat transfer model was used to determine the distances between the three heating assemblies that are responsible for creating the denaturation (96 °C), hybridization (60 °C), and extension (72 °C) temperature zones within the microchip. Predictions from the thermal FEA and semi-analytical model were compared with temperature measurements obtained from an infrared (IR) camera. Flow-field FEAs were also performed to predict the velocity distributions in the regions of the expanding and contracting conduits to study the effects of the microchannel geometry on flow recirculation and bubble nucleation. The flow fields were empirically studied using micro particle image velocimetry (μ-PIV) to validate the flow-field FEA’s and to determine experimental velocities in each of the regions of different width. Successful amplification of a 90 base pair (bp) bacillus anthracis DNA fragment was achieved. PMID:19829760

Efficient excitations of radially and azimuthally polarized Nd3+:YAG ceramic microchip laser by use of subwavelength multilayer concentric gratings composed of Nb2O5/SiO2.

PubMed

Li, Jian-Lang; Ueda, Ken-ichi; Zhong, Lan-xiang; Musha, Mitsuru; Shirakawa, Akira; Sato, Takashi

2008-07-07

Cylindrical vector beams were produced from laser diode end-pumped Nd:YAG ceramic microchip laser by use of two types of subwavelength multilayer gratings as the axisymmetric-polarization output couplers respectively. The grating mirrors are composed of high- and low-refractive- index (Nb(2)O(5)/SiO(2)) layers alternately while each layer is shaped into triangle and concentric corrugations. For radially polarized laser output, the beam power reached 610mW with a polarization extinction ratio (PER) of 61:1 and a slope efficiency of 68.2%; for azimuthally polarized laser output, the beam power reached 626mW with a PER of 58:1 and a slope efficiency of 47.6%. In both cases, the laser beams had near-diffraction limited quality. Small differences of beam power, PER and slope efficiency between radially and azimuthally polarized laser outputs were not critical, and could be minimized by further optimized adjustment to laser cavity and the reflectances of respective grating mirrors. The results manifested, by use of the photonic crystal gratings mirrors and end-pumped microchip laser configuration, CVBs can be generated efficiently with high modal symmetry and polarization purity.

Double-helix micro-channels on microfluidic chips for enhanced continuous on-chip derivatization followed by electrophoretic separation.

PubMed

Peng, Xianglu; Zhao, Lei; Guo, Jinxiu; Yang, Shenghong; Ding, Hui; Wang, Xiayan; Pu, Qiaosheng

2015-10-15

Micro-channels that contain a special inner structure are critical for efficient mixing and chemical reactions. In this paper, we described the facile fabrication of an integrated microchip with double-helix type micro-channels to improve mixing efficiency and to facilitate multi-step derivatization reactions prior to electrophoretic separation. With a prepared microchip, reagents, samples and reaction products could be driven through micro-channels by siphon, and no other pumping device was necessary. To test its performance, reductive amination of aldehydes with 8-aminonaphthalene-1,3,6-trisulfonate acid disodium (ANTS) was attempted via microchip electrophoresis with laser induced fluorescence (LIF). The effect of the geometry of the reaction micro-channel on the reaction's efficiency was evaluated. Under the selected conditions, successful derivatization of five aldehydes was realized for highly reproducible analysis. The relative standard deviations of the peak areas for 30 consecutive injections were in the range of 0.28-1.61%. The method was applied for the determination of aldehydes in real samples with standard addition recoveries of 87.8-102.8%. Good tolerance of organic solvents was achieved, and the proposed method can potentially be employed for rapid screening of excessively added aldehyde food flavoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Tuning the Ignition Performance of a Microchip Initiator by Integrating Various Al/MoO3 Reactive Multilayer Films on a Semiconductor Bridge.

PubMed

Xu, Jianbing; Tai, Yu; Ru, Chengbo; Dai, Ji; Ye, Yinghua; Shen, Ruiqi; Zhu, Peng

2017-02-15

Reactive multilayer films (RMFs) can be integrated into semiconducting electronic structures with the use of microelectromechanical systems (MEMS) technology and represent potential applications in the advancement of microscale energy-demanding systems. In this study, aluminum/molybdenum trioxide (Al/MoO 3 )-based RMFs with different modulation periods were integrated on a semiconductor bridge (SCB) using a combination of an image reversal lift-off process and magnetron sputtering technology. This produced an energetic semiconductor bridge (ESCB)-chip initiator with controlled ignition performance. The effects of the Al/MoO 3 RMFs with different modulation periods on ignition properties of the ESCB initiator were then systematically investigated in terms of flame duration, maximum flame area, and the reaction ratio of the RMFs. These microchip initiators achieved flame durations of 60-600 μs, maximum flame areas of 2.85-17.61 mm 2 , and reaction ratios of ∼14-100% (discharged with 47 μF/30 V) by simply changing the modulation periods of the Al/MoO 3 RMFs. This behavior was also consistent with a one-dimensional diffusion reaction model. The microchip initiator exhibited a high level of integration and proved to have tuned ignition performance, which can potentially be used in civilian and military applications.

Large scale DNA microsequencing device

DOEpatents

Foote, R.S.

1997-08-26

A microminiature sequencing apparatus and method provide a means for simultaneously obtaining sequences of plural polynucleotide strands. The apparatus cosists of a microchip into which plural channels have been etched using standard lithographic procedures and chemical wet etching. The channels include a reaction well and a separating section. Enclosing the channels is accomplished by bonding a transparent cover plate over the apparatus. A first oligonucleotide strand is chemically affixed to the apparatus through an alkyl chain. Subsequent nucleotides are selected by complementary base pair bonding. A target nucleotide strand is used to produce a family of labelled sequencing strands in each channel which are separated in the separating section. During or following separation the sequences are determined using appropriate detection means. 17 figs.

Kansei Biosensor and IT Society

NASA Astrophysics Data System (ADS)

Toko, Kiyoshi

A taste sensor with global selectivity is composed of several kinds of lipid/polymer membranes for transforming information of taste substances into electric signal. The sensor output shows different patterns for chemical substances which have different taste qualities such as saltiness and sourness. Taste interactions such as suppression effect, which occurs between bitterness and sweetness, can be detected and quantified using the taste sensor. The taste and also smell of foodstuffs such as beer, coffee, mineral water, soup and milk can be discussed quantitatively. The taste sensor provides the objective scale for the human sensory expression. Multi-modal communication becomes possible using a taste/smell recognition microchip, which produces virtual taste. We are now standing at the beginning of a new age of communication using digitized taste.

Capillary electrophoresis hyphenated with UV-native-laser induced fluorescence detection (CE/UV-native-LIF).

PubMed

Couderc, François; Ong-Meang, Varravaddheay; Poinsot, Véréna

2017-01-01

Native laser-induced fluorescence using UV lasers associated to CE offers now a large related literature, for now 30 years. The main works have been performed using very expensive Ar-ion lasers emitting at 257 and 275 nm. They are not affordable for routine analyses, but have numerous applications such as protein, catecholamine, and indolamine analysis. Some other lasers such as HeCd 325 nm have been used but only for few applications. Diode lasers, emitting at 266 nm, cheaper, are extensively used for the same topics, even if the obtained sensitivity is lower than the one observed using the costly UV-Ar-ion lasers. This review presents various CE or microchips applications and different UV lasers used for the excitation of native fluorescence. We showed that CE/Native UV laser induced fluorescence detection is very sensitive for detection as well as small aromatic biomolecules than proteins containing Trp and Tyr amino acids. Moreover, it is a simple way to analyze biomolecules without derivatization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simplified transient isotachophoresis/capillary gel electrophoresis method for highly sensitive analysis of polymerase chain reaction samples on a microchip with laser-induced fluorescence detection.

PubMed

Liu, Dayu; Ou, Ziyou; Xu, Mingfei; Wang, Lihui

2008-12-19

We present a sensitive, simple and robust on-chip transient isotachophoresis/capillary gel electrophoresis (tITP/CGE) method for the analysis of polymerase chain reaction (PCR) samples. Using chloride ions in the PCR buffer and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) in the background electrolyte, respectively, as the leading and terminating electrolytes, the tITP preconcentration was coupled with CGE separation with double-T shaped channel network. The tITP/CGE separation was carried out with a single running buffer. The separation process involved only two steps that were performed continuously with the sequential switching of four voltage outputs. The tITP/CGE method showed an analysis time and a separation efficiency comparable to those of standard CGE, while the signal intensity was enhanced by factors of over 20. The limit of detection of the chip-based tITP/CGE method was estimated to be 1.1 ng/mL of DNA in 1x PCR buffer using confocal fluorescence detection following 473 nm laser excitation.

Intelligent microchip networks: an agent-on-chip synthesis framework for the design of smart and robust sensor networks

NASA Astrophysics Data System (ADS)

Bosse, Stefan

2013-05-01

Sensorial materials consisting of high-density, miniaturized, and embedded sensor networks require new robust and reliable data processing and communication approaches. Structural health monitoring is one major field of application for sensorial materials. Each sensor node provides some kind of sensor, electronics, data processing, and communication with a strong focus on microchip-level implementation to meet the goals of miniaturization and low-power energy environments, a prerequisite for autonomous behaviour and operation. Reliability requires robustness of the entire system in the presence of node, link, data processing, and communication failures. Interaction between nodes is required to manage and distribute information. One common interaction model is the mobile agent. An agent approach provides stronger autonomy than a traditional object or remote-procedure-call based approach. Agents can decide for themselves, which actions are performed, and they are capable of flexible behaviour, reacting on the environment and other agents, providing some degree of robustness. Traditionally multi-agent systems are abstract programming models which are implemented in software and executed on program controlled computer architectures. This approach does not well scale to micro-chip level and requires full equipped computers and communication structures, and the hardware architecture does not consider and reflect the requirements for agent processing and interaction. We propose and demonstrate a novel design paradigm for reliable distributed data processing systems and a synthesis methodology and framework for multi-agent systems implementable entirely on microchip-level with resource and power constrained digital logic supporting Agent-On-Chip architectures (AoC). The agent behaviour and mobility is fully integrated on the micro-chip using pipelined communicating processes implemented with finite-state machines and register-transfer logic. The agent behaviour, interaction (communication), and mobility features are modelled and specified on a machine-independent abstract programming level using a state-based agent behaviour language (APL). With this APL a high-level agent compiler is able to synthesize a hardware model (RTL, VHDL), a software model (C, ML), or a simulation model (XML) suitable to simulate a multi-agent system using the SeSAm simulator framework. Agent communication is provided by a simple tuple-space database implemented on node level providing fault tolerant access of global data. A novel synthesis development kit (SynDK) based on a graph-structured database approach is introduced to support the rapid development of compilers and synthesis tools, used for example for the design and implementation of the APL compiler.

Wafer level fabrication of single cell dispenser chips with integrated electrodes for particle detection

NASA Astrophysics Data System (ADS)

Schoendube, Jonas; Yusof, Azmi; Kalkandjiev, Kiril; Zengerle, Roland; Koltay, Peter

2015-02-01

This work presents the microfabrication and experimental evaluation of a dispenser chip, designed for isolation and printing of single cells by combining impedance sensing and drop-on-demand dispensing. The dispenser chip features 50  ×  55 µm (width × height) microchannels, a droplet generator and microelectrodes for impedance measurements. The chip is fabricated by sandwiching a dry film photopolymer (TMMF) between a silicon and a Pyrex wafer. TMMF has been used to define microfluidic channels, to serve as low temperature (75 °C) bonding adhesive and as etch mask during 300 µm deep HF etching of the Pyrex wafer. Due to the novel fabrication technology involving the dry film resist, it became possible to fabricate facing electrodes at the top and bottom of the channel and to apply electrical impedance sensing for particle detection with improved performance. The presented microchip is capable of dispensing liquid and detecting microparticles via impedance measurement. Single polystyrene particles of 10 µm size could be detected with a mean signal amplitude of 0.39  ±  0.13 V (n=439 ) at particle velocities of up to 9.6 mm s-1 inside the chip.

Strategy for signaling molecule detection by using an integrated microfluidic device coupled with mass spectrometry to study cell-to-cell communication.

PubMed

Mao, Sifeng; Zhang, Jie; Li, Haifang; Lin, Jin-Ming

2013-01-15

Cell-to-cell communication is a very important physiological behavior in life entity, and most of human behaviors are related to it. Although cell-to-cell communications are attracting much attention and financial support, rare methods have been successfully developed for in vitro cell-to-cell communication study. In this work, we developed a novel method for cell-to-cell communication study on an integrated microdevice, and signaling molecule and metabolites were online-detected by an electrospray ionization-quadrupole-time-of-flight-mass spectrometer (ESI-Q-TOF-MS) after on-chip solid-phase extraction. Moreover, we presented a "Surface Tension Plug" on a microchip to control cell-to-cell communication. The microdevice consists of three functional sections: cell coculture channel, targets pretreatment, and targets detection sections. To verify the feasibility of cell-to-cell communications on the integrated microdevice, we studied the communication between the 293 and the L-02 cells. Epinephrine and glucose were successfully detected using an ESI-Q-TOF-MS with short analysis time (<10 min). The results demonstrated that the developed microfluidic device is a potentially useful tool for high throughput cell-to-cell communication study.

Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan.

PubMed

Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Kawahara, Natsuko; Hayashi, Daisuke; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

2011-11-01

Neuronal ceroid lipofuscinosis (NCL) constitutes a group of recessively inherited lysosomal storage diseases that primarily affect neuronal cells. Such diseases share certain clinical and pathologic features in human beings and animals. Neuronal ceroid lipofuscinosis in Border Collie dogs was first detected in Australia in the 1980s, and the pathogenic mutation was shown to be a nonsense mutation (c.619C>T) in exon 4 in canine CLN5 gene. In the present study, novel rapid genotyping assays including polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR primer-induced restriction analysis, mutagenically separated PCR, and real-time PCR with TaqMan minor groove binder probes, were developed. The utility of microchip electrophoresis was also evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies in Japan using these assays to determine the current allele frequency in Japan, providing information to control and prevent this disease in the next stage. All assays developed in the current study are available to discriminate these genotypes, and microchip electrophoresis showed a timesaving advantage over agarose gel electrophoresis. Of all assays, real-time PCR was the most suitable for large-scale examination because of its high throughput. The genotyping survey demonstrated that the carrier frequency was 8.1%. This finding suggested that the mutant allele frequency of NCL in Border Collies is high enough in Japan that measures to control and prevent the disease would be warranted. The genotyping assays developed in the present study could contribute to the prevention of NCL in Border Collies.

Controlled On-chip Stimulation of Quantal Catecholamine Release from Chromaffin Cells Using Photolysis of Caged Ca2+ on Transparent Indium-Tin-Oxide Microchip Electrodes

PubMed Central

Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D.

2008-01-01

Photorelease of caged Ca2+ is a uniquely powerful tool to study the dynamics of Ca2+-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca2+ together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm - thick transparent Indium-Tin-Oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (∼20 μm by 20 μm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca2+ cage NP-EGTA and Ca2+ indicator dye Fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca2+, a uniform rise of [Ca2+]i within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca2+]i and a “priming” effect of sub-stimulatory [Ca2+]i on the response of cells to subsequent [Ca2+]i elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca2+ is a suitable stimulation technique for higher-throughput studies of Ca2+-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

A reusable device for electrochemical applications of hydrogel supported black lipid membranes.

PubMed

Mech-Dorosz, Agnieszka; Heiskanen, Arto; Bäckström, Sania; Perry, Mark; Muhammad, Haseena B; Hélix-Nielsen, Claus; Emnéus, Jenny

2015-02-01

Black lipid membranes (BLMs) are significant in studies of membrane transport, incorporated proteins/ion transporters, and hence in construction of biosensor devices. Although BLMs provide an accepted mimic of cellular membranes, they are inherently fragile. Techniques are developed to stabilize them, such as hydrogel supports. In this paper, we present a reusable device for studies on hydrogel supported (hs) BLMs. These are formed across an ethylene tetrafluoroethylene (ETFE) aperture array supported by the hydrogel, which is during in situ polymerization covalently "sandwiched" between the ETFE substrate and a gold electrode microchip, thus allowing direct electrochemical studies with the integrated working electrodes. Using electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy and contact angle measurements, we demonstrate the optimized chemical modifications of the gold electrode microchips and plasma modification of the ETFE aperture arrays facilitating covalent "sandwiching" of the hydrogel. Both fluorescence microscopy and EIS were used to demonstrate the induced spontaneous thinning of a deposited lipid solution, leading to formation of stabilized hsBLMs on average in 10 min. The determined specific membrane capacitance and resistance were shown to vary in the range 0.31-0.49 μF/cm(2) and 45-65 kΩ cm(2), respectively, corresponding to partially solvent containing BLMs with an average life time of 60-80 min. The characterized hsBLM formation and devised equivalent circuit models lead to a schematic model to illustrate lipid molecule distribution in hydrogel-supported apertures. The functionality of stabilized hsBLMs and detection sensitivity of the platform were verified by monitoring the effect of the ion transporter valinomycin.

Radioisotopic, Culture-Based, and Oligonucleotide Microchip Analyses of Thermophilic Microbial Communities in a Continental High-Temperature Petroleum Reservoir†

PubMed Central

Bonch-Osmolovskaya, Elizaveta A.; Miroshnichenko, Margarita L.; Lebedinsky, Alexander V.; Chernyh, Nikolai A.; Nazina, Tamara N.; Ivoilov, Valery S.; Belyaev, Sergey S.; Boulygina, Eugenia S.; Lysov, Yury P.; Perov, Alexander N.; Mirzabekov , Andrei D.; Hippe, Hans; Stackebrandt, Erko; L'Haridon, Stéphane; Jeanthon, Christian

2003-01-01

Activity measurements by radioisotopic methods and cultural and molecular approaches were used in parallel to investigate the microbial biodiversity and its physiological potential in formation waters of the Samotlor high-temperature oil reservoir (Western Siberia, Russia). Sulfate reduction with rates not exceeding 20 nmol of H2S liter−1 day−1 occurred at 60 and 80°C. In upper horizons (AB, A, and B), methanogenesis (lithotrophic and/or acetoclastic) was detected only in wells in which sulfate reduction did not occur. In some of the wells from deeper (J) horizons, high-temperature sulfate reduction and methanogenesis occurred simultaneously, the rate of lithotrophic methanogenesis exceeding 80 nmol of CH4 liter−1 day−1. Enrichment cultures indicated the presence of diverse physiological groups representing aerobic and anaerobic thermophiles and hyperthermophiles; fermentative organotrophs were predominant. Phylogenetic analyses of 15 isolates identified representatives of the genera Thermotoga, Thermoanaerobacter, Geobacillus, Petrotoga, Thermosipho, and Thermococcus, the latter four being represented by new species. Except for Thermosipho, the isolates were members of genera recovered earlier from similar habitats. DNA obtained from three samples was hybridized with a set of oligonucleotide probes targeting selected microbial groups encompassing key genera of thermophilic bacteria and archaea. Oligonucleotide microchip analyses confirmed the cultural data but also revealed the presence of several groups of microorganisms that escaped cultivation, among them representatives of the Aquificales/Desulfurobacterium-Thermovibrio cluster and of the genera Desulfurococcus and Thermus, up to now unknown in this habitat. The unexpected presence of these organisms suggests that their distribution may be much wider than suspected. PMID:14532074

Nanoaquarium: integrated microchips fabricated by ultrafast laser for understanding phenomena and functions of microorganisms

NASA Astrophysics Data System (ADS)

Sugioka, Koji; Hanada, Yasutaka; Midorikawa, Katsumi; Kawano, Hiroyuki; Ishikawa, Ikuko S.; Miyawaki, Atsushi

2011-12-01

We demonstrate to fabricate microfluidic chips integrated with some functional microcomponents such as optical attenuators and optical waveguides by femtosecond laser direct writing for understanding phenomena and functions of microorganisms. Femtosecond laser irradiation followed by annealing and wet etching in dilute hydrofluoric acid solution resulted in fabrication of three-dimensional microfludic structures embedded in a photosensitive glass. The embedded microfludic structures enabled us to easily and efficiently observe Phormidium gliding to the seedling root, which accelerates growth of the vegetable. In addition, integration of optical attenuators and optical waveguides into the microfluidic structures clarified the mechanism of the gliding movement of Phormidium. We termed such integrated microchips nanoaquariums, realizing the highly efficient and functional observation and analysis of various microorganisms.

Implantation of radio frequency identification device (RFID) microchip in disaster victim identification (DVI).

PubMed

Meyer, Harald J; Chansue, Nantarika; Monticelli, Fabio

2006-03-10

The tsunami catastrophe of December 2004 left more than 200,000 dead. Disaster victim identification (DVI) teams were presented with the unprecedented challenge of identifying thousands of mostly markedly putrefied and partially skeletised bodies. To this end, an adequate body tagging method is essential. Conventional body bag tagging in terms of writing on body bags and placing of tags inside body bags proved unsatisfactory and problem prone due to consequences of cold storage, formalin (formaldehyde) embalming and body numbers inside storage facilities. The placement of radio frequency identification device (RFID) microchips inside victim bodies provided a practical solution to problems of body tagging and attribution in the DVI setting encountered by the Austrian DVI team in Thailand in early 2005.

Energy transfer in Tm,Ho:KYW crystal and diode-pumped microchip laser operation.

PubMed

Kurilchik, Sergey; Gusakova, Natali; Demesh, Maxim; Yasukevich, Anatol; Kisel, Viktor; Pavlyuk, Anatoly; Kuleshov, Nikolai

2016-03-21

An investigation of Tm-Ho energy transfer in Tm(5at.%),Ho(0.4at.%):KYW single crystal by two independent techiques was performed. Based on fluorescence dynamics measurements, energy transfer parameters P₇₁ and P₂₈ for direct (Tm→Ho) and back (Ho→Tm) transfers, respectively, as well as equilibrium constant Θ were evaluated. The obtained results were supported by calculation of microscopic interaction parameters according to the Förster-Dexter theory for a dipole-dipole interaction. Diode-pumped continuous-wave operation of Tm,Ho:KYW microchip laser was demonstrated, for the first time to our knowledge. Maximum output power of 77 mW at 2070 nm was achieved at the fundamental TEM₀₀ mode.

Laser heating of aqueous samples on a micro-optical-electro-mechanical system

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

Beer, Neil Reginald; Kennedy, Ian

2013-12-17

A system of heating a sample on a microchip includes the steps of providing a microchannel flow channel in the microchip; positioning the sample within the microchannel flow channel, providing a laser that directs a laser beam onto the sample for heating the sample; providing the microchannel flow channel with a wall section that receives the laser beam and enables the laser beam to pass through wall section of the microchannel flow channel without being appreciably heated by the laser beam; and providing a carrier fluid in the microchannel flow channel that moves the sample in the microchannel flow channelmore » wherein the carrier fluid is not appreciably heated by the laser beam.« less

Analytical solution of the transient temperature profile in gain medium of passively Q-switched microchip laser.

PubMed

Han, Xiahui; Li, Jianlang

2014-11-01

The transient temperature evolution in the gain medium of a continuous wave (CW) end-pumped passively Q-switched microchip (PQSM) laser is analyzed. By approximating the time-dependent population inversion density as a sawtooth function of time and treating the time-dependent pump absorption of a CW end-pumped PQSM laser as the superposition of an infinite series of short pumping pulses, the analytical expressions of transient temperature evolution and distribution in the gain medium for four- and three-level laser systems, respectively, are given. These analytical solutions are applied to evaluate the transient temperature evolution and distribution in the gain medium of CW end-pumped PQSM Nd:YAG and Yb:YAG lasers.

Over 0.5 MW green laser from sub-nanosecond giant pulsed microchip laser

NASA Astrophysics Data System (ADS)

Zheng, Lihe; Taira, Takunori

2016-03-01

A sub-nanosecond green laser with laser head sized 35 × 35 × 35 mm3 was developed from a giant pulsed microchip laser for laser processing on organic superconducting transistor with a flexible substrate. A composite monolithic Y3Al5O12 (YAG) /Nd:YAG/Cr4+:YAG/YAG crystal was designed for generating giant pulsed 1064 nm laser. A fibercoupled 30 W laser diode centered at 808 nm was used with pump pulse duration of 245 μs. The 532 nm green laser was obtained from a LiB3O5 (LBO) crystal with output energy of 150 μJ and pulse duration of 268 ps. The sub-nanosecond green laser is interesting for 2-D ablation patterns.

Dispersion-free pulse duration reduction of passively Q-switched microchip lasers.

PubMed

Lehneis, R; Steinmetz, A; Jauregui, C; Limpert, J; Tünnermann, A

2012-11-01

We present a dispersion-free method for the pulse duration reduction of passively Q-switched microchip laser (MCL) seed sources. This technique comprises two stages: one that carries out the self-phase modulation induced spectral broadening in a waveguide structure and a subsequent spectral filtering stage in order to shorten the pulses in time domain. The setup of a proof-of-principle experiment consists of a fiber-amplified passively Q-switched MCL, a passive single-mode fiber used as nonlinear element in which the spectrum is broadened, and a reflective volume-Bragg-grating acting as bandpass filter. A reduction of the pulse duration from 118 to 32 ps with high temporal quality has been achieved with this setup.

Single-mode oscillation of a diode-pumped Nd:YAG microchip laser at 1835 nm

NASA Astrophysics Data System (ADS)

Lan, Jinglong; Cui, Qin; Wang, Yi; Xu, Bin; Xu, Huiying; Cai, Zhiping

2016-10-01

Single-mode oscillation of a diode-pumped conventional Nd:YAG laser at 1835 nm is demonstrated, for the first time to our knowledge, in the form of microchip configuration. The achieved maximum output power reaches 189 mW with slope efficiency of about 5.5% with respect to absorbed pump power. The laser spectra are measured with linewidth less than 0.08 nm indicating a single longitudinal mode. The output laser beam is also measured to be near diffraction-limited with M2 factors of about 1.2 and 1.5 in x and y directions. Using a mechanical chopper with 50% duty cycle, the maximum output power is improved to 253 mW with slope efficiency of about 9.7%.

Study of the thermal-induced intensity balanced Nd:GdVO4 microchip dual-frequency laser

NASA Astrophysics Data System (ADS)

Cai, Meiling; Hu, Miao; Zhou, Xuefang; Lu, Yang; Zeng, Ran; Li, Qiliang; Wei, Yizhen

2018-01-01

The intensity balance ratio (IBR) tuning mechanism of Nd:GdVO4 monolithic microchip dual-frequency laser (DFL) is presented. The intensity balanced DFL signals are obtained by precisely controlling the heat sink temperature of the Nd:GdVO4 crystal. In experiments, the DFL signal with frequency separation at 64 GHz and IBR above 0.99 is realized with the temperature at 47.6 °C. The other balanced intensity distribution can be reached at -0.9 °C before mode hopping. Moreover, utilizing the fluorescence spectrum and the intensity balance points of Nd:GdVO4 DFL, we obtain the temperature difference between internal and external of Nd:GdVO4 crystal ΔT = 24.0 °C.

Accelerator on a Chip

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

England, Joel

2014-06-30

SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

Accelerator on a Chip

ScienceCinema

England, Joel

2018-01-16

SLAC's Joel England explains how the same fabrication techniques used for silicon computer microchips allowed their team to create the new laser-driven particle accelerator chips. (SLAC Multimedia Communications)

High Efficiency Coupling of Optical Fibres with SU8 Micro-droplet Using Laser Welding Process

NASA Astrophysics Data System (ADS)

Yardi, Seema; Gupta, Ankur; Sundriyal, Poonam; Bhatt, Geeta; Kant, Rishi; Boolchandani, D.; Bhattacharya, Shantanu

2016-09-01

Apart from micro- structure fabrication, ablation, lithography etc., lasers find a lot of utility in various areas like precision joining, device fabrication, local heat delivery for surface texturing and local change of microstructure fabrication of standalone optical micro-devices (like microspheres, micro-prisms, micro-scale ring resonators, optical switches etc). There is a wide utility of such systems in chemical/ biochemical diagnostics and also communications where the standalone optical devices exist at a commercial scale but chip based devices with printed optics are necessary due to coupling issues between printed structures and external optics. This paper demonstrates a novel fabrication strategy used to join standalone optical fibres to microchip based printed optics using a simple SU8 drop. The fabrication process is deployed for fiber to fiber optical coupling and coupling between fiber and printed SU-8 waveguides. A CO2 laser is used to locally heat the coupling made up of SU8 material. Optimization of various dimensional parameters using design of experiments (DOE) on the bonded assembly has been performed as a function of laser power, speed, cycle control, spot size so on so forth. Exclusive optical [RF] modelling has been performed to estimate the transmissibility of the optical fibers bonded to each other on a surface with SU8. Our studies indicate the formation of a Whispering gallery mode (WGM) across the micro-droplet leading to high transmissibility of the signal. Through this work we have thus been able to develop a method of fabrication for optical coupling of standalone fibers or coupling of on-chip optics with off-chip illumination/detection.

Real-Time Detection of Telomerase Activity in Cancer Cells using a Label-Free Electrochemical Impedimetric Biosensing Microchip.

PubMed

Cunci, Lisandro; Vargas, Marina Martinez; Cunci, Roman; Gomez-Moreno, Ramon; Perez, Ivan; Baerga-Ortiz, Abel; Gonzalez, Carlos I; Cabrera, Carlos R

2014-10-15

The enzyme telomerase is present in about 85% of human cancers which makes it not only a good target for cancer treatment but also an excellent marker for cancer detection. Using a single stranded DNA probe specific for telomerase binding and reverse transcription tethered to an interdigital gold electrode array surface, the chromosome protection provided by the telomerase was replicated and followed by Electrochemical Impedance Spectroscopy as an unlabeled biosensor. Using this system designed in-house, easy and affordable, impedance measurements were taken while incubating at 37 °C and promoting the probe elongation. This resulted in up to 14-fold increase in the charge transfer resistance when testing a telomerase-positive nuclear extract from Jurkat cells compared to the heat-inactivated telomerase-negative nuclear extract. The electron transfer process at the Au electrodes was studied before the elongation, at different times after the elongation, and after desorption of non-specific binding.

Two-photon excitation in chip electrophoresis enabling label-free fluorescence detection in non-UV transparent full-body polymer chips.

PubMed

Geissler, David; Belder, Detlev

2015-12-01

One of the most commonly employed detection methods in microfluidic research is fluorescence detection, due to its ease of integration and excellent sensitivity. Many analytes though do not show luminescence when excited in the visible light spectrum, require suitable dyes. Deep-ultraviolet (UV) excitation (<300 nm) allows label-free detection of a broader range of analytes but also mandates the use of expensive fused silica glass, which is transparent to UV light. Herein, we report the first application of label-free deep UV fluorescence detection in non-UV transparent full-body polymer microfluidic devices. This was achieved by means of two-photon excitation in the visible range (λex = 532 nm). Issues associated with the low optical transmittance of plastics in the UV range were successfully circumvented in this way. The technique was investigated by application to microchip electrophoresis of small aromatic compounds. Various polymers, such as poly(methyl methacrylate), cyclic olefin polymer, and copolymer as well as poly(dimethylsiloxane) were investigated and compared with respect to achievable LOD and ruggedness against photodamage. To demonstrate the applicability of the technique, the method was also applied to the determination of serotonin and tryptamine in fruit samples. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

First-in-human testing of a wirelessly controlled drug delivery microchip.

PubMed

Farra, Robert; Sheppard, Norman F; McCabe, Laura; Neer, Robert M; Anderson, James M; Santini, John T; Cima, Michael J; Langer, Robert

2012-02-22

The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1-34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1-34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1-34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1-34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.

Hybrid soft-lithography/laser machined microchips for the parallel generation of droplets†

PubMed Central

Muluneh, M.

2015-01-01

Microfluidic chips have been developed to generate droplets and microparticles with control over size, shape, and composition not possible using conventional methods. However, it has remained a challenge to scale-up production for practical applications due to the inherently limited throughput of micro-scale devices. To address this problem, we have developed a self-contained microchip that integrates many (N = 512) micro-scale droplet makers. This 3 × 3 cm2 PDMS microchip consists of a two-dimensional array of 32 × 16 flow-focusing droplet makers, a network of flow channels that connect them, and only two inputs and one output. The key innovation of this technology is the hybrid use of both soft-lithography and direct laser-micromachining. The microscale resolution of soft lithography is used to fabricate flow-focusing droplet makers that can produce small and precisely defined droplets. Deeply engraved (h ≈ 500 μm) laser-machined channels are utilized to supply each of the droplet makers with its oil phase, aqueous phase, and access to an output channel. The engraved channels' low hydrodynamic resistance ensures that each droplet maker is driven with the same flow rates for highly uniform droplet formation.To demonstrate the utility of this approach, water droplets (d ≈ 80 μm) were generated in hexadecane on both 8 × 1 and 32 × 16 geometries. PMID:24166156

Integrated electrokinetically driven microfluidic devices with pH-mediated solid-phase extraction coupled to microchip electrophoresis for preterm birth biomarkers.

PubMed

Sonker, Mukul; Knob, Radim; Sahore, Vishal; Woolley, Adam T

2017-07-01

Integration in microfluidics is important for achieving automation. Sample preconcentration integrated with separation in a microfluidic setup can have a substantial impact on rapid analysis of low-abundance disease biomarkers. Here, we have developed a microfluidic device that uses pH-mediated solid-phase extraction (SPE) for the enrichment and elution of preterm birth (PTB) biomarkers. Furthermore, this SPE module was integrated with microchip electrophoresis for combined enrichment and separation of multiple analytes, including a PTB peptide biomarker (P1). A reversed-phase octyl methacrylate monolith was polymerized as the SPE medium in polyethylene glycol diacrylate modified cyclic olefin copolymer microfluidic channels. Eluent for pH-mediated SPE of PTB biomarkers on the monolith was optimized using different pH values and ionic concentrations. Nearly 50-fold enrichment was observed in single channel SPE devices for a low nanomolar solution of P1, with great elution time reproducibility (<7% RSD). The monolith binding capacity was determined to be 400 pg (0.2 pmol). A mixture of a model peptide (FA) and a PTB biomarker (P1) was extracted, eluted, injected, and then separated by microchip electrophoresis in our integrated device with ∼15-fold enrichment. This device shows important progress towards an integrated electrokinetically operated platform for preconcentration and separation of biomarkers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Parallel multiphase microflows: fundamental physics, stabilization methods and applications.

PubMed

Aota, Arata; Mawatari, Kazuma; Kitamori, Takehiko

2009-09-07

Parallel multiphase microflows, which can integrate unit operations in a microchip under continuous flow conditions, are discussed. Fundamental physics, stabilization methods and some applications are shown.