An All-Glass Microfluidic Network with Integrated Amorphous Silicon Photosensors for on-Chip Monitoring of Enzymatic Biochemical Assay (original) (raw)
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Sensing and Bio-Sensing Research, 2015
In this paper we present a compact technological demonstrator including on the same glass substrate an electrowetting-on-dielectrics (EWOD) system, a linear array of amorphous silicon photosensor and a capillary-driven microfluidic channel. The proposed system comprises also a compact modular electronics controlling the digital microfluidics through the USB interface of a computer. The system provides therefore both on-chip detection and microfluidic handling needed for the realization of a 'true' Lab-on-Chip. The geometry of the photosensors has been designed to maximize the radiation impinging on the photosensor and to minimize the inter-site crosstalk, while the fabrication process has been optimized taking into account the compatibility of all the technological steps for the fabrication of the EWOD system, the photosensor array and the microfluidics channels. As a proof of the successful integration of the different technological steps we demonstrated the ability of the a-Si:H photosensors to detect the presence of a droplet over an EWOD electrode and the effective coupling between the digital and the continuous microfluidics, that can allow for functionalization, immobilization and recognition of biomolecules without external optical devices or microfluidic interconnections.
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Fresenius' Journal of Analytical Chemistry, 2001
A new, versatile architecture is presented for microfluidic devices made entirely from glass, for use with reagents which would prove highly corrosive for silicon. Chips consist of three layers of glass wafers bonded together by fusion bonding. On the inside wafer faces a network of microfluidic channels is created by photolithography and wet chemical etching. Low dead-volume fluidic connections between the layers are fabricated by spark-assisted etching (SAE), a computer numerical controlled (CNC)-like machining technique new to microfluidic system fabrication. This method is also used to form a vertical, long path-length, optical cuvette through the middle wafer for optical absorbance detection of low-concentration compounds. Advantages of this technique compared with other, more standard, methods are discussed.
Microfluidic chips with integrated amorphous silicon sensors for point-of-care testing
2014
Herein we present a point-of-care device for immunodiagnostic tests. This device integrates, on the same glass substrate, a PDMS microfluidic network, an array of amorphous silicon photosensors for onchip optical detection and a dedicated surface chemistry based on polymer brushes. As proof of principle, a peptide named VEA was immobilized on PHEMA polymer brushes. The survey relies on the formation, inside the microchannels, of a sandwich between primary antibody against VEA and a secondary antibody labeled with HRP, which catalyzes the reaction between luminol and hydrogen peroxide, yielding a chemiluminescent signal detected by the array of photosensors deposited underneath.
Microfluidic Chip With Integrated a-Si:H Photodiodes for Chemiluminescence-Based Bioassays
IEEE Sensors Journal, 2013
On-chip optical detection of chemiluminescent reactions is presented. The device is based on the integration of thin film hydrogenated amorphous silicon photosensors on a functionalized glass substrate ensuring both a good optical coupling and an optimal separation between biological or chemical reagents and the sensing elements. The sensor has been characterized and optimized using the chemiluminescent system composed by the enzyme horseradish peroxidase (HRP) and luminol/peroxide/enhancer cocktail. The detectability of HRP is at the attomole level with a sensitivity of 1.46 fA/fg. Experiments, involving the detection of immobilized bio-specific probes on the functionalized surface have been performed both in bulk and microfluidics regime, proving the ability of the system to effectively detect chemiluminescent reactions and their kinetics. In particular, results achieved using conventional polydimethylsiloxane microfluidics for samples and reagents handling confirmed the good detection capabilities of the proposed system.
Integrated Hydrogenated Amorphous Si Photodiode Detector for Microfluidic Bioanalytical Devices
Analytical Chemistry, 2003
A discrete a-Si:H photodiode is first fabricated on a glass substrate and used to detect fluorescent dye standards using conventional confocal microscopy. In this format, the limit of detection for fluorescein flowing in a 50-µm deep channel is 680 pM (S/N ) 3). A hybrid integrated detection system consisting of a half-ball lens, a ZnS/YF 3 multilayer optical interference filter with a pinhole, and an annular a-Si:H photodiode is also developed that allows the laser excitation to pass up through the central aperture in the detector. Using this integrated detection device, the limit of detection for fluorescein is 17 nM, and DNA fragment sizing and chiral analysis of glutamic acid are successfully performed. The a-Si:H detector exhibits high sensitivity at the emission wavelengths of commonly used fluorescent dyes and is readily microfabricated and integrated at low cost making it ideal for portable microfluidic bioanalyzers and emerging large scale integrated microfluidic technologies.
IEE Proceedings - Nanobiotechnology, 2006
The advantages of integrating microfluidics into photonics-based biosensing for fabricating microreactor type lab-on-a-chip devices carries a lot of advantages, such as smaller sample volume handling, controlled drug delivery and high throughput diagnosis, which is useful for in situ medical diagnosis and point-of-care (POC) testing. A hybrid integrated optical microfluidic system has been developed for the study of single molecules and enzymatic reactions. The method of optical absorption has been employed for biosensing and the feasibility of absorption-based detection on the microfluidic platform has been demonstrated using horseradish peroxidase and hydrogen peroxide, as an example. The results show that the device is useful for the analysis of both the individual chemical specimen and also the study of chemical and biological reaction between two reacting species. The hybrid integration of microfluidics and optical ensembles thus forms the basis for developing the microreactor type lab-on-a-chip device, which would have several important applications in the area of nanobiotechnology.
Hybrid Integrated Silicon Microfluidic Platform for Fluorescence Based Biodetection
Sensors, 2007
The desideratum to develop a fully integrated Lab-on-a-chip device capable of rapid specimen detection for high throughput in-situ biomedical diagnoses and Point-of-Care testing applications has called for the integration of some of the novel technologies such as the microfluidics, microphotonics, immunoproteomics and Micro Electro Mechanical Systems (MEMS). In the present work, a silicon based microfluidic device has been developed for carrying out fluorescence based immunoassay. By hybrid attachment of the microfluidic device with a Spectrometer-on-chip, the feasibility of synthesizing an integrated Lab-on-a-chip type device for fluorescence based biosensing has been demonstrated. Biodetection using the microfluidic device has been carried out using antigen sheep IgG and Alexafluor-647 tagged antibody particles and the experimental results prove that silicon is a compatible material for the present application given the various advantages it offers such as cost-effectiveness, ease of bulk microfabrication, superior surface affinity to biomolecules, ease of disposability of the device etc., and is thus suitable for fabricating Lab-on-a-chip type devices.
Sensors and Actuators B: Chemical, 2009
In this study, we developed a novel microfluidic device for enzyme-based assays that incorporates heterogeneous reaction and microarray-based detection systems. The microfluidic device had two serial chambers connected through microchannels; one for the reaction between analytes and enzymes, and the other for the quantitative detection of analytes. The reaction chamber was filled with glass microbeads covalently bound to enzymes via aminopropyltriethoxysilane (APTES). Enzyme-immobilized microbeads 70 m in diameter were retained within the reaction chamber using a microfilter composed of micropillars with 30 m interspaces. In the detection chamber, a poly(ethylene glycol)-based hydrogel microarray was fabricated using photolithography, which could immobilize other protein molecules or fluorescent dyes for the optical analysis of enzyme-catalyzed reaction. Different concentrations of glucose were detected within the microfluidic system where the reaction chamber was filled with glucose oxidase (GOX)-immobilizing glass microbeads, and a horseradish peroxidase (POD)-entrapping hydrogel microarray was placed in the detection chamber. A sequential bienzymatic reaction resulted in the conversion of non-fluorescent Amplex Red into fluorescent resorufin within the hydrogel microarray and glucose concentrations ranging from 1 to 10 mM were successfully detected by measuring the change of emission intensity of resorufin inside the hydrogel microarray.
Fabrication of Glass-based Microfluidic Devices with Photoresist as Mask
2011
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Silicon photonic sensors incorporated in a digital microfluidic system
Analytical and Bioanalytical Chemistry, 2012
Label-free biosensing with silicon nanophotonic microring resonator sensors has proven to be an excellent sensing technique for achieving high-throughput and high sensitivity, comparing favorably with other labeled and label-free sensing techniques. However, as in any biosensing platform, silicon nanophotonic microring resonator sensors require a fluidic component which allows the continuous delivery of the sample to the sensor surface. This component is typically based on microchannels in PDMS or other materials which add cost and complexity to the system. The use of microdroplets in a digital microfluidic system, instead of continuous flows, is one of the recent trends in the field, where micro-to picoliter-sized droplets are generated, transported, mixed and split, thereby creating miniaturized reaction chambers which can be controlled individually in time and space. This avoids cross-talk between samples or reagents and allows fluid plugs to be manipulated on reconfigurable paths, which cannot be achieved using the more established and more complex technology of microfluidic channels where droplets are controlled in series. It has great potential for high-throughput liquid handling, while avoiding on-chip cross contamination. We present the integration of two miniaturized technologies: label-free silicon nanophotonic microring resonator sensors and digital microfluidics, providing an alternative to the typical microfluidic system based on microchannels. The performance of this combined system is demonstrated by performing proof-of-principle measurements of glucose, sodium chloride and ethanol concentrations. These results show that multiplexed real-time detection and analysis, great flexibility, and portability make the combination of these technologies an ideal platform for easy and fast use in any laboratory.