Fusion of a-Si:H sensor technology with microfluidic bioanalytical devices (original) (raw)
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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.
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.
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 microfluidic biophotonic chip for laser induced fluorescence detection
Biomedical microdevices, 2010
Integrated Lab-on-a-Chip or Micro-Total Analysis Systems offer several advantages for the detection of active chemical and biological species. In this work, an integrated microfluidic biophotonic chip is proposed for carrying out laser induced fluorescence detection. A Spectrometer-on-Chip device, specifically designed for multiple fluorescence detections at different emission wavelengths is integrated with the opto-microfluidic chip fabricated on Silicon-Polymer hybrid platform. The input fiber from the laser source, and output fiber coupled with a Spectrometer-on-Chip were integrated with the microfluidic channel so as to make a robust setup. Fluorescence detection was carried out using Alexafluor 647 tagged antibody particles. The experimental results show that the proposed biophotonic microfluidic device is highly suitable for high throughput detection of chemical and biological specimens.
Journal of Microelectromechanical Systems, 2001
This paper presents the fabrication of a microchemical chip for the detection of fluorescence species in microfluidics. The microfluidic network is wet-etched in a Borofloat 33 (Pyrex) glass wafer and sealed by means of a second wafer. Unlike other similar chemical systems, the detection system is realized with the help of microfabrication techniques and directly deposited on both sides of the microchemical chip. The detection system is composed of the combination of refractive microlens arrays and chromium aperture arrays. The microfluidic channels are 60 m wide and 25 m deep. The utilization of elliptical microlens arrays to reduce aberration effects and the integration of an intermediate (between the two bonded wafers) aluminum aperture array are also presented. The elliptical microlenses have a major axis of 400 m and a minor axis of 350 m. The circular microlens diameters range from 280 to 300 m. The apertures deposited on the outer chip surfaces are etched in a 3000-A-thick chromium layer, whereas the intermediate aperture layer is etched in a 1000-A-thick aluminum layer. The overall thickness of this microchemical system is less than 1.6 mm. The wet-etching process and new bonding procedures are discussed. Moreover, we present the successful detection of a 10-nM Cy5 solution with a signal-to-noise ratio (SNR) of 21 dB by means of this system.
Biosensors, 2017
A lab-on-chip system, integrating an all-glass microfluidics and on-chip optical detection, was developed and tested. The microfluidic network is etched in a glass substrate, which is then sealed with a glass cover by direct bonding. Thin film amorphous silicon photosensors have been fabricated on the sealed microfluidic substrate preventing the contamination of the micro-channels. The microfluidic network is then made accessible by opening inlets and outlets just prior to the use, ensuring the sterility of the device. The entire fabrication process relies on conventional photolithographic microfabrication techniques and is suitable for low-cost mass production of the device. The lab-on-chip system has been tested by implementing a chemiluminescent biochemical reaction. The inner channel walls of the microfluidic network are chemically functionalized with a layer of polymer brushes and horseradish peroxidase is immobilized into the coated channel. The results demonstrate the success...
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.
SPIE Proceedings, 2007
In order to solve the drawbacks of sensitivity and portability in optical biosensors we have developed ultrasensitive and miniaturized photonic silicon sensors able to be integrated in a "lab-on-a-chip" microsystem platform. The sensors are integrated Mach-Zehnder interferometers based on TIR optical waveguides (Si/SiO 2 /Si 3 N 4) of micro/nanodimensions. We have applied this biosensor for DNA testing and for detection of single nucleotide polymorphisms at BRCA-1 gene, involved in breast cancer development, without target labeling. The oligonucleotide probe is immobilized by covalent attachment to the sensor surface through silanization procedures. The hybridization was performed for different DNA target concentrations showing a lowest detection limit at 10 pM. Additionally, we have detected the hybridization of different concentrations of DNA target with two mismatching bases corresponding to a mutation of the BRCA-1 gene. Following the way of the lab-on-a-chip microsystem, integration with the microfluidics has been achieved by using a novel fabrication method of 3-D embedded microchannels using the polymer SU-8 as structural material. The optofluidic chip shows good performances for biosensing.
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.
An Integrated Fluorescence Detection System in Poly(dimethylsiloxane) for Microfluidic Applications
Analytical Chemistry, 2001
This paper describes a prototype of an integrated fluorescence detection system that uses a microavalanche photodiode (µAPD) as the photodetector for microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The prototype device consisted of a reusable detection system and a disposable microfluidic system that was fabricated using rapid prototyping. The first step of the procedure was the fabrication of microfluidic channels in PDMS and the encapsulation of a multimode optical fiber (100-µm core diameter) in the PDMS; the tip of the fiber was placed next to the side wall of one of the channels. The optical fiber was used to couple light into the microchannel for the excitation of fluorescent analytes. The photodetector, a prototype solid-state µAPD array, was embedded in a thick slab (1 cm) of PDMS. A thin (80 µm) colored polycarbonate filter was placed on the top of the embedded µAPD to absorb scattered excitation light before it reached the detector. The µAPD was placed below the microchannel and orthogonal to the axis of the optical fiber. The close proximity (∼200 µm) of the µAPD to the microchannel made it unnecessary to incorporate transfer optics; the pixel size of the µAPD (30 µm) matched the dimensions of the channels (50 µm). A blue light-emitting diode was used for fluorescence excitation. The µAPD was operated in Geiger mode to detect the fluorescence. The detection limit of the prototype (∼25 nM) was determined by finding the minimum detectable concentration of a solution of fluorescein. The device was used to detect the separation of a mixture of proteins and small molecules by capillary electrophoresis; the separation illustrated the suitability of this integrated fluorescence detection system for bioanalytical applications. (71) Waters, L. C.; Jacobson, S. C.; Kroutchinina, N.; Khandurina, J.; Foote, R. S.; Ramsey, J. M. Anal. Chem. 1998, 70, 5172-5176.