Heterogeneous Integration of a LASER Induced Fluorescence Detection Device for Point-of-Care Microfluidic Biochemical An
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Heterogeneous Integration of a LASER Induced Fluorescence Detection Device for Point-of-Care Microfluidic Biochemical Analysis Toshihiro Kamei National Institute of Advanced Industrial Science and Technology (AIST) 1-2-1 Namiki, Tsukuba East Bldg., Tsukuba, Ibaraki 305-8564, Japan ABSTRACT Fluorescence detection is more advantageous than electrochemical detection in terms of high sensitivity, multiplexed detection capability and isolation from analyte. Integration of fluorescence detection, however, is much more difficult. First, it would require heterogeneous integration of various optical components including an excitation source, an optical filter, a lens, a mirror and a detector. Second, most of integrated fluorescence detectors, even though not fully integrated, suffer from high limit of detection (LOD) compared to conventional optical system that consists of discrete optical components. We have reduced laser light scattering in an integrated hydrogenated amorphous Si (a-Si:H) fluorescence detector, significantly improving a limit-of-detection (LOD). The detection platform comprises a microlens and the annular fluorescence detector where a thick SiO2/Ta2O5 multilayer optical interference filter is monolithically integrated on an a-Si:H pin photodiode. With a microfluidic capillary electrophoresis (CE) device mounted on the platform, the integrated system is demonstrated to separate DNA restriction fragment digests with high speed, high sensitivity and high separation efficiency, implying single molecular DNA detection when combined with polymerase chain reaction (PCR). We are now working towards integration of an excitation source to fabricate heterogeneously integrated laser-induced fluorescence detection (LIF) device that would be comprised of an InGaN laser diode, microlenses and the integrated a-Si:H fluorescence detector. INTRODUCTION The manipulation of a minute quantity of fluid (pl – nl) in channels with dimensions of tens to hundreds of micrometers, termed microfluidics, has emerged in the last decade as an interdisciplinary field between chemistry, biology and semiconductor microfabrication technology.[1] Similar to the scaling law for a metal-oxide semiconductor field-effect transistor (MOSFET) in an integrated circuit that, as transistors gets smaller, they can switch faster and use less power, the PCR in a nanolitter reactor has been dramatically speeded up from the conventional microlitter scale. In addition, a unprecedentedly small sample plug of approximately 100 Pm that can be electrokinetically formed in a microchannel network has achieved CE with high speed and high separation efficiency.[2] A variety of approaches toward the goal of more complete process integration have been presented. Microfluidic plumbing technology based on a silicone elastomeric membrane has been used to perform cell sorting and combinatorial screening of protein crystallization conditions.[3-5] Methods for fabricating high density arrays of membrane valves and pumps in glass microfluidic structures have been presented
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