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Fluorescence Detection Based Point-of-care Diagnostics Platforms : Bridging The Gap Between Laboratory And Market
Published 2014 · Engineering
Point-of-Care (PoC) diagnostics delivers optimal healthcare by providing rapid results at lower cost than the corresponding laboratory tests. It’s applications extend beyond healthcare to environmental monitoring for testing of pollutants in the field, tuning athletic performance by testing biochemical parameters directly at the sports facility, agricultural monitoring for plant and animal disease control and even homeland security and social welfare for detection of substance of abuse, explosives. Although such promising applications exist, only a small fraction of PoC type sensor platforms progress from laboratory to the market. It is important to develop sensing platforms keeping in mind the boundaries of technology and cost with respect to the point of care usage. During system integration, it is extremely crucial to consider limitations with respect to size, weight, power, time to result and most importantly cost per unit earlier in the development phase. Instead of solving all problems into a single system, as traditionally done, we followed a diverse and functional approach. Three different system platforms are developed. Each one tackles specific combinations of challenges. This provides a benchmark in terms of performance, cost for each technology integration approach within given set of boundary conditions. First platform demonstrates novel in-coupling of the excitation light from a photoluminescent polymer into a low mode optical waveguide without the use of exotic coupling techniques such as gratings, prism, end face or butt coupling. Second platform integrates mechanical support, microfluidics and optical in-coupling structures into a single plastic substrate using hot embossing technique. Optical diffraction gratings are embossed on one side and simultaneously microfluidics is embossed on the opposite side. The total internal reflection path of the in-coupled light is designed using developed model so that a reflection occurs at the position of the sensing region. We designed, optimized and fabricated the chips for performing in-situ fluorescent immunoassay. Fluorescently labelled antibodies captured on the sensing surface can be photo-excited by evanescent field for surface sensitive detection and live measurements. For end result type of measurements, through excitation with off normal illumination can be chosen. These two different excitation schemes can be selected simply by changing the incident angle. Third platform is developed to be a fully disposable single package for simultaneous detection of three cardiac markers namely CK-MB, Troponin-I and Myoglobin. We demonstrated unique capabilities of organic field effect transistors (FET) as light generation and detection devices. Microfluidics and all optical components such as polarizers, filters are integrated on the disposable chip by lamination. Trans-illumination excitation is used and light sources are low cost inorganic green LEDs or organic light emitters such as OLEDs or Organic Light Emitti¬ng-FETs. Detectors used are silicon photodiodes or organic light sensitive devices such as OPDs or Organic Light Sensing FETs. This system is being further commercially developed system for company Molecular Vision Ltd. We benchmarked all three platforms using fluorescence immunoassay and compared with existing commercial system with respect to cost and performance. We used off the shelf lower cost components in the design taking into account final cost considerations but at the same time testing the limits of performance. Our work has developed niche set of skills and a mind-set vital to establish “Design for Point-of-Care” philosophy.