Microfluidic platform for point-of-need analyte diagnostics based on spatial modulation detection

Abstract

Bio-particle evaluation is undergoing a disruptive transformation that impacts diverse applications from testing in the physician’s office to screening for diseases in developing countries to defense against bio-terrorism. Drivers for this paradigm shift include reducing cost for required performance, lowering mortality rates, reducing morbidity, protecting the warfighter, and improving national security. Bio-sensors based on optical principles offer the greatest potential to realize practical devices that can fully meet SwaP-C. Opto-fluidic systems based on fluorescence from fluorophore-tagged bio-particles offer high performance, e.g., single-molecule detection, but without a clear path to meeting the stringent requirements for SwaP-C. Issues include difficulty of overcoming performance limits related to particle bleaching in a field-deployable system, which is not an issue with photonic resonance techniques. To help sharpen the focus on alternative approaches, this presentation will describe an optical detection technique that delivers high effective sensitivity (i.e., high S/N) without complex optics or bulky, expensive light sources to enable an optofluidic system that can fully meet SwaP-C. The technique termed spatially modulated emission is based on relative movement between an excited bio-particle and a patterned environment to produce a time-dependent signal that is analyzed with correlation techniques. The advantage is high discrimination of the particle signal from background noise. The technique has been used to detect native fluorescence from single cells and benchmarked against high-performance commercial systems on complex biological fluids, specifically, with CD4 monitoring of CD4 T-lymphocytes in whole blood. The spatial modulation technique illustrates the transfer of an advanced technology from one discipline (communications) can overcome limitations in another (bio-medical instrumentation). Specifically, the technique can be viewed as the application of the principles of spread spectrum technology to the field of flow cytometry. Features of spread spectrum include resistance to interference and interception and increased transmission capacity, which relate to its inherent S/N discrimination capability.