Handheld, microfluidic-based detection platform for on-the-flow analyte characterization

Abstract

The strategic landscape for biological and biomedical testing is undergoing a truly disruptive transformation. Today the majority of tests are performed at major, centralized clinical laboratories since compact, robust, and inexpensive instruments for point of care (POC) testing are not available. The principal drivers for POC testing are reducing costs, obtaining timely test results, lowering mortality rates, and reducing morbidity. We have demonstrated a new optical detection technique that delivers high signal-to-noise discrimination without precision optics to enable a flow cytometer that can combine high performance, robustness, compactness, low cost, and ease of use. The enabling technique is termed spatially modulated fluorescence detection. Relative movement between analyte and a predefined patterned environment generates a time-dependent signal, and correlating the detected signal with the known pattern achieves high discrimination of the particle signal from background noise. The basic optical detection technique is broadly applicable and compatible with many silicon photonic systems. The detection technique has been extensive evaluated with measurements of absolute CD4+ and percentage CD4 counts in human blood, which are required for screening, initiation of treatment, and monitoring of HIV-infected patients. To benchmark our technique we performed a direct one-to-one comparison of measurements on the same samples with a commercial instrument (BD FACSCount) and obtained excellent agreement for both absolute CD4 and percentage CD4. We have also assembled a first-generation, compact, handheld, single-parameter instrument based on the spatial modulation technique. The performance of this prototype provides clearly evidence that a multi-parameter, high-performance, compact instrument is fully realizable.