Recent advancements in microfluidics that integrate electrical sensors for whole blood analysis.

Whole blood analysis reveals crucial information about various physiological and pathological conditions, including cancer metastasis, infection, and immune status, among others. Despite this rich information, the complex composition of whole blood usually required multiple sample preparation steps to purify targeted analytes. Traditionally, whole blood preparation processes, including centrifugation, lysis, dilution, or staining, are usually manually operated by well-trained technicians using bench-top instruments. This preparation can require a large blood volume and cannot be directly integrated with detection systems. Recently, various studies have integrated microfluidics with electrical sensors for whole blood analysis, with a focus on cell-based analysis, such as cell type, number, morphology, phenotype, and secreted molecules. These miniaturized systems require less sample and shorter reaction times. Besides, the sample processing and analysis can be fully integrated and automated with minimal operations. We believe these systems can transfer the current whole blood analysis from hospitals or laboratories into clinics or home settings to enable real-time and continuous health condition monitoring in point-of-care settings.

A Microfluidic Device for Simultaneous Extraction of Plasma, Red Blood Cells, and On-Chip White Blood Cell Trapping.

This study reports a microfluidic device for whole blood processing. The device uses the bifurcation law, cross-flow method, and hydrodynamic flow for simultaneous extraction of plasma, red blood cells, and on-chip white blood cell trapping. The results demonstrate successful plasma and red blood cell collection with a minimum dilution factor (0.76x) and low haemolysis effect. The extracted red blood cells can also be applied for blood type tests. Moreover, the device can trap up to ~1,800 white blood cells in 20 minutes. The three components can be collected simultaneously using only 6 µL of whole blood without any sample preparation processes. Based on these features, the microfluidic device enables low-cost, rapid, and efficient whole blood processing functionality that could potentially be applied for blood analysis in resource-limited environments or point-of-care settings.

A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes.

The hemoglobin-A1c test, measuring the ratio of glycated hemoglobin (HbA1c) to hemoglobin (Hb) levels, has been a standard assay in diabetes diagnosis that removes the day-to-day glucose level variation. Currently, the HbA1c test is restricted to hospitals and central laboratories due to the laborious, time-consuming whole blood processing and bulky instruments. In this paper, we have developed a microfluidic device integrating dual CMOS polysilicon nanowire sensors (MINS) for on-chip whole blood processing and simultaneous detection of multiple analytes. The micromachined polymethylmethacrylate (PMMA) microfluidic device consisted of a serpentine microchannel with multiple dam structures designed for non-lysed cells or debris trapping, uniform plasma/buffer mixing and dilution. The CMOS-fabricated polysilicon nanowire sensors integrated with the microfluidic device were designed for the simultaneous, label-free electrical detection of multiple analytes. Our study first measured the Hb and HbA1c levels in 11 clinical samples via these nanowire sensors. The results were compared with those of standard Hb and HbA1c measurement methods (Hb: the sodium lauryl sulfate hemoglobin detection method; HbA1c: cation-exchange high-performance liquid chromatography) and showed comparable outcomes. Finally, we successfully demonstrated the efficacy of the MINS device's on-chip whole blood processing followed by simultaneous Hb and HbA1c measurement in a clinical sample. Compared to current Hb and HbA1c sensing instruments, the MINS platform is compact and can simultaneously detect two analytes with only 5 µL of whole blood, which corresponds to a 300-fold blood volume reduction. The total assay time, including the in situ sample processing and analyte detection, was just 30 minutes. Based on its on-chip whole blood processing and simultaneous multiple analyte detection functionalities with a lower sample volume requirement and shorter process time, the MINS device can be effectively applied to real-time diabetes diagnostics and monitoring in point-of-care settings.