Motorized smart pipette for handheld operation of a microfluidic blood plasma separator

Abstract

Simple and institutionalized testing of circulating biomarkers is essential for rapid cancer diagnosis and prognosis. However, blood sample preparation typically requires time-consuming separation steps and bulky, costly equipment. Although microfluidic separators have been developed for rapid and simple blood separation, their fluidic accessories such as syringe pumps still need to be miniaturized at a lower price before translating the separators into clinical practice. Here, we present a motorized smart pipette as a portable, cost-effective, and controllable pumping tool that can generate stable and high-pressure conditions suitable for high-throughput microfluidic blood separators. The pumping technology is based on a miniature air pump and its feedback control using an open-source microcontroller board. We characterized the pumping performance (controllability and stability) of the proposed technology using a pressure divider and a bang-bang feedback control method in a range of flow rate (166.5–529.0 μL/min). Additionally, we demonstrated the clinical utility of the pumping technology by rapidly separating blood plasma from whole blood and successfully recovering cancer cell-derived exosomes spiked in blood. We achieved high-throughput (≈422.3 μL/min) and high-purity (≈99.8%) plasma separation without hemolysis, recovering ≈90.5% of cancer cell-derived exosomes spiked in blood. With the advantages of high usability and versatility, this method can potentially accelerate the widespread adoption and clinical translation of microfluidics-based liquid biopsy technologies.