(Invited) Microfluidic Chips with Electronic Cell Tracking for Digital Biomedical Assays

Abstract

Detection and analysis of small particles in liquids are of particular interest in numerous applications ranging from bio-medicine to environmental monitoring. By spatially tracking particles/cells as they are manipulated on lab-on-a-chip devices (e.g., determining the microfluidic channel they are sorted into or the location on the microfluidic device where they are captured), many biophysical or biochemical assays can be performed. To obtain such spatial information, however, current lab-on-a-chip assays require subsequent microscopic analysis negating the cost and portability benefits of microfluidic devices. Therefore, a simple integrated sensor that can track particles on a microfluidic chip can enable a new generation of devices with sample-to-answer capability in performing various cellular and molecular assays and will particularly be attractive for point-of-care testing in resource-limited settings. We have introduced the Microfluidic CODES technology [1-3] to electronically track the position of particles as they are processed on a lab-on-a-chip device so that this information can readily be available outside of the laboratory settings. Microfluidic CODES uses the Coulter principle to detect suspended particles flowing in micro-channels through changes in the electrical impedance without any labels. Our technology relies on a network of micropatterned surface electrodes spread across the microfluidic device. Electrodes are designed such that they form unique spatial patterns at different locations on the microfluidic chip. Therefore, particles flowing over electrodes at those locations produce distinguishable signal patterns that are dictated by the underlying electrode pattern. Based on this unique approach, Microfluidic CODES technology allows (1) many sensor signals to be code-multiplexed and read from a single electrical output significantly simplifying the hardware and interface electronics, (2) unique signal patterns to be directly linked to a specific location on the microfluidic device, which can be used for sample characterization. In this talk, I will also introduce several lab-on-a-chip devices with integrated sensor networks for all-electronic cell analysis. First, I will demonstrate an all-electronic flow cytometer as a low-cost alternative to a fluorescence-activated cell sorter (FACS) by combining magnetophoretic cell sorting with Microfluidic CODES. I will present our results from electronic profiling surface expression levels of Epithelial Cell Adhesion Molecule (EpCAM) in a tumor cell population. Second, I will introduce an electronically readable immunoaffinity assay for label-free cell characterization. This device combines the Microfluidic CODES sensor technology with immunoaffinity-based cell capture to create a microfluidic device that electronically reports the prevalence of different antibodies in a cell population without any pre-labeling and by processing a signal obtained from a single electrical readout.