We present a portable system for personalized blood cell counting consisting of a microfluidic impedance cytometer and portable analog readout electronics, feeding into an analog-to-digital converter (ADC), and being transmitted via Bluetooth to a user-accessible mobile application. We fabricated a microfluidic impedance cytometer with a novel portable analog readout. The novel design of the analog readout, which consists of a lock-in-amplifier followed by a high-pass filter stage for subtraction of drift and DC offset, and a post-subtraction high gain stage, enables detection of particles and cells as small as 1 μm in diameter, despite using a low-end 8-bit ADC. The lock-in-amplifier and the ADC were set up to receive and transmit data from a Bluetooth module. In order to initiate the system, as well as to transmit all of the data, a user friendly mobile application was developed, and a proof-of-concept trial was run on a blood sample. Applications such as personalized health monitoring require robust device operation and resilience to clogging. It is desirable to avoid using channels comparable in size to the particles being detected thus requiring high levels of sensitivity. Despite using low-end off-the-shelf hardware, our sensing platform was capable of detecting changes in impedance as small as 0.032%, allowing detection of 3 μm diameter particles in a 300 μm wide channel. The sensitivity of our system is comparable to that of a high-end bench-top impedance spectrometer when tested using the same sensors. The novel analog design allowed for an instrument with a footprint of less than 80 cm. The aim of this work is to demonstrate the potential of using microfluidic impedance spectroscopy for low cost health monitoring. We demonstrated the utility of the platform technology towards cell counting, however, our platform is broadly applicable to assaying wide panels of biomarkers including proteins, nucleic acids, and various cell types.

We demonstrate a novel method for electronically detecting and quantifying protein biomarkers using microfluidic impedance cytometry. Our biosensor, which consists of gold electrodes micro-fabricated in a microchannel, detects the differences between bead aggregates of varying sizes in a micro-pore sandwiched between two micro channels. We perform a sandwich immunoassay, where the complementary antibody pairs are immobilized on two different bead types, and the presence of antigen results in bead aggregation, the amount of which depends on antigen quantity. When single beads or bead aggregates pass through the impedance sensor, differences in impedance change are detected. In this manuscript, we perform a comprehensive theoretical study on the limits imposed on sensitivity of this technique due to electronic noise and also mass transfer and reaction limits. We also experimentally characterize the performance of this technique by validating the technique on an IgG detection assay. A detection limit at the picoMolar level is demonstrated, thus comparable in sensitivity to a sandwich ELISA.

Traditional optical and plasmonic techniques for barcoding of micro-particles for multiplexed bioassays are generally high in throughput, however bulky instrumentation is often required for performing readout. Electrical impedance based detection allows for ultra-compact instrumentation footprint necessary for wearable devices, however to date, the lack of ability to electronically barcode micro-particles has been a long standing bottleneck towards enabling multiplexed electronic biomarker assays. Nanoelectronic barcoding, which to the best of our knowledge is the first impedance based solution for micro-particle barcoding, works by forming tunable nano-capacitors on the surface of micro-spheres, effectively modulating the frequency dependent dielectric properties of the spheres allowing one bead barcode to be distinguished from another. Nanoelectronic barcoding uses a well-known, but unexplored electromagnetic phenomenon of micro-particles: the Clausius-Mossotti (CM) factor spectrum of a Janus particle (JP) shifts depending on the zeta (wall) potential of the metallic half of the microsphere, and the fact that the complex impedance spectrum of a particle directly corresponds to the CM factor spectrum. A one-to-one correspondence will be established between each biomarker and the corresponding engineered microsphere. This transformative new method for barcoding will enable a new class of handheld and wearable biosensors capable of multiplexed continuous temporal bio-monitoring. The proposed nano-electronically barcoded particles utilize both bottom-up synthesis and top-down fabrication to enable precisely engineered frequency dependent dielectric signatures. Multi-frequency lock-in measurements of the complex impedance, in conjunction with multi-variate analysis of impedance data, allows for particle differentiation using a fully functional ultra-compact electronic detector.

No abstract