Microfluidic CODES: a scalable multiplexed electronic sensor for orthogonal detection of particles in microfluidic channels

Abstract

Numerous biophysical and biochemical assays rely on spatial manipulation of particles/cells as they are processed on lab-on-a-chip devices. Analysis of spatially distributed particles on these devices typically requires microscopy negating the cost and size advantages of microfluidic assays. In this paper, we introduce a scalable electronic sensor technology, called microfluidic CODES, that utilizes resistive pulse sensing to orthogonally detect particles in multiple microfluidic channels from a single electrical output. Combining the techniques from telecommunications and microfluidics, we route three coplanar electrodes on a glass substrate to create multiple Coulter counters producing distinct orthogonal digital codes when they detect particles. We specifically design a digital code set using the mathematical principles of Code Division Multiple Access (CDMA) telecommunication networks and can decode signals from different microfluidic channels with >90% accuracy through computation even if these signals overlap. As a proof of principle, we use this technology to detect human ovarian cancer cells in four different microfluidic channels fabricated using soft lithography. Microfluidic CODES offers a simple, all-electronic interface that is well suited to create integrated, low-cost lab-on-a-chip devices for cell- or particle-based assays in resource-limited settings.

Barker-Coded node-pore resistive pulse sensing with built-in coincidence correction

“…It is worth noting that a recently published related work using coded microfluidic devices has been conducted by Liu et al [17] to resolve coincidence events when sensing the multiplexed signals from an array of microfluidic channels. Their signals were differentially encoded with a set of complementary Gold codes, implemented via a complex co-planar electrode array.…”

“…Previous work [14][17] has explored SIC methods for resolving coincidences, but did not consider significant issues and undesirable artifacts, such as baseline drift, manufacturing imperfections, dynamic range of valid detections, and low-resolution parameter estimation, that result in numerous miss-detection or false alarms and biased particle size estimates. We discuss and incorporate a forward model calibration step, an adaptive threshold detection scheme, and a robust regression fit to mitigate these sources of error.…”

Resistive pulse sensing as particle counting and sizing method in microfluidic systems: Designs and applications review

“…Copyright 2017 Springer Nature. Republished with permission of Royal Society of Chemistry from ; permission conveyed through Copyright Clearance Center, Inc…”

“…Copyright 2017 Springer Nature. Republished with permission of Royal Society of Chemistry from [29]; permission conveyed through Copyright Clearance Center, Inc Figure 2A(c) and 3H. The authors successfully introduced a signal processing comprising fitting the differential signal traces by bipolar Gaussian profile resulting in significantly reduced positional dependence issue affecting Coulter-type microfluidic devices with coplanar layout [14].…”

Code-division multiplexed resistive pulse sensor networks for spatio-temporal detection of particles in microfluidic devices

“…Recently, we have introduced a microfluidic platform with an integrated network of multiplexed electronic sensors, called Microfluidic CODES [3], [4], that combines the resistive pulse sensing [5] with the code division multiple access (CDMA) [6]. In Microfluidic CODES, each sensor in the network is formed by a distinctly patterned array of co-planar electrodes and therefore produces a signal distinguishable from other sensors' when it detects a particle.…”