Scaling code-multiplexed electrode networks for distributed Coulter detection in microfluidics

Abstract

Microfluidic devices can discriminate particles based on their properties and map them into different locations on the device. For distributed detection of these particles, we have recently introduced a multiplexed sensing technique called Microfluidic CODES, which combines code division multiple access with Coulter sensing. Our technique relies on micromachined sensor geometries to produce distinct waveforms that can uniquely be linked to specific locations on the microfluidic device. In this work, we investigated the scaling of the code-multiplexed Coulter sensor network through theoretical and experimental analysis. As a model system, we designed and fabricated a microfluidic device integrated with a network of 10 code-multiplexed sensors, each of which was characterized and verified to produce a 31-bit orthogonal digital code. To predict the performance of the sensor network, we developed a mathematical model based on communications and coding theory, and calculated the error rate for our sensor network as a function of the network size and sample properties. We theoretically and experimentally demonstrated the effect of electrical impedance on the signal-to-noise ratio and developed an optimized device. We also introduced a computational approach that can process the sensor network data with minimal input from the user and demonstrated system-level operation by processing suspensions of cultured human cancer cells. Taken together, our results demonstrated the feasibility of deploying large-scale code-multiplexed electrode networks for distributed Coulter detection to realize integrated lab-on-a-chip devices.

Electronic profiling of membrane antigen expressionviaimmunomagnetic cell manipulation

“…While the electrical sensor network can easily be expanded by assigning distinct codes to new sensors, a larger sensor network would unavoidably lead to more cell coincidence associated signal interference that might introduce errors in data processing. 26 From a practical point of view, this would eventually require a dilution of the sample to lower the cell concentration.…”

“…As the sorted cells flowed over these patterned electrodes, they modulated the impedance between electrodes via Coulter principle and produced distinct electrical signals dictated by the underlying electrode pattern. We specifically designed the electrode patterns to produce 31-bit Gold sequences [24][25][26] (Table S1 †) which could mathematically be distinguished due to their orthogonality (Methods). For each microfluidic bin, the arrangement of the negative and positive electrode fingers determined the code sequence, while the common electrode was used to drive the sensor (Fig.…”

“…The digital codes used for multiplexing the electrical sensors were generated as described by Liu et al 26 in the form of 31bit Gold sequences. The 5th order polynomials x 5 + x 3 + 1 and x 5 + x 3 + x 2 + x + 1 were used to represent two linearfeedback shift-registers with the initial states of "10 000".…”

Immunomagnetic leukocyte differential in whole blood on an electronic microdevice

“…To quantify the cells and capture the specific information of each cell, we used the code-multiplexed Coulter sensors. [44][45][46] We designed a total of 16 sensors to be distributed across the device with each one assigned a unique 31-bit digital code from a set of orthogonal gold sequences. 47 Due to the orthogonality of these codes, signals from individual sensors could be distinguished from one another through correlation with a template library.…”

Combinatorial Immunophenotyping of Cell Populations with an Electronic Antibody Microarray

“…Because the code signals were specifically designed to be mutually orthogonal, we could not only classify sensor signals robustly with minimal crosstalk but also resolve signal interferences through an iterative process called successive interference cancellation. [30,35] At the end of this decoding process, the original output This article is protected by copyright. All rights reserved.…”