Multiplexed Label-Free Cytokine Sensing Using a 128x128 CMOS ISFET Array with Flexdym Microfluidic Partitioning

Source: Research paper, written by Utku Noyan; Sahil Shah; Pamela Abshire (October 21, 2026). AI-generated summary by biochip.com, published October 26, 2026. Not independently reviewed.

Utku Noyan, Sahil Shah, and Pamela Abshire developed a chip that measures two inflammation-related proteins using thousands of tiny electronic sensors and a four-well microfluidic layer. The platform detected interleukin-6 (IL-6) and interleukin-10 (IL-10) across a concentration range of 100 femtomolar to 10 nanomolar, with reported detection limits of 14 and less than 1.9 picograms per milliliter, respectively. By combining a dense sensor array with separate chemical zones and a built-in reference, the researchers aim to make label-free measurement of multiple cytokines more practical. The results are laboratory dose-response measurements, not a demonstration of clinical performance in patients.

A dense electronic array for two cytokines

The platform pairs a 128-by-128 array of ion-sensitive field-effect transistors, or ISFETs, with four small wells made from FlexDym, a thermoplastic elastomer. Each well exposes a separate region of the sensor array to a different surface chemistry. Two regions carry antibodies that capture IL-6 or IL-10, one acts as a chemistry-only reference, and the fourth tests whether the IL-6 capture chemistry responds selectively.

An ISFET works somewhat like an electronic pH meter: changes in electrical charge at its sensing surface alter the current flowing through the device. When a cytokine binds to its capture antibody, that local charge change can be measured without adding a fluorescent or other label. The researchers compare the signal in each antibody-coated well with the reference well, helping distinguish target binding from effects such as changes in acidity, temperature, or salt concentration.

What the measurements showed

In single-analyte dose-response tests, the team measured IL-6 and IL-10 across concentrations from 100 femtomolar to 10 nanomolar. The reported detection limit was 14 picograms per milliliter for IL-6 and below 1.9 picograms per milliliter for IL-10. The researchers say the results reach healthy-serum baseline concentrations for IL-10 and the clinically elevated range for IL-6.

The array contains 16,384 pixels, with about 2,176 pixels under each well. Combining readings from many pixels can reduce the influence of noise in any one sensor. The team also compared two chips and found that differences in transistor transconductance, a measure of how strongly a transistor’s current responds to voltage, drove substantial variation between devices. A one-time calibration for each device reduced the reported analyte-measurement variance from about 62% to about 16%.

Why the microfluidic material matters

Many microfluidic devices use polydimethylsiloxane, or PDMS. The researchers note that PDMS can absorb small molecules and release uncrosslinked compounds that may affect measurements. Their FlexDym overlay is made from styrene-ethylene-butylene-styrene, or SEBS, and is designed to reduce those material-related problems. The team reports integrating the overlay with the sensor array and using it to keep the four assay regions chemically separate.

This combination addresses a practical challenge in cytokine sensing: measuring more than one target on a compact electronic platform while retaining a reference for background effects. The study establishes dose-response sensing and device calibration on the chip. It does not establish how the platform performs with patient samples or whether it can deliver a clinical result at the bedside. Further testing would need to assess those questions and the reliability of measurements in real biological samples.

Topics: Microfluidics

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