# SEMI-SIMOA: A Chip-scale Flow-based Single-Molecule Assay at the Point-of-Care using Semiconductor Technology

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $149,101

## Abstract

Project Summary
Over the past two decades, single-molecule assays (SIMOA) have transformed the detection landscape for low-
abundance protein biomarkers, such as cytokines and neurological markers, across a vast dynamic range.
Sourced from a variety of samples, these assays provide exceptional capabilities that enhance our knowledge
of diseases and fine-tune diagnostic methodologies. While various platforms have been developed and
commercialized, they invariably involve intricate workflows and depend on highly specialized, bulky equipment.
Such complexities confine the use of this technology to centralized labs, necessitating controlled environments
and skilled operators.
To meet these challenges, we introduce a compact SIMOA system that seamlessly integrates electronics and
sub-µm sized microfluidics within a single integrated circuit (IC) chip, produced by semiconductor foundries. The
creation of the microfluidics leverages a unique single-step wet-etching process, which facilitates the efficient
integration of thousands of fluidic and electronic channels onto a compact, millimeter-sized CMOS chip. Drawing
from the principles of flow-cytometry-based and nanopore-centric SIMOA platforms, our system electronically
counts individual sandwiched immunocomplexes as they pass through the on-chip 500-nm pores. Notably, the
IC itself stands as the main instrument, enabling results to be directly viewed on a personal device, eliminating
the need for a reader.
The project objective will be achieved by four specific aims: (1) Aim I will focus on implementing the CMOS-
embedded microfluidics, the sensing on-chip pores, integrated on-chip electrodes, and the magnetic separation
module. (2) Aim II will focus on developing resistive-pulse-sensing low-noise readout circuits and signal
processing units for digitization and identification of the binding events. The integrated microfluidics/electronics
system will be packaged, tested, and validated. (3) Aim III will focus on the functionalization of nanoparticles
using target-specific antibodies. We will target three biomarkers, ɑ-synuclein, NfL, and GFAP, that are related to
neurodegenerative diseases. (4) Aim IV will optimize the workflow and validate the assay by benchmarking with
the established commercial SIMOAs. This project holds significant promise; its successful completion could
transform future diagnostics for many diseases that require detecting low-abundant biomarkers, particularly
benefiting settings with limited resources.

## Key facts

- **NIH application ID:** 10951398
- **Project number:** 1R21EB036154-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Jun-Chau Chien
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $149,101
- **Award type:** 1
- **Project period:** 2024-07-05 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951398

## Citation

> US National Institutes of Health, RePORTER application 10951398, SEMI-SIMOA: A Chip-scale Flow-based Single-Molecule Assay at the Point-of-Care using Semiconductor Technology (1R21EB036154-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10951398. Licensed CC0.

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