# Fractionation and Profiling of Heterogeneous Circulating Tumor Cells Using a Hyperuniform- Structured Microchip

> **NIH NIH R21** · TEXAS TECH UNIVERSITY · 2020 · $553,092

## Abstract

Title: Fractionation and Profiling of Heterogeneous Circulating Tumor Cells Using a
Hyperuniform-structured Microchip
Project Summary/Abstract
Circulating tumor cells (CTCs) are highly heterogeneous, and specific CTC subpopulations, rather than the whole,
are responsible for cancer metastasis. Current CTC technologies simply isolate all CTCs in a blood sample
without resolving them into distinct subpopulations, preventing researchers from acquiring true insights into the
metastatic potential of CTCs. As a consequence, correlation between CTC heterogeneity and tumor progression
is largely unknown. In addition, existing CTC characterization methods often involve destructive fixation and
permeabilization protocols, which limit the potential for subsequent phenotypic analysis of CTCs and other
downstream applications. The goal of this proposal is to understand the metastatic potential of CTCs through
effective fractionation and profiling of CTC subpopulations. I propose to isolate, in-situ identify, and selectively
recover CTCs using a microchip with hyperuniform structure. Hyperuniformity (HU) is an emerging concept of a
packing pattern which contains local heterogeneity or randomness and global regularity or homogeneity. My
work, for the first time, will integrate the concept of hyperuniformity into affinity-based microfluidic devices for
CTC isolation. I hypothesize that due to the controlled differences in local flow patterns induced by the
hyperuniform structure, cell arrest in different locations on the microchip will require different adhesive strengths.
Further, this adhesive strength is anticipated to be related to the types and densities of surface markers on the
captured CTCs and therefore, their metastatic character. Specific aims include (1) Design and characterize HU
structured microchip for CTC capture and analyze flow pattern and adhesion force in the device; (2) Capture and
identify subpopulations of CTCs with variable expression of the surface marker using a HU microchip; and (3)
Explore several key factors for potential incorporation of the HU microchip platform into clinical oncology settings.
The HU microchip offers a simple and unique resolution for fractionation of CTCs, as its global homogeneity
provides equal possibility of CTC adherence; and local heterogeneity allows simultaneous differentiation of
subpopulations by analyzing adhesive strength required for individual CTCs. As a result, subpopulations of CTCs
can be identified using only their capture locations on the HU chip without requiring additional post-capture
immunofluorescence characterization. The most significant quantitative milestones are to achieve 80% accuracy
on statistical correlation on: 1) the locations on a HU chip with strength of cell-post interaction, 2) predictions of
location vs. cell type in a cancer cell mixture (PC3 and LNCaP), and 3) achieving 80% accuracy on identification
of released EMT and non-EMT cells from their locations on a HU microchip,...

## Key facts

- **NIH application ID:** 10025872
- **Project number:** 1R21CA240185-01A1
- **Recipient organization:** TEXAS TECH UNIVERSITY
- **Principal Investigator:** Wei Li
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $553,092
- **Award type:** 1
- **Project period:** 2020-08-07 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025872

## Citation

> US National Institutes of Health, RePORTER application 10025872, Fractionation and Profiling of Heterogeneous Circulating Tumor Cells Using a Hyperuniform- Structured Microchip (1R21CA240185-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10025872. Licensed CC0.

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