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Label-Free Leukocyte Biophysical Profiling Using Impedance-Deformability Cytometry for Rapid Cardiovascular Risk

Linwei He1, Hui Min Tay1, Feng Chen2

  • 1School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 28, 2025
PubMed
Summary
This summary is machine-generated.

A new microfluidic method analyzes neutrophil properties to predict cardiovascular disease (CVD) risk in type 2 diabetes mellitus (T2DM). This technique offers a cost-effective approach for early CVD risk stratification in diabetic patients.

Keywords:
biophysical profilingdiabetesimpedance cytometrymicrofluidicstranslational diagnostics

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Area of Science:

  • Biomedical Engineering
  • Cardiovascular Research
  • Diabetology

Background:

  • Type 2 diabetes mellitus (T2DM) is a major global health concern, with cardiovascular disease (CVD) being the primary cause of mortality.
  • Effective CVD risk stratification in T2DM patients is crucial for timely intervention and improved patient outcomes.

Purpose of the Study:

  • To develop a rapid, label-free microfluidic workflow for assessing cardiovascular risk in T2DM patients.
  • To investigate neutrophil biophysical abnormalities as potential biomarkers for CVD risk in T2DM.

Main Methods:

  • A high-throughput single-cell microfluidic technique called "electro-mechano-phenotyping" was employed.
  • Leukocyte biophysical properties (size, deformability, impedance) were analyzed using Uniform Manifold Approximation and Projection (UMAP).
  • The method was validated in vitro and in diabetic and atherosclerosis-prone mouse models, followed by a clinical study.

Main Results:

  • Diabetic patients with CVD (DM-CVD) exhibited a distinct neutrophil impedance signature and pro-inflammatory transcriptomic profile.
  • Key molecular pathways identified include cytoskeletal dysregulation and altered RhoA signaling in DM-CVD neutrophils.
  • Principal component analysis demonstrated high accuracy (AUC = 0.971) in identifying individuals with vascular dysfunction.

Conclusions:

  • Neutrophil impedance profiling is a promising, cost-effective strategy for cardiovascular risk stratification in T2DM.
  • The developed microfluidic workflow enables rapid, label-free assessment of CVD risk.
  • Biophysical neutrophil analysis provides insights into the mechanisms linking T2DM, inflammation, and CVD.