# Develop a novel red blood cell-based microfluidic approach to assess and diagnose ME/CFS

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $224,955

## Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disease with
inconclusive causes and no laboratory-based diagnostic tests. Oxygen tension (PO2)-regulated red blood cell
(RBC) capillary velocity has emerged recently as a new mechanism regulating cerebral capillary perfusion and
measures RBC responses to local hypoxia. Such intrinsic RBC responses to PO2 changes may change distinctly
under different pathological conditions and thus represent a new RBC-based approach for disease diagnosis.
Indeed, our preliminary results showed that RBCs collected from ME/CFS patients exhibited impaired velocity in
a microfluidic capillary in response to reduced PO2 and PO2-regulated RBC capillary velocity was improved
significantly when patients received craniocervical instability surgery, strongly suggesting that PO2-regualted
RBC capillary velocity may represent a new characteristic of ME/CFS that might be used to diagnose ME/CFS
and measure ME/CFS progression. Here, we extend our preliminary study and propose an interdisciplinary
approach combing microfluidics, machine learning and RBC cytokine assay to examine rigorously the accuracy
of PO2-regulated RBC capillary velocity as a new laboratory test for ME/CFS and investigate mechanistically the
roles of RBC cytokine signaling in ME/CFS.
Aim 1 will measure PO2-regulated RBC capillary velocity using RBCs from 96 participants and compare the
results of ME/CFS patients with age, gender and race-matched healthy controls. Furthermore, we will develop
machine-learning algorithms to establish a diagnostic classifier to validate PO2-regulated RBC capillary velocity
as a new laboratory test for ME/CFS and assess its feasibility to differentiate ME/CFS patients with different
disease severity. Mechanistically, we will examine hemoglobin-band 3 interactions in RBCs from ME/CFS
patients and examine their correlations with increased oxidative stress in ME/CFS.
Aim 2 will quantify the cytokine profile in RBCs from ME/CFS patients and compare them with age, gender and
race-matched healthy controls. Furthermore, we will alter the RBC cytokine profile and measure the
corresponding changes of PO2-regulated RBC capillary velocity to examine whether RBC cytokine profile plays
a role in the modulation of PO2-regulated RBC capillary velocity. These experiments will provide a previously
unrecognized RBC cytokine signaling in ME/CFS and add new insights to the immune dysregulation in ME/CFS.
Together, the proposed studies exploit new tools and technology to develop a new laboratory test for ME/CFS
and reveal mechanistims underlying PO2-regulated RBC capillary velocity in ME/CFS, which we believe will
directly improve the diagnosis and treatment of ME/CFS.

## Key facts

- **NIH application ID:** 10806592
- **Project number:** 1R21AI175960-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Jiandi Wan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $224,955
- **Award type:** 1
- **Project period:** 2023-12-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10806592

## Citation

> US National Institutes of Health, RePORTER application 10806592, Develop a novel red blood cell-based microfluidic approach to assess and diagnose ME/CFS (1R21AI175960-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10806592. Licensed CC0.

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