Thesis Develop Microfluidic-based Diagnostic Approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2024, Guo

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Develop Microfluidic-based Diagnostic Approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
2024

• GUO, YAOJUN
• Advisor(s): Wan, Jiandi

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a global health concern,impacting millions of individuals, yet diagnosis remains a challenge due to the absence of consistent laboratory testing methods.

Currently, diagnosis is solely dependent on doctors’ experience and in depth understanding on patients’ medical histories.

This thesis aims to develop an accessible, rapid, and cost-effective laboratory-based diagnostic method for ME/CFS, while also exploring potential applications in treatment monitoring and evaluation using microfluidic approaches.

We achieved this by creating a microfluidic platform to measure capillary velocity of red blood cells (RBCs) at controlled oxygen tensions (PO2).

Our research revealed that RBCs from ME/CFS patients exhibit impaired responses to changes in PO2, as compared to healthy controls.

Such PO2 - regulated RBC capillary velocity was thus used for ME/CFS diagnosis and exhibited an approximately 80% accuracy using machine learning methods.

Additionally, our investigation identified two potential drug candidates, Salmeterol Xinafoate and Xanomeline, which showed promise in improving PO2 - regulated capillary velocity of RBCs from ME/CFS patients.

Moreover, we found that a simple phosphate buffered saline (PBS) wash can recover RBC’s sensitivity to deoxygenation, implying that RBC-cytokine interaction in ME/CFS contributes to PO2 - regulated RBC capillary velocity.

In conclusion, we have developed a diagnostic platform for ME/CFS using a combination of microfluidic techniques and machine learning, offering a cost-effective and simple approach to ME/CFS diagnosis.

It also opens doors for in-depth exploration of the underlying mechanisms of the condition.

This item is under embargo until May 15, 2026.

 

This reminds me of the late Dr Paul Cheney's observations and theories re: poor oxygen desaturation in the blood of PWME which he ascribed to a pH imbalance created by intracellular proton production in atypical respiration metabolism causing blood alkalosis as the body's homeostatic systems respond by providing bicarbonate ions to mop up the acidic overproduction from cells.

The observation that normal RBC desaturation is restored by changing the medium pH to nearer normal with a phosphate buffered saline (PBS) wash is consistent with Dr Cheney's hypothesis.

It might be worth exploring this hypothesis and the biochemical root cause of poor desaturation.

Velocity is not necessarily the only thing impairing oxygen transfer.

 

A difference vs healthy controls does not mean that it's a marker specific to ME. Does the test differentiate between unhealthy non-ME people?

 

This is the reason why I think that the control for ME/CFS should be not only similarly sedentary, but also similarly sick. We don't know if whatever they found here is also present in people who are sick with, say, flu. Biomarkers in particular needs to be present in, and in nothing else other than, ME/CFS.

 

See also the thread for Impaired oxygen sensitivity of red blood cells from ME/CFS, Wan NIH talk 2024

 

If they just used machine learning, and don't have separate training and validation datasets, it could just be overfitting (looking at irrelevant differences)

 

They must. That would be a rookie mistake.

Please tell me they do, otherwise I’m losing a lot of trust in basic conpetancy.

 

It's embargoed until next year so I don't know.