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

Dolphin

Dolphin

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The full thesis for this has just become available

GUO, YAOJUN. (2024). Develop Microfluidic-based Diagnostic Approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). UC Davis. ProQuest ID: GUO_ucdavis_0029D_22812. Merritt ID: ark:/13030/m51d342h. Retrieved from https://escholarship.org/uc/item/0fm949w9

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.
 
A diagnostic test only comparing to healthy controls isn’t of much use yet, but they might have gone with the test framing for their own reasons.

By skimming the figures it doesn’t look like there is clear separation between the groups.

Others will have to comment on the relevance of the measurements.
 
I can attest to one of their drug candidates not doing anything tangible for ME/CFS. Plenty of others asthmatics take it too; we'd have heard if it had significant effects.

The other's used for schizophrenia, and apparently has difficult side effects. There'd need to be a good case for trialling it in people whose symptoms are already so bad they're barely coping.
 
Even in an abstract a PhD candidate needs to be able to show that they extract the critical data and context that make the project worthwhile and present it in a way that satisfies readers' immediate quality-control thoughts. I cannot judge anything from this abstract. I am afraid that there isn't time in science to read through everything with an abstract like this - there is enough stuff that does what you need to keep one busy.
 
Kitty said:
I can attest to one of their drug candidates not doing anything tangible for ME/CFS. Plenty of others asthmatics take it too; we'd have heard if it had significant effects.
Click to expand...
Yes - unless they're arguing that it needs to be injected instead of inhaled or taken at a much higher dosage or some such thing, Salmeterol Xinafoate seems far too common for us not to have heard anecdotes about recovery/improvement. I suppose it is possible that very minor changes could be missed when attributing changes to improvement in asthma/COPD symptoms, but surely one would hope for better.
 
I doubt they mean inhaling it? It seems that inhalation is probably chosen for asthma because it puts the substance exactly where it needs to be in order to work. I doubt it would do much for the more global problem they propose when taken that way.
 
Interesting. I had immediately assumed that being inhaled (frequently alongside corticosteroids, esp. for asthma), it would do a pretty good job of getting into the blood stream.

Here's the method used in the thesis for their in vitro exploration.
3.2.1. Incubation with salmeterol xinafoate and xanomeline.
Dimethyl sulfoxide (DMSO, Sigma-Aldrich, 472301-100ml) was added to salmeterol xinafoate
(Millipore Sigma, S5068 - 10MG) or xanomeline (Cayman Chemical, 10790) to make a stock so-
lution of a concentration of 1 μM and 10 mM respectively. The stock solution was then added in
PBS (ThermoFisher, GibcoTM,20012-PBS, pH = 7.2) containing RBCs to form a final Salmeterol
xinafoate concentration of 1 nM and 10 nM or a final xanomeline concentration of 1 μM and 10
μM. The suspension of RBCs was then incubated for 15mins at room temperature before test, as
shown in figure 3.5
Click to expand...
 
Screenshot 2026-05-26 at 17.17.17.png

Figure 3.9. Improved P O2 - regulated RBC capillary velocity after in vitro drug
treatments on RBCs from ME/CFS subjects. (A) RBCs treated with 1 nM salme-
terol exhibited the highest magnitude and sensitivity of P O2 - regulated capillary
velocity. 9 ME/CFS patients, n = 955 cells before incubation, n = 956 cells and
473 cells for 1 nM and 10 nM respectively. Calculated slope= -0.1406 ± 0.0064,
-0.1738 ± 0.0086, -0.1488 ± 0.0032 (mm/s/mmHg) for 0 nM, 1 nM, and 10 nM
respectively.ns: p > 0.05, *: p < 0.05, **: p < 0.01, ****: p < 0.0001, Mann-
Whitney test. Data are presented as mean ± SEM and each data point represents
the average of RBCs. (B) The magnitude and sensitivity of P O2 - regulated RBC
capillary velocity increased after RBCs were incubated with xanomeline. 8 ME/CFS
patients, n = 905 cells before incubation, n = 690 cells and 917 cells for 1 μM and
10 μM respectively. Calculated slope = -0.1013 ± 0.0081, -0.2039 ± 0.0127, -0.2933
± 0.0094 (mm/s/mmHg) for 0 μM, 1 μM, and 10 μM respectively.ns: p > 0.5,****:
p < 0.0001, Mann-Whitney test. Inhibition of band 3 tyrosin phosphorylation sup-
pressed RBC’ sensitivity to oxygen change. (C) The magnitude and the sensitivity
of RBC capillary velocity to P O2 changes decreased after imatinib incubation. Cal-
culated slope = -0.0292 ± 0.0102, -0.0060 ± 0.0025(mm/s/mmHg) for before and
after imatinib incubation. 1 ME/CFS patients, n = 120 cells and n= 120 cells for
before and after imatinib incubation. ***: p < 0.001, Mann-Whitney test. Each
data point represents the average of RBCs. (D) No significant effect of DMSO on the
slope of P O2 - regulated RBC capillary velocity. Calculated slope (mm/s/mmHg)
= -0.089 ± 0.0035, -0.1 ± 0.006, -0.111 ± 0.024 for 0 % DMSO, 0.01 % DMSO and
1 % DMSO respectively. N = 120 cells for each DMSO concentrations. Data are
presented as mean ± SEM and each data point represents the average of RBCs
Click to expand...

The chosen concentrations were based on reported findings, indicating that 1 nM beta adrenergic
agonist falls within the range capable of enhancing erythrocyte deformability, while 10 nM beta
adrenergic agonist approaches the upper limit. The results, depicted in figure 3.9A, revealed an
increase in RBC capillary velocities at four P O2 levels following incubation with 1 nM salmeterol
xinafoate, whereas a decrease was observed at the same P O2 levels after incubation with 10 nM.
This discrepancy may be attributed to the specificity of salmeterol xinafoate for the β2 receptor,
with 10 nM exceeding the optimal range for enhancing erythrocyte deformability. The sensitivity of
deoxygenation, calculated as the slope, was significantly increased after incubation with both 1 nM
and 10 nM, with 1 nM exhibiting a more pronounced improvement
Click to expand...
Guo et al (2024), 37-8.
 
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