Development of thin-film micro-outlets for spatially constraining local PO2 perturbations to capillaries in vivo
Bibliographic record
Abstract
Objective To develop and validate thin-film micro-outlet devices to study microvascular blood flow responses to localized changes in skeletal muscle oxygen concentration ([O2]). Methods 30 male Sprague-Dawley rats (159–194 g) were anesthetized and instrumented to maintain cardiovascular state. The extensor digitorum longus (EDL) muscle was dissected, isolated, and reflected over a gas exchange chamber (GEC) mounted in the stage of an inverted microscope. The GEC and EDL were coupled via a composite, gas permeable membrane, and a gas impermeable film fabricated with laser machined micro-outlets of specific diameters (200, 400, 600, and 1,000 μm). [O2] in the EDL was dynamically manipulated with step-wise oscillations between 7% (1 min) → 12% (1 min) → 2% (1 min) → 7% (1 min), and step challenges from 7% (1 min) → 2% or 12% (2 min), while recording intravital video for capillary RBC oxygen saturation (SO2) and hemodynamic measurements. Oxygen diffusion between tissue and micro-outlet devices was modelled using a finite element mass transport model to further validate experimental results. Results [O2] oscillations imposed on capillaries directly overlying 400 μm micro-outlets caused significant changes in RBC SO2 at 12% and 2% [O2], compared to 7% [O2] (p < 0.0001). [O2] oscillations caused significant changes in capillary RBC supply rate (SR) at 2% [O2] versus 7%, and were significantly different at 2% compared to 12% [O2] (p < 0.0014). Similarly, [O2] challenges imposed on capillaries overlying 200 μm micro-outlets also caused significant changes in RBC SO2 at 2% [O2], compared to 7% [O2] (p < 0.0001), and caused significant changes in SR at 2% [O2] compared to 7% (p < 0.0001). Conclusion Our composite thin-film devices were fabricated and validated to spatially confine oxygen perturbations to capillaries using micro-outlets of varying diameters. These results demonstrate that our devices can manipulate capillary SO2 and alter capillary RBC SR in vessels directly overlying the micro-outlet without affecting capillary SO2 at a distance from the outlets. Our novel composite thin-film micro-outlet devices demonstrate that capillary blood flow responses can be provoked by manipulating [O2] in tissue regions as small as ∼200 μm in diameter.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".