Optical Estimation of Membrane Potential Values Using Fluorescence Lifetime Imaging Microscopy and Hybrid Chemical-Genetic Voltage Indicators
Bibliographic record
Abstract
Introduction: ), the voltage across a cell membrane, is an important biophysical phenomenon, central to the physiology of cells, tissues, and organisms. Voltage-sensitive fluorescent indicators are a powerful method for interrogating membrane potential in living systems, but most indicators are best suited for detecting changes in membrane potential rather than measuring values of the membrane potential. One promising approach is to use fluorescence lifetime imaging microscopy (FLIM) in combination of chemically synthesized dyes to estimate a value of membrane potential. However, a drawback is that chemically synthesized dyes show poor specificity of staining. Objectives: To address this problem, we applied a chemical-genetic voltage imaging approach to FLIM to enable optical estimation of membrane potential values from genetically defined cells. Results: In this report, we detail the characterization and evaluation of two of these systems in mammalian cells. We further validate the use of a FLIM-based chemical genetic voltage indicator in mammalian neurons. Conclusions: Finally, we discuss opportunities for future improvements to chemical-genetic FLIM-based voltage indicators.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".