Real‐time monitoring of intracellular calcium dynamic mobilization of a single cardiomyocyte in a microfluidic chip pertaining to drug discovery
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Bibliographic record
Abstract
A microfluidic method for real-time quantitative measurement of cellular response pertaining to drug discovery is reported. This method is capable of multiple-step liquid delivery for measuring the drug response of a single cardiomyocyte, due to the improved cell retention by a newly designed chip. The chip, which consists of a cell-retention chamber with a weir structure, was fabricated just by a one-photomask microfabrication procedure followed by on-chip etching. This method differs from the conventional method, which uses two-mask photolithography to fabricate the microchannel (deep etch) and the weir structure (shallow etch). The dimensions of the weir structure have been predicted by a mathematical model, and confirmed by confocal microscopy. Using this microfluidic method, the dynamic [Ca2+]i mobilization in a single cardiomyocyte during its spontaneous contraction was quantified. Furthermore, we measured the cellular response of a cardiomyocyte on (i) a known cardiotonic agent (caffeine), (ii) a cardiotoxic chemotherapeutic drug (daunorubicin), and (iii) an herbal anticancer drug candidate - isoliquiritigenin (IQ) based on the fluorescent calcium measurement. It was found that IQ had produced a less pronounced effect on calcium mobilization( )of the cardiomyocytes whereas caffeine and daunorubicin had much stronger effects on the cells. These three experiments on cardiomyocytes pertaining to drug discovery were only possible after the improved cell retention provided by the new chip design (MV2) required for multiple-step real-time cellular analysis on a microchip, as compared with our old chip design (MV1).
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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 | 0.001 | 0.001 |
| 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 it