Miniaturized microarray-format digital ELISA enabled by lithographic protein patterning.

The search for reliable protein biomarker candidates is critical for early disease detection and treatment. However, current immunoassay technologies are failing to meet increasing demands for sensitivity and multiplexing. Here, the authors have created a highly sensitive protein microarray using the principle of single-molecule counting for signal amplification, capable of simultaneously detecting a panel of cancer biomarkers at sub-pg/mL levels. To enable this amplification strategy, the authors introduce a novel method of protein patterning using photolithography to subdivide addressable arrays of capture antibody spots into hundreds of thousands of individual microwells. This allows for the total sensor area to be miniaturized, increasing the total possible multiplex capacity. With the immunoassay realized on a standard 75x25 mm form factor glass substrate, sample volume consumption is minimized to <10 µL, making the technology highly efficient and cost-effective. Additionally, the authors demonstrate the power of their technology by measuring six secretory factors related to glioma tumor progression in a cohort of mice. This highly sensitive, sample-sparing multiplex immunoassay paves the way for researchers to track changes in protein profiles over time, leading to earlier disease detection and discovery of more effective treatment using animal models.

Applying machine learning to explore the association between biological stress and near misses in emergency medicine residents.

Physician stress is associated with near misses and adverse medical events. However, little is known about physiological mechanisms linking stress to such events. We explored the utility of machine learning to determine whether the catabolic stress hormone cortisol and the anabolic, anti-stress hormone dehydroepiandrosterone sulfate (DHEA-S), as well as the cortisol to DHEA-S ratio relate to near misses in emergency medicine residents during active duty in a trauma 1 emergency department. Compared to statistical models better suited for inference, machine learning models allow for prediction in situations that have not yet occurred, and thus better suited for clinical applications. This exploratory study used multiple machine learning models to determine possible relationships between biomarkers and near misses. Of the various models tested, support vector machine with radial bias function kernels and support vector machine with linear kernels performed the best, with training accuracies of 85% and 79% respectively. When evaluated on a test dataset, both models had prediction accuracies of around 80%. The pre-shift cortisol to DHEA-S ratio was shown to be the most important predictor in interpretable models tested. Results suggest that interventions that help emergency room physicians relax before they begin their shift could reduce risk of errors and improve patient and physician outcomes. This pilot demonstrates promising results regarding using machine learning to better understand the stress biology of near misses. Future studies should use larger groups and relate these variables to information in electronic medical records, such as objective and patient-reported quality measures.