A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening.

High-content imaging for compound and genetic profiling is popular for drug discovery but limited to endpoint images of fixed cells. Conversely, electronic-based devices offer label-free, live cell functional information but suffer from limited spatial resolution or throughput. Here, we introduce a semiconductor 96-microplate platform for high-resolution, real-time impedance imaging. Each well features 4096 electrodes at 25 µm spatial resolution and a miniaturized data interface allows 8× parallel plate operation (768 total wells) for increased throughput. Electric field impedance measurements capture >20 parameter images including cell barrier, attachment, flatness, and motility every 15 min during experiments. We apply this technology to characterize 16 cell types, from primary epithelial to suspension cells, and quantify heterogeneity in mixed co-cultures. Screening 904 compounds across 13 semiconductor microplates reveals 25 distinct responses, demonstrating the platform's potential for mechanism of action profiling. The scalability and translatability of this semiconductor platform expands high-throughput mechanism of action profiling and phenotypic drug discovery applications.

A semiconductor 96-microplate platform for electrical-imaging based high-throughput phenotypic screening.

Profiling compounds and genetic perturbations via high-content imaging has become increasingly popular for drug discovery, but the technique is limited to endpoint images of fixed cells. In contrast, electronic-based devices offer label-free, functional information of live cells, yet current approaches suffer from low-spatial resolution or single-well throughput. Here, we report a semiconductor 96-microplate platform designed for high-resolution real-time impedance "imaging" at scale. Each well features 4,096 electrodes at 25 µm spatial resolution while a miniaturized data interface allows 8× parallel plate operation (768 total wells) within each incubator for enhanced throughputs. New electric field-based, multi-frequency measurement techniques capture >20 parameter images including tissue barrier, cell-surface attachment, cell flatness, and motility every 15 min throughout experiments. Using these real-time readouts, we characterized 16 cell types, ranging from primary epithelial to suspension, and quantified heterogeneity in mixed epithelial and mesenchymal co-cultures. A proof-of-concept screen of 904 diverse compounds using 13 semiconductor microplates demonstrates the platform's capability for mechanism of action (MOA) profiling with 25 distinct responses identified. The scalability of the semiconductor platform combined with the translatability of the high dimensional live-cell functional parameters expands high-throughput MOA profiling and phenotypic drug discovery applications.

Technical Note: ID-card-size dosimeter based on radiochromic films for continuous personnel monitoring.

PURPOSE: This paper is aimed at investigating the feasibility of developing a personal dosimeter of cumulative radiation dose which would incorporate the following features: 1) a small size compared to that of a proximity ID card; 2) instant dose readout; 3) no power source; 4) moderate cost. The dosimeter is proposed as a potential replacement for TLD and OSL dosimeters used by nuclear industry workers and some medical staff groups. METHODS: An original detector design is developed containing a two-color LED, two photodetectors located in one plane covered with a mirror coating. The power necessary for the operation comes from an RFID reader. A small (5x5 mm) piece of Gafchromic EBT3 photochromic film sensitive to both X-ray and gamma radiation is used as a sensor. Irradiation of samples under X-ray and gamma radiation is carried out in the dose range of 0.1 cGy-1 Gy. The transmittance spectra are measured in the 300 nm-1100 nm spectral range. RESULTS: Several prototypes of the dosimeter are presented, the distinctive features of which are the absence of the power source, easy transmitting of the dosimetric data via a RF channel, and a slim form factor. Several sources of dose uncertainties are analyzed and ways to eliminate them are outlined. The average dose confidence interval (α = 0.05) calculated from the response curve is shown to equal 0.02 cGy. This makes it possible to reliably measure doses as low as 0.1 cGy, which corresponds to the minimum value claimed for Gafchromic EBT3. CONCLUSIONS: The proposed idea of an ID-card-size dosimeter is feasible and has a number of advantages over TLD and OSL dosimeters, in particular, instant reading of the dose data using RFID/NFC readers, and a possibility of integrating into ERP systems.

Reducing unintended consequences of e-prescribing on the path to nuanced prescriptions.

A frequency value of "as directed" was added to all medications available for an ambulatory EMR to reduce the number of prescriptions with contradictory instructions. The new frequency value has been rapidly adopted and its use has increased by 15%.

Weight-based pediatric prescribing in ambulatory setting.

Building on a foundation of a dose-based ambulatory prescribing system, an advanced weight-based pediatric prescribing module was successfully implemented. It provides a complete solution for calculating a dispensable dose and choosing optimal drug strength and form.

Implementing renal impairment and geriatric decision support in ambulatory e-prescribing.

An advanced decision support system for prescribing to patients with renal impairment and geriatric patients was successfully implemented in an ambulatory electronic medical record (EMR) system.