AI-enabled epidermal electronic system to automatically monitor a prognostic parameter for hypertension with a smartphone.

We present a wearable, flexible, wireless and smartphone-enabled epidermal electronic system (EES) for the continuous monitoring of a prognostic parameter for hypertension. The thin and lightweight EES can be tightly attached to the chest of a patient and synchronously monitor first lead electrocardiograms (ECG) and seismocardiograms (SCG). To demonstrate the concept, we developed the EES using state-of-the-art cleanroom technologies. Two types of sensors were integrated: A pair of metal electrodes to contact the skin and to record ECG and a vibration sensor based on a thin piezoelectric polymer to record SCG from the same location of the chest, simultaneously. The complete EES was powered by the near field communication functionality of the smartphone. We developed a machine-learning algorithm and trained it on public ECG data and recorded SCG signals to extract characteristic features of the recordings. Binary classifiers were used to automatically annotate peaks. After training, the algorithm was transferred to the smartphone to continuously analyze the timing between particular ECG and SCG peaks and to extract the Weissler's index as a prognostic parameter for hypertension. Tests with data of healthy control persons and clinical experiments with patients diagnosed with cardio-pulmonary hypertension showed a promising prognostic performance. The presented EES technology could be utilized for pre-screening of cardio-pulmonary hypertension, which is a strong burden in our today's healthcare system.

Effect of cell imprinting on viability and drug susceptibility of breast cancer cells to doxorubicin.

This study demonstrates the effect of substrate's geometrical cues on viability and the efficacy of an anti-cancer drug, doxorubicin (DOX), on breast cancer cells. It is hypothesized that the surface topographical properties can mediate the cellular drug intake. Pseudo-three dimensional (3D) platforms were fabricated using imprinting technique from polydimethylsiloxane (PDMS) and gelatin methacryloyl (GelMA) hydrogel to recapitulate topography of cells' membranes. The cells exhibited higher viability on the cell-imprinted platforms for both PDMS and GelMA materials compared to the plain/flat counterparts. For instance, MCF7 cells showed a higher metabolic activity (11.9%) on MCF7-imprinted PDMS substrate than plain PDMS. The increased metabolic activity for the imprinted GelMA was about 44.2% compared to plain hydrogel. The DOX response of cells was monitored for 24 h. Although imprinted substrates demonstrated enhanced biocompatibility, the cultured cells were more susceptible to the drug compared to the plain substrates. In particular, MCF7 cells on imprinted PDMS and GelMA substrates showed 37% and 50% higher in cell death compared to the corresponding plain PDMS and GelMA, respectively. Interestingly, the drug susceptibility of the cells on the imprinted hydrogel was about 70% higher than the cells cultured on imprinted PDMS substrates. Having MCF7 cell-imprinted substrates, DOX responses of two other breast cancer cell lines, SKBR3 and ZR-75-1, were also evaluated. The results support that cell membrane curvature developed by multiscale topography is able to mediate intracellular signaling and drug intake. STATEMENT OF SIGNIFICANCE: Research in biological sciences and drug discovery mostly rely on two dimensional (2D) cell culture techniques which cannot provide a reliable physiologically relevant environment. Lack of extracellular matrix and a large shift in physicochemical properties of conventional 2D substrates can induce aberrant cellular behaviors. While chemical composition, topographical, and mechanical properties of substrates have remarkable impacts on drug susceptibility, gene expression, and protein synthesis, the most cell culture plates are from rigid and plain substrates. A number of (bio)polymeric 3D-platforms have been introduced to resemble innate cell microenvironment. However, their intricate culture protocols restrain their applications in demanding high-throughput drug screening. To address the above concerns, in the present study, a hydrogel-based pseudo-3D substrate with imprinted cell features has been introduced.