PROJECT SUMMARY/ABSTRACT High blood pressure (BP) is the single largest risk factor for cardiovascular disease mortality. Due to the well- known limitations of clinic BP measurement, 24-hour ambulatory BP monitoring with automatic cuff devices has emerged as the gold standard method for hypertension diagnosis. Due to periodic inflation and deflation even at nighttime, the cuff devices are disruptive to patients and could diminish the clinical value of nighttime BP. Hence, cuff-less BP monitoring devices are being widely pursued. Pulse transit time (PTT), the time delay for the pressure wave to travel between two arterial sites, represents the most promising cuff-less BP measurement principle. However, there are several critical barriers in exiting PTT measurements such as: (i) subpar sensor sensitivity; (ii) poor sensor adhesion; (iii) difficulty in converting PTT measurements into BP readings; (iv) difficult in obtaining both diastolic BP (DP) and systolic BP (SP) measurements. To address these issues, the overall objective of this work is to combine arterial tonometry and PTT principles to achieve cuff-less 24-hour ambulatory BP monitoring. This will be achieved by placing two wearable tonometric sensors at arterial sites (proximal and distal) and collecting high-fidelity tonometric waveforms as well as PTT values. Our innovations in this work include: (a) integrating ionic liquid and microstructures (which can accommodate ions under pressure) in piezo-capacitive sensor to enhance both the sensitivity and dynamic range; (b) incorporating micropillars (mimicking gecko’s feet) at the sensor substrate to promote adhesion and improve the fidelity of captured waveforms; (c) calibrating tonometric waveforms with pre-constructed PTT-BP relationships (via postural changes); (d) calibrating tonometric waveforms to extract both DP and SP continuously by leveraging the similar shape of arterial tonometric and BP waveforms. The specific aims are: (1) to develop wearable sensors to obtain high-fidelity tonometric waveforms; (2) to promote the adhesion of wearable patches; (3) to develop PTT-based calibration for extracting both DP and SP; and (4) to validate the system in human studies. Our expected outcome is an accurate, cuff-less, 24-hour BP monitoring system. Successful completion of this project can lead to new clinical practices for ambulatory BP monitoring and post- surgery hypotension surveillance.