All-in-one low-intensity pulsed ultrasound stimulation system using piezoelectric micromachined ultrasonic transducer (pMUT) arrays for targeted cell stimulation.

A novel cell-stimulation system was fabricated using 10 × 29 piezoelectric micromachined ultrasonic transducer (pMUT) arrays for targeted ultrasonic cell stimulation. Both the diameter of a single pMUT element and the edge-to-edge gap were 120 μm, and the size of a pMUT array was 2.27 × 6.84 mm, to be placed at the bottom of a Transwell. The measured resonance frequency of a single pMUT element was 1.48 ± 0.13 MHz and the measured acoustic intensity of the pMUT array was 0.15 ± 0.03 MPa at 1 mm away from the transducer. A pMUT array was mounted on a print circuit board (PCB), which was designed in accordance with the size of a 12-well Transwell. The Transwell was placed on the PCB and wire bonding was performed to electrically connect the PCB and pMUT arrays. After wiring, the PCB and pMUT arrays were coated with 2.6-μm thick parylene-C to ensure biocompatibility and waterproofing. PC12 cells were used for ultrasonic cell stimulation tests to examine the proposed all-in-one low-intensity pulsed ultrasound stimulation system. Various stimulation times and duty cycles were used simultaneously for cell proliferation in a confined cell culture environment. All stimulation groups showed increased cell proliferation rates, in the range 138-166%, versus the proliferation rate of the control group.