Ultrasound scans — greatest recognized for monitoring pregnancies or imaging organs — may also be used to stimulate cells and direct cell operate. A staff of Penn State researchers has developed a neater, more practical option to harness the expertise for biomedical functions.
The staff created a clear, biocompatible ultrasound transducer chip that resembles a microscope glass slide and might be inserted into any optical microscope for simple viewing. Cells might be cultured and stimulated straight on high of the transducer chip and the cells’ ensuing modifications might be imaged with optical microscopy strategies.
Printed within the Royal Society of Chemistry’s journal Lab on a Chip, the paper was chosen as the quilt article for the December 2021 difficulty. Future functions of the expertise may impression stem cell, most cancers and neuroscience analysis.
“Within the typical ultrasound stimulation experiments, a cell tradition dish is positioned in a water bathtub, and a cumbersome ultrasound transducer directs the ultrasound waves to the cells by means of the water medium,” stated Sri-Rajasekhar “Raj” Kothapalli, principal investigator and assistant professor of biomedical engineering at Penn State. “This was a posh setup that did not present reproducible outcomes: The outcomes that one group noticed one other didn’t, even whereas utilizing the identical parameters, as a result of there are a number of issues that would have an effect on the cells’ survival and stimulation whereas they’re in water, in addition to how we visualize them.”
Kothapalli and his collaborators miniaturized the ultrasound stimulation setup by making a clear transducer platform fabricated from a piezoelectric lithium niobate materials. Piezoelectric supplies generate mechanical power when electrical voltage is utilized. The chip’s biocompatible floor permits the cells to be cultured straight on the transducer and used for repeated stimulation experiments over a number of weeks.
When linked to an influence provide, the transducer emits ultrasound waves, which pulse the cells and set off ion inflow and outflux.
To check the setup, Kothapalli and his staff cultured bladder most cancers cells on the chip. They then inserted fluorescent calcium indicators into the cells to permit researchers to obviously see dynamic modifications in cell calcium signaling underneath the microscope throughout stimulation.
“Because the cells are straight sitting on the clear transducer floor, we will verify that each one the cells are equally stimulated on the identical time utilizing a single ultrasound stimulus, not like typical approaches,” Kothapalli, a co-hire with the Penn State Most cancers Institute, stated. “And in contrast to earlier processes, we will get excessive decision photographs of many cells without delay in a single area of view, as a result of we’re in a position to see the cells from a detailed distance.”
By way of the bladder most cancers cell examine, researchers established proof-of-concept for the brand new transducer setup. However they will prolong these findings to make use of the transducer setup in potential future functions, in line with Kothapalli, resembling stem cell differentiation, mechanosensitive neuromodulation, drug supply and the opening of the blood-brain barrier.
“This easy setup might be invaluable for researchers involved in modulating cells and tissues with an ultrasound,” stated Pak Kin Wong, professor of biomedical engineering, mechanical engineering and surgical procedure at Penn State and co-author on the paper. “It may be used to discover novel therapeutic ultrasound functions, resembling targeted ultrasound immunotherapy.”
The ultrasound stimulation chip is low-cost, straightforward to manufacture, compact and scalable in measurement, and disposable and reusable, in line with Haoyang Chen, first writer of the paper and doctoral pupil underneath Kothapalli in biomedical engineering.
“It’s straightforward to develop cells on the chip utilizing commonplace cell culturing strategies,” Chen stated. “The setup offers controllable stimulation parameters for quite a lot of experiments and might be imaged with all typical optical microscopy strategies.”
Along with Kothapalli, Wong and Chen, different contributors to the examine have been Peter Butler, Penn State professor of biomedical engineering and affiliate dean for schooling and graduate skilled applications; biomedical engineering graduate college students Ninghao Zhu, Mohamed Osman and Shubham Khandare; and biomedical engineering undergraduate college students Ryan Biskowitz and Jinyun Liu.
The examine was partially funded by the Penn State Most cancers Institute, a Penn State multidisciplinary seed grant, and the Nationwide Science Basis.
Supplies supplied by Penn State. Authentic written by Mariah Chuprinski. Word: Content material could also be edited for type and size.