Ultrasound scans — greatest identified for monitoring pregnancies or imaging organs — will also be used to stimulate cells and direct cell operate. A crew of Penn State researchers has developed a better, simpler approach to harness the expertise for biomedical purposes.
The crew created a clear, biocompatible ultrasound transducer chip that resembles a microscope glass slide and could be inserted into any optical microscope for simple viewing. Cells could be cultured and stimulated instantly on high of the transducer chip and the cells’ ensuing modifications could be imaged with optical microscopy strategies.
Revealed within the Royal Society of Chemistry’s journal Lab on a Chip, the paper was chosen as the quilt article for the December 2021 subject. Future purposes of the expertise might influence stem cell, most cancers and neuroscience analysis.
“Within the standard ultrasound stimulation experiments, a cell tradition dish is positioned in a water tub, and a cumbersome ultrasound transducer directs the ultrasound waves to the cells by way of the water medium,” mentioned Sri-Rajasekhar “Raj” Kothapalli, principal investigator and assistant professor of biomedical engineering at Penn State. “This was a fancy 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 might 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 made 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 instantly on the transducer and used for repeated stimulation experiments over a number of weeks.
When related 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 crew 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 beneath the microscope throughout stimulation.
“Because the cells are instantly sitting on the clear transducer floor, we are able to affirm that every one the cells are equally stimulated on the similar time utilizing a single ultrasound stimulus, in contrast to standard approaches,” Kothapalli, a co-hire with the Penn State Most cancers Institute, mentioned. “And in contrast to earlier processes, we are able to get excessive decision photos of many cells directly in a single subject of view, as a result of we’re capable of see the cells from a detailed distance.”
By way of the bladder most cancers cell research, researchers established proof-of-concept for the brand new transducer setup. However they’ll lengthen these findings to make use of the transducer setup in potential future purposes, in response to Kothapalli, reminiscent of stem cell differentiation, mechanosensitive neuromodulation, drug supply and the opening of the blood-brain barrier.
“This straightforward setup shall be invaluable for researchers keen on modulating cells and tissues with an ultrasound,” mentioned 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 purposes, reminiscent of targeted ultrasound immunotherapy.”
The ultrasound stimulation chip is low-cost, straightforward to manufacture, compact and scalable in measurement, and disposable and reusable, in response to Haoyang Chen, first writer of the paper and doctoral scholar beneath Kothapalli in biomedical engineering.
“It’s straightforward to develop cells on the chip utilizing commonplace cell culturing strategies,” Chen mentioned. “The setup supplies controllable stimulation parameters for quite a lot of experiments and could be imaged with all standard optical microscopy strategies.”
Along with Kothapalli, Wong and Chen, different contributors to the research 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 research 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. Notice: Content material could also be edited for model and size.