Transparent ultrasound chip improves cell stimulation and imaging

Date:
February 24, 2022
Source:
Penn State
Summary:
Ultrasound scans -- best known for monitoring pregnancies or
imaging organs -- can also be used to stimulate cells and direct
cell function. A team of researchers has developed an easier, more
effective way to harness the technology for biomedical applications.



FULL STORY ========================================================================== Ultrasound scans -- best known for monitoring pregnancies or imaging
organs - - can also be used to stimulate cells and direct cell function. A
team of Penn State researchers has developed an easier, more effective
way to harness the technology for biomedical applications.


==========================================================================
The team created a transparent, biocompatible ultrasound transducer chip
that resembles a microscope glass slide and can be inserted into any
optical microscope for easy viewing. Cells can be cultured and stimulated directly on top of the transducer chip and the cells' resulting changes
can be imaged with optical microscopy techniques.

Published in the Royal Society of Chemistry's journal Lab on a Chip,
the paper was selected as the cover article for the December 2021
issue. Future applications of the technology could impact stem cell,
cancer and neuroscience research.

"In the conventional ultrasound stimulation experiments, a cell culture
dish is placed in a water bath, and a bulky ultrasound transducer
directs the ultrasound waves to the cells through the water medium," said Sri-Rajasekhar "Raj" Kothapalli, principal investigator and assistant
professor of biomedical engineering at Penn State. "This was a complex
setup that didn't provide reproducible results: The results that one group
saw another did not, even while using the same parameters, because there
are several things that could affect the cells' survival and stimulation
while they are in water, as well as how we visualize them." Kothapalli
and his collaborators miniaturized the ultrasound stimulation setup
by creating a transparent transducer platform made of a piezoelectric
lithium niobate material. Piezoelectric materials generate mechanical
energy when electric voltage is applied. The chip's biocompatible surface allows the cells to be cultured directly on the transducer and used for repeated stimulation experiments over several weeks.

When connected to a power supply, the transducer emits ultrasound waves,
which pulse the cells and trigger ion influx and outflux.



==========================================================================
To test the setup, Kothapalli and his team cultured bladder cancer
cells on the chip. They then inserted fluorescent calcium indicators
into the cells to allow researchers to clearly see dynamic changes in
cell calcium signaling under the microscope during stimulation.

"Since the cells are directly sitting on the transparent transducer
surface, we can confirm that all the cells are equally stimulated at
the same time using a single ultrasound stimulus, unlike conventional approaches," Kothapalli, a co- hire with the Penn State Cancer Institute,
said. "And unlike earlier processes, we can get high resolution images
of many cells at once in a single field of view, because we are able to
see the cells from a close distance." Through the bladder cancer cell
study, researchers established proof-of-concept for the new transducer
setup. But they can extend these findings to use the transducer setup
in potential future applications, according to Kothapalli, such as stem
cell differentiation, mechanosensitive neuromodulation, drug delivery
and the opening of the blood-brain barrier.

"This simple setup will be invaluable for researchers interested in
modulating cells and tissues with an ultrasound," said Pak Kin Wong,
professor of biomedical engineering, mechanical engineering and surgery
at Penn State and co-author on the paper. "It can be used to explore
novel therapeutic ultrasound applications, such as focused ultrasound immunotherapy." The ultrasound stimulation chip is low-cost, easy to fabricate, compact and scalable in size, and disposable and reusable,
according to Haoyang Chen, first author of the paper and doctoral student
under Kothapalli in biomedical engineering.

"It is easy to grow cells on the chip using standard cell culturing
methods," Chen said. "The setup provides controllable stimulation
parameters for a variety of experiments and can be imaged with all
conventional optical microscopy techniques." In addition to Kothapalli,
Wong and Chen, other contributors to the study were Peter Butler, Penn
State professor of biomedical engineering and associate dean for education
and graduate professional programs; biomedical engineering graduate
students Ninghao Zhu, Mohamed Osman and Shubham Khandare; and biomedical engineering undergraduate students Ryan Biskowitz and Jinyun Liu.

The study was partially funded by the Penn State Cancer Institute, a Penn
State multidisciplinary seed grant, and the National Science Foundation.

========================================================================== Story Source: Materials provided by Penn_State. Original written by
Mariah Chuprinski. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Haoyang Chen, Ninghao Zhu, Mohamed Osman, Ryan Biskowitz,
Jinyun Liu,
Shubham Khandare, Peter Butler, Pak Kin Wong, Sri-Rajasekhar
Kothapalli.

A transparent low intensity pulsed ultrasound (LIPUS) chip for
high- throughput cell stimulation. Lab on a Chip, 2021; 21 (24):
4734 DOI: 10.1039/D1LC00667C ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220224161549.htm

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