Much smaller and more accurate sensors are needed to address longstanding problems in biomedical research, such as tracking the distribution of drugs throughout the body and monitoring brain chemistry. With sub-second resolution, a novel nanoscale sensor monitors regions 1,000 times smaller than existing technology and tracks minute changes in biological tissue’s chemical composition.
The fabricated and packaged nanodialysis device. Image Credit: University of Illinois Urbana-Champaign
The University of Illinois Urbana-Champaign researchers created the silicon-based device, which utilizes methods created for the production of microelectronics. It can extract chemical content in a matter of milliseconds from highly targeted tissue areas with about 100% effectiveness, thanks to the small size of the device. The journal ACS Nano published a study on this novel nanodialysis device’s capabilities.
With our nanodialysis device, we take an established technique and push it into a new extreme, making biomedical research problems that were impossible before quite feasible now. Moreover, since our devices are made on silicon using microelectronics fabrication techniques, they can be manufactured and deployed on large scales.
Yurii Vlasov, Study Co-Lead and Professor, University of Illinois Urbana-Champaign
From Micro- to Nanodialysis
Nanodialysis is based on microdialysis technology, which involves inserting a probe with a thin membrane into biological tissues. Chemicals flow through the membrane to form a fluid that is pumped out for analysis. The capacity to sample directly from tissue has had a significant influence on subjects such as neurology, pharmacology, and dermatology.
Traditional microdialysis has drawbacks, however. Since the probes only sample a few square millimeters, they can only evaluate average composition across wide areas of tissue. The probe’s enormous size also causes some tissue injury when placed, which could skew the analysis results. Finally, the fluid pushed through the probe moves at a rather fast rate, affecting the efficiency and precision with which chemical concentrations can be measured.
Vlasov added, “Many problems with traditional microdialysis can be solved by using a much smaller device. Going smaller with nanodialysis means more precision, less damage from the tissue placement, chemically mapping the tissue with higher spatial resolution, and a much faster readout time allowing a more detailed picture of the changes in tissue chemistry.”
Slow and Steady
The fluid injected through the probe at an extremely slow flow rate is the key component of nanodialysis. The device maintains 100% efficiency despite capturing the chemical composition of tissue obtained from an area 1,000 times smaller than standard methods by adjusting the flow rate 1,000 times slower than typical microdialysis.
Vlasov noted, “By drastically decreasing the flow rate, it allows the chemicals diffusing into the probe to match the concentrations outside in the tissue. Imagine you are adding dye to a pipe with flowing water. If the flow is too fast, the dye gets diluted to concentrations that are difficult to detect. To avoid dilution, you need to turn the water almost all the way down.”
Silicon Fabrication and Production
It is difficult to miniaturize standard microdialysis devices since they are built using glass probes and polymer membranes. The researchers created a silicon-based device using methods developed to produce electrical chips to construct devices suitable for nanodialysis.
“In addition to enabling us to go smaller, silicon technology makes the devices cheaper. By putting in the time and effort to develop a fabrication process for building our nanodevices on silicon, it is now very straightforward to manufacture them at industrial scales at an incredibly low cost,” Vlasov concluded.
The study was co-led by Rashid Bashir, dean of The Grainger College of Engineering and professor of bioengineering at the University of Illinois Urbana-Champaign.
The ACS Nano has reported these findings.
The National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies Initiative provided funding for this study.
Journal Reference:
Park, I., et. al. (2024) Highly Localized Chemical Sampling at Subsecond Temporal Resolution Enabled with a Silicon Nanodialysis Platform at Nanoliter per Minute Flows. ACS Nano. doi:10.1021/acsnano.3c09776.