A microfluidic silicon nanodialysis platform with in-channel electrochemistry for analyte sampling, timestamping and detection at high spatiotemporal resolution

Detection of neurochemical transients within the brain has led to the better understanding of how underlying neural circuits function and correlate to behavior, as well as contributed to the development of several therapeutic drugs and treatments targeted to a multitude of neurological disorders, neurodegenerative diseases, and injury. Implantable electrochemical sensors are one of the most common methods of neurochemical sensing, as they provide 1.) sub-second temporal resolution to capture chemical transmission, diffusion, and uptake events, 2.) physiologically relevant chemical resolution at ~10-100 nM limits of detection, and 3.) sub-micrometer spatial resolution to target specific brain regions of interest. However, they suffer in long-term performance, as implanted electrodes foul due to adsorption of cells, degradatory enzymes, and redox intermediates, and are unable to be cleaned/re-calibrated once implanted. As such this thesis proposes to integrate electrochemical sensors into miniaturized sampling probes to shield the sensors from the harsh inflammatory response and allow for calibration in-situ while also equipping sampling probes with an embedded electrochemical interface. We first develop a chemical sampling platform that enables local chemical sampling with 100μm spatial resolution and sub-second temporal resolution at high relative recovery in both push-pull perfusion and nanodialysis configurations, with the thinnest integrated membrane (~30nm) demonstrated in our field. We then developed the electrochemical sensing module, embedding the device into the same microfluidic channels of the sampling platform. The device was able to sense changes in concentration of a commonly used redox probe, calibration was demonstrated on-chip, and a 3X increase in signal was observed by introducing convective flow. Lastly, we demonstrated the successful integration of the electrochemical module into the sampling platform and demonstrated that timestamp information with durations as small as 50ms can be written into, stored, and read from the sampled dialysate stream, enabling accurate alignment between external stimuli and chemical dynamics despite flow instabilities common in ultra-miniaturized sampling systems. The technologies developed in this thesis prove promising to address the immediate problems of fouling in implanted electrochemical sensors and stimuli synchronization in sampling probes. Combinations of these modules are actively being deployed in-vivo in the Vlasov group to address previously unanswerable questions in neuroscience due to technological limitations, and we hope that these extended capabilities spread to the rest of the field through our published works.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2024

Author dc:creator

• Brenden, Christopher Kenji

Contributors dc:contributor

• Vlasov, Yurii
• Bashir, Rashid
• Cunningham, Brian
• Shen, Mei

• Microdialysis
• Electrochemistry
• Electrochemical
• Microfluidic
• Nanodialysis
• Push-pull
• Neural Probe
• Neurochemical
• Neurotransmitter
• Silicon
• Microfabrication

Statement dc:rights

• Copyright 2024 Christopher Kenji Brenden

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/125713

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F125713