Scalable Nanomanufacturing Techniques and Their Applications in Biomedicine: From Chemical Patterning to Implantable Neuroprobes

Biomarkers from the human body can provide dynamic and powerful insight a broad spectrum of health conditions. Monitoring biomarkers in body fluids will improve and advance prediction, screening, diagnosis, and treatment of disease. At present, however, the ability to study and to track the everchanging mixtures of chemicals inside and on the human body is limited. For example, chemical communication between neurons plays central roles in information processing in the brain, yet technologies for neurochemical recordings with high chemical, spatial, and temporal resolution are limited, and for some neurotransmitters, nonexistent. For the past five years, I have focused on developing transformative biosensors towards in vivo neurotransmitter monitoring to advance our understanding of brain activity and how behavior arises from this activity.To achieve this goal, we developed ultrathin (~3-nm) In2O3 field-effect transistor (FET) biosensors, where DNA sequences (aptamers) covalently functionalized to the device surfaces enable specific, high-sensitivity molecular recognition. Building on the capabilities of these aptamer-FET biosensors, we developed multiplexed sensors that simultaneously target several important biomarkers, including dopamine, serotonin, glucose, phenylalanine, and cortisol. A high-throughput, wafer-scale, and low-cost nanolithographic approach (chemical lift-off lithography, CLL) was developed and applied for the fabrication of nanoscale FETs, which are the functional core of these sensors. We have advanced CLL by using the self-collapse nature of polymeric stamps to achieve small features (~15 nm). The capability of CLL has been expanded to pattern chemical molecules, biomolecules, metallic nanostructures, and semiconductor nanostructures. We were able to fabricate different types of sensors including plasmonic sensors and FET biosensors using micro- and nanostructured features patterned by CLL. We designed and fabricated implantable neurochemical probes and wearable bioelectronics using micro-electro-mechanical-system technologies. We performed ex vivo and in vivo experiments with implanted neural probes to monitor neurotransmitters, e.g., serotonin, in living, conscious animals. The technologies we are developing will advance our understanding of healthy brain function in relation to complex behavior, as well as corresponding dysfunction in psychiatric and neurodegenerative disorders