Significance and Importance: An award is made to Caltech to engender new tools for studying the immune response to a brain-machine interface in small mammals. To develop the next generation of neural probes for massively parallel stimulation and recording, and facilitate advanced brain-machine interfaces, we must attain a better understanding of the brain's immune response to chronic neural implants. The existing state-of-the-art generally only enables such studies to be performed after an animal has been sacrificed. The technology developed through this research will merge the latest advances in nanobiophotonics, implantable neural probes, and state-of-the-art microfluidics to develop, fabricate, and test next-generation technology that will enable real-time monitoring of the immunogenic response of the brain to implanted neural probes, including the ability to perform real-time monitoring of the use of drug regimens to temper the immune response. The project provides an exceptional opportunity for training interdisciplinary scientists and engineers. In broader outreach, the researchers will collaborate with the Community Science Academy at Caltech to develop an iPAD-facilitated learning module for K-12 use.
overarching goal of the 3-year project will be the design and development neurochemical probes targeted to the detection of cytokines and chemokines in mice and other small animals. Year 1 will focus on demonstration of detection of targets of interest at concentrations of physiological relevance (100pg/mL to 10ng/mL) with photonic micro-ring resonators. Year 2 will focus on the integration of photonic micro-ring resonators with etched microfluidics with dialysate membranes appropriate for the detection of specific chemokine and cytokine targets (a 100kDa molecular weight cut-off will be targeted). Year 3 will focus on the development, fabrication, and calibration of neurochemical probes for use in vivo. Evaluation and calibration of probes will be performed in 'tissue phantoms' made from agarose with dissolved chemokines and cytokines. These will include both targets of interest and potential interferents. We anticipate that by the end of this effort we will be able to provide at least 10 calibrated probes to each of the Siapas (Caltech), Tolias (Baylor College of Medicine) and Laurent (Max Planck Institute for Brain Research) neuroscience research groups for use in vivo. In this third phase we will also begin design discussions in the Alliance for Nanosystems VLSI (very-large-scale integration; co-founded by the PI in 2007) to transfer our Caltech-based fabrication processes to standardized production en masse within our partner's (CEA/LETI) micro-/nano-electronics foundry. The graduate student funded by this effort will learn to employ optical engineering, microfabrication techniques, and neuroscience in order to produce and employ advanced experimental measurement systems. In addition to graduate student education, undergraduate students will contribute to the project through the SURF and MURF (summer- and minority- undergraduate research) programs at Caltech. The K-12 learning module developed as an outreach effort in collaboration with the Community Science Academy at Caltech will include a low-cost, portable, iPAD-interfaced refractometer and demonstration of total internal reflection for use in Pasadena Unified School District and Los Angeles Unified School District classrooms.
This award is being made jointly by two Programs- (1) Biophotonics, in the Division of Chemical, Bioengineering, Environmental and Transport Systems (Engineering Directorate), and (2) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate).
