In vivo performance of a microelectrode neural probe with integrated drug delivery.
OBJECTIVE
The availability of sophisticated neural probes is a key prerequisite in the development of future brain-machine interfaces (BMIs). In this study, the authors developed and validated a neural probe design capable of simultaneous drug delivery and electrophysiology recordings in vivo. Focal drug delivery promises to extend dramatically the recording lives of neural probes, a limiting factor to clinical adoption of BMI technology.


METHODS
To form the multifunctional neural probe, the authors affixed a 16-channel microfabricated silicon electrode array to a fused silica catheter. Three experiments were conducted in rats to characterize the performance of the device. Experiment 1 examined cellular damage from probe insertion and the drug distribution in tissue. Experiment 2 measured the effects of saline infusions delivered through the probe on concurrent electrophysiological measurements. Experiment 3 demonstrated that a physiologically relevant amount of drug can be delivered in a controlled fashion. For these experiments, Hoechst and propidium iodide stains were used to assess insertion trauma and the tissue distribution of the infusate. Artificial CSF (aCSF) and tetrodotoxin (TTX) were injected to determine the efficacy of drug delivery.


RESULTS
The newly developed multifunctional neural probes were successfully inserted into rat cortex and were able to deliver fluids and drugs that resulted in the expected electrophysiological and histological responses. The damage from insertion of the device into brain tissue was substantially less than the volume of drug dispersion in tissue. Electrophysiological activity, including both individual spikes as well as local field potentials, was successfully recorded with this device during real-time drug delivery. No significant changes were seen in response to delivery of aCSF as a control experiment, whereas delivery of TTX produced the expected result of suppressing all spiking activity in the vicinity of the catheter outlet.


CONCLUSIONS
Multifunctional neural probes such as the ones developed and validated within this study have great potential to help further understand the design space and criteria for the next generation of neural probe technology. By incorporating integrated drug delivery functionality into the probes, new treatment options for neurological disorders and regenerative neural interfaces using localized and feedback-controlled delivery of drugs can be realized in the near future.
Rohatgi
Pratik
P
Ann & Robert H. Lurie Biomedical Engineering Building, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. prohatgi@umich.edu
Langhals
Nicholas B
NB
Kipke
Daryl R
DR
Patil
Parag G
PG
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D004567:Electrodes, Implanted; D004594:Electrophysiology / Q000295:instrumentation* / Q000706:statistics & numerical data; D004867:Equipment Design; D006801:Humans; D007260:Infusion Pumps; D007267:Injections / Q000295:instrumentation; D008839:Microelectrodes; D044085:Microfluidics / Q000295:instrumentation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014584:User-Computer Interface