We are developing easy to use microfluidic modules as a tool for researchers studying the effects of chemical gradients on populations of cells. Passive pumping is utilized so that only a pipette is required for operation of the microfluidic flows and generation of gradients. These devices are compatible with standard cell culture techniques including sterilization and incubation as well as optical microscopy. We are currently collaborating with neuroscientists to study the chemical gradient guidance of axonal growth from embryonic neurons with this technology.
Optogenetics allow for stimulation of neural networks using light. Current technologies for leveraging optogenetics are low throughput and can be relatively expensive. We are currently developing a micromachined optical mirror chip that increases throughput for light stimulation studies. This technology is compatible with standard microscopy and cell culture techniques and can be coupled with MEA’s for dual mode (optical and electrical) cell interfacing.
We develop high-performance drug delivery micropumps with unprecedented accuracy capable of delivering a diverse assortment of drugs at the right dose, to the right tissue, and at the right time over the entire course of treatment. In this manner, therapeutic efficacy is maximized while minimizing unintended side effects.
Key system features
Over 50% of individuals in the U.S. suffer from 1 or more chronic diseases, the most common being cancer, mental disorders, diabetes, and heart disease. For many of these diseases, drug therapy is the primary mode of treatment, but development of novel and improved treatment options is lagging behind the staggering increases in chronic disease cases (chronicdiseaseimpact.com). By developing new technologies to address unmet needs at the drug discovery and development stage, we can help mitigate the burden of chronic disease. For many chronic diseases, the timing and amount of drug dosing is critical to the effectiveness of the therapy, and is often tied to biological rhythms. Rodent models are often used to evaluate new potential therapeutics prior to human clinical testing, but technology for chronic drug administration in rats and mice is quite limited, either from the point of view of lack of flow rate control or large size. Our micropump technology is scalable for animals as small as mice, providing researchers with flexibility in chronic drug studies, and will lead to better understanding of and more effective treatments for chronic disease.
The micropump components are an electrochemical bellows actuator, refillable drug reservoir, wireless inductive powering components, catheter, and check valve. By utilizing fabrication techniques from MEMS, or microelectromechanical systems, the actuation components are scalable to small animal models (including mice). The actuation is achieved through electrolysis, in which energy from the conversion of water to hydrogen and oxygen gases is harnessed to actively pump drug from the reservoir. This process generates low heat, requires low power consumption, and enables repeated dosing. The refillable drug reservoir can be sized to accommodate dosing needs for a specific animal model and application, and allows drug to be store adjacent to the target site in the body. A catheter directs the drug to the site. A check valve ensures accurate dosing without contamination or dilution of the drug in the reservoir. By using a wireless inductive powering scheme, the micropump operates without a battery and allows tetherless, unrestricted movement of the animal during the dosing. This is important, as stress from restraint and handling can significantly affect animal behavior and physiology. In addition, an integrated electrochemically-based dose tracking system is capable of real-time tracking and confirmation of delivery. With dose tracking, the micropump has closed-loop feedback for monitoring pump performance that can improve device reliability and increase patient safety.
Neural probe technologies are an integral part of BMI’s (Brain-machine-interfaces). Current neural probes are commercialized and widely in use within the neuroscience community. However, these technologies have limited recording lifetimes once implanted. This is attributed to the chronic irritation caused by the stiff probe material on the surrounding soft brain tissue as the brain pulses from blood flow, resulting in scar formation and loss of neural signals. We are developing a neural probe from the ground up that is biocompatible and possesses long-term recording lifetimes. We use Parylene, a USP Class VI material that is flexible and micromachinable to construct the devices. We can create 3D sheath structures that encourage neural tissue ingrowth once implanted, anchoring the probe into the brain and promoting long-term brain-probe integration.
Inserting the 3D Parylene Sheath Electrode is a traumatic event for the brain, which causes a scar and dead zone to form around the recording sites and limits the probes ability to obtain neural signals. Coating the sheath with bioactive molecules reduces scar tissue formation as well as encourages neuronal survival and integration into the sheath. Currently, the coatings are made by incorporating bioactive drugs into the commercially available hydrogel “Matrigel,” which contains proteins and molecules similar to those found naturally in the neuronal extracellular environment. Future coatings will incorporate the molecules into the biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) to achieve sustained release drug delivery.
In collaboration with researchers in the Earth Sciences Department at USC, we have developed a microfluidic gradient chamber to aid in the study of microbial organization in response to chemical stimuli. We leverage laminar flow to control chemical diffusion gradients on a fine spatial scale. Unlike silicone-based microfluidics, the device is fabricated from silicon microchannels sealed with a glass cover plate so that gas diffusion in the chamber can be controlled.
Many current MEMS sensor technologies require bulk, hermetic packaging that cripples their performance and size advantages in vivo. An effort within the Biomedical Microsystems Laboratory is the development of electrochemical-MEMS (EC-MEMS) sensor technology that instead leverages the wet environment as its sensing mechanism by utilizing a simple electrochemical principle as a transduction mechanism to correlate mechanical phenomena to quantitative measures. In short, the sensor consists of an electrolyte filled microchamber housing a pair of electrodes. Any disruption of the volumetric conduction path between the pair of electrodes would cause a change in measured electrochemical impedance at sufficiently high frequencies. In our sensors, these disruptions of the conduction path stem from either external mechanical forces that deform the top of the microchamber, or changes in hydrostatic pressure that alter the size of a bubble that sits within the chamber. Through these mechanisms, our sensors can measure desired phenomena in a simple-to-fabricate and measure, biocompatible packaging while maintaining form factor advantages of MEMS-based devices.
Arrays of Parylene-based EC-MEMS force sensors aim to instrument current neural interface technology for use as a research tool in exploring the mechanical interactions between implanted prostheses and the surrounding neural tissue. To date, two force sensor arrays have been developed: (1) retinal sensor array designed to explore the tacking forces generated on the retina over the footprint of retinal prosthesis during its tacking-based implantation procedure, and (2) cortical sensor array designed to instrument the length of a ceramic cortical probe to explore the interfacial forces experienced by the probe from the surrounding cortical tissue during insertion as well as while implanted.
Microbubbles respond instantaneously to external pressure variations and thus can be harnessed as pressure transducers when isolated using microchambers. The overall aim is to develop a reliable pressure transducer for detecting physiologically relevant pressures in a wet, in vivo environment, such as those involved in hydrocephalus.
Strain is an important measurement for assessing the function and health of internal organs, but traditional electronics are limited in their ability to survive in the body and lack the flexibility of biological tissues. PDMS-CNT strain sensors combine medical grade silicone rubber and carbon nanotubes to create a conductive material whose resistance increases as it is stretched. The high aspect ratio and excellent conductivity of carbon nanotubes allows this material to be made using low concentrations of carbon nanotubes and preserve silicone’s innate flexibility. This conductive material can be used to make robust, flexible, and biocompatible strain sensors. Our main application of these devices is to measure bladder fullness as part of a closed loop system for controlling micturition in patients with spinal cord injuries.