BioMicroElectricalMechanical Systems

Implantable Micro-electrode Probes

Brain computer interface (BCI) is a method to establish communication between brain neural signals and external devices. Despite the feasibility for short term recordings from neural probes, most devices suffer from a long term tissue response that isolates the probes from adjacent tissue, limiting the recording sensitivity. A smaller, more flexible probe may allow better long term integration with neural tissue by limiting the mechanical disruption of tissue. However, smaller, more flexible probes lack the mechanical strength to penetrate tissue during implantation. Therefore design parameters that might affect brain tissue responses to a long term chronic intracortical neural probe are investigated. The miniaturized probe is coated with an ultrafast degrading tyrosine-derived polycarbonate which is mechanically rigid to allow tissue penetration yet degrades within several hours leaving the flexible probe in place for electrical recordings. A fabrication process that incorporates probe fabrication and polymer coating process was developed with high coating reproducibility and yield. Ongoing studies of mechanical characteristics of the probes and in-vivo evaluation of probes using rat models help identify ideal probe candidates with different design parameters that might affect long term tissue responses.

probes

 

BioElectronics

Theory-driven & Feedback-controlled Electroporation Microdevice

Electroporation is an effective means to permeabilize the cellular membrane and drive exogenous molecules into the cell cytoplasm. Despite extensive research, electroporation protocols are derived empirically and often fail to reach the desired delivery efficiency, reproducibility, and post-pulse cell viability. Recent work done in our group has unraveled the physical principles behind the electroporation transport mechanism and presented unprecedented electroporation protocols that are guided by electrokinetic theory to improve the delivery efficiency in large population cell suspension. In this collaborative project between four research laboratories (The Shreiber Group, Electrohydrodynamic Laboratory and The Shan Group), our goal is to develop a micro-electroporation device capable of monitoring degree of cell permeabilization and apply feedback-controlled pulse parameters iteratively in order to supply cell-specific delivery dosage while maximizing cell viability. This work involves the development of a microfluidic platform & microelectronics that not only enables the continuous and autonomous operation of the device but also permits the monitoring and precise control of the electroporation process.

Microelectroporator

 

Microfluidics

Microfluidic Cell Separation & Sorting

Microfluidic cell separation and sorting techniques have been widely studied with relevance to cell biology research or various diagnostic and therapeutic applications. This project involves in development of a label free, low cost, high throughput device which uses cross flow filtration in order to fractionate particles based on size. The device is multi-compartmental with porous membranes of varying pore sizes incorporated between the compartments within the microfluidic device to perform staged filtration where non-homogenous cell mixtures are fractionated into different compartments and collected for further analysis. By varying the pore size between compartments, particles larger than the pores cannot pass through the membrane to the adjacent compartment and are selectively enriched. (Click to see publication)

cellsort

 

Neural Tissue Engineering

Cell/Tissue Culture in Micro-enviorments

Drug addiction is a neurological disorder which alters the mesolimbic dopamine pathway, known for reward processing. Transition to addiction involves synaptic modification that creates transient and long-term pathway changes. Animal models have elucidated many mechanisms of drugs of abuse, but are limited in their ability to model the role of human genetic variants in addiction. We propose a model that recapitulates mesolimbic pathway connections using human induced neurons. A compartmentalized device separates subtype neurons which communicate through microchannels. We hope through this model we can provide insight into the role of polymorphisms in mediating addiction and provide a platform for therapeutic development.

Modeling

 

Legacy Project - Microfluidic Immunosensing

This project involves the development of autonomous microfluidic immunosensors. These devices will monitor blood or CSF for inflammation markers in research and clinical applications. The sensors are based on antigen-sandwich immunoassays and paramagnetic microbeads. They use a magnetic actuation scheme to control the bead motion within a microchannel. The figure below shows an example of one of the microdevices, made of a PDMS chip on a 750mm x 250mm glass slide. (Click to see publication)

immunoassay

 

Legacy Project - Microfluidic DNA Purification

Microfluidic platforms have been developed to demonstrate DNA purification via liquid extraction techniques at the microscale using an aqueous phase containing either protein, DNA or a complex cell lysate and an immiscible receiving organic (phenol) phase. A serpentine device and short device were used to investigate protein partitioning between the aqueous and organic phase, and DNA purification when both protein and DNA were mixed in the aqueous phase and infused conjunctly with the phenol phase. This two-phase system was studied using both stratified and droplet-based flow conditions. The droplet based flow resulted in a significant improvement of protein partitioning from the aqueous phase into the organic phase due to the convective flow recirculation inside each droplet improving material transport to the organic-aqueous interface. The short device, designed to specifically extract plasmid DNA from bacterial lysates using only droplet-based flows, has a high DNA recovery (>92%) and comparable to the recovery achieved using commercial DNA purification kits and standard macroscale phenol extraction. This study presents the initial steps towards the miniaturization of an efficient on-chip DNA sample preparation using phenol extraction which could be integrated with post-extraction DNA manipulations for integrated genomic analysis modules. (Click to see publication).

DNA

 

 

Legacy Project - Continuous Microfiltration

This project involves the design of a continuous microfiltration-based blood protein extraction system to be used for clinical monitoring of inflammatory responses in patients undergoing cardiac surgery. The system consists of a two compartment mass exchanger with two sets of PDMS microchannels separated by a porous polycarbonate membrane. (Click to see publication)

filtration

 

 

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