Biomedical subjects

Jit Muthuswamy

Publications and source records attributed to Jit Muthuswamy.

8 recordsLinked to original sources

PubMed2007

Structure-property relationships in the optimization of polysilicon thin films for electrical recording/stimulation of single neurons.

We had earlier demonstrated the use of polysilicon microelectrodes for recording electrical activity from single neurons in vivo. Good machinability and compatibility with CMOS processing further make polysilicon an attractive interface material between biological environments on one hand and MEMS technology and digital circuits on the other hand. In this study, we focus on optimizing the polysilicon thin films for (a) electrical recording and (b) stimulation of single neurons by minimizing its electrochemical impedance spectra and maximizing its charge storage/injection capacity respectively. The structure-property relationships in ion-implanted (phosphorus) LPCVD polysilicon thin films under different annealing and doping conditions were carefully assessed during this optimization process. A 2D model of the polysilicon thin film consisting of 4 grains and 3 grain boundaries was constructed and the effect of grain size and grain boundaries on dc resistivity was simulated using device simulator ATLAS. Optimal processing conditions and doping concentrations resulted in a 10-fold decrease in electrochemical impedance from 1.1 kOmega to 0.1 kOmega at 1 kHz (area of polysilicon interface = 4.8 mm(2)). Subsequent characterizations showed that evolution of secondary grains within the polysilicon thin films at optimal doping and annealing conditions (10(21)/cm(3) of phosphorus and annealed at 1200 degrees C) was responsible for decreasing the impedance. Cyclic voltammetry studies demonstrated that charge storage properties of low doped (10(15)/cm(3)) thin films was 111.4 microC/cm(2) in phosphate buffered saline which compares well with platinum wires (approximately 50 microC/cm(2)) and the double-layered capacitance (C(dl)) could be sustained between -1 to 1 V before breakdown and hydrolysis. We conclude that polysilicon can be optimized for recording and stimulating single neurons and can be a valuable interface material between neurons and CMOS or MEMS devices.

Action Potentials↗

PubMed2006

Brain micromotion around implants in the rodent somatosensory cortex.

The magnitude of brain tissue micromotion relative to stationary brain implants and its impact on the viability and function of the surrounding brain tissue due to mechanical stresses is poorly understood. The central goal of this study is to characterize surface micromotion in the somatosensory cortex against stationary cylindrical implants. We used a differential variable reluctance transducer (DVRT) in adult rats (n = 6) to monitor micromotion normal to the somatosensory cortex surface. Experiments were performed both in the presence and in the absence of dura mater and displacement measurements were made at three different locations within craniotomies of two different sizes. In anesthetized rats, pulsatile surface micromotion was observed to be in the order of 10-30 microm due to pressure changes during respiration and 2-4 microm due to vascular pulsatility. Brain displacement values due to respiration were significantly lower in the presence of the dura compared to those without the dura. In addition, large inward displacements of brain tissue between 10-60 microm were observed in n = 3 animals immediately following the administration of anesthesia. Such significant micromotion can impact a wide variety of acute and chronic procedures involving any brain implants, precise neurosurgery or imaging and therefore has to be factored in the design of such procedures.

Animals↗

PubMed2006

Microsystem for transfection of exogenous molecules with spatio-temporal control into adherent cells.

Several non-viral techniques involving the use of liposomes, particle bombardment and electroporation have been used for efficient transfection of plasmids and other molecules into cells. Current approaches target whole or bulk regions of tissue, lacking the desired spatial control over the transfection process. In this study, we present a novel approach using microsystems to achieve spatial and temporal control over the transfection process in adherent cells. A 6x6 MEA (microelectrode array) with 100 microm microelectrode dimension was developed on a silicon substrate using standard microfabrication procedures and passivated with a biocompatible layer. Using finite element models, electric field intensities were simulated and locations of optimal electroporation zones in the cell culture on the microelectrode surface were predicted. The MEA was subsequently tested using 3T3 fibroblasts cultured on the MEA surface for 96 h and stimulation voltages in the range of 2-5 V in the presence of propidium iodide (PI), a cell impermeant dye. Maximum electric field intensities in the z-direction were estimated to be in the range of 320-820 V/cm for applied differential voltages in the range of 2-5 V. Cells directly on the top and on the edges of the stimulating microelectrodes in the MEA were preferentially transfected with PI as predicted by the simulations. The results of these experiments demonstrate that spatial and temporal control of desired regions of transfection in vitro can be achieved using MEAs and electroporation.

Animals↗

PubMed2006

Immobilization and characterization of gamma-aminobutyric acid on gold surface.

gamma-Aminobutyric acid (GABA) is one of two main inhibitory neurotransmitters in the central nervous system that plays an important role in neuronal function and dysfunction. Immobilization of GABA molecules on a rigid surface in an ordered fashion will provide an opportunity to understand some of the fundamental properties related to its structure and function. In this study, we report a novel strategy for immobilization of bioactive GABA on gold substrate. GABA was immobilized in three consecutive steps, namely gold substrate amination, dextran covalent attachment, and GABA immobilization. Surface chemistry was verified at each step using XPS and FTIR. Bioactivity of GABA immobilized on the gold surface was studied using atomic force microscopy to reveal antigen-antibody binding. Nonspecific protein adsorption on the bioactive surface was analyzed quantitatively using anti-GABA antibody and an enzyme linked nonspecific anti-immunoglobulin-G antibody in an ELISA assay. GABA functionalized surface has high affinity for anti-GABA, while showing significantly low affinity for nonspecific anti-IgG antibody. All these data support the presence of a bio-functional immobilized GABA on the gold surface. In conclusion, we report a novel technique for immobilizing bioactive GABA molecules in an orderly fashion on gold substrates.

Coated Materials, Biocompatible↗

PubMed2005

Acoustic sensor for monitoring adhesion of Neuro-2A cells in real-time.

Neuronal adhesion plays a fundamental role in growth, migration, regeneration and plasticity of neurons. However, current methods for studying neuronal adhesion cannot monitor this phenomenon quantitatively in real-time. In this work, we demonstrate the use of an acoustic sensor to measure adhesion of neuro-blastoma cells (Neuro-2A) in real-time. An acoustic sensor consisting of a quartz crystal sandwiched between gold electrodes was placed in a flow cell and filled with 600 microl of phosphate buffered saline (PBS). Two sets of in vitro experiments were performed using sensors that had uncoated gold electrodes and sensors that were coated with a known neuronal adhesion promoter (poly-l-lysine or PLL). The instantaneous resonant frequency and the equivalent motional resistance of the acoustic sensor were monitored every second. Cell Tracker was used to confirm neuronal adhesion to the surface. Addition of 10 microl of media and Neuro-2A cells into the above set-up elicited exponential changes in the resonant frequency and motional resistance of the quartz crystal with time to reach steady state in the range of 2-11 h. The steady-state change in resonant frequency in response to addition of neurons was linearly related to the number of Neuro-2A cells added (R2=0.94). Acoustic sensors coated with the adhesion promoter, PLL showed a much higher change in resonant frequency for approximately the same number of neurons. We conclude that the acoustic sensor has sufficient sensitivity to monitor neuronal adhesion in real-time. This has potential applications in the study of mechanisms of neuron-substrate interactions and the effect of molecular modulators in the extra cellular matrix.

Acoustics↗

PubMed2005

Single neuronal recordings using surface micromachined polysilicon microelectrodes.

Bulk micromachining techniques of silicon have been used successfully in the past several years to microfabricate microelectrodes for monitoring single neurons in acute and chronic experiments. In this study we report for the first time a novel surface micromachining technique to microfabricate a very thin polysilicon microelectrode that can be used for monitoring single-unit activity in the central nervous system. The microelectrodes are 3 mm long and 50 microm x 3.75 microm in cross-section. Excellent signal to noise ratios in the order of 25-35 dB were obtained while recording neuronal action potentials. The microelectrodes successfully penetrated the brains after a microincision of the dura mater. Chronic implantation of the microprobe for up to 33 days produced only minor gliosis. Since the polysilicon shank acts as a conductor, additional processing steps involved in laying conductor lines on silicon substrates are avoided. Further, surface micromachining allows for fabricating extremely thin microelectrodes which could result in decreased inflammatory responses. We conclude that the polysilicon microelectrode reported here could be a complementary approach to bulk-micromachined silicon microelectrodes for chronic monitoring of single neurons in the central nervous system.

Action Potentials↗

PubMed2005

An array of microactuated microelectrodes for monitoring single-neuronal activity in rodents.

Arrays of microelectrodes used for monitoring single- and multi-neuronal action potentials often fail to record from the same population of neurons over a period of time for several technical and biological reasons. We report here a novel Neural Probe chip with a 3-channel microactuated microelectrode array that will enable precise repositioning of the individual microelectrodes within the brain tissue after implantation. Thermal microactuators and associated microelectrodes in the Neural Probe chip are microfabricated using the Sandia's Ultraplanar Multi-level MEMS Technology (SUMMiTV) process, a 5-layer polysilicon micromachining technology of the Sandia National labs, Albuquerque, NM. The Neural Probe chip enables precise bi-directional positioning of the microelectrodes in the brain with a step resolution in the order of 8.8 microm. The thermal microactuators allow for a linear translation of the microelectrodes of up to 5 mm in either direction making it suitable for positioning microelectrodes in deep structures of a rodent brain. The overall translation in either direction was reduced to approximately 2 mm after insulation of the microelectrodes with epoxy for monitoring multi-unit activity. Single unit recordings were obtained from the somatosensory cortex of adult rats over a period of three days demonstrating the feasibility of this technology. Further optimization of the microelectrode insulation and chip packaging will be necessary before this technology can be validated in chronic experiments.

Action Potentials↗

PubMed2005

Electrostatic microactuators for precise positioning of neural microelectrodes.

Microelectrode arrays used for monitoring single and multineuronal action potentials often fail to record from the same population of neurons over a period of time likely due to micromotion of neurons away from the microelectrode, gliosis around the recording site and also brain movement due to behavior. We report here novel electrostatic microactuated microelectrodes that will enable precise repositioning of the microelectrodes within the brain tissue. Electrostatic comb-drive microactuators and associated microelectrodes are fabricated using the SUMMiT V (Sandia's Ultraplanar Multilevel MEMS Technology) process, a five-layer polysilicon micromachining technology of the Sandia National labs, NM. The microfabricated microactuators enable precise bidirectional positioning of the microelectrodes in the brain with accuracy in the order of 1 microm. The microactuators allow for a linear translation of the microelectrodes of up to 5 mm in either direction making it suitable for positioning microelectrodes in deep structures of a rodent brain. The overall translation was reduced to approximately 2 mm after insulation of the microelectrodes with epoxy for monitoring multiunit activity. The microactuators are capable of driving the microelectrodes in the brain tissue with forces in the order of several micro-Newtons. Single unit recordings were obtained from the somatosensory cortex of adult rats in acute experiments demonstrating the feasibility of this technology. Further optimization of the insulation, packaging and interconnect issues will be necessary before this technology can be validated in long-term experiments.

Action Potentials↗