RESUMO
We introduce a photolithography process compatible with soft and rigid substrates, enabling the fabrication of complex 3D interconnected patterns of silver nanowire (AgNW) networks embedded in polydimethylsiloxane (PDMS). Dimensions of the AgNW micropatterns are controlled within the film plane by photolithography, whereas thickness is controlled via a novel and uniform deposition technique using centrifugation. We report the first systematic characterization of the electromechanical properties of such microelectrodes with finest stretchable feature of 15 µm. We observe a geometry-dependent behavior of the gauge factor not only by changing the thickness of the microelectrodes, as it has been commonly reported so far, but also by varying their lateral dimensions. The presented nanocomposites exhibited sheet resistances down to 0.6 Ω/sq, gauge factors ranging from 0.01 to 100, and stretchability above 50% uniaxial strain. This versatile process allows for the production of highly sensitive strain sensors and robust high-density stretchable conductors on a wafer scale with direct implications in mass production of stretchable electronic devices.
RESUMO
The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. The soft implants extracted cortical states in freely behaving animals for brain-machine interface and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Dura-Máter , Estimulação Elétrica/métodos , Eletroquimioterapia/métodos , Eletrodos Implantados , Paralisia/terapia , Próteses e Implantes , Traumatismos da Medula Espinal/terapia , Animais , Materiais Biocompatíveis/uso terapêutico , Interfaces Cérebro-Computador , Elasticidade , Locomoção , Camundongos , Camundongos Endogâmicos , Córtex Motor/fisiopatologia , Imagem Multimodal , Neurônios/fisiologia , Paralisia/etiologia , Paralisia/fisiopatologia , Platina , Silício , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Patterned structures of flexible, stretchable, electrically conductive materials on soft substrates could lead to novel electronic devices with unique mechanical properties allowing them to bend, fold, stretch or conform to their environment. For the last decade, research on improving the stretchability of circuits on elastomeric substrates has made significant progresses but designing printed circuit assemblies on elastomers remains challenging. Here we present a simple, cost-effective, cleanroom-free process to produce large scale soft electronic hardware where standard surface-mounted electrical components were directly bonded onto all-elastomeric printed circuit boards, or soft PCBs. Ag-PDMS tracks were stencil printed onto a PDMS substrate and soft PCBs were made by bonding the top and bottom layers together and filling punched holes with Ag-PDMS to create vias. Silver epoxy was used to bond commercial electrical components and no mechanical failure was observed after hundreds of stretching cycles. We also demonstrate the fabrication of a stretchable clock generator.
RESUMO
We have developed a neurochip to control the adhesion and outgrowth of individual neurons by electrochemical removal of protein repellent molecules from transparent electrodes. The neurochip architecture is based on three parallel indium-tin-oxide (ITO) electrodes on a SiO(2) substrate and a photoresist structure forming a landing spot for the neuron soma and two lateral outgrowth pathways for the neurites. The whole surface was turned protein and cell repellent with poly(ethylene glycol) grafted-poly(L-lysine) (PLL-g-PEG) before enabling neuron soma adhesion by selective PLL-g-PEG removal. After the neuron has settled down a potential was applied to the pathway electrodes to permit the neurite outgrowth along pathways formed by the SU8 structure. We also show the possibility to control cell migration by small pulsed currents. Myoblasts were therefore seeded on a chemical pattern of cell adhesive PLL and cell resistant PLL-g-PEG. The PLL-g-PEG was then removed electrochemically from the electrodes to permit migration onto the cell free electrodes. Electrodes without applied current were confluently overgrown within 24 h but a small pulsed current was able to inhibit cell growth on the bare ITO electrode for more than 72 h. With both techniques, cell adhesion, growth and migration can be controlled dynamically after the cells started to grow on the substrate. This opens new possibilities: we believe the key to control the development of topologically controlled neuron networks or more complex co-cultures is the combination of passive surface modifications and active control over the surface properties at any time of the experiment.
Assuntos
Movimento Celular , Eletricidade , Animais , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Eletrodos , Camundongos , Microscopia Confocal , Mioblastos/citologia , Neuritos/metabolismo , Compostos de Estanho/químicaRESUMO
Using a custom-built, implantable pulse generator, we studied the effects of small pulsed currents on the viability on rat aortic-derived cells (RAOC) in vitro. The pulsed currents (0.37A/m(2)) underwent apoptosis within 24h as shown by the positive staining for cleaved caspase-3 and classically apoptotic morphology. Based on these findings, we examined the effects of nanocurrents in vivo. The pulse generator was implanted subcutaneously in the rat model. The electrode|tissue interface histology revealed no difference between the active platinum surface and the neighboring control surface, however we found a large difference between electrodes that were functional during the entire experiment and non-active electrodes. These non-active electrodes showed an increase in impedance at higher frequencies 21 days post-implantation, whereas working electrodes retained their impedance value for the entire experiment. These results indicate that applied currents can reduce the impedance of implanted electrodes.
Assuntos
Tecnologia Biomédica/instrumentação , Eletricidade , Nanoestruturas/química , Animais , Morte Celular , Sobrevivência Celular , Impedância Elétrica , Eletrodos , Implantação de Prótese , Ratos , Ratos Sprague-DawleyRESUMO
Electrodes have become more and more popular in biomedical and bioengineering applications, where they are used mostly to apply/measure potentials or currents to/from biological systems. Under such conditions, electrochemical reactions commonly occur at the electrode surface. With the aim to better describe these processes we applied constant currents using transparent indium tin oxide microelectrodes to induce a local change in pH, associated with electrolysis. The pH change was monitored optically within the first lateral 170 microm vicinity using microscopy and a pH sensitive fluorescent dye combination as indicator. The data were then fitted with a simple diffusion model. The effect of such an induced pH change was also assessed by measuring the desorption of a cationic polyelectrolyte (poly(l-lysine)-grafted-poly(ethylene glycol)) as a function of the local pH. Since this polymer interacts electrostatically with surfaces in a pH dependent manner, we could show a strong effect in unbuffered solutions while buffered solutions restricted the electrochemically induced pH change below the optical resolution of the microscope. The effect of applied current on the behavior of cells was also studied on myoblasts cultured directly on the microelectrodes. We have found that current densities larger than 0.57 A m(-2) induced cell death within 2 min of exposure. Based on our model we could attribute this to the change in local pH although the effect of other electrochemically created reactive molecules could not be excluded.
Assuntos
Estimulação Elétrica/métodos , Microeletrodos , Modelos Biológicos , Mioblastos/fisiologia , Mioblastos/efeitos da radiação , Animais , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Simulação por Computador , Relação Dose-Resposta à Radiação , Mioblastos/citologia , Doses de Radiação , RatosRESUMO
Severe lesions of the rodent or human spinal cord lead to permanent paralysis of the legs. Here, we review novel evidences suggesting that interventions combining pharmacological and electrical stimulations of the spinal cord have a high potential to promote the recovery of locomotion following severe spinal cord injuries in humans. These strategies are based on the existence of webs of circuits and receptors embedded in the spinal motor infrastructure that each modulate specific aspects of locomotor movements. We show that chemical or electrical stimulations can engage specific elements of this spinal machinery, thus resulting in distinct patterns of locomotion in paralyzed spinal rats. In turn, simultaneous chemical stimulations of neural receptors and/or electrical stimulations of multiple spinal segments can synergistically facilitate locomotor movements. These preliminary results provide a strong rationale for the development of neuroprosthetic chemotrode and electrode arrays that would enable a detailed and distributed access to the different elements of the spinal motor infrastructure. Such novel biomedical technologies may offer unparalleled potential to induce multiple and flexible locomotor states in paralyzed subjects.