Analysis Of Flexible Multimodal Implantable Optoelectronic Devices For Spinal Cord Injury Repair And Monitoring

Spinal cord injury is a traumatic event that can lead not only to devastating neurological deficits and disability but also to dysfunction of other organs along with it.At the same time,the medical treatment and post-operative rehabilitation of spinal cord injuries are not only physically and mentally devastating for the patients themselves,but it is also a huge burden for the relatives and collateral groups.Currently,commonly used means of spinal cord injury repair such as scaffolds,stem cells,small molecules(inhibitors/activators),rehabilitation and combination therapies are not effective in promoting axonal extension in the fibrous scar and the formation of synapses with post-injury neurons to transmit neurophysiological signals.However,the combination of flexible electronics and optogenetics will make it possible to manipulate the spatiotemporal neuronal activity of neuronal populations in a highly selective manner.Based on the above,this paper aims to investigate and design a flexible implantable optogenetic device with temperature and physiological electrical signal monitoring function in a distantly crossed group of rats(Sprague Dawley,SD).Analysis of optogenetic principles and SD rat body morphology to obtain preliminary size and functional requirements for device design.On this basis,the functional units of the device including light-emitting diodes(LEDs),temperature sensors,and microneedle array electrodes are selected and combined with mechanical analysis for structural design;in vivo thermal blood simulation was performed for heat generation during LED operation and tensile simulation analysis was performed for the device’s serpentine wire design;Design reasonable device fabrication process and complete corresponding experiments to achieve device fabrication;conduct device performance tests and in vivo experiments and analysis.The main research of this paper is as follows:(1)A brief introduction to optogenetics,SD rats’ body measurements and analysis;analysis of substrate material characteristics,selection of suitable substrate materials;construction of a theoretical model of circular serpentine wire island bridge structure,analysis to obtain a reasonable size of the serpentine wire;according to the optogenetic principle of light source requirements,choose the appropriate LED;according to the characteristics of various metals,design resistive temperature sensor;according to the island bridge structure to obtain the equivalent microneedle array density relationship analysis,to obtain a suitable island bridge microneedle array form.(2)Based on Pennes’ biological heat transfer equation,the heat transfer equation of rats with spinal cord injury and loss of self-temperature regulation is simplified to that of passive heat transfer.The analytical model of the device implanted in the rat is simplified,and the simulation analysis is carried out with LED heat generation conditions at different power,and the warming process and the maximum temperature point of the biological and the device are obtained,all of which meet the requirement of biocompatibility in the maximum temperature rise less than 2℃.The overall device is simplified,and the three serpentine wires,which play a major role in stretching,are subjected to different displacement loads for stretching simulation analysis and achieve61 mm and 30% elongation in the length direction to meet the stretching requirements.(3)The device preparation process was designed and the experimental devices were characterized considering the compatibility of the existing equipment with the material properties.The temperature sensor is prepared by sputtering titanium gold and patterned etching of the underlying circuit on a silicon wafer with Poly Methyl Methacrylate(PMMA)as the sacrificial layer and Polyimide(PI)as the underlying substrate material.The surface energy of liquid PI is controlled by temperature and time using Polydimethylsiloxane(PDMS)stamp to transfer LEDs;Lithography of SU-8 to prepare microneedle arrays;copper plus double-layer photoresist lift-off method to achieve functional unit metal interconnection.Using Parylene C as an encapsulation layer,copper is used as a mask for reactive ion etching to remove the encapsulation material from the pads and the tips and pores of the microneedles.The outer contour of the device is obtained by laser cutting,and the final device is obtained by removing PMMA with acetone infiltration into the PI substrate.(4)The prepared complete devices were subjected to performance tests for LED,temperature sensor,microneedle arrays,and serpentine wires as well as in vivo implantation experiments,respectively.The performance test results show that each functional unit has excellent performance and can meet the requirements of surgery,mouse growth,and optogenetic principles,and also verify the reliability of heat generation simulation during LED operation and serpentine wires stretching performance simulation.In vivo experiments verified the positive effect of the device implanted in rats for one month to help repair spinal cord injury.