Advances in the field of nature-inspired/derived biomaterials have been revolutionizing the production of next-generation biomedical devices over the past few years, and will continue to make impacts in the field. Of special interest is the application of biodegradable materials in the fabrication of fully organic, intrinsically flexible, thin film devices. Components with precisely patterned micro- or nano-scale circuits can provide different functions as microelectrodes, biosensors, and supercapacitors. Advantages include the ability to provide conformal contact at non-planar biointerfaces, being able to be degraded at controllable rate, and invoking minimal reactions within the body. These factors present great potential as implantable devices for in-vivo applications, while also addressing concerns with “electronic waste” by being intrinsically degradable. The fabrication of such flexible bioelectronics requires a careful optimization of mechanical properties, electrical conductivity, and precise fabrication using materials that are often not easily adapted to such processes. One option of particular interest is the construction of biocompatible and biodegradable, flexible bioelectronics based on silk proteins. In this work, we present the combination of photo-crosslinkable silk proteins and conductive polymers to precisely fabricate flexible devices for the sensing of different targets of interest. A facile and scalable photolithography is applied to fabricate flexible substrates with conductive micropatterns which show tunable electrical and mechanical properties. Competitive conductivity, as well as excellent biocompatibility and controllable biodegradability are shown. Through this work, the possibility of making next-generation, fully organic, flexible bioelectronics is explored.
An implantable sensor is being created that allows measurement of blood glucose through fluorescent detection of an embedded chemical assay. The sensor is based on the competitive binding reaction between the protein Concanavalin A and various saccharide molecules, specifically a glycodendrimer and glucose. Previous studies have shown the ability of an embedded chemical assay using Con A and dextran with shorter wavelength dyes to both sense changes in glucose and generate sufficient fluorescent emission to pass through the dermal tissue. However, due to the chemical constituents of the assay, multivalent binding was evident resulting in poor spectral change due to glucose within the biological range. Use of a glycodendrimer and longer wavelength dyes has improved the sensor’s spectral change due to glucose and the overall signal to noise ratio of the sensor. In this work, a description of this sensor and the results obtained from it will be presented showing a large dynamic range of fluorescence with glucose.
A preliminary in vivo study using photopolymerized poly(ethylene glycol) (PEG) microspheres containing tetramethylrhodamine isothiocyanate labeld concanavalin A (TRITC-Con A) fluroescein isothiocyanate labeld dextran (FITX-dextran) as an implantable glucose sensor was performed using hairless rats. The glucose sensor works by affinity reaction between the two fluorescent labeled molecules binding together to form a fluorescent energy transfer system in which the FITC peak is quenched by the TRITC peak. The addition of glucose to the sensors local environment displces the dextran disrupting the FRET pair and the quenching. The change in fluroescent peak ratio (TRITC/FITC) therefore can be related to glucose. The microspheres in this study were implanted below the dermal skin layer of the lower abdomen by injection. A bolus injection of glucose was given through the tail vein to simulate glucose consumption. Spectra were obtained by shining and collecting light through the skin using an optical fiber delivery system via a 488nm argon laser and a spectrophometer. The preliminary results showed quantifiable changes in the ratio between the two peaks in response to the changae in glucose levels in the interstitial fluid of the rat.