Photolithographic micropatterning of organic, flexible biomaterials and its applications

A current trend in biodevices has involved a shift from traditional rigid platforms to flexible and stretchable formats. These flexible devices are expected to have a significant impact on future healthcare, disease diagnostics and therapeutics. However, the fabrication of such flexible devices has been limited by the choice of materials. Biomimetic composites of naturally derived and synthetic polymers provide exciting opportunities to develop mechanically flexible, physiologically compliant, and degradable bioelectronic systems. 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. In this work, we present a combination of photo-crosslinkable silk proteins and conductive polymers to precisely fabricate flexible devices and cell culture substrate. A facile and scalable photolithography is applied to fabricate flexible substrates with conductive and non- conductive micropatterns which show tuneable electrical and mechanical properties. We also demonstrate an approach to engineer flexibility in materials through the creation of patterned defects inspired from Kirigami- the Japanese art of paper cutting. Mechanically flexible, free- standing, optically transparent, large-area biomaterial sheets with precisely defined and computationally designed microscale cuts can be formed using a single-step photolithographic process. As composites with conducting polymers, flexible, intrinsically electroactive sheets can be formed. Through this work, the possibility of making next- generation, fully organic, flexible bioelectronics is explored.https://scholarscompass.vcu.edu/gradposters/1099/thumbnail.jp

NATURE-INSPIRED MATERIAL STRATEGIES TOWARDS FUNCTIONAL DEVICES

Naturally sourced, renewable biomaterials possess outstanding advantages for a multitude of biomedical applications owing to their biodegradability, biocompatibility, and excellent mechanical properties. Of interest in this dissertation are silk (protein) and chitin (polysaccharide) biopolymers for the fabrication of functional biodevices. One of the major challenges restricting these materials beyond their traditional usage as passive substrate materials is the ability to combine them with high-resolution fabrication techniques. Initial research work is directed towards the fabrication of micropatterned, flexible 2D substrates of silk fibroin and chitin using bench-top photolithographic techniques. Research is focused on imparting electrochemical properties to silk proteins using conducting polymers (PEDOT: PSS and PANI) and a naturally occurring semiconductor, eumelanin. The utility of conducting biomimetic composites in device applications was demonstrated by the fabrication of fully organic silk based flexible electrochemical biosensors. The biosensors display excellent detection of dopamine and ascorbic acid with high sensitivity. A flexible silk-PEDOT: PSS based temperature sensor is also demonstrated for the accurate monitoring of skin surface temperature. Finally, the challenge of conformability at the biological interface is addressed using structure-based design strategies. Inspiration from the Japanese art of paper cutting was taken for the formation of patterned cuts on silk fibroin films using photolithography. Micropatterned cuts can increase the conformability of films to soft biological interfaces by enhancing their strain tolerance. By doping with polyaniline (PANI), flexible, intrinsically conductive silk kirigami sheets could be fabricated. Such systems have potential in personalized healthcare monitoring devices, improving efficient disease detection and diagnosis

Wavelet-based multifractal analysis of laser biopsy imagery

In this work, we report a wavelet based multi-fractal study of images of dysplastic and neoplastic HE- stained human cervical tissues captured in the transmission mode when illuminated by a laser light (He-Ne 632.8nm laser). It is well known that the morphological changes occurring during the progression of diseases like cancer manifest in their optical properties which can be probed for differentiating the various stages of cancer. Here, we use the multi-resolution properties of the wavelet transform to analyze the optical changes. For this, we have used a novel laser imagery technique which provides us with a composite image of the absorption by the different cellular organelles. As the disease progresses, due to the growth of new cells, the ratio of the organelle to cellular volume changes manifesting in the laser imagery of such tissues. In order to develop a metric that can quantify the changes in such systems, we make use of the wavelet-based fluctuation analysis. The changing self- similarity during disease progression can be well characterized by the Hurst exponent and the scaling exponent. Due to the use of the Daubechies' family of wavelet kernels, we can extract polynomial trends of different orders, which help us characterize the underlying processes effectively. In this study, we observe that the Hurst exponent decreases as the cancer progresses. This measure could be relatively used to differentiate between different stages of cancer which could lead to the development of a novel non-invasive method for cancer detection and characterization.Comment: 9 pages, 11 figures, 1 table, to appear in the Proceedings of SPIE Photonics West, BiOS 201

Biofunctional Silk Kirigami With Engineered Properties.

The fabrication of multifunctional materials that interface with living environments is a problem of great interest. A variety of structural design concepts have been integrated with functional materials to form biodevices and surfaces for health monitoring. In particular, approaches based on kirigami-inspired cuts can engineer flexibility in materials through the creation of patterned defects. Here, the fabrication of a biodegradable and biofunctional "silk kirigami" material is demonstrated. Mechanically flexible, free-standing, optically transparent, large-area biomaterial sheets with precisely defined and computationally designed microscale cuts can be formed using a single-step photolithographic process. Using modeling techniques, it is shown how cuts can generate remarkable "self-shielding" leading to engineered elastic behavior and deformation. As composites with conducting polymers, flexible, intrinsically electroactive sheets can be formed. Importantly, the silk kirigami sheets are biocompatible, can serve as substrates for cell culture, and be proteolytically resorbed. The unique properties of silk kirigami suggest a host of applications as transient, "green", functional biointerfaces, and flexible bioelectronics

Micropatterned silk-fibroin/eumelanin composite films for bioelectronic applications

There has been growing interest in the use of natural bionanomaterials and nanostructured systems for diverse biomedical applications. Such materials can confer unique functional properties as well as address concerns pertaining to sustainability in production. In this work, we propose the biofabrication of micropatterned silk fibroin/eumelanin composite thin films to be used in electroactive and bioactive applications in bioelectronics and biomedical engineering. Eumelanin is the most common form of melanin, naturally derived from the ink of cuttlefish, having antioxidant and electroactive properties. Another natural biomaterial, the protein silk fibroin, is modified with photoreactive chemical groups, which allows the formation of electroactive eumelanin thin films with different microstructures. The silk fibroin/eumelanin composites are fabricated to obtain thin films as well as electroactive microstructures using UV curing. Here, we report for the first time the preparation, characterization, and physical, electrochemical, and biological properties of these natural silk fibroin/eumelanin composite films. Higher concentrations of eumelanin incorporated into the films exhibit a higher charge storage capacity and good electroactivity even after 100 redox cycles. In addition, the microscale structure and the cellular activity of the fibroin/eumelanin films are assessed for understanding of the biological properties of the composite. The developed micropatterned fibroin/eumelanin films can be applied as natural electroactive substrates for bioapplications (e.g., bioelectronics, sensing, and theranostics) because of their biocompatible properties.The authors acknowledge the FRONTHERA project (Frontiers of technology for theranostics of cancer, metabolic and neurodegenerative diseases) n degrees NORTE-01-0145-FEDER0000232, the European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement n degrees 668983. FoReCaST (Forefront Research in 3D Disease Cancer Models as in vitro Screening Technologies), and FCT grants POCI-01-0145-FEDER-031590, PD/BD/150546/2019 and PTDC/BTM-ORG/28168/2017. VKY acknowledges support from the National Science Foundation (CBET1704435)

Differing self-similarity in light scattering spectra: A potential tool for pre-cancer detection

The fluctuations in the elastic light scattering spectra of normal and dysplastic human cervical tissues analyzed through wavelet transform based techniques reveal clear signatures of self-similar behavior in the spectral fluctuations. Significant differences in the power law behavior ascertained through the scaling exponent was observed in these tissues. The strong dependence of the elastic light scattering on the size distribution of the scatterers manifests in the angular variation of the scaling exponent. Interestingly, the spectral fluctuations in both these tissues showed multi-fractality (non-stationarity in fluctuations), the degree of multi-fractality being marginally higher in the case of dysplastic tissues. These findings using the multi-resolution analysis capability of the discrete wavelet transform can contribute to the recent surge in the exploration for non-invasive optical tools for pre-cancer detection.Comment: 13 pages, 14 figure

Backing of 2-(diethylamino)-N-(2, 6-dimethylphenyl)-acetamide with molecular, electronic and docking studies

In this study, the anaesthetic compound 2-(diethylamino)-N-(2, 6-dimethylphenyl)-acetamide (DEAL) was optimized with the B3LYP-6-311+G (d, p) density functional theory method. Hyper conjugative interactions revealed the bioactivity of the molecule by natural bond orbital analysis. The current–potential curves were noted at well-defined scan rates by cyclic voltammetry. The solvation free energy was calculated by applying the solvation model on density. Molecular docking simulations were carried out to understand the pharmacokinetic behaviour of the drug. Besides, total energy levels of HOMO-LUMO orbitals, Mulliken atomic charges, natural population analysis and polarizability properties of the molecule were calculated. We found that the secondary amide increases the stability of this molecule. The π → π∗ interactions increase the biological activity of the compound, leading to a very high stabilization

Portable, Disposable, Biomimetic Electrochemical Sensors for Analyte Detection in a Single Drop of Whole Blood

Current diagnostics call for rapid, sensitive, and selective screening of physiologically important biomarkers. Point-of-care (POC) devices for the rapid, reliable, and easy acquisition of bioinformation at, or near the patient, offer opportunities for better healthcare management. Electrochemical biosensors with high sensitivity and ease of miniaturization are advantageous for such applications. We report a photolithographically micropatterned PEDOT:PSS and silk protein-based fully organic 3-electrode sensor (O3ES) for ultralow volume (single drop—10 µL) detection of analytes in whole blood. The O3ES produces reliable electrochemical signals in whole blood from a mouse model with minimal biofouling interference. The O3ES is demonstrated as a portable device for the simultaneous detection of dopamine, ascorbic acid and uric acid using voltammetry techniques. The O3ES displays excellent sensitivity towards each analyte in whole blood, and in the presence of each other. The water-based, ambient processing of the sensors allows the immobilization of enzymes in the organic working electrode. Amperometric detection of uric acid via uricase with high sensitivity in whole blood is demonstrated. Finally, the performance of the O3ES under enzymatic degradation is studied by monitoring sensitivity over an operating lifetime of ~14 days. This work demonstrates the realization of low-cost, disposable POC sensors capable of detecting blood metabolites using ultralow sample volumes

Quantum chemical insight into molecular structure, density functional theory calculations, vibrational dynamics, natural population analysis, Hirshfeld analysis, and molecular docking approach to chalcone 1-4-bromophenyl-3-(2-methoxyphenyl)prop-2-en-1-one

<p>The structure of the novel chalcone 1-4-bromophenyl-3-(2-methoxyphenyl)prop-2-en-1-one has been characterized by Fourier transform infrared and Fourier transform Raman. Density functional theory with Becke, 3-parameter, Lee-Yang-Parr functional was used for the optimization of geometry. The comprehensive assignments of the vibrational spectra have been performed with the aid of normal coordinate analysis. Stability of the molecule and intra/intermolecular charge transfer have been analyzed using natural bond orbital analysis. The existence of intermolecular C-H⋯O, blueshifted hydrogen bond was investigated by bond length variation. Hirshfeld and two-dimensional fingerprint plot analyses have been performed to study the nature of interactions present in the molecule. The docked complex gives a constancy of −8.2 kcal/mol toward the androgen receptor.</p

Portable, Disposable, Biomimetic Electrochemical Sensors for Analyte Detection in a Single Drop of Whole Blood

Current diagnostics call for rapid, sensitive, and selective screening of physiologically important biomarkers. Point-of-care (POC) devices for the rapid, reliable, and easy acquisition of bioinformation at, or near the patient, offer opportunities for better healthcare management. Electrochemical biosensors with high sensitivity and ease of miniaturization are advantageous for such applications. We report a photolithographically micropatterned PEDOT:PSS and silk protein-based fully organic 3-electrode sensor (O3ES) for ultralow volume (single drop—10 µL) detection of analytes in whole blood. The O3ES produces reliable electrochemical signals in whole blood from a mouse model with minimal biofouling interference. The O3ES is demonstrated as a portable device for the simultaneous detection of dopamine, ascorbic acid and uric acid using voltammetry techniques. The O3ES displays excellent sensitivity towards each analyte in whole blood, and in the presence of each other. The water-based, ambient processing of the sensors allows the immobilization of enzymes in the organic working electrode. Amperometric detection of uric acid via uricase with high sensitivity in whole blood is demonstrated. Finally, the performance of the O3ES under enzymatic degradation is studied by monitoring sensitivity over an operating lifetime of ~14 days. This work demonstrates the realization of low-cost, disposable POC sensors capable of detecting blood metabolites using ultralow sample volumes