Multifunctional Skin-Like Electronics for Quantitative, Clinical Monitoring of Cutaneous Wound Healing

Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here, an electronic sensor platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing is reported. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of “epidermal” electronics system in a realistic clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management

A review of emerging technologies enabling improved solid oral dosage form manufacturing and processing

Tablets are the most widely utilized solid oral dosage forms because of the advantages of self-administration, stability, ease of handling, transportation, and good patient compliance. Over time, extensive advances have been made in tableting technology. This review aims to provide an insight about the advances in tablet excipients, manufacturing, analytical techniques and deployment of Quality by Design (QbD). Various excipients offering novel functionalities such as solubility enhancement, super-disintegration, taste masking and drug release modifications have been developed. Furthermore, co-processed multifunctional ready-to-use excipients, particularly for tablet dosage forms, have benefitted manufacturing with shorter processing times. Advances in granulation methods, including moist, thermal adhesion, steam, melt, freeze, foam, reverse wet and pneumatic dry granulation, have been proposed to improve product and process performance. Furthermore, methods for particle engineering including hot melt extrusion, extrusion-spheronization, injection molding, spray drying / congealing, co-precipitation and nanotechnology-based approaches have been employed to produce robust tablet formulations. A wide range of tableting technologies including rapidly disintegrating, matrix, tablet-in-tablet, tablet-in-capsule, multilayer tablets and multiparticulate systems have been developed to achieve customized formulation performance. In addition to conventional invasive characterization methods, novel techniques based on laser, tomography, fluorescence, spectroscopy and acoustic approaches have been developed to assess the physical-mechanical attributes of tablet formulations in a non- or minimally invasive manner. Conventional UV-Visible spectroscopy method has been improved (e.g., fiber-optic probes and UV imaging-based approaches) to efficiently record the dissolution profile of tablet formulations. Numerous modifications in tableting presses have also been made to aid machine product changeover, cleaning, and enhance efficiency and productivity. Various process analytical technologies have been employed to track the formulation properties and critical process parameters. These advances will contribute to a strategy for robust tablet dosage forms with excellent performance attributes

Stimuli-responsive zinc (Ii) coordination polymers: A novel platform for supramolecular chromic smart tools

The unique role of the zinc (II) cation prompted us to cut a cross-section of the large and complex topic of the stimuli-responsive coordination polymers (CPs). Due to its flexible coordination environment and geometries, easiness of coordination–decoordination equilibria, “optically innocent” ability to “clip” the ligands in emissive architectures, non-toxicity and sustainability, the zinc (II) cation is a good candidate for building supramolecular smart tools. The review summarizes the recent achievements of zinc-based CPs as stimuli-responsive materials able to provide a chromic response. An overview of the past five years has been organised, encompassing 1, 2 and 3D responsive zinc-based CPs; specifically zinc-based metallorganic frameworks and zinc-based nanosized polymeric probes. The most relevant examples were collected following a consequential and progressive approach, referring to the structure–responsiveness relationship, the sensing mechanisms, the analytes and/or parameters detected. Finally, applications of highly bioengineered Zn-CPs for advanced imaging technique have been discussed

Properties characterization of PDMS/Beeswax composite

Mestrado de dupla diplomação com a UTFPR - Universidade Tecnológica Federal do ParanáPolydimethylsiloxane (PDMS) is one of the elastomers belonging to the polymers that has received the most attention, as it is a material with good thermal stability, biocompatibility, flexibility, low cost and hyperplastic characteristics. As well as PDMS, beeswax, too, has attracted the attention of researchers, as it is a biodegradable material, thermally stable and of natural origin. These materials can be used in areas such as microfluidic systems, medical devices, electronic components, among others. PDMS mixed with beeswax is able to improve hydrophobic properties, abrasion and corrosion resistance, thermal stability and high temperature transparency. However, the manufacturing process used to mix PDMS and waxes requires some steps, such as heating, mixing and degassing, however, conventional methods do not follow a standardized process, resulting in products with low repeatability. To overcome this limitation, a vacuum chamber was developed and built with the objective of optimizing the manufacturing process. Another important factor is the use of beeswax, as it is a natural product, the composition is different depending on the climate and region. For this reason, in this study, the chemical characterization of beeswax was performed. Subsequently, experimental tests were carried out with the composite of PDMS and beeswax. Samples were manufactured using the multifunctional vacuum chamber developed in this dissertation. The samples were submitted to tensile, hardness, DMA, TGA, spectrometry and wettability tests in order to analyze the mechanical, optical and wettability properties. The manufacture of the multifunctional vacuum chamber allowed the production of samples with more uniform properties and made the process more efficient. In the DMA test, the composite showed thermal stability up to 200°C, together with high transparency at 80°C, when compared to pure PDMS. In the wettability test, the composite proved to increase the contact angle close to 150°C, presenting a super-hydrophobic surface.O polidimetilsiloxano (PDMS) é um dos elastómeros pertencente aos polímeros que mais tem recebido atenção, por ser um material com boa estabilidade térmica, biocompatibilidade, flexibilidade, baixo custo e características hiperplásticas. Assim como o PDMS, a cera de abelha, também, tem atraído a atenção dos investigadores, por se tratar de um material biodegradável, termicamente estável e de origem natural. Esses materiais podem ser utilizados em áreas como sistemas microfluídicos, dispositivos médicos, componentes eletrónicos, entre outros. O PDMS misturado com cera de abelha, mostra-se capaz de melhorar as propriedades hidrofóbicas, resistência à abrasão e corrosão, estabilidade térmica e transparência a alta temperatura. Porém, o processo de fabricação utilizado para misturar PDMS e ceras requer algumas etapas, como aquecer, misturar e desgaseificar, contudo, os métodos convencionais não seguem um processo normalizado, originando produtos com baixa repetibilidade. Para contornar esta limitação, desenvolveu-se e construiu-se uma câmara de vácuo com o objetivo de otimizar o processo de fabricação. Outro fator importante é a utilização da cera de abelha por ser um produto natural, a composição é diferente dependendo do clima e da região. Por esse motivo, neste estudo foi realizado a caracterização química da cera de abelha. Posteriormente, foram realizados testes experimentais com o compósito de PDMS e cera de abelha. O fabrico das amostras foi efetuado utilizando a câmara de vácuo multifuncional desenvolvida nesta dissertação. As amostras foram submetidas a ensaios de tração, dureza, DMA, TGA, espectrometria e de molhabilidade com o intuito de analisar as propriedades mecânicas, óticas e de molhabilidade. A fabricação da câmara de vácuo multifuncional permitiu a produção das amostras com propriedades mais uniformes e tornou o processo mais eficiente. No ensaio de DMA, o compósito mostrou uma estabilidade térmica até os 200°C, juntamente com a alta transparência a 80°C, quando comparado ao PDMS puro. No ensaio de molhabilidade, o compósito provou aumentar o ângulo de contacto perto dos 150°C, apresentado uma superfície super-hidrofóbica

Sustainable Devices by Design: Thermal- and Plasma-Enabled Nanofabrication of Hierarchical Carbon Nanostructures for Bioelectronics and Supercapacitors

Graphene is promising to enable diverse technological advancements. However, major technical challenges arise in its fabrication and integration as active functional materials. This body of work exemplifies a host of thermal- and plasma-enabled techniques, designed to realize sustainable and controlled methodologies for nano-assembly. Importantly, these techniques may be tailored and broadly incorporated to harness the unique functional properties of graphene, and a host of other hierarchical nanomaterials. Together, these concepts may pave the realization of next-generation nanotechnologies which hold promise for a sustainable future

Modular Instrumentation for Controlling and Monitoring In-Vitro Cultivation Environment and Image-based Functionality Measurements of Human Stem Cells

Artificial animal cell culture was successfully developed by Ross Harrison in 1907. But it was not until the 1940’s and 1950’s that several developments occurred, which expedited the cell culturing in-vitro (C-Vitro) to be a consistent and reproducible technique to study isolated living-cells in a controlled environment. Currently, CVitro is one of the major tools in cellular and molecular biology both in the academia and industry. They are extensively utilised to study the cellular physiology/biochemistry, to screen drugs/therapeutic compounds, to understand the effects of drugs/toxic compounds and also to identify the pathways of carcinogenesis/mutagenesis. It is also used in large scale manufacturing of vaccines and therapeutic proteins. In any experimental setup, it is important that the C-Vitro model should represent the physiological phenomena of interest with reasonable accuracy so that all experimental results are statistically consistent and reproducible. In this direction, sensors and measurement systems play important roles in in-situ detection and/or control/manipulation of cells/tissues/environment. This thesis aimed to develop new technology for tailored cell culturing and integrated measurements. Firstly, design and assembly of a portable Invert-upright microscope interchangeable modular cell culturing platform (iuCMP) was envisioned. In contrast to conventional methods, micro-scaled systems mimic the cells' natural microenvironment more precisely, facilitating accurate and tractable models. The iuCMP integrates modular measurement schemes with a mini culture chamber using biocompatible cell-friendly materials, automated environment-control (temperature and gas concentrations), oxygen sensing and simultaneous functional measurements (electrophysiological and image-based). Time lapse microscopy is very useful in cell biology, but integration of advanced >i>in-vitro/device based biological systems (e.g. lab/organ/body-on-chips, or mini-bioreactors/microfluidic systems) into conventional microscopes can be challenging in several circumstances due to multiple reasons. But in iuCMP the main advantage is, the microscope can be switched either as an inverted or as an upright system and therefore can accommodate virtually any in-vitro device. It can capture images from regions that are otherwise inaccessible by conventional microscopes, for example, cells cultured on physical or biochemical sensor systems. The modular design also allows accommodating more sensor or measurement systems quite freely. We have demonstrated the system for video-based beating analysis of cardiomyocytes, cell orientation analysis on nanocellulose, and simultaneous long-term in-situ microscopy with oxygen and temperature sensing in hypoxia. In an example application, the system was utilised for long-term temperature stressing and simultaneous mechanobiological analysis of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). For this the iuCMP together with a temperature sensor plate (TSP) and a novel non-invasive beating analysis software (CMaN—cardiomyocyte function analysis tool, scripted as a subpart of this thesis), was applied for automated temperature response studies in hiPSC-CM cultures. In-situ temperature sensing is usually challenging with bulky external sensors, but TSPs solved this issue. In the temperature response study, we showed that the relationship between hiPSC-CM beating frequency and temperature is non-linear and measured the Q10 temperature coefficients. Moreover, we observed the hiPSC-CM contractile networking, including propagation of the action potential signal between dissociated clusters and their non-invasive measurements. It was the first case where these events were reported in hiPSC-CM clusters and their noninvasive measurements by image processing. The software CMaN comes with a user-friendly interface and, is equipped with features for batch processing, movement centre detection and cluster finding. It can extract six different signals of the contractile motion of cardiomyocytes (clusters or single cells) per processing. This ensures a minimum of one useful beating signal even in the cases of complex beating videos. On the processing end, compared to similar tools, CMaN is faster, more sensitive, and computationally less expensive and allows ROI based processing. In the case of healthy cells, the waveform of the signal from the CMaN resembles an ECG signal with positive and negative segments, allowing the computation of contraction and relaxation features separately. In addition to iuCMP, a Modular optical pH measurement system (MO-pH) for 24/7 non-contact cell culture measurements was also developed. The MO-pH incorporates modular sterilisable optical parts and is used in phenol-red medium cell cultures. The modular assembly of MO-pH cassettes is unique and reusable. Measurements are carried out in a closed flow system without wasting any culture medium and requires no special manual attention or recalibrations during culture. Furthermore, a new absorption correction model was put forward that minimised errors caused e.g. by biolayers in spectrometric pH measurement, which improved the pH measurement accuracy. MO-pH has been applied in long-term human adipose stem cells (hASC) expansion cultures in CO2 dependent and independent media. Additionally, the MO-pH was also utilised to comprehend the behaviour of pH, temperature and humidity in water jacked incubators as well as to record the pH response as a function of temperature in the presence and absence of CO2 in the context of stem cell cultures. The resulting plots clearly showed the interplay between measured parameters indicating a few stress sources present all through the culture. Additionally, it provided an overall picture of behaviour of critical control parameters in an incubator and pointed out the need for bioprocess systems with automatic process monitoring and smart control for maximum yield, optimal growth and maintenance of the cells. Besides, we also integrated MO-pH into flasks with reclosable lids (RL-F) and tested its applicability in stem cell cultures. A standalone system around an RL-F flask was built by combining the cell culture, medium perfusion and optical measurements. The developed RL-F system has been successfully tested in ASC-differentiation cultures. Finally, a few trial experiments for image-based pH estimation aimed for iuCMP have also been carried out. This includes tests with LCD illumination, optical projection tomography, and webcam systems. In reality, the pH is not distributed uniformly in tissues, and has shown a gradient of up to 1.0 pH unit within 1 cm distance. Therefore, producing reliable pH maps also in in-vitro can be important in understanding various common pathologies and location of lesions. A reliable and adequately developed long-term pH mapping method will be an important addition into the iuCMP