Sensor Systems for Impaired Healing Markers, Concepts and Applications for Objective Wound Assessment

In the pathological healing of chronic wounds the ordered sequence of tissue restoration is disturbed. As a consequence, chronic wounds fail to heal within months and pose a major impact on the patient by pain, odor, leakage, and the risk of infection and the health care system by its constant treatment. Introducing objective wound assessment by sensor technology into clinical routine would help to guide treatment procedures and improve the healing outcome. The aim of this research study was the development of simple and effective concepts to evaluate the wound status at the point of care. Requirements for point of care testing include a fast and flexible device use by untrained personal, reduced time and costs, as well as reliable and easy to interpret results. The complex nature of wounds can be divided into the different regimes of physical appearance, biochemical status and microbiological environment, which influence each other. Each regime is tackled separately in this work by identifying possible parameters for wound analysis from the literature and the design of sensor concepts to quantify these candidates. A miniaturized, wearable sensor system for the integration in a wound dressing was developed to collect healing relevant, physiological data. The sensor measures optical reflectance, heart rate, arterial oxigenation, surface pH, moisture and temperature. The function of the sensor system was verified in a porcine wound model. A combination of surface pH, reflected infrared, and red light showed to be the most significant parameter, associated with the healing progress. For the measurement of biochemical parameters a microfluidic platform for the preparation of biosensing hydrogels by in situ polymerization was designed. Introducing functional structures for gel patterning in the chip fabrication allows for rapid assay customization. Simple handling and functionality were illustrated by assays for matrix metalloproteinase, an important factor in chronic wound healing. In addition, the demonstrated assays for total protein concentration and cell counts indicate the possibilities for a wide range of fast and simple diagnostics. The last part of the thesis discusses microfluidic technologies for rapid analysis of bacteria. Preconcentration of bacteria by on-chip electrophoresis and detection by a simple optical setup are presented. Furthermore, devices for rapid and parallel growth-based bacterial identification and antibiotic testing in microfluidic cultures were designed. The presented results and demonstrated tools show that medical analysis can be improved by sensor technologies that are simple to operate and yield fast results at the point of care

Sensor Systeme für chronische Wunden Marker, Konzepte und Anwendungen für objektive Wundbewertung

In the pathological healing of chronic wounds the ordered sequence of tissue restoration is disturbed. As a consequence, chronic wounds fail to heal within months and pose a major impact on the patient by pain, odor, leakage, and the risk of infection and the health care system by its constant treatment. Introducing objective wound assessment by sensor technology into clinical routine would help to guide treatment procedures and improve the healing outcome. The aim of this research study was the development of simple and effective concepts to evaluate the wound status at the point of care. Requirements for point of care testing include a fast and flexible device use by untrained personal, reduced time and costs, as well as reliable and easy to interpret results. The complex nature of wounds can be divided into the different regimes of physical appearance, biochemical status and microbiological environment, which influence each other. Each regime is tackled separately in this work by identifying possible parameters for wound analysis from the literature and the design of sensor concepts to quantify these candidates. A miniaturized, wearable sensor system for the integration in a wound dressing was developed to collect healing relevant, physiological data. The sensor measures optical reflectance, heart rate, arterial oxigenation, surface pH, moisture and temperature. The function of the sensor system was verified in a porcine wound model. A combination of surface pH, reflected infrared, and red light showed to be the most significant parameter, associated with the healing progress. For the measurement of biochemical parameters a microfluidic platform for the preparation of biosensing hydrogels by in situ polymerization was designed. Introducing functional structures for gel patterning in the chip fabrication allows for rapid assay customization. Simple handling and functionality were illustrated by assays for matrix metalloproteinase, an important factor in chronic wound healing. In addition, the demonstrated assays for total protein concentration and cell counts indicate the possibilities for a wide range of fast and simple diagnostics. The last part of the thesis discusses microfluidic technologies for rapid analysis of bacteria. Preconcentration of bacteria by on-chip electrophoresis and detection by a simple optical setup are presented. Furthermore, devices for rapid and parallel growth-based bacterial identification and antibiotic testing in microfluidic cultures were designed. The presented results and demonstrated tools show that medical analysis can be improved by sensor technologies that are simple to operate and yield fast results at the point of care

Microfluidic concentration of bacteria by on-chip electrophoresis

In this contribution, we present a system for efficient preconcentration of pathogens without affecting their viability. Development of miniaturized molecular diagnostic kits requires concentration of the sample, molecule extraction, amplification, and detection. In consequence of low analyte concentrations in real-world samples, preconcentration is a critical step within this workflow. Bacteria and viruses exhibit a negative surface charge and thus can be electrophoretically captured from a continuous flow. The concept of phaseguides was applied to define gel membranes, which enable effective and reversible collection of the target species. E. coli of the strains XL1-blue and K12 were used to evaluate the performance of the device. By suppression of the electroosmotic flow both strains were captured with efficiencies of up to 99%. At a continuous flow of 15 μl/min concentration factors of 50.17 ± 2.23 and 47.36 ± 1.72 were achieved in less than 27 min for XL1-blue and K12, respectively. These results indicate that free flow electrophoresis enables efficient concentration of bacteria and the presented device can contribute to rapid analyses of swab-derived samples