A Simple Method for the Detection of Biofilms Using a Heatable Capacitive Sensor Structure (CSS): Description, Proof of Concept, and Some Technical Improvements.

This article presents a novel method for the detection of biofilms based on a heatable, capacitive sensor structure (CSS). Biofilms are capable of strongly binding large amounts of water to their extracellular biopolymer matrix, which is detectable via its dielectric properties. A main challenge is to determine the difference between the inherent occurring presence of moisture in the ecosystem, which is necessary to form a biofilm and an actual formed biofilm. Therefore, the CSS is carefully heated to evaporate unbound surface moisture and determine whether there is a remaining residual alternation of the capacitance in comparison to the dry state. As a reproduceable substitute for complex, real biofilms, a hygroscopic, medical hydrogel-based on polysaccharides was used and applied by spray coating. Printed circuit boards (PCB) in different geometries and materials were used as CSS and compared in terms of their performance. A layer-thickness of 20 µm for the hydrogel coating to be sufficiently detected was defined as a realistic condition based on known values for real biofilms cited in literature. For this thickness a double-meander structure proves to be preferable over interdigitating and spiral geometries. It does offer a 30% lower, yet sufficient sensitivity, but shows advantages in manufacturing (one layer instead of two) and conductive heating capability. In the experiments, free water showed virtually no residual change, while the hydrogel-coated CSS still shows an approx. 300% higher value compared to a dry capacity. Yet, the overall small capacities of about 6-30 pF in dry state are difficult to measure and therefore sensitive to interferences and noise, which results in a high deviation. The principle of measurement can be evaluated as proofed by the carried out experiments, though offering room for improvement in the design of the study. The new method might be especially useful for pipes (e.g., hydrodynamically ineffective sensors installed in a pipe wall) if they at least are not permanently flooded with an aqueous medium, but can occasionally dry. If the internal surface is still only moist, it can be dried by initial heating.

Oxygenation Status in Chronic Leg Ulcer After Topical Hemoglobin Application May Act as a Surrogate Marker to Find the Best Treatment Strategy and to Avoid Ineffective Conservative Long-term Therapy.

PURPOSE: Chronic leg ulcers can be a challenge to treat and long-term therapy a significant cost factor in western public health budgets. Objective wound assessment assays enabling selection of appropriate wound therapy regimes would be desirable. Oxygenation status in ulcer tissue has obtained increased attention as a relevant factor in wound healing. To increase oxygenation in wounds, a topical hemoglobin spray was developed. Although favorable results have been noted, the link between clinical efficacy and the mode of action has not been demonstrated. The aims were to determine if changes in tissue oxygenation can be measured after topical application of hemoglobin on chronic wounds and to evaluate the findings in terms of therapy strategies. PROCEDURES: Photoacoustic imaging was used to measure the local oxygen saturation (StO2) in leg ulcers before and after hemoglobin spray treatment. Sclerosis of the leg ulcers was histopathologically graded and the change in wound size was documented in a follow-up examination. RESULTS: Measuring 49 patients, an increase in StO2 after topical hemoglobin application from on average 66.1 to 71 % (p = 0.017) after 20 min was observed. Depending on the increase in StO2 (>10 % or <10 %) patients were stratified into a Responder and a Non-Responder group. Wound size significantly decreased in the Responder Group (p = 0.001), while no significant difference in the Non-Responder group (p = 0.950) was noted. CONCLUSION: Our findings suggest that the likelihood of wound healing under conservative therapy can be predicted by measuring changes in StO2 after topical hemoglobin application. This assay may reduce treatment time and costs by avoiding ineffective conservative long-term therapy. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00005993.

A novel, non-invasive diagnostic clinical procedure for the determination of an oxygenation status of chronic lower leg ulcers using peri-ulceral transcutaneous oxygen partial pressure measurements: results of its application in chronic venous insufficiency (CVI).

The basis for the new procedure is the simultaneous transcutaneous measurement of the peri-ulceral oxygen partial pressure (tcPO(2)), using a minimum of 4 electrodes which are placed as close to the wound margin as possible, additionally, as a challenge the patient inhales pure oxygen for approximately 15 minutes. In order to evaluate the measurement data and to characterise the wounds, two new oxygen parameters were defined: (1) the oxygen characteristic (K-PO(2)), and (2) the oxygen inhomogeneity (I-PO(2)) of a chronic wound. The first of these is the arithmetic mean of the two lowest tcPO(2) measurement values, and the second is the variation coefficient of the four measurement values. Using the K-PO(2) parameter, a grading of wound hypoxia can be obtained. To begin with, the physiologically regulated (and still compensated) hypoxia with K-PO(2) values of between 35 and 40 mmHg is distinguished from the pathological decompensated hypoxia with K-PO(2) values of between 0 and 35 mmHg; the first of these still stimulates self-healing (within the limits of the oxygen balance). The decompensated hypoxia can be (arbitrarily) divided into "simple" hypoxia (Grade I), intense hypoxia (Grade II) and extreme hypoxia (Grade III), with the possibility of intermediate grades (I/II and II/III).Measurements were carried out using the new procedure on the skin of the right inner ankle of 21 healthy volunteers of various ages, and in 17 CVI (chronic venous insufficiency) wounds. Sixteen of the 17 CVI wounds (i.e., 94%) were found to be pathologically hypoxic, a state which was not found in any of the healthy volunteers. The oxygen inhomogeneity (I-PO(2)) of the individual chronic wounds increased exponentially as a function of the hypoxia grading (K-PO(2)), with a 10-fold increase with extreme hypoxia in contrast to a constant value of approximately 14% in the healthy volunteers. This pronounced oxygen inhomogeneity explains inhomogeneous wound healing, resulting in the so-called mosaic wounds. The hypoxia grades found in all of the chronic wounds was seen to be evenly distributed with values ranging from 0 to 40 mmHg, and therefore extremely inhomogeneous. In terms of oxygenation, chronic wounds are therefore inhomogeneous in two respects: (1) within the wound itself (intra-individual wound inhomogeneity) and (2) between different wounds (inter-individual wound inhomogeneity). Due to the extreme oxygen inhomogeneity, single measurements are not diagnostically useful. In healthy individuals the oxygen inhalation challenge (see above) results in synchronised tcPO(2) oscillations occurring at minute rhythms, which are not seen in CVI wounds. These oscillations can be interpreted as a sign of a functioning arterial vasomotor system.The new procedure is suitable for the routine characterisation of chronic wounds in terms of their oxygen status, and correspondingly, their metabolically determining (and limiting) potential for healing and regeneration. The oxygen characteristic K-PO(2) can furthermore be used as a warning of impending ulceration, since the oxygen provision worsens over time prior to the demise of the ulcerated tissue, thus making a controlled prophylaxis possible.

Complete healing of chronic wounds of a lower leg with haemoglobin spray and regeneration of an accompanying severe dermatoliposclerosis with intermittent normobaric oxygen inhalation (INBOI): a case report.

A new healing procedure has been developed on the basis of the successful treatment of therapy-resistant hypoxic (and practically anoxic) leg ulcerations located within a heavy dermatoliposclerosis. The procedure involves an initial intra-ulceral application of haemoglobin followed by the intermittent administration of normobaric oxygen via inhalation. Haemoglobin is capable of externally supplying the granulating wound bed with oxygen at low partial pressure in a physiological manner, like a micro lung, so that oxidative stress can be avoided. A long-term daily administration of oxygen from within - including the peri-ulceral skin - is achieved by intermittent normobaric oxygen inhalation (INBOI) regularly throughout the day in the form of 1-hour sessions.Using this combined healing treatment during haemoglobin applications the ulcerations healed within about 1 month, and subsequently with INBOI therapy within further approx. 4 months the peri-ulceral skin regenerated as far as the oxygenation status was concerned: The peri-ulceral transcutaneous oxygen partial pressure (tcPO(2)) of zero (measured during breathing of normal air) rose to a satisfactory value of approx. 35 mmHg. After 28 months of treatment, the completely hypoxic and degenerated skin on the leg had practically returned to normal with a PO(2) of 45 mmHg. Furthermore, the skin dermatoliposclerosis regressed. The skin regeneration was long-lasting, which was probably related to cellular tissue regeneration with an increase in the capillary density, whereby it had to be maintained by regular oxygen inhalation (INBOI maintaining treatment). By unintended intra-individual therapy variations it is evidenced that local hypoxia was the reason for skin degeneration: 3 x 1 h oxygen inhalation were sufficient for the healing treatment; 2 x 1 h sufficed for maintenance, whereas 2 x 0.5 h did not.The new procedure carries practically no risks, is simple, cheap and effective. Whereas the application of haemoglobin requires professional supervision, the oxygen inhalation can be carried out at home following initial guidance and monitoring by a physician. Using this novel method, the therapy-resistant ulceration could be closed within 5 months, during which daily outpatient care was only necessary for 1 month. The successful outcome of the treatment in terms of improvement of oxygen supply can monitored at any time using peri-ulceral tcPO(2) measurements, whereby, due to the inhomogeneity of the values, measurements at a minimum of two locations at the wound edge are strongly recommended and more measurements at more skin locations would be preferable.Besides its use in the healing of ulcers, the new procedure is also suitable for the prevention of ulceration development (prophylactic INBOI treatment) in skin rendered susceptible due to the presence of hypoxia. Here, peri-ulceral transcutaneous oxygen partial pressures of below 10 mmHg should be considered as being critical and are an indication for a prophylactic oxygen inhalation treatment. The new procedure may also be suitable even before the peri-ulceral oxygen partial pressure falls below 10 mmHg. Four measures for rehabilitation, conservation, and prevention with regard to a healed chronic wound are proposed.