Volume 4, Issue 2 - Topic Issue: Sensors in diagnostics and monitoring / Issue Editors: Jürgen Helfmann and Uwe Netz

Personalized medicine is revolutionizing modern health care. The aim of personalized diagnostics is to provide rapid, portable and simple tests that will reduce diagnosis time. They enable rapid analysis performed near the patient and provide specific details of the patient’s condition so that a personalized treatment can be made. This review focuses on the recent advances in optical diagnostic techniques based on surface plasmon resonance (SPR) and surface-enhanced Raman scattering spectroscopy (SERS) for translational medical diagnostics. In the first part, recent developments in SPR biosensors for infectious disease diagnosis are presented including the first two-dimensional multiplex influenza SPR biosensor for H1N1 (influenza A) and H3N2 (seasonal influenza) detection. In the second part, advances in SERS, which is another ultra-sensitive optical diagnostic technique for various cancer detection applications in pre-clinical and clinical settings, are reviewed.

Abstract: Various studies have shown promising results in using Raman spectroscopy (RS) for the detection of skin cancers. In-vivo evaluations showed similar results to those found by trained dermatologists using dermoscopy, the current clinical practice for skin cancer diagnosis. However, dermoscopy is highly subjective which would make an objective, non-invasive diagnostic method useful. Although successful results were achieved, RS is barely applied in clinical routine yet. This review summarizes studies of Raman spectroscopy for skin cancer diagnosis ex vivo and in vivo . The latter has special demands that often lead to a tradeoff between applicability and classification performance. The necessary steps are explained for instrumentation design, handling, data analysis and clinical testing on groups with a sufficient amount of subjects in order to promote the application of RS in a routine clinical setting. A number of methods are summarized which attempt to overcome the ongoing challenge of reducing large background signals. Modifications of RS by combination with other diagnostic methods are summarized that can give a new perspective to future developments in RS.

Background and objective: Thin films of bacteria, proteins and other biochemical substances are always found on surfaces exposed to the environment. Optical methods enable innovative tools for the detection of such films, as residua of proteins and other substances that exhibit fluorescence when excited with UV light. Sensor design: This paper presents and evaluates a specially designed handheld measuring device for this purpose. Results: The sensor is able to detect low concentrations of organic contamination with measurement times shorter than a second. The results presented in this paper show that detection of contamination levels of bovine serum albumin down to 200 ng/cm 2 is possible on non-fluorescent substrate materials. Conclusion: Future development of handheld optical devices suitable for the detection or analysis of various compounds could be based on these results.

Background and objective: To evaluate a novel skin tone meter (STM) to categorize skin tones into one of the six categories of the Fitzpatrick skin type (FST) classification system, thus optimizing safety in light-based dermatological procedures. This numerical classification method measures several components; principally the reaction of human skin to ultraviolet (UV) light exposure, which is used to help predict skin response in laser and intense pulsed light (IPL) treatments. Materials and methods: Two-hundred twenty volunteers of varying ethnic origin, age and gender were enrolled in a preliminary study. The subjects’ Fitzpatrick skin type was ascertained by a standardized questionnaire that determined their reaction to significant sunlight exposure. A calibrated prototype STM device (consisting of an optical head at 460 nm, detector, microprocessor, and a liquid crystal display) was used to measure the subjects’ inner arm skin; which typically has little UV exposure and minimal hair, and compared the obtained value with measurements taken from a skin color chart and digital photographs. To evaluate device performance (within subject) across different skin states, a section of skin from the inner arm of a sub-group of eight volunteers was marked into test areas using a template. The skin in each area was then prepared ( i ) with a control area, ( ii ) by degreasing with acetone for 1 min to represent dry skin, ( iii ) with a fine layer of coupling gel to represent hydrated skin, ( iv ) with a thin layer of petrolatum (Vaseline) to represent oily skin, and ( v ) with saline solution applied then dried to represent dried perspiration. Results: There was a consistent trend between the STM prototype and the assessed skin tone derived from a proprietary skin color chart against the measurement on skin across a range of skin conditions. Conclusion: The presented preliminary study demonstrated the subjective nature of the FST classification system and the weakness of skin tone self-assessment by an individual, as judged by expert assessors. The FST classification requires an objective measurement to replace the textual description for each skin tone. It may significantly decrease the risk of potential side effects through overtreatment, and extend treatment to a wider patient population with light-based dermatological procedures.

Background and objective: This article describes a new sensor for monitoring oxygen saturation (sO 2 ) and hematocrit (Hct) of blood during cardiopulmonary bypass. The sensor is calibrated without blood and does not need to be adjusted by laboratory blood parameter analysis when in operation. Materials and methods: The optical sensor presented here uses near-infrared spatially resolved reflectance spectroscopy. The primary calibration model for a master sensor is derived from the measurement of circulating human blood from a number of different patients with references taken from standard laboratory analysis of blood parameters. Transfer of the calibration model from the master sensor to new sensors is performed by measurement of an optical standard made of artificial material with defined and controlled optical properties. Results: The predicted values of sO 2 and Hct exhibit an accuracy of 1.2% for sO 2 and 1.1% for Hct compared to the reference values. The optical standard yields optical signals similar to the measurement of blood. After calibration transfer, the mean accuracy of the measurement of 10 sensors is 1.3% for sO 2 and 1.2% for Hct. Conclusion: A new sensor with high degree of accuracy for sO 2 and Hct compared to commercially available sensor systems is presented. The calibration transfer using optical standards gives a comparable degree of accuracy. The method could be adapted for use with existing sensors. No animal blood needs to be used in calibration process anymore.

There is currently no non-invasive measurement method available on the market for the quality control of red cell concentrates (RCCs). As the level of free hemoglobin is an indicator for hemolysis resulting from destroyed or overaged red blood cells, it is an important parameter to assess the quality and usability of RCCs before transfusion. A new optical device has been developed and tested to enable the measurement of the free hemoglobin concentration non-invasively in RCCs.

A change in the water distribution of the human body, such as water retention in the skin, can be a symptom of a pathological condition including heart failure. Therefore, a sensor for the non-invasive quantification of the water content of the skin could be useful where continuous monitoring of patients is required to detect and avoid life threatening conditions. As water is a major absorber of tissue in the near-infrared wavelength range, the water content can be determined based on reflectance measurements. Measuring the diffuse reflectance at multiple distances from the point of illumination allows the determination of absorption in scattering media such as skin. The aim of this project was to develop a small and portable sensor based on light emitting diodes and photodiodes. Evaluation of the first functional sensor design has showed that the water content of tissue phantoms can be predicted with a prediction error of 1%. Further developments towards a sensor that can be applied in a future field study are ongoing.