Digital Resilience Biomarkers for Personalized Health Maintenance and Disease Prevention.

Health maintenance and disease prevention strategies become increasingly prioritized with increasing health and economic burden of chronic, lifestyle-related diseases. A key element in these strategies is the empowerment of individuals to control their health. Self-measurement plays an essential role in achieving such empowerment. Digital measurements have the advantage of being measured non-invasively, passively, continuously, and in a real-world context. An important question is whether such measurement can sensitively measure subtle disbalances in the progression toward disease, as well as the subtle effects of, for example, nutritional improvement. The concept of resilience biomarkers, defined as the dynamic evaluation of the biological response to an external challenge, has been identified as a viable strategy to measure these subtle effects. In this review, we explore the potential of integrating this concept with digital physiological measurements to come to digital resilience biomarkers. Additionally, we discuss the potential of wearable, non-invasive, and continuous measurement of molecular biomarkers. These types of innovative measurements may, in the future, also serve as a digital resilience biomarker to provide even more insight into the personal biological dynamics of an individual. Altogether, digital resilience biomarkers are envisioned to allow for the measurement of subtle effects of health maintenance and disease prevention strategies in a real-world context and thereby give personalized feedback to improve health.

Raman spectroscopy as a promising tool for noninvasive point-of-care glucose monitoring.

Self-monitoring of glucose is important for managing diabetes. Noninvasive glucose monitors are not yet available, but patients would benefit highly from such a device. We present results that may lead to a novel, point-of-care noninvasive system to measure blood glucose based on Raman spectroscopy. A hospitalized cohort of 111 subjects was measured using a custom-made Raman spectrometer system. Blood glucose reference samples were used to correlate Raman data to glucose levels, using advanced preprocessing and analysis algorithms. A correlation coefficient (R (2)) of .83 was found correlating independent Raman-based predictions on reference blood glucose for the full cohort. Stratification of the cohort in gender-specific groups raised correlation levels to .88 (females) and .94 (males). Glucose could be measured noninvasively with average errors as low as 0.9 mM. We conclude that this novel system shows promising results for the advance of noninvasive, point-of-care glucose monitoring.

Real-time detection of viable microorganisms by intracellular phototautomerism.

BACKGROUND: To date, the detection of live microorganisms present in the environment or involved in infections is carried out by enumeration of colony forming units on agar plates, which is time consuming, laborious and limited to readily cultivable microorganisms. Although cultivation-independent methods are available, they involve multiple incubation steps and do mostly not discriminate between dead or live microorganisms. We present a novel generic method that is able to specifically monitor living microorganisms in a real-time manner. RESULTS: The developed method includes exposure of cells to a weak acid probe at low pH. The neutral probe rapidly permeates the membrane and enters the cytosol. In dead cells no signal is obtained, as the cytosolic pH reflects that of the acidic extracellular environment. In live cells with a neutral internal pH, the probe dissociates into a fluorescent phototautomeric anion. After reaching peak fluorescence, the population of live cells decays. This decay can be followed real-time as cell death coincides with intracellular acidification and return of the probe to its uncharged non-fluorescent state. The rise and decay of the fluorescence signal depends on the probe structure and appears discriminative for bacteria, fungi, and spores. We identified 13 unique probes, which can be applied in the real-time viability method described here. Under the experimental conditions used in a microplate reader, the reported method shows a detection limit of 10(6) bacteria ml(-1), while the frequently used LIVE/DEAD BacLight Syto9 and propidium iodide stains show detection down to 10(6) and 10(7) bacteria ml(-1), respectively. CONCLUSIONS: We present a novel fluorescence-based method for viability assessment, which is applicable to all bacteria and eukaryotic cell types tested so far. The RTV method will have a significant impact in many areas of applied microbiology including research on biocidal activity, improvement of preservation strategies and membrane permeation and stability. The assay allows for high-throughput applications and has great potential for rapid monitoring of microbial content in air, liquids or on surfaces.