Non-invasive biomedical research and diagnostics enabled by innovative compact lasers

For over half a century, laser technology has undergone a technological revolution. These technologies, particularly semiconductor lasers, are employed in a myriad of fields. Optical medical diagnostics, one of the emerging areas of laser application, are on the forefront of application around the world. Optical methods of non- or minimally invasive bio-tissue investigation offer significant advantages over alternative methods, including rapid real-time measurement, non-invasiveness and high resolution (guaranteeing the safety of a patient). These advantages demonstrate the growing success of such techniques. In this review, we will outline the recent status of laser technology applied in the biomedical field, focusing on the various available approaches, particularly utilising compact semiconductor lasers. We will further consider the advancement and integration of several complimentary biophotonic techniques into single multimodal devices, the potential impact of such devices and their future applications. Based on our own studies, we will also cover the simultaneous collection of physiological data with the aid a multifunctional diagnostics system, concentrating on the optimisation of the new technology towards a clinical application. Such data is invaluable for developing algorithms capable of delivering consistent, reliable and meaningful diagnostic information, which can ultimately be employed for the early diagnosis of disease conditions in individuals from around the world

Computational model of bladder tissue based on its measured optical properties

Urinary bladder diseases are a common problem throughout the world and often difficult to accurately diagnose. Furthermore, they pose a heavy financial burden on health services. Urinary bladder tissue from male pigs was spectrophotometrically measured and the resulting data used to calculate the absorption, transmission, and reflectance parameters, along with the derived coefficients of scattering and absorption. These were employed to create a "generic" computational bladder model based on optical properties, simulating the propagation of photons through the tissue at different wavelengths. Using the Monte-Carlo method and fluorescence spectra of UV and blue excited wavelength, diagnostically important biomarkers were modeled. Additionally, the multifunctional noninvasive diagnostics system "LAKK-M" was used to gather fluorescence data to further provide essential comparisons. The ultimate goal of the study was to successfully simulate the effects of varying excited radiation wavelengths on bladder tissue to determine the effectiveness of photonics diagnostic devices. With increased accuracy, this model could be used to reliably aid in differentiating healthy and pathological tissues within the bladder and potentially other hollow organs

A pilot study using laser-based technique for non-invasive diagnostics of hypertensive conditions in mice

Endothelial dysfunction is directly linked to preeclampsia, a maternal hypertensive condition that is life threating for both the mother and the baby. Epidemiological studies show that women with a history of pre-eclampsia have an elevated risk for cardiovascular disease. Here we report a new non-invasive diagnostic test for preeclampsia in mice that allows us to non-invasively assess the condition of the animals during the experiment and treatment in established models of preeclampsia. A laser-based multifunctional diagnostics system (LAKK-M) was chosen to carry out non-invasive analysis of multiple parameters. The device was used to simultaneously record the microcirculatory blood flow and oxygen saturation, as well as fluorescence levels of endogenous fluorophores. Preliminary experiments were conducted on adenoviral (Ad-)- mediated overexpression of sFlt-1 (Ad-sFlt-1) to mimic preeclampsialike symptoms in mice. The recorded data displayed the ability of the LAKK-M diagnostics device to detect significant differences in perfusion measurements between the control and Ad-sFlt-1 treatment. Preliminary results provide a potential avenue to employ these diagnostics technology to monitor and aid in maintaining control of live animal conditions throughout the experiment and treatment

The study of synchronization of rhythms of microvascular blood flow and oxygen saturation during adaptive changes

Multi-functional laser non-invasive diagnostic systems, such as "LAKK-M", allow the study of a number of microcirculatory parameters, including blood microcirculatory index (Im) (by laser Doppler flowmetry, LDF) and oxygen saturation (StO2) of skin tissue (by tissue reflectance oximetry, TRO). Such systems may provide significant information relevant to physiology and clinical medicine. The aim of this research was to use such a system to study the synchronization of microvascular blood flow and oxygen saturation rhythms under normal and adaptive change conditions. Studies were conducted with 8 healthy volunteers - 3 females and 5 males of 21-49 years. Each volunteer was subjected to basic 3 minute tests. The volunteers were observed for between 1-4 months each, totalling 422 basic tests. Measurements were performed on the palmar surface of the right middle finger and the forearm medial surface. Wavelet analysis was used to study rhythmic oscillations in LDF- and TRO-data. Tissue oxygen consumption (from arterial and venal blood oxygen saturation and nutritive flux volume) was calculated for all volunteers during "adaptive changes" as (617±123 AU) and (102±38 AU) with and without arteriovenous anastomoses (AVAs) respectively. This demonstrates increased consumption compared to normal (495±170 AU) and (69±40 AU) with and without AVAs respectively. Data analysis demonstrated the emergence of resonance and synchronization of rhythms of microvascular blood flow and oxygen saturation as an adaptive change in myogenic oscillation (vasomotion) resulting from exercise and potentially from psychoemotional stress. Synchronization of myogenic rhythms during adaptive changes suggest increased oxygen consumption resulting from increased microvascular blood flow velocity

Di-chromatic InGaN based color tuneable monolithic LED with high color rendering index

We demonstrate a phosphor free, dichromatic GaN-based monolithic white LED with vertically stacked green and blue emitting multiple quantum wells. The optimal thickness of GaN barrier layer between green and blue quantum wells used is 8 nm. This device can be tuned over a wide range of correlated color temperature (CCT) to achieve warm white (CCT = 3600 K) to cool white (CCT = 13,000 K) emission by current modulation from 2.3 A/cm2 to 12.9 A/cm2. It is also demonstrated for the first time that a color rendering index (CRI) as high as 67 can be achieved with such a dichromatic source. The observed CCT and CRI tunability is associated with the spectral power evolution due to the pumping-induced carrier redistribution

Studies of age-related changes in blood perfusion coherence using wearable blood perfusion sensor system

Laser Doppler flowmetry (LDF) was used for detection of age-related changes in the blood microcirculation. The LDF signal was simultaneously recorded from the 3rd fingers' pads of both hands. Amplitudes of the blood flow oscillations and wavelet coherence of the signals were used for the data analysis. A statistical difference in the synchronisation of myogenic oscillations was found between the two studied age groups. Myogenic oscillations of blood perfusion in the younger group had a higher wavelet coherence parameter than in the older group. Observed site-specific and age-related differences in blood perfusion can be used in the future in the design of experimental studies of the blood microcirculation system in patients with different pathologies

Wearable sensor system for multipoint measurements of blood perfusion: pilot studies in patients with diabetes mellitus

The growing interest in the development of new wearable electronic devices for mobile healthcare provides great opportunities for the development of methods for assessing blood perfusion in this direction. Laser Doppler flowmetry (LDF) is one of the promising methods. A fine analysis of capillary blood ow structure and rhythm in the time and frequency domains, coupled with a new possibility of round-the-clock monitoring can provide valuable diagnostic information about the state of microvascular blood ow. In this study, wearable implementation of laser Doppler flowmetry was utilised for microcirculatory function assessment in patients with diabetes and healthy controls of two distinct age groups. Four wearable laser Doppler flowmetry monitors were used for the analysis of blood microcirculation. Thirty-seven healthy volunteers and 18 patients with type 2 diabetes mellitus participated in the study. The results of the studies have shown that the average perfusion differs between healthy volunteers of distinct age groups and between healthy volunteers of the younger age group and patients with diabetes mellitus. It was noted that the average level of perfusion measured on the wrist in the two groups of healthy volunteers has no statistically significant differences found in similar measurements on the fingertips. The wearable implementation of LDF can become a truly new diagnostic interface to monitor cardiovascular parameters, which could be of interest for diagnostics of conditions associated with microvascular disorders

Laser Doppler flowmetry in blood and lymph monitoring, technical aspects and analysis

The aim of this work was to study the possibilities of the laser Doppler flowmetry method for the joint study of microhaemo- and lymph circulation of human skin. Conducting a series of experimental studies allowed to trace the relationship of recorded signals of microcirculation of blood flow and lymph flow, as well as to study their oscillation nature by using wavelet analysis

Temperature-dependent internal quantum efficiency of blue high-brightness light-emitting diodes

Internal quantum efficiency (IQE) of a blue high-brightness InGaN/GaN light-emitting diode (LED) was evaluated from the external quantum efficiency measured as a function of current at various temperatures ranged between 13 and 440 K. Processing the data with a novel evaluation procedure based on the ABC-model, we have determined the temperature-dependent IQE of the LED structure and light extraction efficiency of the LED chip. Separate evaluation of these parameters is helpful for further optimization of the heterostructure and chip designs. The data obtained enable making a guess on the temperature dependence of the radiative and Auger recombination coefficients, which may be important for identification of dominant mechanisms responsible for the efficiency droop in III-nitride LEDs. Thermal degradation of the LED performance in terms of the emission efficiency is also considered

Distributed feedback InGaN/GaN laser diodes

We have realised InGaN/GaN distributed feedback laser diodes emitting at a single wavelength in the 42X nm wavelength range. Laser diodes based on Gallium Nitride (GaN) are useful devices in a wide range of applications including atomic spectroscopy, data storage and optical communications. To fully exploit some of these application areas there is a need for a GaN laser diode with high spectral purity, e.g. in atomic clocks, where a narrow line width blue laser source can be used to target the atomic cooling transition. Previously, GaN DFB lasers have been realised using buried or surface gratings. Buried gratings require complex overgrowth steps which can introduce epi-defects. Surface gratings designs, can compromise the quality of the p-type contact due to dry etch damage and are prone to increased optical losses in the grating regions. In our approach the grating is etched into the sidewall of the ridge. Advantages include a simpler fabrication route and design freedom over the grating coupling strength.Our intended application for these devices is cooling of the Sr+ ion and for this objective the laser characteristics of SMSR, linewidth, and power are critical. We investigate how these characteristics are affected by adjusting laser design parameters such as grating coupling coefficient and cavity length