Despite extensive studies on different types of nanoparticles as potential drug carriers, the application of red blood cells (RBCs) as natural transport agents for systemic drug delivery is ...considered a new paradigm in modern medicine and possesses great potential. There is a lack of studies on the influence of drug carriers of different compositions on RBCs, especially regarding their potential impact on human health. Here, we apply conventional microscopy to observe the formation of RBC aggregates and optical tweezers to quantitatively assess the mutual interaction of RBCs incubated with inorganic and polymeric nanoparticles. Scanning electron microscopy is utilized for direct observation of nanoparticle localization on RBC membranes. The experiments are performed in a platelet-free blood plasma mimicking the RBC natural environment. We show that nanodiamonds influence mutual RBC interactions more antagonistically than other nanoparticles, resulting in higher aggregation forces and the formation of larger cell aggregates. In contrast, polymeric particles do not cause anomalous RBC aggregation. The results emphasize the application of optical tweezers for the direct quantitative assessment of the mutual interaction of RBCs influenced by nanomaterials.
Conceptual engineering design and optimization of laser-based imaging techniques and optical diagnostic systems used in the field of biomedical optics requires a clear understanding of the ...light-tissue interaction and peculiarities of localization of the detected optical radiation within the medium. The description of photon migration within the turbid tissue-like media is based on the concept of radiative transfer that forms a basis of Monte Carlo (MC) modeling. An opportunity of direct simulation of influence of structural variations of biological tissues on the probing light makes MC a primary tool for biomedical optics and optical engineering. Due to the diversity of optical modalities utilizing different properties of light and mechanisms of light-tissue interactions a new MC code is typically required to be developed for the particular diagnostic application. In current paper introducing an object oriented concept of MC modeling and utilizing modern web applications we present the generalized online computational tool suitable for the major applications in biophotonics. The computation is supported by NVIDEA CUDA Graphics Processing Unit providing acceleration of modeling up to 340 times.
Significance: Biological tissues are typically characterized by high anisotropic scattering and may also exhibit linear form birefringence. Both scattering and birefringence bias the phase shift ...between transverse electric field components of polarized light. These phase alterations are associated with particular structural malformations in the tissue. In fact, the majority of polarization-based techniques are unable to distinguish the nature of the phase shift induced by birefringence or scattering of light.
Aim: We explore the distinct contributions of scattering and birefringence in the phase retardation of circularly polarized light propagated in turbid tissue-like scattering medium.
Approach: The circularly polarized light in frame of Stokes polarimetry approach is used for the screening of biotissue phantoms and chicken skin samples. The change of optical properties in chicken skin is accomplished by optical clearing, which reduces scattering, and mechanical stretch, which induces birefringence. The change of optical properties of skin tissue is confirmed by spectrophotometric measurements and second-harmonic generation imaging.
Results: The contributions of scattering and birefringence in the phase retardation of circularly polarized light propagated in biological tissues are distinguished by the locus of the Stokes vector mapped on the Poincaré sphere. The phase retardation of circularly polarized light due to scattering alterations is assessed. The value of birefringence in chicken skin is estimated as 0.3 × 10 − 3, which agrees with alternative studies. The change of birefringence of skin tissue due to mechanical stretch in the order of 10 − 6 is detected.
Conclusions: While the polarimetric parameters on their own do not allow distinguishing the contributions of scattering and birefringence, the resultant Stokes vector trajectory on the Poincaré sphere reveals the role of scattering and birefringence in the total phase retardation. The described approach, applied independently or in combination with Mueller polarimetry, can be beneficial for the advanced characterization of various types of malformations within biological tissues.
Optical tweezers (OTs) are innovative instruments utilized for the manipulation of microscopic biological objects of interest. Rapid improvements in precision and degree of freedom of multichannel ...and multifunctional OTs have ushered in a new era of studies in basic physical and chemical properties of living tissues and unknown biomechanics in biological processes. Nowadays, OTs are used extensively for studying living cells and have initiated far-reaching influence in various fundamental studies in life sciences. There is also a high potential for using OTs in haemorheology, investigations of blood microcirculation and the mutual interplay of blood cells. In fact, in spite of their great promise in the application of OTs-based approaches for the study of blood, cell formation and maturation in erythropoiesis have not been fully explored. In this review, the background of OTs, their state-of-the-art applications in exploring single-cell level characteristics and bio-rheological properties of mature red blood cells (RBCs) as well as the OTs-assisted studies on erythropoiesis are summarized and presented. The advance developments and future perspectives of the OTs' application in haemorheology both for fundamental and practical in-depth studies of RBCs formation, functional diagnostics and therapeutic needs are highlighted.
Aging and diabetes lead to protein glycation and cause dysfunction of collagen-containing tissues. The accompanying structural and functional changes of collagen significantly contribute to the ...development of various pathological malformations affecting the skin, blood vessels, and nerves, causing a number of complications, increasing disability risks and threat to life. In fact, no methods of non-invasive assessment of glycation and associated metabolic processes in biotissues or prediction of possible skin complications, e.g., ulcers, currently exist for endocrinologists and clinical diagnosis. In this publication, utilizing emerging photonics-based technology, innovative solutions in machine learning, and definitive physiological characteristics, we introduce a diagnostic approach capable of evaluating the skin complications of diabetes mellitus at the very earlier stage. The results of the feasibility studies, as well as the actual tests on patients with diabetes and healthy volunteers, clearly show the ability of the approach to differentiate diabetic and control groups. Furthermore, the developed in-house polarization-based hyperspectral imaging technique accomplished with the implementation of the artificial neural network provides new horizons in the study and diagnosis of age-related diseases.
Polarization-based optical techniques have become increasingly popular in the field of biomedical diagnosis. In the current report we exploit the directional awareness of circularly and/or ...elliptically polarized light backscattered from turbid tissue-like scattering media. We apply circularly and elliptically polarized laser light which illuminates the samples of interest, and a standard optical polarimeter is used to observe the polarization state of light backscattered a few millimeters away from the point of incidence. We demonstrate that the Stokes vector of backscattered light depicted on a Poincaré sphere can be used to assess a turbid tissue-like scattering medium. By tracking the Stokes vector of the detected light on the Poincaré sphere, we investigate the utility of this approach for characterization of cancerous and non-cancerous tissue samples in vitro. The obtained results are discussed in the framework of a phenomenological model and the results of a polarization tracking Monte Carlo model, developed in house. Schematic illustration of the experimental approach utilizing circularly and elliptically polarized light for probing turbid tissue-like scattering media.
Layered topographic maps of the depolarisation due to diffuse biological tissues are produced using a polarisation-holographic Mueller matrix method approach. Histological sections of myocardial ...tissue with a spatially structured optically anisotropic fibrillar network, and parenchymal liver tissue with a polycrystalline island structure are successfully mapped. The topography of the myocardium maps relates to the scattering multiplicity within the volume and the specific morphological structures of the biological crystallite networks. The overall depolarisation map is a convolution of the effects of these two factors. Parenchymal liver tissues behave broadly similarly, but the different biological structures present cause the degree of scattering multiplicity to increase more rapidly with increasing phase. Through statistical analysis, the dependences of the magnitudes of the first to fourth order statistical moments are determined. These moments characterise the changing distributions of the depolarisation values through the volume of biological tissues with different morphological structures. Parenchymal liver tissue depolarisation maps are characterised by larger mean and variance, and less skewness and kurtosis, compared to the distributions for the myocardium. This work demonstrates that a polarisation-holographic Mueller matrix method can be applied to the assessment of the 3D morphology of biological tissues, with applications in disease diagnosis.
Last decades the effects of localization and focusing of light in turbid randomly inhomogeneous tissue-like scattering medium have been attracting a particular attention. Weak localization of light ...in disordered and weakly ordered biological tissue, polarization memory effect, correlations in transmission matrices, focusing light by wavefronts shaping have been widely exploited. Here, we represent an experimentally observed and theoretically confirmed new type of spatial localization of light within biological tissues. General description of the observed phenomenon based on Monte Carlo ray tracing model is provided. We find that innate body arrangements of individual adipocytes can act as a cascade of quasi-ordered microscale lenses confining propagation of light within adipose tissues similar to lens lightguides. The observed spatially-resolved longitudinal multi-focusing of light within disordered adipose biological tissues can naturally lead greater spatial control and enhance light-tissue interactions.
Prostate cancer is the second most common cancer globally in men, and in some countries is now the most diagnosed form of cancer. It is necessary to differentiate between benign and malignant ...prostate conditions to give accurate diagnoses. We aim to demonstrate the use of a 3D Mueller matrix method to allow quick and easy clinical differentiation between prostate adenoma and carcinoma tissues with different grades and Gleason scores. Histological sections of benign and malignant prostate tumours, obtained by radical prostatectomy, were investigated. We map the degree of depolarisation in the different prostate tumour tissues using a Mueller matrix polarimeter set-up, based on the superposition of a reference laser beam with the interference pattern of the sample in the image plane. The depolarisation distributions can be directly related to the morphology of the biological tissues. The dependences of the magnitude of the 1st to 4th order statistical moments of the depolarisation distribution are determined, which characterise the distributions of the depolarisation values. To determine the diagnostic potential of the method three groups of histological sections of prostate tumour biopsies were formed. The first group contained 36 adenoma tissue samples, while the second contained 36 carcinoma tissue samples of a high grade (grade 4: poorly differentiated-4 + 4 Gleason score), and the third group contained 36 carcinoma tissue samples of a low grade (grade 1: moderately differentiated-3 + 3 Gleason score). Using the calculated values of the statistical moments, tumour tissues are categorised as either adenoma or carcinoma. A high level (> 90%) accuracy of differentiation between adenoma and carcinoma samples was achieved for each group. Differentiation between the high-grade and low-grade carcinoma samples was achieved with an accuracy of 87.5%. The results demonstrate that Mueller matrix mapping of the depolarisation distribution of prostate tumour tissues can accurately differentiate between adenoma and carcinoma, and between different grades of carcinoma. This represents a first step towards the implementation of 3D Mueller matrix mapping for clinical analysis and diagnosis of prostate tumours.
We introduce a Mueller-matrix imaging polarization-based approach for the quantitative digital screening of the polycrystalline structure of fibrillary-based biological tissues in vitro. The ...morphometric evaluation of histological sections of myocardium was performed utilizing the high-order statistical moments calculated based on the spatial distribution of linear and circular birefringence and dichroism obtained experimentally. We demonstrate that spatial distributions of phase of light and optical anisotropy of scattering inherent to fibrillar networks of myocardium at different necrotic stages can be effectively used as a quantitative marker of stages of myosin fibril degradation. Processing the images of phase of light scattered in biological tissues with high order statistical analysis provides a functional tool for the quantitative characterization of necrotic conditions of the myocardium.
PDF
