Non-invasive submilligram level quantification of in vivo blood components with slitless high-sensitivity spectrometer and noncooled NIR detector

Author(s):  
Ryosuke Kuribayashi ◽  
Hiromitsu Furukawa
2016 ◽  
Vol 187 ◽  
pp. 329-339 ◽  
Author(s):  
Benjamin Gardner ◽  
Nicholas Stone ◽  
Pavel Matousek

Here we demonstrate for the first time the viability of characterising non-invasively the subsurface temperature of SERS nanoparticles embedded within biological tissues using spatially offset Raman spectroscopy (SORS). The proposed analytical method (T-SESORS) is applicable in general to diffusely scattering (turbid) media and features high sensitivity and high chemical selectivity. The method relies on monitoring the Stokes and anti-Stokes bands of SERS nanoparticles in depth using SORS. The approach has been conceptually demonstrated using a SORS variant, transmission Raman spectroscopy (TRS), by measuring subsurface temperatures within a slab of porcine tissue (5 mm thick). Root-mean-square errors (RMSEs) of 0.20 °C were achieved when measuring temperatures over ranges between 25 and 44 °C. This unique capability complements the array of existing, predominantly surface-based, temperature monitoring techniques. It expands on a previously demonstrated SORS temperature monitoring capability by adding extra sensitivity stemming from SERS to low concentration analytes. The technique paves the way for a wide range of applications including subsurface, chemical-specific, non-invasive temperature analysis within turbid translucent media including: the human body, subsurface monitoring of chemical (e.g. catalytic) processes in manufacture quality and process control and research. Additionally, the method opens prospects for control of thermal treatment of cancer in vivo with direct non-invasive feedback on the temperature of mediating plasmonic nanoparticles.


2020 ◽  
Author(s):  
Mehmet S. Ozturk ◽  
Marta G. Montero ◽  
Ling Wang ◽  
Lucas M. Chaible ◽  
Martin Jechlinger ◽  
...  

Preclinical breast tumor models are an invaluable tool to systematically study tumor progression and treatment response, yet methods to non-invasively monitor the involved molecular and mechanistic properties under physiologically relevant conditions are limited. Here we present an intravital mesoscopic fluorescence molecular tomography (henceforth IFT) approach that is capable of tracking fluorescently labeled tumor cells in a quantitative manner inside the mammary gland of living mice. Our mesoscopic approach is entirely non-invasive and thus permits prolonged observational periods of several months. The relatively high sensitivity and spatial resolution further enable inferring the overall number of oncogene-expressing tumor cells as well as their tumor volume over the entire cycle from early tumor growth to residual disease following the treatment phase. We find that sheer tumor volume, as commonly assessed by other imaging modalities, is not well correlated to tumor cell quantity, hence our IFT approach is a promising new method for studying tumor growth dynamics in a quantitative and longitudinal fashion in-vivo.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii232-ii232
Author(s):  
Dominique Bozec ◽  
Anirudh Sattiraju ◽  
Alexandros Bouras ◽  
Joe Gerald Jesu Raj ◽  
Daniel Rivera ◽  
...  

Abstract Longitudinal tracking of tumor growth using non-invasive bioluminescence imaging (BLI) is a key approach for in vivo cancer studies, but the current method of firefly luciferase (Fluc) BLI has quantitative limitations, as it is only suited for detection of tumors of considerable sizes at advanced stage, typically in the order of >105 cells. Recently, Akaluciferase (Akaluc) has been developed as an alternative BLI system that offers higher signal strength and better light penetration of tissue due to its red-shifted emission. Here, we established Akaluc BLI as a new sensitive method for in vivo tracking of glioblastoma (GBM) expansion in intracranial transplant models. In multiple GBM cell lines, including the frequently used U87MG and GL261, as well as patient-derived glioma stem cells (GSC), we demonstrate that Akaluc-expressing GBM cells produced more than 50-times brighter BLI signals in vitro and up to 100-fold higher signal intensities in vivo over Fluc-expressing counterparts. The higher sensitivity of Akaluc BLI permits early in vivo detection of intracranial GBM transplants starting as early as 4 hours after implantation and with as little as 5,000 transplanted GSC. We also reveal a prolonged engraftment period in intracranial GSC transplants before wide dissemination into host brain parenchyma. Akaluc BLI is also advantageous for longitudinal monitoring of therapeutic effects of chemoradiation for GBM and detection of early phase of tumor relapse. Thus, Akaluc BLI offers an important addition to the tool box for cancer research. SIGNIFICANCE: The high sensitivity of Akaluc bioluminescence is a significant improvement for the non-invasive tracking of tumors in preclinical cancer studies, including detection of small incipient tumors and micro-metastasis.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mehmet S. Ozturk ◽  
Marta G. Montero ◽  
Ling Wang ◽  
Lucas M. Chaible ◽  
Martin Jechlinger ◽  
...  

AbstractPreclinical breast tumor models are an invaluable tool to systematically study tumor progression and treatment response, yet methods to non-invasively monitor the involved molecular and mechanistic properties under physiologically relevant conditions are limited. Here we present an intravital mesoscopic fluorescence molecular tomography (henceforth IFT) approach that is capable of tracking fluorescently labeled tumor cells in a quantitative manner inside the mammary gland of living mice. Our mesoscopic approach is entirely non-invasive and thus permits prolonged observational periods of several months. The relatively high sensitivity and spatial resolution further enable inferring the overall number of oncogene-expressing tumor cells as well as their tumor volume over the entire cycle from early tumor growth to residual disease following the treatment phase. Our IFT approach is a promising method for studying tumor growth dynamics in a quantitative and longitudinal fashion in-vivo.


Author(s):  
Marat Mukhtarov ◽  
Olga Markova ◽  
Eleonore Real ◽  
Yves Jacob ◽  
Svetlana Buldakova ◽  
...  

Genetically encoded probes have become powerful tools for non-invasive monitoring of ions, distributions of proteins and the migration and formation of cellular components. We describe the functional expression of two molecular probes for non-invasive fluorescent monitoring of intracellular Cl ([Cl] i ) and the functioning of glycine receptor (GlyR) channels. The first probe is a recently developed cyan fluorescent protein–yellow fluorescent protein-based construct, termed Cl-Sensor, with relatively high sensitivity to Cl ( K app ∼30 mM). In this study, we describe its expression in retina cells using in vivo electroporation and analyse changes in [Cl] i at depolarization and during the first three weeks of post-natal development. An application of 40 mM K + causes an elevation in [Cl] i of approximately 40 mM. In photoreceptors from retina slices of a 6-day-old rat (P6 rat), the mean [Cl] i is approximately 50 mM, and for P16 and P21 rats it is approximately 30–35 mM. The second construct, termed BioSensor-GlyR, is a GlyR channel with Cl-Sensor incorporated into the cytoplasmic domain. This is the first molecular probe for spectroscopic monitoring of the functioning of receptor-operated channels. These types of probes offer a means of screening pharmacological agents and monitoring Cl under different physiological and pathological conditions and permit spectroscopic monitoring of the activity of GlyRs expressed in heterologous systems and neurons.


2021 ◽  
Author(s):  
Jianan Qu ◽  
ZHONGYA QIN ◽  
ZHENTAO SHE ◽  
CONGPING CHEN ◽  
WANJIE WU ◽  
...  

High-resolution optical imaging of deep tissue in-situ such as the living brain is fundamentally challenging because of the aberration and scattering of light. In this work, we develop an innovative adaptive optics three-photon microscope based on direct focus sensing and shaping that can accurately measure and effectively compensate for both low- and high-order specimen-induced aberrations and recover near-diffraction-limited performance at depth. A conjugate adaptive optics configuration with remote focusing enables in vivo imaging of fine neuronal structures in the mouse cortex through the intact skull up to a depth of 750 um below pia, making high-resolution microscopy in cortex near non-invasive. Functional calcium imaging with high sensitivity and accuracy, and high-precision laser-mediated microsurgery through the intact skull were demonstrated. Moreover, we also achieved in vivo high-resolution imaging of the deep cortex and subcortical hippocampus up to 1.1 mm below pia within the intact brain.


Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3624
Author(s):  
Jiarui Wang ◽  
Hannah Lindley-Hatcher ◽  
Xuequan Chen ◽  
Emma Pickwell-MacPherson

The non-ionizing and non-invasive nature of THz radiation, combined with its high sensitivity to water, has made THz imaging and spectroscopy highly attractive for in vivo biomedical applications for many years. Among them, the skin is primarily investigated due to the short penetration depth of THz waves caused by the high attenuation by water in biological samples. However, a complete model of skin describing the THz–skin interaction is still needed. This is also fundamental to reveal the optical properties of the skin from the measured THz spectrum. It is crucial that the correct model is used, not just to ensure compatibility between different works, but more importantly to ensure the reliability of the data and conclusions. Therefore, in this review, we summarize the models applied to skin used in the THz regime, and we compare their adaptability, accuracy, and limitations. We show that most of the models attempt to extract the hydration profile inside the skin while there is also the anisotropic model that displays skin structural changes in the stratum corneum.


2012 ◽  
Vol 6 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Himanshu Khashu ◽  
CS Baiju ◽  
Sumidha Rohatgi Bansal ◽  
Amit Chhillar

ABSTRACT The current clinical diagnostic criterias which were introduced almost half a century ago continue to function as the basis of oral diagnosis in today's clinical practice. Evolvement with time is now brought us to the era of biomarkers. It's a new paradigm for periodontal diagnosis which is of immense benefit in managing periodontitis patients. Biomarkers are tell – tale molecules that can be used to monitor health status, disease onset, treatment response and outcome. These biomarkers can be obtained from blood components such as: serum or plasma. However because of it's being an invasive procedure other body fluids such as saliva and GCF are being considered for potential source of biomarkers. The simple and non-invasive nature of saliva collection and its high sensitivity assay development has led to the salivary biomarkers being a promising future for periodontal diagnosis.


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