scholarly journals NMR microsystem for label-free characterization of 3D nanoliter microtissues

2020 ◽  
Author(s):  
Marco Grisi ◽  
Gaurasundar M. Conley ◽  
Kyle J. Rodriguez ◽  
Erika Riva ◽  
Lukas Egli ◽  
...  
Keyword(s):  
Early Stage ◽  
Cmos Technology ◽  
Time Frame ◽  
Ease Of Use ◽  
Chemical Information ◽  
Spectroscopic Techniques ◽  
Label Free ◽  
Alcoholic Fatty Liver ◽  
Non Invasive

AbstractPerforming chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise1. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical information in-vivo is nuclear magnetic resonance (NMR)2,3. For its renowned informative power and ability to foster discoveries and life-saving applications4,5, efficient NMR at microscopic scales is highly sought after6–10, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease (NAFLD), demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.

scholarly journals NMR microsystem for label-free characterization of 3D nanoliter microtissues

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marco Grisi ◽  
Gaurasundar M. Conley ◽  
Kyle J. Rodriguez ◽  
Erika Riva ◽  
Lukas Egli ◽  
...  
Keyword(s):  
Early Stage ◽  
Cmos Technology ◽  
Time Frame ◽  
Ease Of Use ◽  
Chemical Information ◽  
Spectroscopic Techniques ◽  
Label Free ◽  
Alcoholic Fatty Liver ◽  
Non Invasive

AbstractPerforming chemical analysis at the nanoliter (nL) scale is of paramount importance for medicine, drug development, toxicology, and research. Despite the numerous methodologies available, a tool for obtaining chemical information non-invasively is still missing at this scale. Observer effects, sample destruction and complex preparatory procedures remain a necessary compromise. Among non-invasive spectroscopic techniques, one able to provide holistic and highly resolved chemical information in-vivo is nuclear magnetic resonance (NMR). For its renowned informative power and ability to foster discoveries and life-saving applications, efficient NMR at microscopic scales is highly sought after, but so far technical limitations could not match the stringent necessities of microbiology, such as biocompatible handling, ease of use, and high throughput. Here we introduce a novel microsystem, which combines CMOS technology with 3D microfabrication, enabling nL NMR as a platform tool for non-invasive spectroscopy of organoids, 3D cell cultures, and early stage embryos. In this study we show its application to microlivers models simulating non-alcoholic fatty liver disease, demonstrating detection of lipid metabolism dynamics in a time frame of 14 days based on 117 measurements of single 3D human liver microtissues.

Radiation treatment monitoring with DCE-US in CWR22 prostate tumor xenografts

2018 ◽  
Vol 60 (6) ◽  
pp. 788-797 ◽  
Author(s):  
Natalia Arteaga-Marrero ◽  
Jose F Mainou-Gomez ◽  
Cecilie Brekke Rygh ◽  
Nataliya Lutay ◽  
Dieter Roehrich ◽  
...  
Keyword(s):  
Radiation Treatment ◽  
Early Stage ◽  
Treated Group ◽  
Time Frame ◽  
Pharmacokinetic Analysis ◽  
Special Focus ◽  
Non Invasive ◽  
Contrast Enhanced ◽  
Dose Deposition

Background Longitudinal monitoring of potential radiotherapy treatment effects can be determined by dynamic contrast-enhanced ultrasound (DCE-US). Purpose To assess functional parameters by means of DCE-US in a murine subcutaneous model of human prostate cancer, and their relationship to dose deposition and time-frame after treatment. A special focus has been placed to evaluate the vascular heterogeneity of the tumor and on the most suitable data analysis approach that reflects this heterogeneity. Material and Methods In vivo DCE-US was acquired 24 h and 48 h after radiation treatment with a single dose of 7.5 Gy and 10 Gy, respectively. Tumor vasculature was characterized pixelwise using the Brix pharmacokinetic analysis of the time-intensity curves. Results Longitudinal changes were detected ( P < 0.001) at 24 h and 48 h after treatment. At 48 h, the eliminating rate constant of the contrast agent from the plasma, kel, was correlated ( P ≤ 0.05) positively with microvessel density (MVD; rτ = 0.7) and negatively with necrosis (rτ = –0.6) for the treated group. Furthermore, Akep, a parameter related to transcapillary transport properties, was also correlated to MVD (rτ = 0.6, P ≤ 0.05). Conclusion DCE-US has been shown to detect vascular changes at a very early stage after radiotherapy, which is a great advantage since DCE-US is non-invasive, available at most hospitals, and is low in cost compared to other techniques used in clinical practice.

scholarly journals Label-free concurrent 5-modal microscopy (Co5M) resolves unknown spatio-temporal processes in wound healing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Markus Seeger ◽  
Christoph Dehner ◽  
Dominik Jüstel ◽  
Vasilis Ntziachristos
Keyword(s):  
Wound Healing ◽  
Label Free ◽  
Third Harmonic ◽  
Two Photon ◽  
Non Invasive ◽  
Photon Excitation ◽  
Free Mode ◽  
Spatio Temporal ◽  
And Function

AbstractThe non-invasive investigation of multiple biological processes remains a methodological challenge as it requires capturing different contrast mechanisms, usually not available with any single modality. Intravital microscopy has played a key role in dynamically studying biological morphology and function, but it is generally limited to resolving a small number of contrasts, typically generated by the use of transgenic labels, disturbing the biological system. We introduce concurrent 5-modal microscopy (Co5M), illustrating a new concept for label-free in vivo observations by simultaneously capturing optoacoustic, two-photon excitation fluorescence, second and third harmonic generation, and brightfield contrast. We apply Co5M to non-invasively visualize multiple wound healing biomarkers and quantitatively monitor a number of processes and features, including longitudinal changes in wound shape, microvascular and collagen density, vessel size and fractality, and the plasticity of sebaceous glands. Analysis of these parameters offers unique insights into the interplay of wound closure, vasodilation, angiogenesis, skin contracture, and epithelial reformation in space and time, inaccessible by other methods. Co5M challenges the conventional concept of biological observation by yielding multiple simultaneous parameters of pathophysiological processes in a label-free mode.

scholarly journals A rotationally focused flow (RFF) microfluidic biosensor by density difference for early-stage detectable diagnosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noori Kim ◽  
Kyungsup Han ◽  
Pei-Chen Su ◽  
Insup Kim ◽  
Yong-Jin Yoon
Keyword(s):  
Early Detection ◽  
Optical Sensors ◽  
Early Stage ◽  
Point Of Care ◽  
Low Cost ◽  
Ease Of Use ◽  
Wavelength Shift ◽  
Label Free ◽  
Protein Biomarkers ◽  
Microfluidic Biosensor

AbstractLabel-free optical biosensors have received tremendous attention in point-of-care testing, especially in the emerging pandemic, COVID-19, since they advance toward early-detection, rapid, real-time, ease-of-use, and low-cost paradigms. Protein biomarkers testings require less sample modification process compared to nucleic-acid biomarkers’. However, challenges always are in detecting low-concentration for early-stage diagnosis. Here we present a Rotationally Focused Flow (RFF) method to enhance sensitivity(wavelength shift) of label-free optical sensors by increasing the detection probability of protein-based molecules. The RFF is structured by adding a less-dense fluid to focus the target-fluid in a T-shaped microchannel. It is integrated with label-free silicon microring resonators interacting with biotin-streptavidin. The suggested mechanism has demonstrated 0.19 fM concentration detection along with a significant magnitudes sensitivity enhancement compared to single flow methods. Verified by both CFD simulations and fluorescent flow-experiments, this study provides a promising proof-of-concept platform for next-generation lab-on-a-chip bioanalytics such as ultrafast and early-detection of COVID-19.

scholarly journals Serum Amyloid A3 Promoter-Driven Luciferase Activity Enables Visualization of Diabetic Kidney Disease

2022 ◽  
Vol 23 (2) ◽  
pp. 899
Author(s):  
Tolulope Peter Saliu ◽  
Nao Yazawa ◽  
Kotaro Hashimoto ◽  
Kenshu Miyata ◽  
Ayane Kudo ◽  
...  
Keyword(s):  
Functional Foods ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Serum Amyloid ◽  
Luciferase Reporter ◽  
Non Invasive ◽  
In Vivo Bioluminescence Imaging ◽  
Bioluminescence Signal ◽  
Direct Cytotoxicity

The early detection of diabetic nephropathy (DN) in mice is necessary for the development of drugs and functional foods. The purpose of this study was to identify genes that are significantly upregulated in the early stage of DN progression and develop a novel model to non-invasively monitor disease progression within living animals using in vivo imaging technology. Streptozotocin (STZ) treatment has been widely used as a DN model; however, it also exhibits direct cytotoxicity to the kidneys. As it is important to distinguish between DN-related and STZ-induced nephropathy, in this study, we compared renal responses induced by the diabetic milieu with two types of STZ models: multiple low-dose STZ injections with a high-fat diet and two moderate-dose STZ injections to induce DN. We found 221 genes whose expression was significantly altered during DN development in both models and identified serum amyloid A3 (Saa3) as a candidate gene. Next, we applied the Saa3 promoter-driven luciferase reporter (Saa3-promoter luc mice) to these two STZ models and performed in vivo bioluminescent imaging to monitor the progression of renal pathology. In this study, to further exclude the possibility that the in vivo bioluminescence signal is related to renal cytotoxicity by STZ treatment, we injected insulin into Saa3-promoter luc mice and showed that insulin treatment could downregulate renal inflammatory responses with a decreased signal intensity of in vivo bioluminescence imaging. These results strongly suggest that Saa3 promoter activity is a potent non-invasive indicator that can be used to monitor DN progression and explore therapeutic agents and functional foods.

scholarly journals Fluorescent Nanoparticle Probes for Cancer Imaging

2005 ◽  
Vol 4 (6) ◽  
pp. 593-602 ◽  
Author(s):  
Swadeshmukul Santra ◽  
Debamitra Dutta ◽  
Glenn A. Walter ◽  
Brij M. Moudgil
Keyword(s):  
Early Stage ◽  
Cancer Imaging ◽  
Cellular Level ◽  
Design Synthesis ◽  
Nanoparticle Probes ◽  
Non Invasive ◽  
Fluorescent Nanoparticle ◽  
Nanoparticle Design ◽  
Inexpensive Technique

Optical imaging technique has strong potential for sensitive cancer diagnosis, particularly at the early stage of cancer development. This is a sensitive, non-invasive, non-ionizing (clinically safe) and relatively inexpensive technique. Cancer imaging with optical technique however greatly relies upon the use of sensitive and stable optical probes. Unlike the traditional organic fluorescent probes, fluorescent nanoparticle probes such as dye-doped nanoparticles and quantum dots (Qdots) are bright and photostable. Fluorescent nanoparticle probes are shown to be very effective for sensitive cancer imaging with greater success in the cellular level. However, cancer imaging in an in vivo setup has been recently realized. There are several challenges in developing fluorescent nanoparticle probes for in vivo cancer imaging applications. In this review, we will discuss various aspects of nanoparticle design, synthesis, surface functionalization for bioconjugation and cancer cell targeting. A brief overview of in vivo cancer imaging with Qdots will also be presented.

scholarly journals An integrated approach to protein discovery and detection from complex biofluids

2022 ◽  
Author(s):  
Gordon T Luu ◽  
Chang Ge ◽  
Yisha Tang ◽  
Kailiang Li ◽  
Stephanie M Cologna ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ovarian Cancer ◽  
Early Stage ◽  
Integrated Approach ◽  
Screening Methods ◽  
High Grade ◽  
Label Free ◽  
Non Invasive ◽  
Cystatin A ◽  
Protein Discovery

Ovarian cancer, a leading cause of cancer related deaths among women, has been notoriously difficult to routinely screen for and diagnose early. Researchers and clinicians continue to seek routinely usable, non-invasive, screening methods as early detection significantly improves survival. Biomarker screening is ideal; however, currently available ovarian cancer biomarkers lack desirable sensitivity and specificity. Furthermore, the most fatal forms, high grade serous cancers often originate in the fallopian tube; therefore, sampling from the vaginal environment provides more proximal sources for tumor detection. To address these shortcomings and leverage proximal sampling, we developed an untargeted mass spectrometry microprotein profiling method and identified a signature of cystatin A, validated this protein in an animal model, and sought to overcome the limits of detection inherent to mass spectrometry by demonstrating that cystatin A is present at 100 pM concentrations using a label-free microtoroid resonator. The findings highlight the potential utility for early-stage detection where cystatin A levels would be low.

scholarly journals A non-invasive nanoparticles for multimodal imaging of ischemic myocardium in rats

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiajing Chen ◽  
Yanan Zhang ◽  
Hui Zhang ◽  
Liang Zhang ◽  
Lingjuan Liu ◽  
...  
Keyword(s):  
Multimodal Imaging ◽  
Early Stage ◽  
Heart Diseases ◽  
Dynamic Imaging ◽  
Ischemic Myocardium ◽  
Time Dynamic ◽  
Non Invasive ◽  
Rat Hearts ◽  
Imaging Results

Abstract Background Ischemic heart disease (IHD) is the leading cause of morbidity and mortality worldwide, and imposes a serious economic load. Thus, it is crucial to perform a timely and accurate diagnosis and monitoring in the early stage of myocardial ischemia. Currently, nanoparticles (NPs) have emerged as promising tools for multimodal imaging, because of their advantages of non-invasion, high-safety, and real-time dynamic imaging, providing valuable information for the diagnosis of heart diseases. Results In this study, we prepared a targeted nanoprobe (termed IMTP-Fe3O4-PFH NPs) with enhanced ultrasound (US), photoacoustic (PA), and magnetic resonance (MR) performance for direct and non-invasive visual imaging of ischemic myocardium in a rat model. This successfully designed nanoprobe had excellent properties such as nanoscale size, good stability, phase transformation by acoustic droplet vaporization (ADV), and favorable safety profile. Besides, it realized obvious targeting performance toward hypoxia-injured cells as well as model rat hearts. After injection of NPs through the tail vein of model rats, in vivo imaging results showed a significantly enhanced US/PA/MR signal, well indicating the remarkable feasibility of nanoprobe to distinguish the ischemic myocardium. Conclusions IMTP-Fe3O4-PFH NPs may be a promising nanoplatform for early detection of ischemic myocardium and targeted treatment under visualization for the future.

scholarly journals OCT2Hist: Non-Invasive Virtual Biopsy Using Optical Coherence Tomography

2021 ◽  
Author(s):  
Yonatan Winetraub ◽  
Edwin Yuan ◽  
Itamar Terem ◽  
Caroline Yu ◽  
Warren Chan ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Ground Truth ◽  
Disease Diagnosis ◽  
Optical Coherence ◽  
Label Free ◽  
Generative Adversarial Network ◽  
Non Invasive ◽  
Adversarial Network ◽  
Trained Neural Network

Histological haematoxylin and eosin–stained (H&E) tissue sections are used as the gold standard for pathologic detection of cancer, tumour margin detection, and disease diagnosis1. Producing H&E sections, however, is invasive and time-consuming. Non-invasive optical imaging modalities, such as optical coherence tomography (OCT), permit label-free, micron-scale 3D imaging of biological tissue microstructure with significant depth (up to 1mm) and large fields-of-view2, but are difficult to interpret and correlate with clinical ground truth without specialized training3. Here we introduce the concept of a virtual biopsy, using generative neural networks to synthesize virtual H&E sections from OCT images. To do so we have developed a novel technique, “optical barcoding”, which has allowed us to repeatedly extract the 2D OCT slice from a 3D OCT volume that corresponds to a given H&E tissue section, with very high alignment precision down to 25 microns. Using 1,005 prospectively collected human skin sections from Mohs surgery operations of 71 patients, we constructed the largest dataset of H&E images and their corresponding precisely aligned OCT images, and trained a conditional generative adversarial network4 on these image pairs. Our results demonstrate the ability to use OCT images to generate high-fidelity virtual H&E sections and entire 3D H&E volumes. Applying this trained neural network to in vivo OCT images should enable physicians to readily incorporate OCT imaging into their clinical practice, reducing the number of unnecessary biopsy procedures.

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