scholarly journals Liquid Biopsies in Lung Cancer: Four Emerging Technologies and Potential Clinical Applications

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 331 ◽  
Author(s):  
Dimple Chudasama ◽  
Periklis Katopodis ◽  
Nick Stone ◽  
Jennifer Haskell ◽  
Hannah Sheridan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Raman Spectroscopy ◽  
Raman Spectra ◽  
Full Potential ◽  
Rna Seq ◽  
Liquid Biopsies ◽  
Promising Alternative ◽  
Disease Evolution ◽  
Blood Samples ◽  
Non Invasive

Background: Liquid biopsies offer a promising alternative to tissue samples, providing non-invasive diagnostic approaches or serial monitoring of disease evolution. However, certain challenges remain, and the full potential of liquid biopsies has yet to be reached. Here we report several methodological approaches to interrogate liquid biopsies using circulating tumour cell (CTC) enumeration and characterisation, transcriptomics, Raman spectroscopy, and copy number instability (CNI) scores using blood samples of lung cancer (LC) patients. Methods: We choose LC; since it still is the most common cause of cancer-related mortality worldwide, and therefore there is a need for development of new non-invasive diagnostic/prognostic technologies. Changes in gene expression were assessed using RNA-seq, and in CTCs using ImageStream, an imaging flow-cytometer. CNI scores, from paired tissue/ctDNA were also explored. Raman spectroscopy was used to provide chemical fingerprints of plasma samples. Results: CTCs were detected in all LC patients (n = 10). We observed a significant increase in CTC levels in LC patients (n = 10) compared to controls (n = 21). A similar CNI was noted in the tissue and plasma of 2 patients, where higher CNI scores corresponded with poorer outcome. Significant changes in Raman spectra (carotenoid concentrations) were noted in LC patients (n = 20) compared to controls (n = 10). RNA-seq revealed differential expression of 21 genes between LC cases and controls in both LC tissue and blood samples. Conclusions: Liquid biopsies can potentially provide a more comprehensive picture of the disease compared to a single tissue biopsy. CTC enumeration is feasible and sensitive for LC patients. Molecular profiling of CTCs is also possible from total blood. CNI scores and Raman spectra require further investigation. Further work is being undertaken to explore these methods of detection in a larger LC cohort.

scholarly journals A Noninvasive Accurate Measurement of Blood Glucose Levels with Raman Spectroscopy of Blood in Microvessels

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1500 ◽  
Author(s):  
Nan Li ◽  
Hang Zang ◽  
Huimin Sun ◽  
Xianzhi Jiao ◽  
Kangkang Wang ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Blood Glucose ◽  
Raman Spectra ◽  
Interstitial Fluid ◽  
Time Lag ◽  
Back Propagation ◽  
Principal Component ◽  
Oral Glucose ◽  
Multiple Characteristic ◽  
Non Invasive

Raman spectra of human skin obtained by laser excitation have been used to non-invasively detect blood glucose. In previous reports, however, Raman spectra thus obtained were mainly derived from the epidermis and interstitial fluid as a result of the shallow penetration depth of lasers in skin. The physiological process by which glucose in microvessels penetrates into the interstitial fluid introduces a time delay, which inevitably introduces errors in transcutaneous measurements of blood glucose. We focused the laser directly on the microvessels in the superficial layer of the human nailfold, and acquired Raman spectra with multiple characteristic peaks of blood, which indicated that the spectra obtained predominantly originated from blood. Incorporating a multivariate approach combining principal component analysis (PCA) and back propagation artificial neural network (BP-ANN), we performed noninvasive blood glucose measurements on 12 randomly selected volunteers, respectively. The mean prediction performance of the 12 volunteers was obtained as an RMSEP of 0.45 mmol/L and R2 of 0.95. It was no time lag between the predicted blood glucose and the actual blood glucose in the oral glucose tolerance test (OGTT). We also applied the procedure to data from all 12 volunteers regarded as one set, and the total predicted performance was obtained with an RMSEP of 0.27 mmol/L and an R2 of 0.98, which is better than that of the individual model for each volunteer. This suggested that anatomical differences between volunteer fingernails do not reduce the prediction accuracy and 100% of the predicted glucose concentrations fall within Region A and B of the Clarke error grid, allowing acceptable predictions in a clinically relevant range. The Raman spectroscopy detection of blood glucose from microvessels is of great significance of non-invasive blood glucose detection of Raman spectroscopy. This innovative method may also facilitate non-invasive detection of other blood components.

scholarly journals Raman Spectroscopy as a Potential Tool for Detection of Brucella spp. in Milk

2012 ◽  
Vol 78 (16) ◽  
pp. 5575-5583 ◽  
Author(s):  
Susann Meisel ◽  
Stephan Stöckel ◽  
Mandy Elschner ◽  
Falk Melzer ◽  
Petra Rösch ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Single Cell ◽  
Raman Spectra ◽  
Detection System ◽  
Support Vector ◽  
Promising Alternative ◽  
Content Type ◽  
Micro Raman Spectroscopy ◽  
Genotypic Characteristics ◽  
Potential Tool

ABSTRACTDetection ofBrucella, causing brucellosis, is very challenging, since the applied techniques are mostly time-demanding and not standardized. While the common detection system relies on the cultivation of the bacteria, further classical typing up to the biotype level is mostly based on phenotypic or genotypic characteristics. The results of genotyping do not always fit the existing taxonomy, and misidentifications between genetically closely related genera cannot be avoided. This situation gets even worse, when detection from complex matrices, such as milk, is necessary. For these reasons, the availability of a method that allows early and reliable identification of possibleBrucellaisolates for both clinical and epidemiological reasons would be extremely useful. We evaluated micro-Raman spectroscopy in combination with chemometric analysis to identifyBrucellafrom agar plates and directly from milk: prior to these studies, the samples were inactivated via formaldehyde treatment to ensure a higher working safety. The single-cell Raman spectra of differentBrucella,Escherichia,Ochrobactrum,Pseudomonas, andYersiniaspp. were measured to create two independent databases for detection in media and milk. Identification accuracies of 92% forBrucellafrom medium and 94% forBrucellafrom milk were obtained while analyzing the single-cell Raman spectra via support vector machine. Even the identification of the other genera yielded sufficient results, with accuracies of >90%. In summary, micro-Raman spectroscopy is a promising alternative for detectingBrucella. The measurements we performed at the single-cell level thus allow fast identification within a few hours without a demanding process for sample preparation.

scholarly journals Detection of Age-Related Changes in Tendon Molecular Composition by Raman Spectroscopy—Potential for Rapid, Non-Invasive Assessment of Susceptibility to Injury

2020 ◽  
Vol 21 (6) ◽  
pp. 2150
Author(s):  
Nai-Hao Yin ◽  
Anthony W. Parker ◽  
Pavel Matousek ◽  
Helen L. Birch
Keyword(s):  
Raman Spectroscopy ◽  
Raman Spectra ◽  
Flexor Tendon ◽  
Biological Tissues ◽  
Ring Structure ◽  
Total N ◽  
Non Invasive ◽  
Age Related ◽  
Superficial Digital Flexor Tendon

The lack of clinical detection tools at the molecular level hinders our progression in preventing age-related tendon pathologies. Raman spectroscopy can rapidly and non-invasively detect tissue molecular compositions and has great potential for in vivo applications. In biological tissues, a highly fluorescent background masks the Raman spectral features and is usually removed during data processing, but including this background could help age differentiation since fluorescence level in tendons increases with age. Therefore, we conducted a stepwise analysis of fluorescence and Raman combined spectra for better understanding of the chemical differences between young and old tendons. Spectra were collected from random locations of vacuum-dried young and old equine tendon samples (superficial digital flexor tendon (SDFT) and deep digital flexor tendon (DDFT), total n = 15) under identical instrumental settings. The fluorescence-Raman spectra showed an increase in old tendons as expected. Normalising the fluorescence-Raman spectra further indicated a potential change in intra-tendinous fluorophores as tendon ages. After fluorescence removal, the pure Raman spectra demonstrated between-group differences in CH2 bending (1450 cm−1) and various ring-structure and carbohydrate-associated bands (1000–1100 cm−1), possibly relating to a decline in cellular numbers and an accumulation of advanced glycation end products in old tendons. These results demonstrated that Raman spectroscopy can successfully detect age-related tendon molecular differences.

scholarly journals Non-invasive analysis of stored red blood cells using diffuse resonance Raman spectroscopy

The Analyst ◽  
2018 ◽  
Vol 143 (24) ◽  
pp. 5950-5958 ◽  
Author(s):  
Rekha Gautam ◽  
Joo-Yeun Oh ◽  
Rakesh P. Patel ◽  
Richard A. Dluhy
Keyword(s):  
Raman Spectroscopy ◽  
Red Blood Cells ◽  
Raman Spectra ◽  
Blood Cells ◽  
Resonance Raman Spectroscopy ◽  
Resonance Raman ◽  
Non Invasive

A method to acquire the Raman spectra of sub-surface components using diffusely focused radiation in a microscope sampling configuration is described.

scholarly journals Optimization of rVAR2-Based Isolation of Cancer Cells in Blood for Building a Robust Assay for Clinical Detection of Circulating Tumor Cells

2020 ◽  
Vol 21 (7) ◽  
pp. 2401 ◽  
Author(s):  
Nicolai T. Sand ◽  
Tobias B. Petersen ◽  
Sara R. Bang-Christensen ◽  
Theresa D. Ahrens ◽  
Caroline Løppke ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Magnetic Beads ◽  
Liquid Biopsies ◽  
Blood Samples ◽  
Non Invasive ◽  
Clinical Detection

Early detection and monitoring of cancer progression is key to successful treatment. Therefore, much research is invested in developing technologies, enabling effective and valuable use of non-invasive liquid biopsies. This includes the detection and analysis of circulating tumor cells (CTCs) from blood samples. Recombinant malaria protein VAR2CSA (rVAR2) binds a unique chondroitin sulfate modification present on the vast majority of cancers and thereby holds promise as a near-universal tumor cell-targeting reagent to isolate CTCs from complex blood samples. This study describes a technical approach for optimizing the coupling of rVAR2 to magnetic beads and the development of a CTC isolation platform targeting a range of different cancer cell lines. We investigate both direct and indirect approaches for rVAR2-mediated bead retrieval of cancer cells and conclude that an indirect capture approach is most effective for rVAR2-based cancer cell retrieval.

scholarly journals The Analysis of Platelet-Derived circRNA Repertoire as Potential Diagnostic Biomarker for Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4644
Author(s):  
Silvia D’Ambrosi ◽  
Allerdien Visser ◽  
Mafalda Antunes-Ferreira ◽  
Ankie Poutsma ◽  
Stavros Giannoukakos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Blood Platelets ◽  
Small Cell ◽  
Rna Seq ◽  
Small Cell Lung ◽  
Liquid Biopsies ◽  
Asymptomatic Individuals ◽  
Nsclc Patients

Tumor-educated Platelets (TEPs) have emerged as rich biosources of cancer-related RNA profiles in liquid biopsies applicable for cancer detection. Although human blood platelets have been found to be enriched in circular RNA (circRNA), no studies have investigated the potential of circRNA as platelet-derived biomarkers for cancer. In this proof-of-concept study, we examine whether the circRNA signature of blood platelets can be used as a liquid biopsy biomarker for the detection of non-small cell lung cancer (NSCLC). We analyzed the total RNA, extracted from the platelet samples collected from NSCLC patients and asymptomatic individuals, using RNA sequencing (RNA-Seq). Identification and quantification of known and novel circRNAs were performed using the accurate CircRNA finder suite (ACFS), followed by the differential transcript expression analysis using a modified version of our thromboSeq software. Out of 4732 detected circRNAs, we identified 411 circRNAs that are significantly (p-value < 0.05) differentially expressed between asymptomatic individuals and NSCLC patients. Using the false discovery rate (FDR) of 0.05 as cutoff, we selected the nuclear receptor-interacting protein 1 (NRIP1) circRNA (circNRIP1) as a potential biomarker candidate for further validation by reverse transcription–quantitative PCR (RT-qPCR). This analysis was performed on an independent cohort of platelet samples. The RT-qPCR results confirmed the RNA-Seq data analysis, with significant downregulation of circNRIP1 in platelets derived from NSCLC patients. Our findings suggest that circRNAs found in blood platelets may hold diagnostic biomarkers potential for the detection of NSCLC using liquid biopsies.

scholarly journals Self-absorption corrected non-invasive transmission Raman spectroscopy (of biological tissue)

The Analyst ◽  
2021 ◽  
Author(s):  
Benjamin Gardner ◽  
Pavel Matousek ◽  
Nicholas Stone
Keyword(s):  
Raman Spectroscopy ◽  
Raman Spectra ◽  
Biological Tissue ◽  
Non Invasive ◽  
Transmission Raman

Higher contrast of subsurface Raman spectra is achievable with self-absorption corrected transmission Raman spectroscopy. (Desired signal in red, interfering matrix artefacts in blue.)

Chemometric analysis of integrated FTIR and Raman spectra obtained by non-invasive exfoliative cytology for the screening of oral cancer

The Analyst ◽  
2019 ◽  
Vol 144 (4) ◽  
pp. 1309-1325 ◽  
Author(s):  
Aritri Ghosh ◽  
Sreyan Raha ◽  
Susmita Dey ◽  
Kabita Chatterjee ◽  
Amit Roy Chowdhury ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Oral Cancer ◽  
Early Detection ◽  
Ftir Spectroscopy ◽  
Raman Spectra ◽  
Early Detection Of Cancer ◽  
Screening Tools ◽  
Exfoliative Cytology ◽  
Non Invasive ◽  
Biological Analytes

FTIR spectroscopy and Raman spectroscopy of biological analytes are increasingly explored as screening tools for early detection of cancer.

scholarly journals Liquid Biopsies: Applications for Cancer Diagnosis and Monitoring

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 349
Author(s):  
Ivana Martins ◽  
Ilda Patrícia Ribeiro ◽  
Joana Jorge ◽  
Ana Cristina Gonçalves ◽  
Ana Bela Sarmento-Ribeiro ◽  
...  
Keyword(s):  
Residual Disease ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Management Tool ◽  
Liquid Biopsies ◽  
Disease Evolution ◽  
Non Invasive ◽  
Routine Clinical Setting ◽  
Tumor Types ◽  
Near Future

The minimally—or non-invasive detection of circulating tumor-derived components in biofluids, such as blood, liquid biopsy is a revolutionary approach with significant potential for the management of cancer. Genomic and transcriptomic alterations can be accurately detected through liquid biopsies, which provide a more comprehensive characterization of the heterogeneous tumor profile than tissue biopsies alone. Liquid biopsies could assist diagnosis, prognosis, and treatment selection, and hold great potential to complement current surveilling strategies to monitor disease evolution and treatment response in real-time. In particular, these are able to detect minimal residual disease, to predict progression, and to identify mechanisms of resistance, allowing to re-orient treatment strategies in a timelier manner. In this review we gathered current knowledge regarding the role and potential of liquid biopsies for the diagnosis and follow-up of cancer patients. The presented findings emphasize the strengths of liquid biopsies, revealing their chance of improving the diagnosis and monitoring of several tumor types in the near future. However, despite growing evidence supporting their value as a management tool in oncology, some limitations still need to be overcome for their implementation in the routine clinical setting.

scholarly journals Prediction of Trained Panel Sensory Scores for Beef with Non-Invasive Raman Spectroscopy

Chemosensors ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Jamie Cafferky ◽  
Raquel Cama-Moncunill ◽  
Torres Sweeney ◽  
Paul Allen ◽  
Andrew Cromie ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Raman Spectra ◽  
Sensory Quality ◽  
Predictive Accuracy ◽  
Sensory Panel ◽  
Non Invasive ◽  
Trained Panel ◽  
After Effect ◽  
Non Destructive

The objective of this study was to investigate Raman spectroscopy as a tool for the prediction of sensory quality in beef. Raman spectra were collected from M. longissimus thoracis et lumborum (LTL) muscle on a thawed steak frozen 48 h post-mortem. Another steak was removed from the muscle and aged for 14 days before being assessed for 12 sensory traits by a trained panel. The most accurate coefficients of determination of cross validation (R2CV) calibrated within the current study were for the trained sensory panel textural scores; particularly tenderness (0.46), chewiness (0.43), stringiness (0.35) and difficulty to swallow (0.33), with practical predictions also achieved for metallic flavour (0.52), fatty after-effect (0.44) and juiciness (0.36). In general, the application of mathematical spectral pre-treatments to Raman spectra improved the predictive accuracy of chemometric models developed. This study provides calibrations for valuable quality traits derived from a trained sensory panel in a non-destructive manner, using Raman spectra collected at a time-point compatible with meat management systems.

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