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16 pages, 1266 KiB

Open AccessArticle

Multivariate Statistical Analysis of Surface Enhanced Raman Spectra of Human Serum for Alzheimer’s Disease Diagnosis

by Elena Ryzhikova, Nicole M. Ralbovsky, Lenka Halámková, Dzintra Celmins, Paula Malone, Eric Molho, Joseph Quinn, Earl A. Zimmerman and Igor K. Lednev

Appl. Sci. 2019, 9(16), 3256; https://doi.org/10.3390/app9163256 - 9 Aug 2019

Cited by 45 | Viewed by 5254

Abstract

Alzheimer’s disease (AD) is the most common form of dementia worldwide and is characterized by progressive cognitive decline. Along with being incurable and lethal, AD is difficult to diagnose with high levels of accuracy. Blood serum from Alzheimer’s disease (AD) patients was analyzed [...] Read more.

Alzheimer’s disease (AD) is the most common form of dementia worldwide and is characterized by progressive cognitive decline. Along with being incurable and lethal, AD is difficult to diagnose with high levels of accuracy. Blood serum from Alzheimer’s disease (AD) patients was analyzed by surface-enhanced Raman spectroscopy (SERS) coupled with multivariate statistical analysis. The obtained spectra were compared with spectra from healthy controls (HC) to develop a simple test for AD detection. Serum spectra from AD patients were further compared to spectra from patients with other neurodegenerative dementias (OD). Colloidal silver nanoparticles (AgNPs) were used as the SERS-active substrates. Classification experiments involving serum SERS spectra using artificial neural networks (ANNs) achieved a diagnostic sensitivity around 96% for differentiating AD samples from HC samples in a binary model and 98% for differentiating AD, HC, and OD samples in a tertiary model. The results from this proof-of-concept study demonstrate the great potential of SERS blood serum analysis to be developed further into a novel clinical assay for the effective and accurate diagnosis of AD. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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13 pages, 4968 KiB

Open AccessFeature PaperArticle

Molecular Specific and Sensitive Detection of Pyrazinamide and Its Metabolite Pyrazinoic Acid by Means of Surface Enhanced Raman Spectroscopy Employing In Situ Prepared Colloids

by Anna Muehlig, Izabella J. Jahn, Jan Heidler, Martin Jahn, Karina Weber, Patricia Sheen, Mirko Zimic, Dana Cialla-May and Juergen Popp

Appl. Sci. 2019, 9(12), 2511; https://doi.org/10.3390/app9122511 - 20 Jun 2019

Cited by 5 | Viewed by 4612

Abstract

The prodrug pyrazinamide (PZA) is metabolized by the mycobacteria to pyrazinoic acid (POA), which is expelled into the extracellular environment. PZA resistance is highly associated to a lack of POA efflux. Thus, by detecting a reduction of the concentration of POA in the [...] Read more.

The prodrug pyrazinamide (PZA) is metabolized by the mycobacteria to pyrazinoic acid (POA), which is expelled into the extracellular environment. PZA resistance is highly associated to a lack of POA efflux. Thus, by detecting a reduction of the concentration of POA in the extracellular environment, by means of lab-on-a-chip (LoC)-SERS (surface-enhanced Raman spectroscopy), an alternative approach for the discrimination of PZA resistant mycobacteria is introduced. A droplet-based microfluidic SERS device has been employed to illustrate the potential of the LoC-SERS method for the discrimination of PZA resistant mycobacteria. The two analytes were detected discretely in aqueous solution with a limit of detection of 27 µm for PZA and 21 µm for POA. The simultaneous detection of PZA and POA in aqueous mixtures could be realized within a concentration range from 20 μm to 50 μm for PZA and from 50 μm to 80 μm for POA. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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14 pages, 5060 KiB

Open AccessArticle

Microfluidics-Driven Fabrication of a Low Cost and Ultrasensitive SERS-Based Paper Biosensor

by Alexandra Teixeira, Juan F. Hernández-Rodríguez, Lei Wu, Kevin Oliveira, Krishna Kant, Paulina Piairo, Lorena Diéguez and Sara Abalde-Cela

Appl. Sci. 2019, 9(7), 1387; https://doi.org/10.3390/app9071387 - 2 Apr 2019

Cited by 20 | Viewed by 4425

Abstract

Surface-enhanced Raman scattering (SERS) spectroscopy stands out due to its sensitivity, selectivity, and multiplex ability. The development of ready-to-use, simple, and low-cost SERS substrates is one of the main challenges of the field. In this paper, the intrinsic reproducibility of microfluidics technology was [...] Read more.

Surface-enhanced Raman scattering (SERS) spectroscopy stands out due to its sensitivity, selectivity, and multiplex ability. The development of ready-to-use, simple, and low-cost SERS substrates is one of the main challenges of the field. In this paper, the intrinsic reproducibility of microfluidics technology was used for the fabrication of self-assembled nanoparticle structures over a paper film. The paper SERS substrates were fabricated by assembling anisotropic particles, gold nanostars (GNSs), and nanorods (NRs) onto paper to offer an extra enhancement to reach ultra-sensitive detection limits. A polydimethylsiloxane PDMS-paper hybrid device was used to control the drying kinetics of the nanoparticles over the paper substrate. This method allowed a high reproducibility and homogeneity of the fabrication of SERS substrates that reach limits of detection down to the picomolar range. This simple and low-cost fabrication of a paper-based sensing device was tested for the discrimination of different cell lineages. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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8 pages, 1472 KiB

Open AccessArticle

The Detection of Long-Chain Bio-Markers Using Atomic Force Microscopy

by Mark S. Anderson

Appl. Sci. 2019, 9(7), 1280; https://doi.org/10.3390/app9071280 - 27 Mar 2019

Cited by 10 | Viewed by 2813

Abstract

The detection of long-chain biomolecules on mineral surfaces is presented using an atomic force microscope (AFM). This is achieved by using the AFM’s ability to manipulate molecules and measure forces at the pico-newton scale. We show that a highly characteristic force-distance signal is [...] Read more.

The detection of long-chain biomolecules on mineral surfaces is presented using an atomic force microscope (AFM). This is achieved by using the AFM’s ability to manipulate molecules and measure forces at the pico-newton scale. We show that a highly characteristic force-distance signal is produced when the AFM tip is used to detach long-chain molecules from a surface. This AFM force spectroscopy method is demonstrated on bio-films, spores, fossils and mineral surfaces. The method works with AFM imaging and correlated tip enhanced infrared spectroscopy. The use of AFM force spectroscopy to detect this class of long chain bio-markers has applications in paleontology, life detection and planetary science. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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10 pages, 3557 KiB

Open AccessArticle

Breast Cancer Diagnosis by Surface-Enhanced Raman Scattering (SERS) of Urine

by Vlad Moisoiu, Andreea Socaciu, Andrei Stefancu, Stefania D. Iancu, Imre Boros, Cristian D. Alecsa, Claudiu Rachieriu, Angelica R. Chiorean, Daniela Eniu, Nicolae Leopold, Carmen Socaciu and Dan T. Eniu

Appl. Sci. 2019, 9(4), 806; https://doi.org/10.3390/app9040806 - 25 Feb 2019

Cited by 68 | Viewed by 7568

Abstract

Background: There is an ongoing research for breast cancer diagnostic tools that are cheaper, more accurate and more convenient than mammography. Methods: In this study, we employed surface-enhanced Raman scattering (SERS) for analysing urine from n = 53 breast cancer patients and n [...] Read more.

Background: There is an ongoing research for breast cancer diagnostic tools that are cheaper, more accurate and more convenient than mammography. Methods: In this study, we employed surface-enhanced Raman scattering (SERS) for analysing urine from n = 53 breast cancer patients and n = 22 controls, with the aim of discriminating between the two groups using multivariate data analysis techniques such as principal component analysis—linear discriminant analysis (PCA-LDA). The SERS spectra were acquired using silver nanoparticles synthesized by reduction with hydroxylamine hydrochloride, which were additionally activated with Ca²⁺ 10⁻⁴ M. Results: The addition of Ca(NO₃)₂ 10⁻⁴ M promoted the specific adsorption to the metal surface of the anionic purine metabolites such as uric acid, xanthine and hypoxanthine. Moreover, the SERS spectra of urine were acquired without any filtering or processing step for removing protein traces and other contaminants. Using PCA-LDA, the SERS spectra of urine from breast cancer patients were classified with a sensitivity of 81%, a specificity of 95% and an overall accuracy of 88%. Conclusion: The results of this preliminary study contribute to the translation of SERS in the clinical setting and highlight the potential of SERS as a novel screening strategy for breast cancer. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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11 pages, 2813 KiB

Open AccessArticle

Full-Scale Label-Free Surface-Enhanced Raman Scattering Analysis of Mouse Brain Using a Black Phosphorus-Based Two-Dimensional Nanoprobe

by Tiejun Guo, Fangsheng Ding, Dongling Li, Wen Zhang, Liren Cao and Zhiming Liu

Appl. Sci. 2019, 9(3), 398; https://doi.org/10.3390/app9030398 - 24 Jan 2019

Cited by 11 | Viewed by 4133

Abstract

The brain takes the vital role in human physiological and psychological activities. The precise understanding of the structure of the brain can supply the material basis for the psychological behavior and cognitive ability of human beings. In this study, a fast molecular fingerprint [...] Read more.

The brain takes the vital role in human physiological and psychological activities. The precise understanding of the structure of the brain can supply the material basis for the psychological behavior and cognitive ability of human beings. In this study, a fast molecular fingerprint analysis of mouse brain tissue was performed using surface-enhanced Raman scattering (SERS) spectroscopy. A nanohybrid consisting of flake-like black phosphorus (BP) and Au nanoparticles (BP-AuNSs) served as the novel SERS substrate for the spectral analysis of brain tissue. BP-AuNSs exhibited outstanding SERS activity compared to the traditional citrate-stabilized Au nanoparticles, which could be largely ascribed to the plentiful hot spots formed in the BP nanosheet. Rapid, full-scale and label-free SERS imaging of mouse brain tissue was then realized with a scanning speed of 56 ms per pixel. Fine textures and clear contour were observed in the SERS images of brain tissue, which could be well in accordance with the classical histological analysis; however, it could avoid the disadvantages in the processing procedure of tissue section. Additionally, the SERS spectra illustrated plentiful biochemical fingerprint of brain tissue, which indicated the molecular composition of various encephalic regions. The SERS difference spectrum of the left versus right hemisphere revealed the biochemical difference between the two hemispheres, which helped to uncover the psychological and cognitive models of the left and right hemispheres. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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Review

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26 pages, 4690 KiB

Open AccessReview

Recent Advancement in the Surface-Enhanced Raman Spectroscopy-Based Biosensors for Infectious Disease Diagnosis

by Logan Hamm, Amira Gee and A. Swarnapali De Silva Indrasekara

Appl. Sci. 2019, 9(7), 1448; https://doi.org/10.3390/app9071448 - 6 Apr 2019

Cited by 33 | Viewed by 8684

Abstract

Diagnosis is the key component in disease elimination to improve global health. However, there is a tremendous need for diagnostic innovation for neglected tropical diseases that largely consist of mosquito-borne infections and bacterial infections. Early diagnosis of these infectious diseases is critical but [...] Read more.

Diagnosis is the key component in disease elimination to improve global health. However, there is a tremendous need for diagnostic innovation for neglected tropical diseases that largely consist of mosquito-borne infections and bacterial infections. Early diagnosis of these infectious diseases is critical but challenging because the biomarkers are present at low concentrations, demanding bioanalytical techniques that can deliver high sensitivity with ensured specificity. Owing to the plasmonic nanomaterials-enabled high detection sensitivities, even up to single molecules, surface-enhanced Raman spectroscopy (SERS) has gained attention as an optical analytical tool for early disease biomarker detection. In this mini-review, we highlight the SERS-based assay development tailored to detect key types of biomarkers for mosquito-borne and bacterial infections. We discuss in detail the variations of SERS-based techniques that have developed to afford qualitative and quantitative disease biomarker detection in a more accurate, affordable, and field-transferable manner. Current and emerging challenges in the advancement of SERS-based technologies from the proof-of-concept phase to the point-of-care phase are also briefly discussed. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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24 pages, 3793 KiB

Open AccessReview

Enhancing Disease Diagnosis: Biomedical Applications of Surface-Enhanced Raman Scattering

by Malama Chisanga, Howbeer Muhamadali, David I. Ellis and Royston Goodacre

Appl. Sci. 2019, 9(6), 1163; https://doi.org/10.3390/app9061163 - 19 Mar 2019

Cited by 54 | Viewed by 8587

Abstract

Surface-enhanced Raman scattering (SERS) has recently gained increasing attention for the detection of trace quantities of biomolecules due to its excellent molecular specificity, ultrasensitivity, and quantitative multiplex ability. Specific single or multiple biomarkers in complex biological environments generate strong and distinct SERS spectral [...] Read more.

Surface-enhanced Raman scattering (SERS) has recently gained increasing attention for the detection of trace quantities of biomolecules due to its excellent molecular specificity, ultrasensitivity, and quantitative multiplex ability. Specific single or multiple biomarkers in complex biological environments generate strong and distinct SERS spectral signals when they are in the vicinity of optically active nanoparticles (NPs). When multivariate chemometrics are applied to decipher underlying biomarker patterns, SERS provides qualitative and quantitative information on the inherent biochemical composition and properties that may be indicative of healthy or diseased states. Moreover, SERS allows for differentiation among many closely-related causative agents of diseases exhibiting similar symptoms to guide early prescription of appropriate, targeted and individualised therapeutics. This review provides an overview of recent progress made by the application of SERS in the diagnosis of cancers, microbial and respiratory infections. It is envisaged that recent technology development will help realise full benefits of SERS to gain deeper insights into the pathological pathways for various diseases at the molecular level. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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21 pages, 7073 KiB

Open AccessReview

Identification and Analysis of Exosomes by Surface-Enhanced Raman Spectroscopy

by Anastasiia Merdalimova, Vasiliy Chernyshev, Daniil Nozdriukhin, Polina Rudakovskaya, Dmitry Gorin and Alexey Yashchenok

Appl. Sci. 2019, 9(6), 1135; https://doi.org/10.3390/app9061135 - 18 Mar 2019

Cited by 34 | Viewed by 7719

Abstract

The concept of liquid biopsy has emerged as a novel approach for cancer screening, which is based on the analysis of circulating cancer biomarkers in body fluids. Among the various circulating cancer biomarkers, including Food and Drug Administration (FDA)-approved circulating tumor cells (CTC) [...] Read more.

The concept of liquid biopsy has emerged as a novel approach for cancer screening, which is based on the analysis of circulating cancer biomarkers in body fluids. Among the various circulating cancer biomarkers, including Food and Drug Administration (FDA)-approved circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), exosomes have attracted tremendous attention due to their ability to diagnose cancer in its early stages with high efficiency. Recently, surface-enhanced Raman spectroscopy (SERS) has been applied for the detection of cancer exosomes due to its high sensitivity, specificity, and multiplexing capability. In this article, we review recent progress in the development of SERS-based technologies for in vitro identification of circulating cancer exosomes. The accent is made on the detection strategies and interpretation of the SERS data. The problems of detecting cancer-derived exosomes from patient samples and future perspectives of SERS-based diagnostics are also discussed. Full article

(This article belongs to the Special Issue Surfaced Enhanced Raman Scattering (SERS) in Disease Diagnosis)

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