Surface-enhanced Raman spectroscopy

In the decade after being awarded the Nobel Prize in Chemistry in 2002, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been widely used as an analytical chemistry tool for the detection of large and small molecules (e.g., polymers, proteins, peptides, nucleic acids, amino acids, lipids, etc.) and for clinical analysis and research (e.g., pathogen identification, genetic disorders screening, cancer diagnosis, etc.). In view of the fast development of MALDI-TOF MS in clinical usage, this review systematically summarizes the most important applications of MALDI-TOF MS in clinical analysis and research by analyzing MALDI TOF MS-related reviews collected in the Web of Science database. On the basis of the analysis of keyword co-occurrence of over 2000 review articles, four themes consisting of “pathogen identification”, “disease diagnosis”, “nucleic acids analysis”, and “small molecules analysis” were found. For each theme, the review further outlined their application implications, analytical methods, and systems as well as limitations that need to be addressed. Overall, the review summarizes and elaborates on the clinical applications of MALDI-TOF MS, providing a comprehensive picture for researchers embarking on MALDI TOF MS-related clinical analysis and research.

MALDI-TOF Mass Spectrometry in Clinical Analysis and Research

Rapid and accurate detection of foodborne pathogens is a powerful and effective strategy to prevent the outbreak of foodborne diseases. Conventional detection methods like the plate counting and molecular diagnosis strategies are still not suitable for timely and rapid on-site detection due to the cumbersome operations, requirement of trained operators and sophisticated instruments. Microfluidics provide a powerful tool for pathogen detection due to the intrinsic advantages including easy integration, miniaturization, portability, and small sample consumption. Up to now, many research works have reported the combination of microfluidics with various detection techniques and signal amplification technologies to achieve the rapid and sensitive detection of foodborne pathogens. In this review, we mainly summarized the significant developed microfluidic based devices for pathogenic bacteria detection over the past five years, including (1) integration of sample preparation techniques like cell capture and enrichment, and nucleic acid related sample preparation methods on chip; (2) various detection methods, such as colorimetric, fluorescence, chemiluminescence, and mass spectrometry; (3) microfluidic paper-based analytical devices, particularly for the applications in resource-limited settings, remote areas or on-site detection. The limitations and advantages of these methods were summarized and discussed in order to comprehensively understand the latest microfluidic-based detection techniques for foodborne pathogens. Finally, the future challenges and directions for pathogens detection based on microfluidic based biosensors were also discussed and summarized. 

Recent advances in microfluidic devices for foodborne pathogens detection

Abstract Raman spectroscopy, as a label-free optical technology, has widely applied in tumor diagnosis. Relying on the different Raman technologies, conventional diagnostic methods can be used for the diagnosis of benign, malignant and subtypes of tumors. In the past 3 years, in addition to traditional diagnostic methods, the application of artificial intelligence (AI) in various technologies based on Raman technologies has been developing at an incredible speed. Based on this, three technical methods from single spot acquisition (conventional Raman spectroscopy, surface-enhanced Raman spectroscopy) to Raman imaging are respectively introduced and analyzed the diagnosis process of these technical methods. Meanwhile, the emerging AI applications of tumor diagnosis within these methods are highlighted and presented. Finally, the challenges and limitations of existing diagnostic methods, and the prospects of AI-enabled diagnostic methods are presented. 

/pdf/recent-application-of-raman-spectroscopy-in-tumor-diagnosis-3de4kl21.pdf

Recent application of Raman spectroscopy in tumor diagnosis: from conventional methods to artificial intelligence fusion

Electrochemical nano biosensors for the detection of extracellular vesicles exosomes: From the benchtop to everywhere?

Bacterial infections cause considerable morbidity and expensive healthcare costs. The prescription of broad-spectrum antimicrobial drugs results in failure of treatment or overtreatment and exacerbates the spread of multidrug-resistant pathogens. There is an emergent demand for rapid and accurate methods to identify pathogens and conduct personalized therapy. Here, we develop a herringbone microfluidic chip integrated with vancomycin modified magnetic beads (herringbone-VMB microchip) to enrich pathogens. The enriched pathogens are identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The herringbone-VMB microchip applies passive mixing of bacterial samples by generating microvortices, which significantly enhances the interaction between bacteria and vancomycin modified magnetic beads and leads to more efficient enrichment compared to in-tube extraction. Four common pathogens in urinary tract infections are utilized to validate the method, and the capture efficiency of the bacteria from urine is up to 90%. The whole procedure takes 1.5 hours from enrichment to identification. This method shows potential in shortening the turnaround time in the clinical diagnosis of bacterial infections.

Highly efficient enrichment and identification of pathogens using a herringbone microfluidic chip and by MALDI-TOF mass spectrometry.

Osteosarcoma is the most frequent primary bone cancer, particularly among children and adolescents. The early diagnosis of osteosarcoma is significant for timely clinical treatment to reduce the mortality of patients. Exosomes play a significant role in intercellular communication and serve as promising biomarkers in liquid biopsy for the diagnosis and monitoring of tumors. Herein, we report the utility of surface-enhanced Raman scattering (SERS) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for rapid identification of osteosarcoma. We firstly profiled the intrinsic SERS signals and MALDI-TOF mass fingerprints of different subgroups of extracellular vesicles (EVs) and the corresponding cells, demonstrating that the SERS signals and MALDI-TOF mass spectra of exosomes from different types of cells were more discriminative compared to those of large and medium EVs and the cells themselves. Then, we characterized plasma-derived exosomes of 15 osteosarcoma patients and 15 healthy volunteers using SERS and MALDI-TOF MS, revealing distinctive biochemical differences in the spectra. We further utilized a data fusion approach to combine the two types of spectroscopic techniques, differentiating osteosarcoma patients from healthy controls with higher precision than either technique. The results reveal that the non-invasive liquid biopsy method using SERS and MALDI-TOF MS fingerprinting of exosomes has great potential for rapid diagnosis of osteosarcoma.

SERS and MALDI-TOF MS based plasma exosome profiling for rapid detection of osteosarcoma.

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Highly efficient enrichment and identification of pathogens using a herringbone microfluidic chip and by MALDI-TOF mass spectrometry.

SERS and MALDI-TOF MS based plasma exosome profiling for rapid detection of osteosarcoma.