Nanoscale Structural Characterization of Individual Viral Particles Using Atomic Force Microscopy Infrared Spectroscopy (AFM-IR) and Tip-Enhanced Raman Spectroscopy (TERS)

Abstract

Viruses are infections species that infect a large spectrum of living systems. Although displaying a wide variety of shapes and sizes, they are all composed of nucleic acid encapsulated into a protein capsid. After virions enter the host cell, they replicate to produce multiple copies of themselves. They then lyse the host, releasing virions to infect new cells. The high proliferation rate of viruses is the underlying cause of their fast transmission among living species. Although many viruses are harmless, some of them are responsible for severe diseases such as AIDS, viral hepatitis, and flu. Traditionally, electron microscopy is used to identify and characterize viruses. This approach is time- and labor-consuming, which is problematic upon pandemic proliferation of previously unknown viruses, such as H1N1 and COVID-19. Herein, we demonstrate a novel diagnosis approach for label-free identification and structural characterization of individual viruses that is based on a combination of nanoscale Raman and infrared spectroscopy. Using atomic force microscopy–infrared (AFM-IR) spectroscopy, we were able to probe structural organization of the virions of Herpes Simplex Type 1 viruses and bacteriophage MS2. We also showed that tip-enhanced Raman spectroscopy (TERS) could be used to reveal protein secondary structure and amino acid composition of the virus surface. Our results show that AFM-IR and TERS provide different but complementary information about the structure of complex biological specimens. This structural information can be used for fast and reliable identification of viruses. This nanoscale bimodal imaging approach can be also used to investigate the origin of viral polymorphism and study mechanisms of virion assembly.

Diagnosing COVID-19 in human serum using Raman spectroscopy: a preliminary study

“…Masterson et al (2020) proposed a method of "liquid biopsy" based on the evaluation of microRNA of cancers in plasma through surface-enhanced Raman spectroscopy (SERS) and plasmon-enhanced fluorescence (PEF), a method that could be expanded to the diagnosis of COVID-19 [25]. Also, Dou et al (2020) showed that viruses could be identified in a label-free way by tipenhanced Raman spectroscopy (TERS), by revealing protein secondary structure and amino acid composition of the virus surface [26]. Carvalho and Nogueira (2020) suggested in a "letter to the editor" that the vibrational techniques such as Raman and Fourier-transform infrared (FT-IR) spectroscopies could address the challenges for early and fast diagnosis of COVID-19 [27].…”

“…The copyright holder for this preprint this version posted August 10, 2021. ; https://doi.org/10.1101/2021.08.09.21261798 doi: medRxiv preprint Also, Dou et al (2020) showed that viruses could be identified in a label-free way by tipenhanced Raman spectroscopy (TERS), by revealing protein secondary structure and amino acid composition of the virus surface [26]. Carvalho and Nogueira (2020) suggested in a "letter to the editor" that the vibrational techniques such as Raman and Fourier-transform infrared (FT-IR) spectroscopies could address the challenges for early and fast diagnosis of COVID-19 [27].…”

Development of Marine-Derived Compounds for Cancer Therapy

“…A novel detecting method, single-cell Raman spectroscopy (scRS) coupled with one-dimensional convolutional neural networks (1DCNN) was explored to identify individual marine microorganisms quickly and accurately [163]. Moreover, combined microscopy-infrared (AFM-IR) spectroscopy and tip-enhanced Raman spectroscopy (TERS) provided a novel and automated approach to identify the structure of viruses [164].…”

Identification of Chemical Bonds and Microstructure of Hydrated Tricalcium Silicate (C3S) by a Coupled Micro-Raman/BSE-EDS Evaluation

“…Thus, it needs to be further validated with more extended experiments and other potential methods. For example, AFM-IR and TERS [49][50][51] could be a useful method, and molecular dynamics simulation (MS) will provide more detailed structure compositions. In addition, the microstructure of hardened cement paste is highly dependent on the cement type [52], service environment [53,54], such as blended cement [55], and clinker composition [56]-the results would need to be further evaluated.…”