Skip to main content

Microbial phenomics linking the phenotype to function: The potential of Raman spectroscopy

This article has been updated

Abstract

Raman spectroscopy is a promising tool for identifying microbial phenotypes based on single cell Raman spectra reflecting cellular biochemical biomolecules. Recent studies using Raman spectroscopy have mainly analyzed phenotypic changes caused by microbial interactions or stress responses (e.g., antibiotics) and evaluated the microbial activity or substrate specificity under a given experimental condition using stable isotopes. Lack of labelling and the nondestructive pretreatment and measurement process of Raman spectroscopy have also aided in the sorting of microbial cells with interesting phenotypes for subsequently conducting physiology experiments through cultivation or genome analysis. In this review, we provide an overview of the principles, advantages, and status of utilization of Raman spectroscopy for studies linking microbial phenotypes and functions. We expect Raman spectroscopy to become a next-generation phenotyping tool that will greatly contribute in enhancing our understanding of microbial functions in natural and engineered systems.

This is a preview of subscription content, access via your institution.

Change history

  • 11 March 2021

    The word “Function” in the title has been misspelled.

References

  • Ambriz-Aviña, V., Contreras-Garduño, J.A., and Pedraza-Reyes, M. 2014. Applications of flow cytometry to characterize bacterial physiological responses. Biomed. Res. Int. 2014, 461941.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Angel, R., Panhölzl, C., Gabriel, R., Herbold, C., Wanek, W., Richter, A., Eichorst, S.A., and Woebken, D. 2018. Application of stableisotope labelling techniques for the detection of active diazotrophs. Environ. Microbiol. 20, 44–61.

    CAS  PubMed  Article  Google Scholar 

  • Athamneh, A.I.M., Alajlouni, R.A., Wallace, R.S., Seleem, M.N., and Senger, R.S. 2014. Phenotypic profiling of antibiotic response signatures in Escherichia coli using Raman spectroscopy. Antimicrob. Agents Chemother. 58, 1302–1314.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Berry, D., Mader, E., Lee, T.K., Woebken, D., Wang, Y., Zhu, D., Palatinszky, M., Schintlmeister, A., Schmid, M.C., Hanson, B.T., et al. 2015. Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells. Proc. Natl. Acad. Sci. USA 112, E194–E203.

    CAS  PubMed  Article  Google Scholar 

  • Bódi, Z., Farkas, Z., Nevozhay, D., Kalapis, D., Lázár, V., Csörgõ, B., Nyerges, A., Szamecz, B., Fekete, G., Papp, B., et al. 2017. Phenotypic heterogeneity promotes adaptive evolution. PLoS Biol. 15, e2000644.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Bolnick, D.I., Amarasekare, P., Araújo, M.S., Bürger, R., Levine, J.M., Novak, M., Rudolf, V.H.W., Schreiber, S.J., Urban, M.C., and Vasseur, D.A. 2011. Why intraspecific trait variation matters in community ecology. Trends Ecol. Evol. 26, 183–192.

    PubMed  PubMed Central  Article  Google Scholar 

  • Breuch, R., Klein, D., Siefke, E., Hebel, M., Herbert, U., Wickleder, C., and Kaul, P. 2020. Differentiation of meat-related microorganisms using paper-based surface-enhanced Raman spectroscopy combined with multivariate statistical analysis. Talanta 219, 121315.

    CAS  PubMed  Article  Google Scholar 

  • Butler, H.J., Ashton, L., Bird, B., Cinque, G., Curtis, K., Dorney, J., Esmonde-White, K., Fullwood, N.J., Gardner, B., Martin-Hirsch, P.L., et al. 2016. Using Raman spectroscopy to characterize biological materials. Nat. Protoc. 11, 664–687.

    CAS  PubMed  Article  Google Scholar 

  • Castelle, C.J. and Banfield, J.F. 2018. Major new microbial groups expand diversity and alter our understanding of the tree of life. Cell 172, 1181–1197.

    CAS  Article  PubMed  Google Scholar 

  • Cui, L., Chen, P., Chen, S., Yuan, Z., Yu, C., Ren, B., and Zhang, K. 2013. In situ study of the antibacterial activity and mechanism of action of silver nanoparticles by surface-enhanced Raman spectroscopy. Anal. Chem. 85, 5436–5443.

    CAS  PubMed  Article  Google Scholar 

  • Davidson, C.J. and Surette, M.G. 2008. Individuality in Bacteria. Annu. Rev. Genet. 42, 253–268.

    CAS  PubMed  Article  Google Scholar 

  • Dhar, N. and McKinney, J.D. 2007. Microbial phenotypic heterogeneity and antibiotic tolerance. Curr. Opin. Microbiol. 10, 30–38.

    CAS  PubMed  Article  Google Scholar 

  • Franzosa, E.A., McIver, L.J., Rahnavard, G., Thompson, L.R., Schirmer, M., Weingart, G., Lipson, K.S., Knight, R., Caporaso, J.G., Segata, N., et al. 2018. Species-level functional profiling of metagenomes and metatranscriptomes. Nat. Methods 15, 962–968.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Goodacre, R., Timmins, E.M., Burton, R., Kaderbhai, N., Woodward, A.M., Kell, D.B., and Rooney, P.J. 1998. Rapid identification of urinary tract infection bacteria using hyperspectral whole-organism fingerprinting and artificial neural networks. Microbiology 144, 1157–1170.

    CAS  PubMed  Article  Google Scholar 

  • Gray, D.S., Tan, J.L., Voldman, J., and Chen, C.S. 2004. Dielectrophoretic registration of living cells to a microelectrode array. Biosens. Bioelectron. 19, 1765–1774.

    CAS  PubMed  Article  Google Scholar 

  • Harz, M., Rösch, P., and Popp, J. 2009. Vibrational spectroscopy-a powerful tool for the rapid identification of microbial cells at the single-cell level. Cytometry A 75, 104–113.

    CAS  PubMed  Article  Google Scholar 

  • Hatzenpichler, R., Krukenberg, V., Spietz, R.L., and Jay, Z.J. 2020. Next-generation physiology approaches to study microbiome function at single cell level. Nat. Rev. Microbiol. 18, 241–256.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  • Heyse, J., Buysschaert, B., Props, R., Rubbens, P., Skirtach, A.G., Waegeman, W., and Boon, N. 2019. Coculturing bacteria leads to reduced phenotypic heterogeneities. Appl. Environ. Microbiol. 85, e02814–18.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Ho, C.S., Jean, N., Hogan, C.A., Blackmon, L., Jeffrey, S.S., Holodniy, M., Banaei, N., Saleh, A.A.E., Ermon, S., and Dionne, J. 2019. Rapid identification of pathogenic bacteria using Raman spectroscopy and deep learning. Nat. Commun. 10, 4927.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Huang, W.E., Stoecker, K., Griffiths, R., Newbold, L., Daims, H., Whiteley, A.S., and Wagner, M. 2007. Raman-FISH: combining stable-isotope Raman spectroscopy and fluorescence in situ hybridization for the single cell analysis of identity and function. Environ. Microbiol. 9, 1878–1889.

    CAS  PubMed  Article  Google Scholar 

  • Hungate, B.A., Mau, R.L., Schwartz, E., Caporaso, J.G., Dijkstra, P., van Gestel, N., Koch, B.J., Liu, C.M., McHugh, T.A., Marks, J.C., et al. 2015. Quantitative microbial ecology through stable isotope probing. Appl. Environ. Microbiol. 81, 7570–7581.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Jehlička, J., Edwards, H.G.M., and Oren, A. 2014. Raman spectroscopy of microbial pigments. Appl. Environ. Microbiol. 80, 3286–3295.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Jing, X., Gou, H., Gong, Y., Su, X., Xu, L., Ji, Y., Song, Y., Thompson, I.P., Xu, J., and Huang, W.E. 2018. Raman-activated cell sorting and metagenomic sequencing revealing carbon-fixing bacteria in the ocean. Environ. Microbiol. 20, 2241–2255.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Kubryk, P., Kölschbach, J.S., Marozava, S., Lueders, T., Meckenstock, R.U., Niessner, R., and Ivleva, N.P. 2015. Exploring the potential of stable isotope (Resonance) Raman microspectroscopy and surface-enhanced raman scattering for the analysis of microorganisms at single cell level. Anal. Chem. 87, 6622–6630.

    CAS  PubMed  Article  Google Scholar 

  • Kubryk, P., Niessner, R., and Ivleva, N.P. 2016. The origin of the band at around 730 cm−1 in the SERS spectra of bacteria: a stable isotope approach. Analyst 141, 2874–2878.

    CAS  PubMed  Article  Google Scholar 

  • Kuhar, N., Sil, S., Verma, T., and Umapathy, S. 2018. Challenges in application of Raman spectroscopy to biology and materials. RSC Adv. 8, 25888–25908.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Kusić, D., Kampe, B., Rösch, P., and Popp, J. 2014. Identification of water pathogens by Raman microspectroscopy. Water Res. 48, 179–189.

    PubMed  Article  CAS  Google Scholar 

  • Kuzmin, A.N., Pliss, A., and Prasad, P.N. 2017. Ramanomics: new omics disciplines using micro Raman spectrometry with biomolecular component analysis for molecular profiling of biological structures. Biosensors 7, 52.

    PubMed Central  Article  CAS  Google Scholar 

  • Lee, K.S., Palatinszky, M., Pereira, F.C., Nguyen, J., Fernandez, V.I., Mueller, A.J., Menolascina, F., Daims, H., Berry, D., Wagner, M., et al. 2019. An automated Raman-based platform for the sorting of live cells by functional properties. Nat. Microbiol. 4, 1035–1048.

    CAS  PubMed  Article  Google Scholar 

  • Li, H.Z., Bi, Q.F., Yang, K., Zheng, B.X., Pu, Q., and Cui, L. 2019. D2O-isotope-labeling approach to probing phosphate-solubilizing Bacteria in complex soil communities by single-cell Raman spectroscopy. Anal. Chem. 91, 2239–2246.

    CAS  PubMed  Article  Google Scholar 

  • Li, M., Canniffe, D.P., Jackson, P.J., Davison, P.A., FitzGerald, S., Dickman, M.J., Burgess, J.G., Hunter, C.N., and Huang, W.E. 2012. Rapid resonance Raman microspectroscopy to probe carbon dioxide fixation by single cells in microbial communities. ISME J. 6, 875–885.

    CAS  PubMed  Article  Google Scholar 

  • Lyu, Y., Yuan, X., Glidle, A., Fu, Y., Furusho, H., Yang, T., and Yin, H. 2020. Automated Raman based cell sorting with 3D microfluidics. Lab Chip 20, 4235–4245.

    CAS  PubMed  Article  Google Scholar 

  • Majed, N., Chernenko, T., Diem, M., and Gu, A.Z. 2012. Identification of functionally relevant populations in enhanced biological phosphorus removal processes based on intracellular polymers profiles and insights into the metabolic diversity and heterogeneity. Environ. Sci. Technol. 46, 5010–5017.

    CAS  PubMed  Article  Google Scholar 

  • Matthäus, C., Krafft, C., Dietzek, B., Brehm, B.R., Lorkowski, S., and Popp, J. 2012. Noninvasive imaging of intracellular lipid metabolism in macrophages by Raman microscopy in combination with stable isotopic labeling. Anal. Chem. 84, 8549–8556.

    PubMed  Article  CAS  Google Scholar 

  • Meisel, S., Stöckel, S., Elschner, M., Melzer, F., Rösch, P., and Popp, J. 2012. Raman spectroscopy as a potential tool for detection of Brucella spp. in milk. Appl. Environ. Microbiol. 78, 5575–5583.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Muhamadali, H., Chisanga, M., Subaihi, A., and Goodacre, R. 2015. Combining Raman and FT-IR spectroscopy with quantitative isotopic labeling for differentiation of E. coli cells at community and single cell levels. Anal. Chem. 87, 4578–4586.

    CAS  PubMed  Article  Google Scholar 

  • Mukherjee, R., Verma, T., Nandi, D., and Umapathy, S. 2020. Understanding the effects of culture conditions in bacterial growth: A biochemical perspective using Raman microscopy. J. Biophotonics 13, e201900233.

    CAS  PubMed  Article  Google Scholar 

  • Müller, A.L., Pelikan, C., de Rezende, J.R., Wasmund, K., Putz, M., Glombitza, C., Kjeldsen, K.U., Jørgensen, B.B., and Loy, A. 2018. Bacterial interactions during sequential degradation of cyanobacterial necromass in a sulfidic arctic marine sediment. Environ. Microbiol. 20, 2927–2940.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Novelli-Rousseau, A., Espagnon, I., Filiputti, D., Gal, O., Douet, A., Mallard, F., and Josso, Q. 2018. Culture-free antibiotic-susceptibility determination from single-bacterium Raman spectra. Sci. Rep. 8, 3957.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Pereira, F.C., Wasmund, K., Cobankovic, I., Jehmlich, N., Herbold, C.W., Lee, K.S., Sziranyi, B., Vesely, C., Decker, T., Stocker, R., et al. 2020. Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization. Nat. Commun. 11, 5104.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Pichardo-Molina, J., Frausto-Reyes, C., Barbosa-García, O., Huerta-Franco, R., González-Trujillo, J., Ramírez-Alvarado, C., Gutiérrez-Juárez, G., and Medina-Gutiérrez, C. 2007. Raman spectroscopy and multivariate analysis of serum samples from breast cancer patients. Lasers Med. Sci. 22, 229–236.

    CAS  PubMed  Article  Google Scholar 

  • Premasiri, W.R., Lee, J.C., Sauer-Budge, A., Théberge, R., Costello, C.E., and Ziegler, L.D. 2016. The biochemical origins of the surface-enhanced Raman spectra of bacteria: a metabolomics profiling by SERS. Anal. Bioanal. Chem. 408, 4631–4647.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Read, D.S., Woodcock, D.J., Strachan, N.J.C., Forbes, K.J., Colles, F.M., Maiden, M.C.J., Clifton-Hadley, F., Ridley, A., Vidal, A., Rodgers, J., et al. 2013. Evidence for phenotypic plasticity among multihost Campylobacter jejuni and C. coli lineages, obtained using ribosomal multilocus sequence typing and Raman spectroscopy. Appl. Environ. Microbiol. 79, 965–973.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Redding, B., Schwab, M.J., and Pan, Y. 2015. Raman spectroscopy of optically trapped single biological micro-particles. Sensors 15, 19021–19046.

    PubMed  Article  PubMed Central  Google Scholar 

  • Rösch, P., Harz, M., Schmitt, M., Peschke, K.D., Ronneberger, O., Burkhardt, H., Motzkus, H.W., Lankers, M., Hofer, S., Thiele, H., et al. 2005. Chemotaxonomic identification of single bacteria by micro-Raman spectroscopy: application to clean-room-relevant biological contaminations. Appl. Environ. Microbiol. 71, 1626–1637.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Rosenthal, K., Oehling, V., Dusny, C., and Schmid, A. 2017. Beyond the bulk: disclosing the life of single microbial cells. FEMS Microbiol. Rev. 41, 751–780.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Samek, O., Obruča, S., Šiler, M., Sedláček, P., Benešová, P., Kučera, D., Márova, I., Ježek, J., Bernatová, S., and Zemánek, P. 2016. Quantitative Raman spectroscopy analysis of polyhydroxyalkanoates produced by Cupriavidus necator H16. Sensors 16, 1808.

    Article  CAS  PubMed Central  Google Scholar 

  • Schiessl, K.T., Hu, F., Jo, J., Nazia, S.Z., Wang, B., Price-Whelan, A., Min, W., and Dietrich, L.E.P. 2019. Phenazine production promotes antibiotic tolerance and metabolic heterogeneity in Pseudomonas aeruginosa biofilms. Nat. Commun. 10, 762.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Song, Y., Cui, L., López, J.A.S., Xu, J., Zhu, Y.G., Thompson, I.P., and Huang, W.E. 2017a. Raman-deuterium isotope probing for in-situ identification of antimicrobial resistant bacteria in Thames River. Sci. Rep. 7, 16648.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Song, Y., Kaster, A.K., Vollmers, J., Song, Y., Davison, P.A., Frentrup, M., Preston, G.M., Thompson, I.P., Murrell, J.C., Yin, H., et al. 2017b. Single-cell genomics based on Raman sorting reveals novel carotenoid-containing bacteria in the Red Sea. Microb. Biotechnol. 10, 125–137.

    CAS  PubMed  Article  Google Scholar 

  • Stöckel, S., Kirchhoff, J., Neugebauer, U., Rösch, P., and Popp, J. 2016. The application of Raman spectroscopy for the detection and identification of microorganisms. J. Raman Spectrosc. 47, 89–109.

    Article  CAS  Google Scholar 

  • Taheri-Araghi, S., Brown, S.D., Sauls, J.T., McIntosh, D.B., and Jun, S. 2015. Single-cell physiology. Annu. Rev. Biophys. 44, 123–142.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Taylor, G.T., Suter, E.A., Li, Z.Q., Chow, S., Stinton, D., Zaliznyak, T., and Beaupre, S.R. 2017. Single-cell growth rates in photoautotrophic populations measured by stable isotope probing and resonance Raman microspectrometry. Front. Microbiol. 8, 1449.

    PubMed  PubMed Central  Article  Google Scholar 

  • Teng, L., Wang, X., Wang, X., Gou, H., Ren, L., Wang, T., Wang, Y., Ji, Y., Huang, W.E., and Xu, J. 2016. Label-free, rapid and quantitative phenotyping of stress response in E. coli via ramanome. Sci. Rep. 6, 34359.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Tong, L., Ramser, K., and Käll, M. 2012. Optical tweezers for Raman spectroscopy. In Kumar, C.S.S.R. (ed.), Raman Spectroscopy for Nanomaterials Characterization, pp. 507–530. Springer, Berlin, Heidelberg, Germany.

    Chapter  Google Scholar 

  • Verma, T., Annappa, H., Singh, S., Umapathy, S., and Nandi, D. 2020. Profiling antibiotic resistance in Escherichia coli strains displaying differential antibiotic susceptibilities using Raman spectroscopy. J. Biophotonics e202000231. doi: https://doi.org/10.1002/jbio.202000231.

  • Wagner, M. 2009. Single-cell ecophysiology of microbes as revealed by Raman microspectroscopy or secondary ion mass spectrometry imaging. Annu. Rev. Microbiol. 63, 411–429.

    CAS  PubMed  Article  Google Scholar 

  • Wang, D., He, P., Wang, Z., Li, G., Majed, N., and Gu, A.Z. 2020a. Advances in single cell Raman spectroscopy technologies for biological and environmental applications. Curr. Opin. Biotechnol. 64, 218–229.

    CAS  PubMed  Article  Google Scholar 

  • Wang, Y., Huang, W.E., Cui, L., and Wagner, M. 2016. Single cell stable isotope probing in microbiology using Raman microspectroscopy. Curr. Opin. Biotechnol. 41, 34–42.

    CAS  PubMed  Article  Google Scholar 

  • Wang, Y., Ji, Y., Wharfe, E.S., Meadows, R.S., March, P., Goodacre, R., Xu, J., and Huang, W.E. 2013a. Raman activated cell ejection for isolation of single cells. Anal. Chem. 85, 10697–10701.

    CAS  PubMed  Article  Google Scholar 

  • Wang, Y., Song, Y., Zhu, D., Ji, Y., Wang, T., McIlvenna, D., Yin, H., Xu, J., and Huang, W.E. 2013b. Probing and sorting single cells: the application of a Raman-activated cell sorter. Spectroscopy Europe 25, 16–20.

    Google Scholar 

  • Wang, X., Xin, Y., Ren, L., Sun, Z., Zhu, P., Ji, Y., Li, C., Xu, J., and Ma, B. 2020b. Positive dielectrophoresis-based Raman-activated droplet sorting for culture-free and label-free screening of enzyme function in vivo. Sci. Adv. 6, eabb3521.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Wei, L., Hu, F., Chen, Z., Shen, Y., Zhang, L., and Min, W. 2016. Live-cell bioorthogonal chemical imaging: stimulated Raman scattering microscopy of vibrational probes. Acc. Chem. Res. 49, 1494–1502.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Xu, Y. and Zhao, F. 2018. Single-cell metagenomics: challenges and applications. Protein Cell 9, 501–510.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Xu, J., Zhu, D., Ibrahim, A.D., Allen, C.C.R., Gibson, C.M., Fowler, P.W., Song, Y., and Huang, W.E. 2017. Raman deuterium isotope probing reveals microbial metabolism at the single-cell level. Anal. Chem. 89, 13305–13312.

    CAS  PubMed  Article  Google Scholar 

  • Yang, K., Li, H.Z., Zhu, X., Su, J.Q., Ren, B., Zhu, Y.G., and Cui, L. 2019. Rapid antibiotic susceptibility testing of pathogenic bacteria using heavy-water-labeled single-cell Raman spectroscopy in clinical samples. Anal. Chem. 91, 6296–6303.

    CAS  PubMed  Article  Google Scholar 

  • Yuan, X., Song, Y., Song, Y., Xu, J., Wu, Y., Glidle, A., Cusack, M., Ijaz, U.Z., Cooper, J.M., Huang, W.E., et al. 2018. Effect of laser irradiation on cell function and its implications in Raman spectroscopy. Appl. Environ. Microbiol. 84, e02508–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, H. and Liu, K.K. 2008. Optical tweezers for single cells. J. R. Soc. Interface 5, 671–690.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Zhang, P., Ren, L., Zhang, X., Shan, Y., Wang, Y., Ji, Y., Yin, H., Huang, W.E., Xu, J., and Ma, B. 2015. Raman-activated cell sorting based on dielectrophoretic single-cell trap and release. Anal. Chem. 87, 2282–2289.

    CAS  PubMed  Article  Google Scholar 

Download references

Acknowledgments

This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry (IPET) through The Strategic Initiative for Microbiomes in Agriculture and Food, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (Project No. 918014-4), Research Program for Agricultural Science & Technology Development (Project No. PJ01419401), National Institute of Agricultural Sciences, Rural Development Administration and National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2019R1A4A1024764).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tae Kwon Lee.

Additional information

Conflict of Interest

We have no conflicts of interest to report.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hong, JK., Kim, S.B., Lyou, E.S. et al. Microbial phenomics linking the phenotype to function: The potential of Raman spectroscopy. J Microbiol. 59, 249–258 (2021). https://doi.org/10.1007/s12275-021-0590-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-021-0590-1

Keywords

  • Raman spectroscopy
  • phenotype
  • bacteria
  • stable isotope
  • cell sorting