{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T20:37:24Z","timestamp":1774989444979,"version":"3.50.1"},"reference-count":115,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","doi-asserted-by":"publisher","award":["390713860"],"award-info":[{"award-number":["390713860"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","doi-asserted-by":"publisher","award":["CRC 1076 AquaDiva"],"award-info":[{"award-number":["CRC 1076 AquaDiva"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Collaborative Research Center AquaDiva","award":["390713860"],"award-info":[{"award-number":["390713860"]}]},{"name":"Collaborative Research Center AquaDiva","award":["CRC 1076 AquaDiva"],"award-info":[{"award-number":["CRC 1076 AquaDiva"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Due to its high spatial resolution, Raman microspectroscopy allows for the analysis of single microbial cells. Since Raman spectroscopy analyzes the whole cell content, this method is phenotypic and can therefore be used to evaluate cellular changes. In particular, labeling with stable isotopes (SIPs) enables the versatile use and observation of different metabolic states in microbes. Nevertheless, static measurements can only analyze the present situation and do not allow for further downstream evaluations. Therefore, a combination of Raman analysis and cell sorting is necessary to provide the possibility for further research on selected bacteria in a sample. Here, a new microfluidic approach for Raman-activated continuous-flow sorting of bacteria using an optical setup for image-based particle sorting with synchronous acquisition and analysis of Raman spectra for making the sorting decision is demonstrated, showing that active cells can be successfully sorted by means of this microfluidic chip.<\/jats:p>","DOI":"10.3390\/s24144503","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T08:16:57Z","timestamp":1720772217000},"page":"4503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Raman-Activated, Interactive Sorting of Isotope-Labeled Bacteria"],"prefix":"10.3390","volume":"24","author":[{"given":"Sepehr","family":"Razi","sequence":"first","affiliation":[{"name":"Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance\u2014Leibniz Health Technologies, 07745 Jena, Germany"},{"name":"Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, 07743 Jena, Germany"}]},{"given":"Nicolae","family":"Tarcea","sequence":"additional","affiliation":[{"name":"Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance\u2014Leibniz Health Technologies, 07745 Jena, Germany"},{"name":"Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, 07743 Jena, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2896-500X","authenticated-orcid":false,"given":"Thomas","family":"Henkel","sequence":"additional","affiliation":[{"name":"Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance\u2014Leibniz Health Technologies, 07745 Jena, Germany"}]},{"given":"Ramya","family":"Ravikumar","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, 07743 Jena, Germany"}]},{"given":"Aikaterini","family":"Pistiki","sequence":"additional","affiliation":[{"name":"Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance\u2014Leibniz Health Technologies, 07745 Jena, Germany"}]},{"given":"Annette","family":"Wagenhaus","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, 07743 Jena, Germany"}]},{"given":"Sophie","family":"Girnus","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, 07743 Jena, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9498-0841","authenticated-orcid":false,"given":"Martin","family":"Taubert","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, 07743 Jena, Germany"},{"name":"Aquatic Geomicrobiology, Institute of Biodiversity, Friedrich Schiller University Jena, 07743 Jena, Germany"}]},{"given":"Kirsten","family":"K\u00fcsel","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, 07743 Jena, Germany"},{"name":"Aquatic Geomicrobiology, Institute of Biodiversity, Friedrich Schiller University Jena, 07743 Jena, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6179-3719","authenticated-orcid":false,"given":"Petra","family":"R\u00f6sch","sequence":"additional","affiliation":[{"name":"Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, 07743 Jena, Germany"}]},{"given":"J\u00fcrgen","family":"Popp","sequence":"additional","affiliation":[{"name":"Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance\u2014Leibniz Health Technologies, 07745 Jena, Germany"},{"name":"Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, 07743 Jena, Germany"},{"name":"Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, 07743 Jena, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","first-page":"100187","article-title":"In situ identification of environmental microorganisms with Raman spectroscopy","volume":"11","author":"Cui","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s42995-020-00064-w","article-title":"From ecophysiology to cultivation methodology: Filling the knowledge gap between uncultured and cultured microbes","volume":"3","author":"Salam","year":"2021","journal-title":"Mar. Life Sci. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6666","DOI":"10.1038\/s41598-019-43182-x","article-title":"Development of a novel cultivation technique for uncultured soil bacteria","volume":"9","author":"Chaudhary","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.mimet.2004.02.004","article-title":"The filtration-acclimatization method for isolation of an important fraction of the not readily cultivable bacteria","volume":"57","author":"Hahn","year":"2004","journal-title":"J. Microbiol. Methods"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4757-0611-6_1","article-title":"The Analysis of Natural Microbial Populations by Ribosomal RNA Sequences","volume":"Volume 9","author":"Marshall","year":"1986","journal-title":"Advances in Microbial Ecology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev.micro.57.030502.090759","article-title":"The uncultured microbial majority","volume":"57","author":"Rappe","year":"2003","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/s41396-021-01163-x","article-title":"Bolstering fitness via CO2 fixation and organic carbon uptake: Mixotrophs in modern groundwater","volume":"16","author":"Taubert","year":"2021","journal-title":"ISME J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/1462-2920.14010","article-title":"Tracking active groundwater microbes with D2O labeling to understand their ecosystem function","volume":"20","author":"Taubert","year":"2018","journal-title":"Environ. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1039\/D0AN02319A","article-title":"Metabolism in action: Stable isotope probing using vibrational spectroscopy and SIMS reveals kinetic and metabolic flux of key substrates","volume":"146","author":"Chisanga","year":"2021","journal-title":"Analyst"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pucetaite, M., Ohlsson, P., Persson, P., and Hammer, E. (2021). Shining new light into soil systems: Spectroscopy in microfluidic soil chips reveals microbial biogeochemistry. Soil Biol. Biochem., 153.","DOI":"10.1016\/j.soilbio.2020.108078"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/jxb\/erac437","article-title":"In situ control of root-bacteria interactions using optical trapping in transparent soil","volume":"74","author":"Ge","year":"2023","journal-title":"J. Exp. Bot."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Azemtsop Matanfack, G., R\u00fcger, J., Stiebing, C., Schmitt, M., and Popp, J. (2020). Imaging the Invisible-Bioorthogonal Raman Probes for Imaging of Cells and Tissues. J. Biophotonics, 13.","DOI":"10.1002\/jbio.202000129"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s43586-021-00075-6","article-title":"Raman microspectroscopy for microbiology","volume":"1","author":"Lee","year":"2021","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pistiki, A., Salbreiter, M., Sultan, S., R\u00f6sch, P., and Popp, J. (2022). Application of Raman spectroscopy in the hospital environment. Transl. Biophotonics, 4.","DOI":"10.1002\/tbio.202200011"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jrs.4844","article-title":"The application of Raman spectroscopy for the detection and identification of microorganisms","volume":"47","author":"Kirchhoff","year":"2016","journal-title":"J. Raman Spectrosc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0167-7012(00)00169-X","article-title":"Single-cell analysis of bacteria by Raman microscopy: Spectral information on the chemical composition of cells and on the heterogeneity in a culture","volume":"42","author":"Schuster","year":"2000","journal-title":"J. Microbiol. Methods"},{"key":"ref_17","first-page":"161","article-title":"Raman Spectroscopy as a Modern Diagnostic Technology for Study and Indication of Infectious Agents (Review)","volume":"11","author":"Andryukov","year":"2019","journal-title":"CTM"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8009","DOI":"10.1128\/AEM.05573-11","article-title":"Use of stable isotopes to measure the metabolic activity of the human intestinal microbiota","volume":"77","author":"Reichardt","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s43705-022-00142-3","article-title":"Single-cell stable isotope probing in microbial ecology","volume":"2","author":"Alcolombri","year":"2022","journal-title":"ISME Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.copbio.2016.04.018","article-title":"Single cell stable isotope probing in microbiology using Raman microspectroscopy","volume":"41","author":"Wang","year":"2016","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1039\/C7FD00150A","article-title":"Quantitative detection of isotopically enriched E. coli cells by SERS","volume":"205","author":"Chisanga","year":"2017","journal-title":"Faraday Discuss."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Azemtsop Matanfack, G., Pistiki, A., R\u00f6sch, P., and Popp, J. (2021). Raman Stable Isotope Labeling of Single Bacteria in Visible and Deep UV-Ranges. Life, 11.","DOI":"10.3390\/life11101003"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1039\/C6AN00306K","article-title":"The origin of the band at around 730 cm\u22121 in the SERS spectra of bacteria: A stable isotope approach","volume":"141","author":"Kubryk","year":"2016","journal-title":"Analyst"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17087","DOI":"10.1021\/acs.est.3c04247","article-title":"In Situ Discrimination and Cultivation of Active Degraders in Soils by Genome-Directed Cultivation Assisted by SIP-Raman-Activated Cell Sorting","volume":"57","author":"Li","year":"2023","journal-title":"Environ. Sci. Technol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E194","DOI":"10.1073\/pnas.1420406112","article-title":"Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells","volume":"112","author":"Berry","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7714","DOI":"10.1021\/acs.analchem.1c01076","article-title":"Monitoring Deuterium Uptake in Single Bacterial Cells via Two-Dimensional Raman Correlation Spectroscopy","volume":"93","author":"Taubert","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11429","DOI":"10.1021\/acs.analchem.0c02443","article-title":"Influence of Carbon Sources on Quantification of Deuterium Incorporation in Heterotrophic Bacteria: A Raman-Stable Isotope Labeling Approach","volume":"92","author":"Taubert","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7759","DOI":"10.1021\/acs.analchem.1c04097","article-title":"Phenotypic Differentiation of Autotrophic and Heterotrophic Bacterial Cells using Raman Deuterium Labeling","volume":"94","author":"Taubert","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7574","DOI":"10.1021\/acs.analchem.6b01046","article-title":"Demonstration of Carbon Catabolite Repression in Naphthalene Degrading Soil Bacteria via Raman Spectroscopy Based Stable Isotope Probing","volume":"88","author":"Guo","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1021\/acs.est.1c04952","article-title":"Identifying the Active Phenanthrene Degraders and Characterizing Their Metabolic Activities at the Single-Cell Level by the Combination of Magnetic-Nanoparticle-Mediated Isolation, Stable-Isotope Probing, and Raman-Activated Cell Sorting (MMI-SIP-RACS)","volume":"56","author":"Li","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s00253-018-9459-6","article-title":"Heavy water-labeled Raman spectroscopy reveals carboxymethylcellulose-degrading bacteria and degradation activity at the single-cell level","volume":"103","author":"Olaniyi","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jing, X., Gong, Y., Xu, T., Davison, P.A., MacGregor-Chatwin, C., Hunter, C.N., Xu, L., Meng, Y., Ji, Y., and Ma, B. (2022). Revealing CO2-Fixing SAR11 Bacteria in the Ocean by Raman-Based Single-Cell Metabolic Profiling and Genomics. Biodes. Res., 2022.","DOI":"10.34133\/2022\/9782712"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/1462-2920.13954","article-title":"Application of stable-isotope labelling techniques for the detection of active diazotrophs","volume":"20","author":"Angel","year":"2018","journal-title":"Environ. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5082","DOI":"10.1021\/acs.analchem.7b05080","article-title":"Functional Single-Cell Approach to Probing Nitrogen-Fixing Bacteria in Soil Communities by Resonance Raman Spectroscopy with 15N2 Labeling","volume":"90","author":"Cui","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lima, C., Muhamadali, H., and Goodacre, R. (2022). Simultaneous Raman and Infrared Spectroscopy of Stable Isotope Labelled Escherichia coli. Sensors, 22.","DOI":"10.3390\/s22103928"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s43705-022-00188-3","article-title":"Single-cell Raman-activated sorting and cultivation (scRACS-Culture) for assessing and mining in situ phosphate-solubilizing microbes from nature","volume":"2","author":"Jing","year":"2022","journal-title":"ISME Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1021\/acs.analchem.8b04820","article-title":"D2O-Isotope-Labeling Approach to Probing Phosphate-Solubilizing Bacteria in Complex Soil Communities by Single-Cell Raman Spectroscopy","volume":"91","author":"Li","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/1751-7915.13519","article-title":"Raman-deuterium isotope probing to study metabolic activities of single bacterial cells in human intestinal microbiota","volume":"13","author":"Wang","year":"2020","journal-title":"Microb. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8872","DOI":"10.1021\/acs.analchem.1c01015","article-title":"Culture-Free Identification and Metabolic Profiling of Microalgal Single Cells via Ensemble Learning of Ramanomes","volume":"93","author":"Baladehi","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00181-21","DOI":"10.1128\/mSystems.00181-21","article-title":"One-Cell Metabolic Phenotyping and Sequencing of Soil Microbiome by Raman-Activated Gravity-Driven Encapsulation (RAGE)","volume":"6","author":"Jing","year":"2021","journal-title":"mSystems"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13305","DOI":"10.1021\/acs.analchem.7b03461","article-title":"Raman Deuterium Isotope Probing Reveals Microbial Metabolism at the Single-Cell Level","volume":"89","author":"Xu","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Weber, F., Zaliznyak, T., Edgcomb, V.P., and Taylor, G.T. (2021). Using Stable Isotope Probing and Raman Microspectroscopy To Measure Growth Rates of Heterotrophic Bacteria. Appl. Environ. Microbiol., 87.","DOI":"10.1128\/AEM.01460-21"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e202217412","DOI":"10.1002\/anie.202217412","article-title":"An Isotope-Labeled Single-Cell Raman Spectroscopy Approach for Tracking the Physiological Evolution Trajectory of Bacteria toward Antibiotic Resistance","volume":"62","author":"Yang","year":"2023","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9443","DOI":"10.1021\/acs.analchem.6b01602","article-title":"Reverse and Multiple Stable Isotope Probing to Study Bacterial Metabolism and Interactions at the Single Cell Level","volume":"88","author":"Wang","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/s41564-019-0394-9","article-title":"An automated Raman-based platform for the sorting of live cells by functional properties","volume":"4","author":"Lee","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41596-020-00427-8","article-title":"Optofluidic Raman-activated cell sorting for targeted genome retrieval or cultivation of microbial cells with specific functions","volume":"16","author":"Lee","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1039\/D0LC00679C","article-title":"Automated Raman based cell sorting with 3D microfluidics","volume":"20","author":"Lyu","year":"2020","journal-title":"Lab a Chip"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbpa.2016.04.002","article-title":"Raman activated cell sorting","volume":"33","author":"Song","year":"2016","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1021\/acs.analchem.8b04757","article-title":"Recent Advances in Microfluidic Techniques for Systems Biology","volume":"91","author":"Sun","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cobme.2019.09.014","article-title":"Active microfluidic systems for cell sorting and separation","volume":"13","author":"Sivaramakrishnan","year":"2020","journal-title":"Curr. Opin. Biomed. Eng."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/elps.202000048","article-title":"Microfluidic device for concentration and SERS-based detection of bacteria in drinking water","volume":"42","author":"Krafft","year":"2021","journal-title":"Electrophoresis"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Kraus, D., Kleiber, A., Ehrhardt, E., Leifheit, M., Horbert, P., Urban, M., Gleichmann, N., Mayer, G., Popp, J., and Henkel, T. (2021). Three step flow focusing enables image-based discrimination and sorting of late stage 1 Haematococcus pluvialis cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0249192"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1039\/C7LC01217A","article-title":"Injection molded lab-on-a-disc platform for screening of genetically modified E. coli using liquid-liquid extraction and surface enhanced Raman scattering","volume":"18","author":"Morelli","year":"2018","journal-title":"Lab a Chip"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Torul, H., Arslan, Z., Tezcan, T., Kayis, E., \u00c7alimci, M., Gumustas, A., Yildirim, E., K\u00fclah, H., and Tamer, U. (2023). Microfluidic-based blood immunoassays. J. Pharmac. Biomed. Anal., 228.","DOI":"10.1016\/j.jpba.2023.115313"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1039\/C8AN00037A","article-title":"Optical guiding-based cell focusing for Raman flow cell cytometer","volume":"143","author":"Verma","year":"2018","journal-title":"Analyst"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1021\/ac503974e","article-title":"Raman-activated cell sorting based on dielectrophoretic single-cell trap and release","volume":"87","author":"Zhang","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1021\/acs.accounts.1c00001","article-title":"High-Throughput Raman Flow Cytometry and Beyond","volume":"54","author":"Lindley","year":"2021","journal-title":"Acc. Chem. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Fu, X.Z., Zhang, Y.Y., Xu, Q., Sun, X.M., and Meng, F.D. (2021). Recent Advances on Sorting Methods of High-Throughput Droplet-Based Microfluidics in Enzyme Directed Evolution. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.666867"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2101567","DOI":"10.1002\/admt.202101567","article-title":"High-Throughput Raman-Activated Cell Sorting in the Fingerprint Region","volume":"7","author":"Lindley","year":"2022","journal-title":"Adv. Mater. Technol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"117444","DOI":"10.1016\/j.trac.2023.117444","article-title":"Emerging single-cell microfluidic technology for microbiology","volume":"170","author":"Song","year":"2024","journal-title":"TrAC-Trends Anal. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"17012","DOI":"10.1021\/acs.analchem.1c03495","article-title":"Classification and Identification of Archaea Using Single-Cell Raman Ejection and Artificial Intelligence: Implications for Investigating Uncultivated Microorganisms","volume":"93","author":"Wang","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Daniel, F., Kesterson, D., Lei, K., Hord, C., Patel, A., Kaffenes, A., Congivaram, H., and Prakash, S. (2022). Application of Microfluidics for Bacterial Identification. Pharmaceuticals, 15.","DOI":"10.3390\/ph15121531"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41378-019-0063-4","article-title":"Isolation of intact bacteria from blood by selective cell lysis in a microfluidic porous silica monolith","volume":"5","author":"Han","year":"2019","journal-title":"Microsyst. Nanoeng."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Han, J.Y., Yeh, M., and DeVoe, D.L. (2023). Nanogap traps for passive bacteria concentration and single-point confocal Raman spectroscopy. Biomicrofluidics, 17.","DOI":"10.1063\/5.0142118"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00216-017-0609-y","article-title":"A droplet-based microfluidic chip as a platform for leukemia cell lysate identification using surface-enhanced Raman scattering","volume":"410","author":"Hassoun","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1021\/acs.analchem.3c03852","article-title":"Stable SERS Detection of Lactobacillus fermentum Using Optical Tweezers in a Microfluidic Environment","volume":"96","author":"Shang","year":"2023","journal-title":"Anal. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wei, Q.Y., Dong, Q.R., and Pu, H.B. (2023). Multiplex Surface-Enhanced Raman Scattering: An Emerging Tool for Multicomponent Detection of Food Contaminants. Biosensors, 13.","DOI":"10.3390\/bios13020296"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1021\/acs.analchem.3c03515","article-title":"Novel Digital SERS-Microfluidic Chip for Rapid and Accurate Quantification of Microorganisms","volume":"96","author":"Wen","year":"2024","journal-title":"Anal. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"144328","DOI":"10.1016\/j.scitotenv.2020.144328","article-title":"Mini-metagenome analysis of psychrophilic electroactive biofilms based on single cell sorting","volume":"762","author":"Yang","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1002\/imt2.117","article-title":"Single-cell rapid identification, in situ viability and vitality profiling, and genome-based source-tracking for probiotics products","volume":"2","author":"Zhang","year":"2023","journal-title":"iMeta"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1002\/jbio.201600316","article-title":"On-Chip spectroscopic assessment of microbial susceptibility to antibiotics within 3.5 hours","volume":"10","author":"Kirchhoff","year":"2017","journal-title":"J. Biophotonics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8217","DOI":"10.1038\/srep08217","article-title":"Detection of vancomycin resistances in enterococci within 3 (1\/2) hours","volume":"5","author":"Beleites","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10717","DOI":"10.1021\/ac4021616","article-title":"A combined dielectrophoresis-Raman setup for the classification of pathogens recovered from the urinary tract","volume":"85","author":"Ramoji","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Chu, P.Y., Nguyen, T.N.A., Wu, A.Y., Huang, P.S., Huang, K.L., Liao, C.J., Hsieh, C.H., and Wu, M.H. (2023). The Utilization of Optically Induced Dielectrophoresis (ODEP)-Based Cell Manipulation in a Microfluidic System for the Purification and Sorting of Circulating Tumor Cells (CTCs) with Different Sizes. Micromachines, 14.","DOI":"10.3390\/mi14122170"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1039\/C9RA05886A","article-title":"Study on non-bioparticles and Staphylococcus aureus by dielectrophoresis","volume":"10","author":"Chen","year":"2020","journal-title":"RSC Adv."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1002\/elps.201800389","article-title":"Simultaneous isolation and label-free identification of bacteria using contactless dielectrophoresis and Raman spectroscopy","volume":"40","author":"Hanson","year":"2019","journal-title":"Electrophoresis"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"P\u00e1ez-Avil\u00e9s, C., Juanola-Feliu, E., Punter-Villagrasa, J., Del Moral Zamora, B., Homs-Corbera, A., Colomer-Farrarons, J., Miribel-Catala, P.L., and Samitier, J. (2016). Combined Dielectrophoresis and Impedance Systems for Bacteria Analysis in Microfluidic On-Chip Platforms. Sensors, 16.","DOI":"10.3390\/s16091514"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3390\/mi5020204","article-title":"Raman-Spectroscopy Based Cell Identification on a Microhole Array Chip","volume":"5","author":"Neugebauer","year":"2014","journal-title":"Micromachines"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/j.1758-2229.2008.00002.x","article-title":"Raman tweezers sorting of single microbial cells","volume":"1","author":"Huang","year":"2009","journal-title":"Environ. Microbiol. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Pil\u00e1t, Z., Bernatov\u00e1, S., Jezek, J., Kirchhoff, J., Tannert, A., Neugebauer, U., Samek, O., and Zem\u00e1nek, P. (2018). Microfluidic Cultivation and Laser Tweezers Raman Spectroscopy of E. coli under Antibiotic Stress. Sensors, 18.","DOI":"10.20944\/preprints201804.0163.v1"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"122216","DOI":"10.1016\/j.saa.2022.122216","article-title":"Accurate identification of living Bacillus spores using laser tweezers Raman spectroscopy and deep learning","volume":"289","author":"Du","year":"2023","journal-title":"Spectrochim. Acta A"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Keloth, A., Anderson, O., Risbridger, D., and Paterson, L. (2018). Single Cell Isolation Using Optical Tweezers. Micromachines, 9.","DOI":"10.20944\/preprints201806.0371.v1"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"123383","DOI":"10.1016\/j.talanta.2022.123383","article-title":"Laser tweezers Raman spectroscopy combined with deep learning to classify marine bacteria","volume":"244","author":"Liu","year":"2022","journal-title":"Talanta"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S1872-2040(08)60105-X","article-title":"Application and Progress of Raman Tweezers in Single Cells","volume":"37","author":"Ai","year":"2009","journal-title":"Chin. J. Anal. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6410","DOI":"10.1364\/BOE.503628","article-title":"Rapid identification of pathogens in blood serum via Raman tweezers in combination with advanced processing methods","volume":"14","author":"Samek","year":"2023","journal-title":"Biomed. Opt. Express"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Baron, V.O., Chen, M.Z., Hammarstrom, B., Hammond, R.J.H., Glynne-Jones, P., Gillespie, S.H., and Dholakia, K. (2020). Real-time monitoring of live mycobacteria with a microfluidic acoustic-Raman platform. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-0915-3"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1021\/acs.analchem.9b05357","article-title":"Cell Separations and Sorting","volume":"92","author":"Witek","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Reiter, N., Auchter, J., Weber, M., Berensmeier, S., and Schwaminger, S.P. (2022). Magnetophoretic Cell Sorting: Comparison of Different 3D-Printed Millifluidic Devices. Magnetochem., 8.","DOI":"10.3390\/magnetochemistry8100113"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1039\/b803598a","article-title":"An integrated optofluidic platform for Raman-activated cell sorting","volume":"8","author":"Lau","year":"2008","journal-title":"Lab a Chip"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1140\/epjp\/s13360-021-01152-1","article-title":"Rapid detection of antibiotic sensitivity of Staphylococcus aureus by Raman tweezers","volume":"136","author":"Sery","year":"2021","journal-title":"Eur. Phys. J. Plus"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1007\/s11433-013-5355-3","article-title":"Optical tweezers technique and its applications","volume":"56","author":"Guo","year":"2013","journal-title":"Sci. China-Phys. Mech. Astron."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1039\/D3LC00784G","article-title":"Microfluidic approaches in microbial ecology","volume":"24","author":"Ugolini","year":"2024","journal-title":"Lab a Chip"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1039\/c0lc00536c","article-title":"Towards a fast, high specific and reliable discrimination of bacteria on strain level by means of SERS in a microfluidic device","volume":"11","author":"Walter","year":"2011","journal-title":"Lab a Chip"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00253-020-11081-1","article-title":"Development overview of Raman-activated cell sorting devoted to bacterial detection at single-cell level","volume":"105","author":"Yan","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"B\u00f6ke, J.S., Kraus, D., and Henkel, T. (2021). Microfluidic Network Simulations Enable On-Demand Prediction of Control Parameters for Operating Lab-on-a-Chip-Devices. Processes, 9.","DOI":"10.3390\/pr9081320"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chemolab.2016.03.024","article-title":"Automatization of spike correction in Raman spectra of biological samples","volume":"155","author":"Ryabchykov","year":"2016","journal-title":"Chemom. Intell. Lab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4410","DOI":"10.1039\/C7AY01363A","article-title":"Common mistakes in cross-validating classification models","volume":"9","author":"Guo","year":"2017","journal-title":"Anal. Methods"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.aca.2012.11.007","article-title":"Sample size planning for classification models","volume":"760","author":"Beleites","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40486-018-0064-3","article-title":"Sorting and manipulation of biological cells and the prospects for using optical forces","volume":"6","author":"Atajanov","year":"2018","journal-title":"Micro Nano Syst. Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1515\/nanoph-2019-0055","article-title":"Optical trapping in vivo: Theory, practice, and applications","volume":"8","author":"Stilgoe","year":"2019","journal-title":"Nanophotonics"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"13712","DOI":"10.1073\/pnas.0602043103","article-title":"Swimming efficiency of bacterium Escherichia coli","volume":"103","author":"Chattopadhyay","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s10404-014-1502-z","article-title":"Toward microfluidic design automation: A new system simulation toolkit for the in silico evaluation of droplet-based lab-on-a-chip systems","volume":"18","author":"Gleichmann","year":"2014","journal-title":"Microfluid. Nanofluid."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/andp.18451400402","article-title":"Ueber den Durchgang eines elektrischen Stromes durch eine Ebene, insbesondere durch eine kreisf\u00f6rmige","volume":"140","author":"Kirchhoff","year":"2006","journal-title":"Ann. Phys."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00348-017-2362-6","article-title":"Microparticle tracking velocimetry as a tool for microfluidic flow measurements","volume":"58","author":"Salipante","year":"2017","journal-title":"Exp. Fluids"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.comgeo.2014.02.005","article-title":"Reprint of: Delaunay refinement algorithms for triangular mesh generation","volume":"47","author":"Shewchuk","year":"2014","journal-title":"Comput. Geom."},{"key":"ref_106","unstructured":"Cedilnik, A., Geveci, B., Moreland, K., Ahrens, J., and Favre, J. (2006, January 8\u201310). Remote Large Data Visualization in the ParaView Framework. Proceedings of the Eurographics Symposium on Parallel Graphics and Visualization, Lisbon, Portugal."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00348-021-03283-8","article-title":"On the micro-PIV accuracy and reliability utilizing non-Gaussian particle images","volume":"62","author":"Blahout","year":"2021","journal-title":"Exp. Fluids"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1021\/ac302910x","article-title":"Stable isotope probing and Raman spectroscopy for monitoring carbon flow in a food chain and revealing metabolic pathway","volume":"85","author":"Li","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1021\/ac049753k","article-title":"Raman Microscopic Analysis of Single Microbial Cells","volume":"76","author":"Huang","year":"2004","journal-title":"Anal. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e02508-17","DOI":"10.1128\/AEM.02508-17","article-title":"Effect of Laser Irradiation on Cell Function and Its Implications in Raman Spectroscopy","volume":"84","author":"Yuan","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Klein, D., Breuch, R., Reinm\u00fcller, J., Engelhard, C., and Kaul, P. (2022). Discrimination of Stressed and Non-Stressed Food-Related Bacteria Using Raman-Microspectroscopy. Foods, 11.","DOI":"10.3390\/foods11101506"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"103611","DOI":"10.1016\/j.vibspec.2023.103611","article-title":"Probing the Onset of the Bacterial Membrane Photodamage in Time using a Raman Optical Tweezer","volume":"129","author":"Bhat","year":"2023","journal-title":"Vib. Spectrosc."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"120381","DOI":"10.1016\/j.saa.2021.120381","article-title":"Laser induced degradation of bacterial spores during micro-Raman spectroscopy","volume":"265","author":"Malyshev","year":"2022","journal-title":"Spectrochim. Acta A"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Nilsson, D.P., Jonsmoen, U.L., Malyshev, D., \u00d6berg, R., Wiklund, K., and Andersson, M. (2023). Physico-chemical characterization of single bacteria and spores using optical tweezers. Res. Microbiol., 174.","DOI":"10.1016\/j.resmic.2023.104060"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"103332","DOI":"10.1016\/j.vibspec.2021.103332","article-title":"Rapid identification of live and dead Salmonella by surface-enhanced Raman spectroscopy combined with convolutional neural network","volume":"118","author":"Zhang","year":"2022","journal-title":"Vib. Spectrosc."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/14\/4503\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:15:29Z","timestamp":1760109329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/14\/4503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":115,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["s24144503"],"URL":"https:\/\/doi.org\/10.3390\/s24144503","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,11]]}}}