Plasmonic Colloidosome-Coupled MALDI-TOF MS for Bacterial Heteroresistance Study at Single-Cell Level
Abstract
Antimicrobial resistance (AMR) is a long-term public health challenge worldwide, and it is increasingly recognized to be a heteroresistance phenomenon in an isogenic bacterial population. When the minority population of resistant bacteria with strong AMR is not handled in time, such a subpopulation can be enriched leading to the further development of bacterial AMR. However, conventional AMR studies based on ensemble-averaged data from a large population fail to characterize the bacterial heterogeneity. In this work, we develop a method using plasmonic colloidosomes and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) to study single bacterial cell AMR. The plasmonic colloidosomes act simultaneously as bacteria containers and sample spots for MALDI-TOF MS detection. Cells of β-lactamase-producing Escherichia coli ( E. coli ) are trapped in colloidosome containers (∼200 μm in diameter) in the presence of antibiotic drug ampicillin (AMP). Benefiting from the fast reaction kinetics in microcompartments, the hydrolysis product of AMP by bacteria can be detected by MALDI-TOF MS within 40 min. The colloidosomes as MALDI sample spots also benefit sensitive detection and accurate quantification of AMP and its hydrolysis product. It was found that even an isogenic population could consist of a mixture of bacteria that have different resistance degrees to antibiotics. Taking the β-lactamase-producing E. coli as an example, 20% of the bacterial individuals have relatively strong activity in hydrolyzing AMP. It is expected that the colloidosome-based platform would reveal a prospective application in full characterization of single bacterial cell AMR.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Single-cell assays, including flow cytometry, scRNA-seq, and microfluidics-based assays, allow analysis of gene expression, cell viability, and drug tolerance in individual fungal cells.
“These include techniques such as flow cytometry, single-cell RNA sequencing (scRNA-seq), and microfluidics-based assays, allowing for the analysis of gene expression, cell viability, and drug tolerance in individual fungal cells [170,171].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [171]
Cites
Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions
Frens, G. (1973) · Nature Physical Science · doi:10.1038/physci241020a0 · Cited by 8,373 · see citing works
Colloidosomes: Selectively Permeable Capsules Composed of Colloidal Particles
Dinsmore, A. D., Hsu, M. F., Nikolaides, M. G., et al. (2002) · Science · doi:10.1126/science.1074868 · Cited by 2,071 · see citing works
Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices
Jorgensen, J. H., & Ferraro, M. J. (2009) · Clinical Infectious Diseases · doi:10.1086/647952 · Cited by 1,894 · see citing works
Selection of Resistant Bacteria at Very Low Antibiotic Concentrations
Gullberg, E., Cao, S., Berg, O. G., Ilbäck, C., Sandegren, L., Hughes, D., & Andersson, D. I. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002158 · Cited by 1,667 · see citing works
Organic Reactions in Microdroplets: Reaction Acceleration Revealed by Mass Spectrometry
Yan, X., Bain, R. M., & Cooks, R. G. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201602270 · Cited by 583 · see citing works
Collins, D. J., Neild, A., deMello, A. J., Liu, A. Q., & Ai, Y. (2015) · Lab on a Chip · doi:10.1039/c5lc00614g · Cited by 529 · see citing works
Antimicrobial heteroresistance: An emerging field in need of clarity
El-Halfawy, O. M., & Valvano, M. A. (2015) · Clinical Microbiology Reviews · doi:10.1128/cmr.00058-14 · Cited by 489 · see citing works
Sparbier, K., Schubert, S., Weller, U., et al. (2011) · Journal of Clinical Microbiology · doi:10.1128/jcm.05737-11 · Cited by 320 · see citing works
Hrabák, J., Chudáčková, E., & Walková, R. (2013) · Clinical Microbiology Reviews · doi:10.1128/cmr.00058-12 · Cited by 303 · see citing works
Fallah-Araghi, A., Meguellati, K., Baret, J., Harrak, A. E., Mangeat, T., Karplus, M., Ladame, S., Marques, C. M., & Griffiths, A. D. (2014) · Physical Review Letters · doi:10.1103/physrevlett.112.028301 · Cited by 295 · see citing works
Compartmentalized Droplets for Continuous Flow Liquid–Liquid Interface Catalysis
Zhang, M., Wei, L., Chen, H., Du, Z., Binks, B. P., & Yang, H. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b04265 · Cited by 238 · see citing works
Kalsi, S., Valiadi, M., Tsaloglou, M., Parry-Jones, L. A., Jacobs, A. M. S., Watson, R. J., Turner, C., Amos, R. T., Hadwen, B., Buse, J., et al. (2015) · Lab on a Chip · doi:10.1039/c5lc00462d · Cited by 164 · see citing works
Ben, F. D., Turetta, M., Celetti, G., Piruska, A., Bulfoni, M., Cesselli, D., Huck, W. T. S., & Scoles, G. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201602328 · Cited by 127 · see citing works
Phan‐Quang, G. C., Lee, H. K., Phang, I. Y., et al. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201504027 · Cited by 121 · see citing works
Lu, Y., Gao, J., Zhang, D. D., Gau, V., Liao, J. C., & Wong, P. K. (2013) · Analytical Chemistry · doi:10.1021/ac4004248 · Cited by 111 · see citing works
High-density micro-arrays for mass spectrometry
Urban, P. L., Jefimovs, K., Amantonico, A., Fagerer, S. R., Schmid, T., Mädler, S., Puigmartí‐Luis, J., Goedecke, N., & Zenobi, R. (2010) · Lab on a Chip · doi:10.1039/c0lc00211a · Cited by 109 · see citing works
Schoepp, N. G., Khorosheva, E. M., Schlappi, T. S., Curtis, M. S., Humphries, R. M., Hindler, J. A., & Ismagilov, R. F. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201602763 · Cited by 94 · see citing works
Jacobs, M. I., Davies, J. F., Lee, L., Davis, R. D., Houle, F. A., & Wilson, K. R. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b03704 · Cited by 92 · see citing works
Neumann, E. K., Do, T. D., Comi, T. J., & Sweedler, J. V. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201811951 · Cited by 82 · see citing works
Kang, W., Sarkar, S., Lin, Z. S., McKenney, S., & Konry, T. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b00939 · Cited by 76 · see citing works
Phenotyping antibiotic resistance with single-cell resolution for the detection of heteroresistance
Lyu, F., Pan, M., Patil, S., Wang, J., Matin, A., Andrews, J. R., & Tang, S. K. Y. (2018) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2018.05.047 · Cited by 63 · see citing works
Quantitative Determination of Acetylcholine and Choline in Microdialysis Samples by MALDI-TOF MS
Persike, M., Zimmermann, M., Klein, J., & Karas, M. (2010) · Analytical Chemistry · doi:10.1021/ac902130h · Cited by 56 · see citing works
A 3D easily-assembled Micro-Cross for droplet generation
Wu, P., Wang, Y., Luo, Z., et al. (2013) · Lab on a Chip · doi:10.1039/c3lc51126j · Cited by 50 · see citing works
Iino, R., Matsumoto, Y., Nishino, K., Yamaguchi, A., & Noji, H. (2013) · Frontiers in Microbiology · doi:10.3389/fmicb.2013.00300 · Cited by 45 · see citing works
Applications and challenges for single-bacteria analysis by flow cytometry
Wu, L., Wang, S., Song, Y., Wang, X., & Yan, X. (2015) · Science China Chemistry · doi:10.1007/s11426-015-5518-3 · Cited by 40 · see citing works
Probing minority population of antibiotic-resistant bacteria
Huang, T., Zheng, Y. Q., Yan, Y., et al. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.01.054 · Cited by 26 · see citing works
Yi, J., Wang, X., Dai, Y., et al. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.9b04038 · Cited by 25 · see citing works
Self-citationPhan‐Quang, G. C., Lee, H. K., & Ling, X. Y. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201602565 · Cited by 23 · see citing works
John, H., Rychlik, M., Thiermann, H., et al. (2018) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.8264 · Cited by 21 · see citing works
Highly sensitive bacterial susceptibility test against penicillin using parylene-matrix chip
Park, J. M., Kim, J.-I., Song, H.-W., Noh, J.-Y., Kang, M., & Pyun, J. (2015) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2015.04.059 · Cited by 16 · see citing works
Plasmonic Colloidosome-Based Single Cell Detector: A Strategy for Individual Cell Secretion Sensing
Wang, X., Ji, J., Liu, T., et al. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b04850 · Cited by 12 · see citing works
Water-in-oil microcompartments for the study of biomimetic drug metabolism
Dai, Y., Yang, Y., Liu, B., & Qiao, L. (2020) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2020.02.096 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance
Su, Y., Li, Y., Yi, Q., Xu, Y., Sun, T., & Li, Y. (2025) · Journal of Fungi · doi:10.3390/jof11020143 · Cited by 18 · see citing works
“These include techniques such as flow cytometry, single-cell RNA sequencing (scRNA-seq), and microfluidics-based assays, allowing for the analysis of gene expression, cell viability, and drug tolerance in individual fungal cells [170,171].”
- Authors
- Dai, Y., Li, C., Yi, J., Qin, Q., Liu, B., & Qiao, L.
- Affiliations
- Fudan University (CN)
- Second Military Medical University (CN)
- Corresponding author
- Qiao, Liang
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-05-04
- Volume
- 92
- Issue
- 12
- Pages
- 8051-8057
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W3023353895
- Cited by
- 31
- References
- 32
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 5
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science and Technology Commission of Shanghai Municipality (17JC1401900, 18441901000)
- National Natural Science Foundation of China (21934001, 81671849)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- antimicrobial resistance, single-cell analysis, MALDI-TOF mass spectrometry, beta-lactamase, Escherichia coli, microcompartments, antibiotic detection
- MeSH terms
- Anti-Bacterial Agents, beta-Lactamases, Escherichia coli, Microbial Sensitivity Tests, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Drug Resistance, Bacterial, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review