Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-13535-1
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Funding
- EPSRC [EP/P011985/1]
- World Premier International Research Center Initiative (WPI), MEXT, Japan
- BBSRC [BB/M022080/1, BB/R022429/1]
- National Natural Science Foundation of China [31870990]
- JST PRESTO [JPMJPR14FA]
- CRUK programme award [CRUK C37/A18784]
- Newton International Fellowship Royal Society
- Wellcome Trust [108429/Z/15/Z]
- Russian Science Foundation [19-79-30062]
- NUST MISiS grant [kappa4-2017-048]
- Imperial College Research Fellowship
- CRUK program [C46704/A23110]
- JSPS KAKENHI [15K15029, 17K08531]
- ERC consolidator grant NanoPD
- Grants-in-Aid for Scientific Research [17K08531, 15K15029] Funding Source: KAKEN
- Russian Science Foundation [19-79-30062] Funding Source: Russian Science Foundation
- BBSRC [BB/L005816/1, BB/D020875/1, BB/M022080/1, BB/R022429/1] Funding Source: UKRI
- EPSRC [EP/I007482/1, EP/P012809/1, EP/P011985/1] Funding Source: UKRI
- Wellcome Trust [108429/Z/15/Z] Funding Source: Wellcome Trust
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Dynamic mapping of extracellular pH (pHe) at the single-cell level is critical for understanding the role of H+ in cellular and subcellular processes, with particular importance in cancer. While several pHe sensing techniques have been developed, accessing this information at the single-cell level requires improvement in sensitivity, spatial and temporal resolution. We report on a zwitterionic label-free pH nanoprobe that addresses these longstanding challenges. The probe has a sensitivity > 0.01 units, 2 ms response time, and 50 nm spatial resolution. The platform was integrated into a double-barrel nanoprobe combining pH sensing with feedback-controlled distance dependance via Scanning Ion Conductance Microscopy. This allows for the simultaneous 3D topographical imaging and pHe monitoring of living cancer cells. These classes of nanoprobes were used for real-time high spatio-temporal resolution pHe mapping at the subcellular level and revealed tumour heterogeneity of the peri-cellular environments of melanoma and breast cancer cells.
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