Realizing The Biological and Biomedical Potential of Nanoscale Imaging Using A Pipette Probe

Abstract

Cells naturally operate on the nanoscale level, with molecules combining together to form complex molecular machines, which can work together to enable normal cell function or go wrong as in the case of many diseases. Visualizing these key processes on the nanoscale has been difficult and two main approaches have been used to date; nanometer resolution imaging of fixed cells using electron microscopy, or imaging live cells using optical or fluorescence microscopy, with a resolution of a few hundred nanometers. Scanning probe microscopy has the potential to allow live cells to be imaged at nanoscale resolution and a noncontact method based on the use of a nanopipette probe has been developed over the last 10 years that allows both topographic and functional imaging. The rapid progress in this area of research over the last 4 years is reviewed in this article, which shows that imaging of complex cellular structures and tissues is now possible and that these methods are now sufficiently mature to provide new insights into important diseases.

Keywords::

• fluorescence resonance energy transfer
• FRET
• hopping probe ion conductance microscopy
• HPICM
• live cell imaging
• scanning electrochemical microscopy
• scanning ion conductance microscopy
• SECM
• SICM

Financial & competing interests disclosure

David Klenerman, Andrew Shevshuk and Yuri Korchev are share holders in the spin-out company Ionscope, which sells scanning ion conductance microscopes. David Klenerman, Andrew Shevshuk, Yuri Korchev and Pavel Novak are also consultants to the company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

David Klenerman, Andrew Shevshuk and Yuri Korchev are share holders in the spin-out company Ionscope, which sells scanning ion conductance microscopes. David Klenerman, Andrew Shevshuk, Yuri Korchev and Pavel Novak are also consultants to the company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.