Scanning ion conductivity microscopy

A scanning ion conductance microscope ( English scanning ion conductance microscope , SICM) is a microscope , the electrically non-conductive samples by means of an ion current mapping.

The scanning ion conductivity microscope was developed in 1989 by PK Hansma, B. Drake, O. Marti, SA Gould and CB Prater.

Scanning ion conductivity microscopic image of a cell layer of rat cardiomyocytes . Figure from Miragoli et al., JR Soc. Interface, 2011

Measuring principle

The measured variable in scanning ion conductivity microscopy is the ion conductivity of the area near the opening of a glass micro- or nanocapillary filled with electrolyte solution - the probe - which is immersed in an electrolyte solution in which the sample is located. By applying a voltage between two metal electrodes, one of which is in the probe and the other in the bath solution, an ion current flows through the opening of the probe. The conductivity of the SICM can be approximated by the sum of several individual conductivities. If the distance between the probe opening and the sample is large (in the range of several opening diameters of the probe), the conductivity (or its reciprocal value, the resistance ) is dominated by the conductivity across the probe tip and the probe opening. In the case of distances between the probe and the sample in the area of ​​the opening diameter of the probe, the insulating sample surface in the area directly in front of the probe opening influences the ion current and reduces the conductivity in this area. This so-called leak conductivity depends on the distance between the probe and the sample and is also significantly lower than the other conductivities, so that a determination of the total conductivity of the system is a good approximation for the leak conductivity that is used to determine the distance between the sample and probe to determine.

Mathematical description

Sketch of a typical SICM capillary including the names of the geometric parameters used in the text

Usually, extended glass capillaries are used as probes in the SICM, which can be approximated as conical hollow tips. Based on analysis by the scanning electrochemical microscope, the resistance of the probe can be calculated as ${\displaystyle R_{\mathrm {S} }}$

${\displaystyle R_{\mathrm {S} }={\frac {1}{\kappa }}\cdot {\frac {L}{\pi r_{0}r_{i}}}}$

can be approximated, where the specific conductivity of the electrolyte used denotes, the length of the tapered area and the opening radius of the upper and lower end of the capillary, see also the figure on the right. The distance-dependent leakage resistance can be used as a simple approximation ${\displaystyle \kappa }$ ${\displaystyle L}$ ${\displaystyle r_{0}}$ ${\displaystyle r_{i}}$ ${\displaystyle R_{\mathrm {L} }(d)}$

${\displaystyle R_{L}(d)={\frac {1}{\kappa }}\cdot {\frac {3/2\ln(r_{\mathrm {a} }/r_{\mathrm {i} })}{\pi d}}}$

to be viewed as. refers to the distance between the probe opening and the surface. ${\displaystyle d}$

The ion current in the SICM can be viewed as the total current across these two resistors and approximated using Ohm's law :

${\displaystyle I(d)={\frac {U}{R_{\mathrm {S} }+R_{\mathrm {L} }(d)}}}$

Since the conductivity of a SICM can be determined by current or resistance measurement (see Determination of the conductivity ), the resistance is also considered, which is linked to current and voltage via Ohm's law and therefore describes both methods.

The distance-dependent resistance of the SICM is therefore:

${\displaystyle R(d)=R_{\mathrm {S} }+R_{\mathrm {L} }(d)}$

For most imaging examinations, it is not necessary to know the absolute value of the resistance value; what is interesting is the ratio of the resistance to the resistance of the system at a large distance between the probe and the sample. Since it tends to zero for large distances , the resistance for an "infinite" distance between sample and probe results : ${\displaystyle R_{\mathrm {L} }}$ ${\displaystyle R_{\infty }}$

${\displaystyle R_{\infty }\approx R_{\mathrm {S} }.}$

If you put the current resistance in relation to it , i.e. form the normalized resistance , the description of the resistance in the SICM is simplified ${\displaystyle R_{\infty }}$ ${\displaystyle R_{\mathrm {n} }}$

${\displaystyle {\frac {R(d)}{R_{\infty }}}=R_{\mathrm {n} }(d)=1+R_{\mathrm {L} }(d)/R_{\mathrm {S} }=1+{\frac {3}{2}}\cdot {\frac {\ln(r_{\mathrm {a} }/r_{\mathrm {i} })\cdot r_{0}\cdot r_{\mathrm {i} }}{L}}\cdot {\frac {1}{d}}}$

Representation of the course of the normalized resistance as a function of the distance between sample and probe. All sizes are shown as multiples of the probe diameter in order to be independent of the actual probe diameter.

Since the geometric parameters of the measuring probe do not change during a measurement, these can be summarized in a device constant so that ${\displaystyle C}$

${\displaystyle R_{\mathrm {n} }(d)=1+{\frac {C}{d}}}$

is obtained. Since, according to the manufacturer's instructions, the glasses drawn out into glass capillaries usually have a constant ratio of inner to outer diameter , the opening radius of the probe flows linearly into the parameter for the same length . ${\displaystyle L}$ ${\displaystyle C}$

The above equation describes an asymptotic approximation from (for ) to infinity (for ), in which the curvature of the asymptote is given by the parameter . ${\displaystyle 1}$ ${\displaystyle d\rightarrow \infty }$ ${\displaystyle d\rightarrow 0}$ ${\displaystyle C}$

The relationships described above are only approximations based on geometric considerations. Current investigations are approaching the description of the SICM using finite element simulations . It turns out that the relationships described above only apply to simplified sample geometries.

Determination of conductivity

According to Ohm's law, the conductivity is calculated as the quotient of the applied voltage and the measured current. This results in two options for determining the conductivity of a SICM depending on the distance between the sample and the probe:

1. Using a constant voltage, the current that flows is measured. The present in this case, use of the current as a measurement signal at a constant voltage from the electrochemistry as amperometry known in the electrophysiology of the designation is voltage terminal common (English: voltage clamp ).
2. Alternatively, the voltage applied to the metal electrodes used can be modulated so that a constant current flows. In this case, the voltage and not the current is the measured variable. This measurement method is known in electrochemistry as voltammetry , in electrophysiology it is called a current clamp .

Elimination of slow changes in potential

Silver-silver chloride electrodes (Ag / AgCl electrodes) are often used as metal electrodes in SICMs , and physiological salt solutions are used as electrolyte solutions, in particular to depict living cells. In general, the potentials at the interfaces between the Ag / AgCl electrode and the electrolyte are assumed to be constant. In practice, however, these potentials change slowly, which results in changes in the conductivity of the SICM, which in turn affect the determination of the leakage conductivity. In order to carry out SICM measurements independently of slow potential changes, current or voltage pulses of constant magnitude were applied instead of a constant current or a constant voltage. The height of the resulting voltage or current pulse is independent of potential changes on the metal electrodes and serves as a measured variable. Another method to minimize impairments caused by potential drift on the metal electrodes is to repeatedly determine the conductivity of the SICM when the distance between the sample and the probe is large during a measurement. In this way, the changed basic conductivity is taken into account when determining the leakage conductivity, so that the incorrect detection of conductivity changes due to slow potential changes instead of changes in the distance between the sample and the probe is avoided.

construction

Sketch of a typical SICM setup

A SICM consists of the measuring probe and an associated measuring amplifier, which must have a high input resistance in order to be able to measure the current flow across the resistance of the measuring probe, usually from a few to a few hundred megohms. Depending on the type of conductivity determination, either a potentiostat ( voltage clamp ) or a galvanostat ( current clamp ) is used.

The probe and the sample are attached so that they can be moved relative to one another in all three spatial directions, which is achieved by piezoelectric actuators . Both SICMs are described in which the probe or the sample can be moved in all three spatial directions, as well as those in which the probe can be moved vertically and the sample can be moved laterally.

In order to enable manual pre-positioning and selection of the sample, SICMs are usually built on inverted light microscopes . The structure is therefore similar to that of an electrophysiological measuring stand, such as is used for patch-clamp measurements .

Measurement modes

Different operating modes for SICM. Figure from Happel et al., Sensors 12, 2012

Since the development of the first SICM, the methodology has been improved through additional measurement or operating modes. In contrast to the elimination of slow potential drifts explained above, the operating modes explained below differ in how the probe is guided over the sample.

Scanning at constant height

In this mode, the measuring probe is moved over the sample at a constant vertical position. The distance between probe and sample is determined by the conductivity determined. As can be seen in the illustration of the normalized resistance against the distance between probe and sample, a change in conductivity can only be registered in the area of ​​a few probe diameters, which is also restricted by the measurement noise . For this reason, this measuring mode can only be used to examine samples whose surface has only slight differences in height. Larger height differences can either not be detected (if the distance between the probe and the sample is too great) or cause the probe to move sideways into the sample (if the sample is higher than the vertical position of the probe).

Direct current mode (DC mode)

In direct current mode (DC mode), the probe is first brought closer to the sample until a specified change in resistance is reached. The probe is then moved sideways across the sample using the resistance of the system directly as a feedback signal to change the vertical probe position. The probe moves along the sample at a constant distance (which is why this mode is also called constant-distance mode ).

Alternating current mode (AC mode)

This mode is similar to DC mode. In addition, in this mode, the position of the sample tip is modulated by a few nanometers and with a few kilohertz , whereby a sinusoidal measurement signal is generated if the distance between the sample and the probe tip is sufficiently small. The amplitude of the measurement signal is used as the feedback signal in this mode . The change in amplitude is steeper compared to the direct change in the current in DC mode, so that the sample can be detected at a greater distance.

Backstep or hopping mode

The fundamental difference between this measurement mode and the above is that this mode operates pixel by pixel, whereas the above. Modes work picture line by picture line.

After the measuring probe has approached the sample to be examined, the probe is pulled back a certain distance and only then positioned laterally and again brought closer to the measuring object. This method allows the recording of objects with abrupt, large differences in height. However, since a complete approximation of the sample has to be carried out for each image point to be recorded, this measurement mode is in comparison to the above. considerably slower. Some improvements in the temporal resolution have been achieved by adjusting the distance that the measuring probe is pulled back after a first recording of the sample with low resolution in a subsequent higher-resolution measurement

The designation of this measurement mode in the literature is not uniform. It was first used in 2002 under the name backstep-mode . However, the lateral resolution demonstrated in this publication was roughly equivalent to that of conventional light microscopes. The first recordings in this mode, which offered a resolution well below the diffraction limit , used the designation hopping ion conductance microscopy or hopping mode . Combinations of SICM and scanning electrochemical microscopy use the term standing approach mode .

Applications

Electrophysiological measurements on dendritic spines with the help of the SICM. From Novak et al., Neuron 2013

Several review articles have been published that present the possibilities and applications of the SICM.

Since the SICM puts less stress on the sample than other probe microscopy methods such as atomic force microscopy , it is particularly suitable for multiple determination of the topography of living cells over a longer period of time. It also enables the determination of the cell volume of cells that form a dense cell lawn as well as of individual cells that change their position over a longer period of time , for example during cell migration or cell growth . In addition, the application of pressure through the measuring probe enables the modulus of elasticity of living cells to be determined. Outside of the life sciences, the SICM can be used to map the local charge of surfaces or to deposit specific molecules into a structure on a surface.

The SICM can be combined with various other techniques. In combination with confocal fluorescence microscopy, SICM enabled the localization of ATP- dependent potassium channels in the cell membrane, the discovery of a mechanism for constricting the vesicles in clathrin-mediated endocytosis and a mechanism for the endocytosis of nanoparticles . In combination with Förster resonance energy transfer measurements, SICM made it possible to show that the distribution of the β ₂ -adrenergic receptor differs in healthy cells and heart failure cell models.

Due to the technical and technical similarity to electrophysiological measurement setups, SICM was combined with patch-clamp measurements. The controlled interruption of the measuring probe makes it possible to first record the topography of nerve cells in high resolution and then to derive it electrophysiologically from subcellular structures such as dendritic spines .

literature

• Andrew I. Shevchuk et al .: An alternative mechanism of clathrin-coated pit disclosure revealed by ion conductance microscopy . In: The Journal of Cell Biology . tape 197 , no. 4 , May 14, 2012, p. 499–508 , doi : 10.1083 / jcb.201109130 , PMID 22564416 (The article is now freely available and contains some short videos of SICM recordings in combination with fluorescence recordings on endocytosis.).

Web links

• Video of the different scan modes of the SICM .

Individual evidence

1. ^ PK Hansma, B. Drake, O. Marti, SA Gould, CB Prater: The scanning ion-conductance microscope . In: Science . tape 243 , no. 4891 , February 3, 1989, ISSN  0036-8075 , p. 641-643 , doi : 10.1126 / science.2464851 .
2. ↑ M. Miragoli, A. Moshkov, P. Novak, A. Shevchuk, VO Nikolaev, I. El-Hamamsy, CM Potter, P. Wright, SH Kadir, AR Lyon, JA Mitchell, AH Chester, D. Klenerman, MJ Lab, YE Korchev, SE Harding, J. Gorelik: Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cells . In: Journal of the Royal Society, Interface . tape 8 , no. 60 , June 2011, p. 913-925 , doi : 10.1098 / rsif.2010.0597 , PMID 21325316 .
3. ↑ Allen J. Bard, Fu Ren F. Fan, Juhyoun. Kwak, Ovadia. Lev: Scanning electrochemical microscopy. Introduction and principles . In: Analytical Chemistry . tape 61 , no. January 2 , 1989, ISSN  0003-2700 , pp. 132-138 , doi : 10.1021 / ac00177a011 .
4. ↑ ^{a b} H. Nitz, J. Kamp, H. Fuchs: A Combined Scanning Ion Conductance and Shear Force Microscope. In: Probe Microscopy . tape 1 , 1998, p. 187-200 .
5. ↑ John Rheinlaender, Tilman E. Schaffer: formation image resolution, and height measurement in scanning ion conductance microscopy . In: Journal of Applied Physics . tape 105 , no. 9 , 2009, ISSN  0021-8979 , p. 094905 , doi : 10.1063 / 1.3122007 .
6. ↑ Samantha Del Linz, Eero Willman, Matthew Caldwell, David Klenerman, Anibal Fernández, Guy Moss: Contact-Free Scanning and Imaging with the Scanning Ion Conductance Microscope . In: Analytical Chemistry . tape 86 , no. 5 , March 4, 2014, ISSN  0003-2700 , p. 2353 , doi : 10.1021 / ac402748j .
7. ↑ Denis Thatenhorst, Johannes Rheinlaender, Tilman E. Schäffer, Irmgard D. Dietzel, Patrick Happel: Effect of Sample Slope on Image Formation in Scanning Ion Conductance Microscopy . In: Analytical Chemistry . tape 86 , no. 19 , October 7, 2014, ISSN  0003-2700 , p. 9838 , doi : 10.1021 / ac5024414 .
8. ↑ ^{a b c} S.A. Mann, G. Hoffmann, A. Hengstenberg, W. Schuhmann, ID Dietzel: Pulse-mode scanning ion conductance microscopy — a method to investigate cultured hippocampal cells . In: Journal of Neuroscience Methods . tape 116 , no. 2 , May 2002, ISSN  0165-0270 , p. 113–117 , doi : 10.1016 / S0165-0270 (02) 00023-7 .
9. ↑ ^{a b c} Pavel Novak, Chao Li, Andrew I. Shevchuk, Ruben Stepanyan, Matthew Caldwell, Simon Hughes, Trevor G. Smart, Julia Gorelik, Victor P. Ostanin, Max J. Lab, Guy WJ Moss, Gregory I. Frolenkov , David Klenerman, Yuri E. Korchev: Nanoscale live-cell imaging using hopping probe ion conductance microscopy . In: Nature Methods . tape 6 , no. 4 , March 1, 2009, ISSN  1548-7091 , p. 279-281 , doi : 10.1038 / nmeth.1306 .
10. ↑ YE Korchev, M. .. Milovanovic, CL Bashford, DC Bennett, EV Sviderskaya, I. Vodyanoy, MJ Lab: Specialized scanning ion conductance microscope for imaging of living cells . In: Journal of Microscopy . tape 188 , no. 1 , October 1997, ISSN  0022-2720 , p. 17-23 , doi : 10.1046 / j.1365-2818.1997.2430801.x .
11. ↑ J. Gorelik, A. Shevchuk, M. Ramalho, M. Elliott, C. Lei, CF Higgins, MJ Lab, D. Klenerman, N. Krauzewicz, Y. Korchev: Scanning surface confocal microscopy for simultaneous topographical and fluorescence imaging: Application to single virus-like particle entry into a cell . In: Proceedings of the National Academy of Sciences . tape 99 , no. 25 , December 10, 2002, ISSN  0027-8424 , p. 16018-16023 , doi : 10.1073 / pnas.252458399 .
12. ↑ Yuri E. Korchev, Meera Raval, Max J. Lab, Julia Gorelik, Christopher RW Edwards, Trevor Rayment, David Klenerman: Hybrid Scanning Ion Conductance and Scanning Near-Field Optical Microscopy for the Study of Living Cells . In: Biophysical Journal . tape 78 , no. 5 , May 2000, ISSN  0006-3495 , pp. 2675-2679 , doi : 10.1016 / S0006-3495 (00) 76811-1 .
13. ↑ ^{a b} Patrick Happel, Denis Thatenhorst, Irmgard Dietzel: Scanning Ion Conductance Microscopy for Studying Biological Samples . In: Sensors . tape 12 , no. December 12 , 2012, ISSN  1424-8220 , p. 14983-15008 , doi : 10.3390 / s121114983 .
14. Jump up ↑ Andrew I. Shevchuk, Julia Gorelik, Sian E. Harding, Max J. Lab, David Klenerman, Yuri E. Korchev: Simultaneous Measurement of Ca2 + and Cellular Dynamics: Combined Scanning Ion Conductance and Optical Microscopy to Study Contracting Cardiac Myocytes . In: Biophysical Journal . tape 81 , no. 3 , September 2001, ISSN  0006-3495 , p. 1759-1764 , doi : 10.1016 / S0006-3495 (01) 75826-2 .
15. ^ David Pastré, Hideki Iwamoto, Jie Liu, Gabor Szabo, Zhifeng Shao: Characterization of AC mode scanning ion-conductance microscopy . In: Ultramicroscopy . tape 90 , no. 1 , December 2001, ISSN  0304-3991 , p. 13-19 , doi : 10.1016 / S0304-3991 (01) 00096-1 .
16. ↑ P. Happel, G. Hoffmann, SA Mann, ID Dietzel: Monitoring cell movements and volume changes with pulse-mode scanning ion conductance microscopy . In: Journal of Microscopy . tape 212 , no. 2 , November 2003, ISSN  0022-2720 , p. 144-151 , doi : 10.1046 / j.1365-2818.2003.01248.x .
17. ↑ Yasufumi Takahashi, Yu Hirano, Tomoyuki Yasukawa, Hitoshi Shiku, Hiroshi Yamada, Tomokazu Matsue: Topographic, Electrochemical, and Optical Images Captured Using Standing Approach Mode Scanning Electrochemical / Optical Microscopy . In: Langmuir . tape 22 , no. December 25 , 2006, ISSN  0743-7463 , p. 10299-10306 , doi : 10.1021 / la0611763 .
18. ↑ ^{a b} Pavel Novak, Julia Gorelik, Umesh Vivekananda, Andrew I. Shevchuk, Yaroslav S. Ermolyuk, Russell J. Bailey, Andrew J. Bushby, Guy WJ Moss, Dmitri A. Rusakov, David Klenerman, Dimitri M. Kullmann, Kirill E. Volynski, Yuri E. Korchev: Nanoscale-Targeted Patch-Clamp Recordings of Functional Presynaptic Ion Channels . In: Neuron . tape 79 , no. 6 , September 2013, ISSN  0896-6273 , p. 1067 , doi : 10.1016 / j.neuron.2013.07.012 .
19. ^ MJ Lab, A. Bhargava, PT Wright, J. Gorelik: The scanning ion conductance microscope for cellular physiology . In: AJP: Heart and Circulatory Physiology . tape 304 , no. 1 , January 1, 2013, ISSN  0363-6135 , p. H1 – H11 , doi : 10.1152 / ajpheart.00499.2012 .
20. ↑ D. Klenerman, A. Shevchuk, P. Novak, YE Korchev, SJ Davis: Imaging the cell surface and its organization down to the level of single molecules . In: Philosophical Transactions of the Royal Society B: Biological Sciences . tape 368 , no. 1611 , December 24, 2012, ISSN  0962-8436 , p. 20120027–20120027 , doi : 10.1098 / rstb.2012.0027 .
21. ↑ Chiao-Chen Chen, Yi Zhou, Lane A. Baker: Scanning Ion Conductance Microscopy . In: Annual Review of Analytical Chemistry . tape 5 , no. 1 , July 19, 2012, ISSN  1936-1327 , p. 207-228 , doi : 10.1146 / annurev-anchem-062011-143203 .
22. ↑ John Rheinlaender, Nicholas A. Geisse, Roger Proksch, Tilman E. Schaffer: Comparison of Scanning Ion Conductance Microscopy with atomic force microscopy for cell imaging . In: Langmuir . tape 27 , no. 2 , January 18, 2011, ISSN  0743-7463 , p. 697 , doi : 10.1021 / la103275y .
23. ↑ Yuri E. Korchev, Julia Gorelik, Max J. Lab, Elena V. Sviderskaya, Caroline L. Johnston, Charles R. Coombes, Igor Vodyanoy, Christopher RW Edwards: Cell Volume Measurement Using Scanning Ion Conductance Microscopy . In: Biophysical Journal . tape 78 , no. 1 , January 2000, ISSN  0006-3495 , p. 451 , doi : 10.1016 / S0006-3495 (00) 76607-0 , PMID 10620308 .
24. ↑ Patrick Happel, Kerstin Möller, Nina K. Schwering, Irmgard D. Dietzel: Migrating Oligodendrocyte Progenitor Cells Swell Prior to Soma Dislocation . In: Scientific Reports . tape 3 , May 9, 2013, ISSN  2045-2322 , doi : 10.1038 / srep01806 .
25. ↑ Astrid Gesper, Denis Thatenhorst, Stefan Wiese, Teresa Tsai, Irmgard D. Dietzel, Patrick Happel: Long-term, long-distance recording of a living migrating neuron by scanning ion conductance microscopy . In: Scanning . February 2015, ISSN  0161-0457 , doi : 10.1002 / sca.21200 .
26. ↑ ^{a b} Mario Pellegrino, Monica Pellegrini, Paolo Orsini, Elisabetta Tognoni, Cesare Ascoli, Paolo Baschieri, Franco Dinelli: Measuring the elastic properties of living cells through the analysis of current displacement curves in scanning ion conductance microscopy . In: Pflügers Archive - European Journal of Physiology . tape 464 , no. 3 , September 2012, ISSN  0031-6768 , p. 307 , doi : 10.1007 / s00424-012-1127-6 .
27. ↑ John Rheinlaender, Tilman E. Schaffer: Mapping the mechanical stiffness of live cells with the scanning ion conductance microscope . In: Soft Matter . tape 9 , no. 12 , 2013, ISSN  1744-683X , p. 3230 , doi : 10.1039 / C2SM27412D .
28. ↑ Kim McKelvey, Sophie L. Kinnear, David Perry, Dmitry Momotenko, Patrick R. Unwin: Surface Charge Mapping with a Nanopipette . In: Journal of the American Chemical Society . tape 136 , no. 39 , October 2014, ISSN  0002-7863 , p. 13735 , doi : 10.1021 / ja506139u .
29. ↑ Kit T. Rodolfa, Andreas Bruckbauer, Dejian Zhou, Yuri E. Korchev, David Klenerman: Two-Component Graded Deposition of Biomolecules with a Double-Barreled Nanopipette . In: Angewandte Chemie International Edition . tape 44 , no. 42 , October 28, 2005, ISSN  1433-7851 , p. 6854 , doi : 10.1002 / anie.200502338 .
30. ↑ Yuri E. Korchev, Yuri A. Negulyaev, Christopher RW Edwards, Igor Vodyanoy, Max J. Lab: Functional localization of single active ion channels on the surface of a living cell . In: Nature Cell Biology . tape 2 , no. 9 , 2000, ISSN  1465-7392 , p. 616 , doi : 10.1038 / 35023563 .
31. ^ AI Shevchuk, P. Novak, M. Taylor, IA Diakonov, A. Ziyadeh-Isleem, M. Bitoun, P. Guicheney, MJ Lab, J. Gorelik, CJ Merrifield, D. Klenerman, YE Korchev: An alternative mechanism of clathrin-coated pit closure revealed by ion conductance microscopy . In: The Journal of Cell Biology . tape 197 , no. 4 , May 14, 2012, ISSN  0021-9525 , p. 499 , doi : 10.1083 / jcb.201109130 .
32. ↑ Pavel Novak, Andrew Shevchuk, Pakatip Ruenraroengsak, Michele Miragoli, Andrew J. Thorley, David Klenerman, Max J. Lab, Teresa D. Tetley, Julia Gorelik, Yuri E. Korchev: Imaging Single Nanoparticle Interactions with Human Lung Cells Using Fast Ion Conductance microscopy . In: Nano Letters . tape 14 , no. 3 , March 12, 2014, ISSN  1530-6984 , p. 1202 , doi : 10.1021 / nl404068p .
33. ↑ VO Nikolaev, A. Moshkov, AR Lyon, M. Miragoli, P. Novak, H. Paur, MJ Lohse, YE Korchev, SE Harding, J. Gorelik: β2-Adrenergic Receptor redistribution in Heart Failure Changes cAMP compartmentation . In: Science . tape 327 , no. 5973 , March 25, 2010, ISSN  0036-8075 , p. 1653 , doi : 10.1126 / science.1185988 .
34. ↑ Julia Gorelik, Yuchun Gu, Hilmar A. Spohr, Andrew I. Shevchuk, Max J. Lab, Sian E. Harding, Christopher RW Edwards, Michael Whitaker, Guy WJ Moss, David CH Benton, Daniel Sánchez, Alberto Darszon, Igor Vodyanoy , David Klenerman, Yuri E. Korchev: Ion Channels in Small Cells and Subcellular Structures Can Be Studied with a Smart Patch-Clamp System . In: Biophysical Journal . tape 83 , no. 6 , December 2002, ISSN  0006-3495 , p. 3296 , doi : 10.1016 / S0006-3495 (02) 75330-7 .