Scanning Ion Conductance Microscopy for Studying Biological Samples

Abstract

Scanning ion conductance microscopy (SICM) is a scanning probe technique that utilizes the increase in access resistance that occurs if an electrolyte filled glass micro-pipette is approached towards a poorly conducting surface. Since an increase in resistance can be monitored before the physical contact between scanning probe tip and sample, this technique is particularly useful to investigate the topography of delicate samples such as living cells. SICM has shown its potential in various applications such as high resolution and long-time imaging of living cells or the determination of local changes in cellular volume. Furthermore, SICM has been combined with various techniques such as fluorescence microscopy or patch clamping to reveal localized information about proteins or protein functions. This review details the various advantages and pitfalls of SICM and provides an overview of the recent developments and applications of SICM in biological imaging. Furthermore, we show that in principle, a combination of SICM and ion selective micro-electrodes enables one to monitor the local ion activity surrounding a living cell.

Phase modulation mode of scanning ion conductance microscopy

“…To date, the modulated frequency is in the range from 1 kHz to 2 kHz. 11 This low modulated frequency limits the band width of the overall feedback loop, therefore slows the scanning speed. 12 The time required to scan a full frame with the AC mode is between 15 and 40 min.…”

Experimental Studies of Resolution in Scanning Ion Conductance Microscopy

“…SICM has proven useful in a number of applications, especially for imaging biological samples. 2 With recent improvements in instrumental performance, detailed studies of image formation and resolution are of special interest. Lateral resolution has been reported in previously performed studies with contradictory conclusions.…”

In-Phase Bias Modulation Mode of Scanning Ion Conductance Microscopy With Capacitance Compensation

“…Because of its noninvasive, high-resolution, and non-force contact imaging characteristics, SICM has become a promising tool in different fields. In biology [3], it is used for noninvasive imaging [4], nano-injection [5], singlecell nanobiopsy [6], noncontact mechanical stimulation [7], and smart patch clamp [8]. In electrochemistry, it is used for simultaneous topographical and electrochemical detection [9], [10] and mapping the surface activity of individual nanoparticles [11], whereas in physics, it is used to provide a novel light source for scanning near-field optical microscopy [12].…”

“…ENBW is determined by the time constant T const and slope setting, and a simplified calculated formula is also concluded in the manual (pages [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. When the slope setting is constant at 24 dB/oct, the relationship between ENBW and T const is ENBW = 5/(64T const ).…”