Nanopore-based scanning system and method
US-2025376725-A1 · Dec 11, 2025 · US
US9709598B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-9709598-B2 |
| Application number | US-201615167666-A |
| Country | US |
| Kind code | B2 |
| Filing date | May 27, 2016 |
| Priority date | Feb 1, 2008 |
| Publication date | Jul 18, 2017 |
| Grant date | Jul 18, 2017 |
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A method for interrogating a surface using scanning ion conductance microscopy (SICM), comprising the steps of: a) repeatedly bringing a SICM probe into proximity with the surface at discrete, spaced locations in a region of the surface and measuring surface height at each location; b) estimating surface roughness or other characteristic for the region based upon the surface height measurements; and c) repeatedly bringing the probe into proximity with the surface at discrete, spaced locations in the region, the number and location of which is based upon the estimated surface roughness or other characteristic in the region, and obtaining an image of the region with a resolution adapted to the surface roughness or other characteristic.
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We claim: 1. A method for interrogating a surface using scanning ion conductance microscopy (SICM), comprising the steps of: a) repeatedly bringing a SICM probe into proximity with the surface at discrete, spaced precursor points in a region of the surface to obtain a precursor point surface height measurement for each of the precursor points; b) estimating surface roughness for the region by analyzing the distribution of the precursor point surface height measurements; c) determining a number and location of discrete, spaced additional points based upon the estimated surface roughness; d) repeatedly bringing the probe into proximity with the surface at the additional points to obtain an additional point surface height measurement for each of the additional points; and e) combining the precursor point and additional point surface height measurements to obtain an image of the region with a resolution adapted to the surface roughness. 2. The method according to claim 1 , wherein steps (b) to (d) are repeated recursively for sub-regions according to the required image resolution. 3. The method according to claim 1 , wherein the step of bringing the probe into proximity with the surface at each precursor or additional point is performed by approaching each precursor or additional point from a distance greater than the height of the surface at that precursor or additional point. 4. The method according to claim 1 , wherein lateral movement of the probe occurs only when the probe is distant from the surface. 5. The method according to claim 1 , wherein, during the step of bringing the scanning probe into proximity with the surface at each precursor or additional point, the approach is terminated when a measured probe current reaches a threshold value. 6. The method according to claim 5 , wherein the threshold value is based upon the probe current measured when the probe is distant from the surface. 7. The method according to claim 5 , wherein the approach is terminated when probe current is reduced by 0.25% to 1%. 8. The method according to claim 6 , wherein for each measurement, the distance travelled by the probe, from the position distant from the surface to the position at the threshold value, is greater than 1 μm. 9. The method according to claim 1 , wherein, during the step of bringing the scanning probe into proximity with the surface, the approach rate or speed is constant. 10. The method according to claim 1 , wherein a local relationship between probe current and distance from probe to surface is determined for each precursor or additional point. 11. The method according to claim 1 , wherein a differential map of the surface is obtained by, for each precursor or additional point, obtaining a first scanning measurement when the probe is distant from the surface and a second scanning measurement when the probe is in proximity to the surface and subtracting the second scanning measurement from the first, to obtain the differential map. 12. The method according to claim 11 , wherein an agent or other stimulus is applied at the tip of the probe and measurements of response to the agent or stimulus are made together with each first or second scanning measurement to provide a differential map of the surface. 13. The method according to claim 11 , carried out in the presence of a fluorophore the intensity of which is increased by a surface structure, wherein a laser beam is focused at the tip of the probe to induce fluorescence, wherein a scanning measurement is obtained together with each first or second scanning measurement, and wherein subtraction of the second fluorescence measurement from the first reveals local changes in fluorescence. 14. The method according to claim 11 , wherein, during the step of bringing the probe into proximity with the surface at each precursor or additional point, the approach is terminated, and an image is obtained, when a measured probe current reaches multiple different threshold values. 15. The method according to claim 14 , wherein the approach is terminated when probe current is reduced by 1%, 5% and 10%. 16. The method according to claim 1 , wherein steps (b) to (d) are carried out using estimated surface roughness. 17. The method according to claim 1 , wherein steps (b)to (d) are carried out by measuring the presence of a fluorescence signal. 18. The method according to claim 5 , wherein an image is obtained at multiple different threshold values for measured probe current, where differences in the results obtained provide information on the mechanical properties of the surface or reveals information on structures underneath the surface. 19. The method according to claim 1 , wherein step (d) is carried out at multiple different voltages, where differences in the results obtained provide information on the mechanical properties of the surface or reveals information on structures underneath the surface. 20. The method according to claim 1 , wherein the region is square, the precursor points are located at each of the square region's corners and steps (c) to (e) are performed following a determination that the maximum difference between any of the precursor point surface height measurements is greater than a predefined roughness threshold. 21. The method according to claim 1 , further comprising estimating height range in sub-regions within the region and, if that range is large enough, considering a subset of the additional points as a new set of precursor points and making measurements at further additional points, more closely spaced than the previously measured additional points. 22. The method according to claim 21 , wherein the further estimating height range, considering a subset of additional points, and making measurements steps are applied recursively until a limit determined by the scanning resolution of the probe and its controlling system is reached.
SICM [Scanning Ion-Conductance Microscopy] or apparatus therefor, e.g. SICM probes · CPC title
Feedback mechanisms, i.e. wherein the signal for driving the probe is modified by a signal coming from the probe itself · CPC title
Coarse scanning or positioning · CPC title
Methods or apparatus for measurement or analysis of nanostructures · CPC title
Scanning or positioning arrangements, i.e. arrangements for actively controlling the movement or position of the probe · CPC title
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