The disclosure relates to devices and instruments for detecting and individually analyzing biomolecules, biomolecular complexes and biomolecules with ligands attached thereon.

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.

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.

Disclosed herein are methods and systems for controlled ejection of desired material onto surfaces including in single cells using nanopipettes, as well as ejection onto and into cells. Some embodiments are directed to a method and system comprising nanopipettes combined with an xyz controller for depositing a user defined pattern on an arbitrary substrate for the purpose of controlled cell adhesion and growth. Alternate embodiments are directed to a method and system comprising nanopipettes combined with an xyz controller and electronic control of a voltage differential in a bore of the nanopipette electroosmotically injecting material into a cell in a high-throughput manner and with minimal damage to the cell. Yet other embodiments are directed to method and system comprising functionalized nanopipettes combined with scanning ion conductance microscopy for studying molecular interactions and detection of biomolecules inside a single living cell.

Disclosed herein are methods and systems for controlled ejection of desired material onto surfaces including in single cells using nanopipettes, as well as ejection onto and into cells. Some embodiments are directed to a method and system comprising nanopipettes combined with an xyz controller for depositing a user defined pattern on an arbitrary substrate for the purpose of controlled cell adhesion and growth. Alternate embodiments are directed to a method and system comprising nanopipettes combined with an xyz controller and electronic control of a voltage differential in a bore of the nanopipette electroosmotically injecting material into a cell in a high-throughput manner and with minimal damage to the cell. Yet other embodiments are directed to method and system comprising functionalized nanopipettes combined with scanning ion conductance microscopy for studying molecular interactions and detection of biomolecules inside a single living cell.

A polymeric micro-arm apparatus and method to use the same. The apparatus comprises of an elongated hollow polymeric structure with a distal end and a proximal end, an opening near the distal end, a main body attached to the polymeric structure means to move the polymeric structure, means to generate fluid flow through the opening, means to measure a flowrate of the fluid flow through the opening; and an element embedded in the polymeric structure, wherein the element is configured to detect when the polymeric structure contacts an object and measures the force that the object exerts upon the polymeric structure.

A method for interrogating a surface of a sample bathed in electrolyte solution using SICM, comprising: controlling the potential between first and second electrodes bathed in the electrolyte solution to induce an ion current in the electrolyte solution, a submerged portion of the first electrode being contained within a micropipette and the second electrode being external to the micropipette; recording the ion current whilst controlling the micropipette to move with respect to a stage supporting the sample; and determining, from the ion current and calibration data, the surface height profile of the sample. Said potential can be controlled according to a spread spectrum modulated signal. Said micropipette motion can be according to an AC mode pattern having a modulation frequency greater than a resonant frequency of an assembly of the micropipette, first electrode and a first piezoelectric actuator configured to control z-axis motion of said micropipette.

A method for interrogating a surface of a sample bathed in electrolyte solution using SICM, comprising: controlling the potential between first and second electrodes bathed in the electrolyte solution to induce an ion current in the electrolyte solution, a submerged portion of the first electrode being contained within a micropipette and the second electrode being external to the micropipette; recording the ion current whilst controlling the micropipette to move with respect to a stage supporting the sample; and determining, from the ion current and calibration data, the surface height profile of the sample. Said potential can be controlled according to a spread spectrum modulated signal. Said micropipette motion can be according to an AC mode pattern having a modulation frequency greater than a resonant frequency of an assembly of the micropipette, first electrode and a first piezoelectric actuator configured to control z-axis motion of said micropipette.