Abstract: Various aspects of the present invention are generally directed to systems and methods for imaging at high spatial and/or temporal resolutions. In one aspect, the present invention is generally directed to an optical microscopy system and related methods adapted for high spatial and temporal resolution of dynamic processes. The system may be used in conjunction with fluorescence imaging wherein the fluorescence may be mediated by voltage-indicating proteins. In some cases, time resolutions may be enhanced by fitting predefined temporal waveforms to signal values received from an image. The system may also contain a high numerical aperture objective lens and a zoom lens located in an imaging optical path to an object region. Other aspects of the present invention are generally directed to techniques of making or using such systems, kits involving such systems, manufactured storage devices able to implement such systems or methods, and the like.

Abstract: The invention provides methods for characterizing cellular physiology by incorporating into an electrically excitable cell an optical reporter of, and an optical actuator of, electrical activity. A signal is obtained from the optical reporter in response to a stimulation of the cell. Either or both of the optical reporter and actuator may be based on genetically-encoded rhodopsins incorporated into the cell. The invention provides all optical methods that may be used instead of, or as a complement to, traditional patch clamp technologies and that can provide rapid, accurate, and flexible assays of cellular physiology.

Abstract: The invention provides methods, cells and constructs for optical measurement of membrane potential. These methods can be used in cells that are not accessible to presently available methods using electrodes. The methods can be directed to, for example, high-throughput drug screening assays to determine agents that can affect membrane potential of a target cell.

Abstract: A curved surface is placed tangent to a slide and displaces a sample liquid from the point or line of contact outward. Imaging indicates a region where fluorescence is observed, and the location of the fluorescence indicates the molecular size. The radius of curvature of the lens is known, the distance from the (center) point of contact of the observed fluorescence is measured with a microscope and the distance of the lens surface to the slide's surface can then be calculated. This distance represents the size of the molecule or ensemble of molecules emitting. Similarly, absorbance, etc. could be measured with a light source below the slide.

Abstract: Sub-micron objects are manipulated. According to an example embodiment of the present invention, Brownian motion effects are mitigated to facilitate the analysis and/or manipulation of sub-micron objects. In some applications, an electric field is applied to facilitate the manipulation of sub-micron objects in solution, facilitating the analysis of the manipulated objects. In other applications, fluid flow is used to effect the manipulation of sub-micron objects in solution.

Abstract: A structure and method for improving the spatial resolution of a scanning probe microscope (SPM) tip, which has been coated with a layer of chemically-synthesized nanoparticles. The nanoparticles are either single-species or heterogeneous, such that the single-species nanoparticles can be either ferromagnetic, paramagnetic, superparamagnetic, antiferromagnetic, ferrimagnetic, magneto-optic, ferroelectric, piezoelectric, superconducting, semiconducting, magnetically-doped semiconducting, insulating, fluorescent, or chemically catalytic. The layer of nanoparticles is at least two nanoparticles thick, or alternatively, is a single layer of nanoparticles thick, or alternatively, is a single layer of nanoparticles thick and covers only the tip apex portion of the tip, or alternatively, only a single nanoparticle is affixed to the tip apex. Alternatively, the layer of nanoparticles is transformed into an electrically-continuous magnetic film by annealing at a high temperature.

Abstract: A new field of technology, near-field photolithography, is proposed. In near-field photolithography, an opaque pattern having a nanoscale resolution is made using a modified scanning tunneling microscope to deposit the opaque material on an electrically conductive material. A transparent sheet of indium tin oxide is patterned with a plurality of opaque copper deposits having a nanoscale resolution. The patterned indium tin oxide is then used as a photolithographic mask in the optical near-field. Near-field resolution is not diffraction limited, and near-field photolithography is able to pattern objects with sub-wavelength resolution. As a result, smaller semiconductor microchips can be manufactured and a new nanotechnology, e.g., nanomachines, can be developed. The scanning tunneling microscope (STM) is used as an "electrochemical paintbrush" to transfer the copper from a massive copper supply to the STM electrode tip and then to the ITO surface without degrading the STM tip.