Abstract: Provided herein are compositions and methods for detecting conformational changes in a protein using surface-selective techniques in conjunction with a cell-free support interface. The protein generally comprises a lipid tail. The compositions and methods are useful in identifying agents that modify the conformation and activity of such proteins and protein complexes.

Abstract: Methods are disclosed for tethering a biological entity to a substrate comprising: (a) forming a supported lipid bilayer on a surface of a substrate, wherein the supported lipid bilayer comprises an anchor molecule conjugated to a first affinity tag that is present in the lipid bilayer at a concentration greater than or equal to 5 mole percent; and (b) contacting the supported lipid bilayer with a biological entity, wherein the biological entity comprises an nonlinear-active label and a second affinity tag capable of binding to the first affinity tag, thereby tethering the biological entity to the supported lipid bilayer in an oriented fashion.

Abstract: Methods, devices, and systems are disclosed for determining protein structure and dynamics using second harmonic generation (SHG) and related surface-selective nonlinear optical techniques.

Abstract: Methods, devices, and systems for using two-photon fluorescence measurements, either alone or in combination with other nonlinear optical measurements such as second harmonic generation, sum frequency generation, or difference frequency generation, to determine structural parameters such as mean tilt angle and distribution width for tethered nonlinear-active biomolecules are described. The disclosed methods, devices, and systems may also be used to perform structural comparisons of two or more biomolecular samples; to detect changes in biomolecule conformation upon binding of a ligand; and to screen candidate binding partners to identify compounds that modulate the conformation of the biomolecule.

Abstract: Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

Abstract: Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

Abstract: Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

Abstract: Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

Abstract: Methods are disclosed for tethering a biological entity to a substrate comprising: (a) forming a supported lipid bilayer on a surface of a substrate, wherein the supported lipid bilayer comprises an anchor molecule conjugated to a first affinity tag that is present in the lipid bilayer at a concentration greater than or equal to 5 mole percent; and (b) contacting the supported lipid bilayer with a biological entity, wherein the biological entity comprises an nonlinear-active label and a second affinity tag capable of binding to the first affinity tag, thereby tethering the biological entity to the supported lipid bilayer in an oriented fashion.

Abstract: Methods, devices, and systems are disclosed for determining protein structure and dynamics using second harmonic generation (SHG) and related surface-selective nonlinear optical techniques.

Abstract: Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques.

Abstract: Described herein are methods useful for screening candidate biochemical entities targeting a target biochemical entity and methods useful for identifying a binding moiety for a target biochemical entity. The invention provides methods of screening drug candidates targeting a target biomolecule, comprising selecting a drug candidate based on a signal difference between a first signal and a second signal. The signal difference indicates a difference in an in vivo or in vitro pharmacological property. The first signal is produced upon binding between the target biomolecule and a first candidate by contacting the target biomolecule with the first candidate, and the second signal is produced upon binding between the target biomolecule and a second candidate by contacting the target biomolecule with the second candidate.

Abstract: A nonlinear optical technique, such as second or third harmonic or sum or difference frequency generation, is used to detect binding interactions, or the degree or extent of binding, that comprise a conformational change. In one aspect of the present invention, the nonlinear optical technique detects a conformational change in a probe due to target binding. In another aspect of the invention, the nonlinear optical technique screens candidate probes by detecting a conformational change due to a probe-target interaction. In another aspect of the invention, the nonlinear optical technique screens candidate modulators of a probe-target interaction by detecting a conformational change in the presence of the modulator.

Abstract: A solid state electric device includes templated charge-carrier-transporting channel layer interposed between a pair of conductive substrates. The templated charge-carrier-transporting channel layer includes a layer of a first charge-carrier-transporting material having one or more regions defined using templating techniques, in which a second charge-carrier-transporting material is deposited. The second charge-carrier-transporting material is distributed within the templated charge-carrier-transporting channel layer such that, predominantly, only a single contiguous part of the second charge-carrier-transporting material is interposed between the first conductive substrate and the second conductive substrate along any imaginary normal axis extending between the two conductive substrates.

Abstract: A solid state electric device includes a templated charge-carrier-transporting channel layer interposed between a pair of conductive substrates. The templated charge-carrier-transporting channel layer is made of a layer of a first charge-carrier-transporting material having one or more regions defined using templating techniques, in which regions a second charge-carrier-transporting material is deposited. The second charge-carrier-transporting material regions are distributed within the templated charge-carrier-transporting channel layer such that, predominantly, only a single contiguous part of the second charge-carrier-transporting material is interposed between the first conductive substrate and the second conductive substrate along any imaginary normal axis extending between the two conductive substrates.

Abstract: A surface-selective nonlinear optical technique, such as second harmonic or sum frequency generation, is used to detect target-probe binding reactions or their effects, at an interface, in the presence of indicators. In addition, the direction of the nonlinear light is scattered from the interface in a well-defined direction and therefore its incidence at a detector some distance from the interface may be easily mapped to a specific and known location at the interface.

Abstract: A solid state electric device includes templated charge-carrier-transporting channel layer interposed between a pair of conductive substrates. The templated charge-carrier-transporting channel layer includes a layer of a first charge-carrier-transporting material having one or more regions defined using templating techniques, in which a second charge-carrier-transporting material is deposited. The second charge-carrier-transporting material is distributed within the templated charge-carrier-transporting channel layer such that, predominantly, only a single contiguous part of the second charge-carrier-transporting material is interposed between the first conductive substrate and the second conductive substrate along any imaginary normal axis extending between the two conductive substrates.