A detector has an internal sensing space, and includes a light source unit for emitting light into the sensing space, a reflector for reflecting the light, a sample supply for providing a sample into a path of the light, a first sensor unit for sensing the light reflected by the reflector, and a second sensor unit for sensing at least one of scattered light and fluorescence by the sample. The light source and the first and second sensor units are arranged in the sensing space.

Methods for producing a high resolution image of a sample are provided. In some embodiments, the method includes: detecting first and second sets of spatially-dependent emission signals from a sample labeled with a fluorescent polymeric dye; and producing a high resolution fluorescence image of the sample from the detected first and second sets of spatially-dependent emission signals. In some embodiments, the sample is a cell. Also provided are systems for imaging a sample that include a high resolution light microscope including a light source configured to irradiate a field of view with an excitation light; a photodetector configured to detect an emission signal: and a polarization modulator disposed in the light pathway between the light source and the photodetector; and a sample labelled with a polymeric dye and disposed in the field of view.

A method measuring the phase transition characteristics of a macromolecule, the method comprising: generating a stream of micro-droplets comprising at least one constituent, of which one constituent comprises the macromolecule, varying the conditions in the micro-droplets; and measuring the relative concentrations of the constituents of, and the phases of the macromolecule present in, the micro-droplets.

A protein-based probe for detecting the presence of one of two distinct states of a target membrane-associated molecule by means of polarization microscopy is disclosed. The probe contains an anchoring moiety consisting of at least one lipidated peptide and/or at least one transmembrane α-helical peptide, a peptide linker moiety having the length of at least 5 amino acids, wherein at least 50% of the amino acids forming the linker are selected from glycine, serine, and threonine, a fluorescent moiety, and an affinity binding moiety capable of binding the target membrane-associated molecule. The moieties are arranged in the order a-b-c-d or d-c-b-a in the direction from the N-terminus to the C-terminus. Methods of detecting presence or absence of the target molecule, detecting activated or inactive forms of the target molecule, and detecting the activation of the target molecule are also described.

Systems and methods for three-dimensional fluorescence polarization excitation that generates maps of positions and orientation of fluorescent molecules in three or more dimensions are disclosed.

A system (1) for measuring the optical activity of a sample (2) comprises at least one frequency modulation device (3), at least one synchronization device (4), and at least one detection device (5). The frequency modulation device (3) is configured to modulate a frequency of incident electromagnetic radiation being emitted from a sample (2) and/or being irradiated on to a sample (2) with at least one frequency modulation signal (Sf). The synchronization device (4) is configured to receive the at least one frequency modulation signal (Sf) and to emit at least one detection modulation signal (Sd) being synchronized with the at least one frequency modulation signal (Sf). The system (1) is configured such that the detection device (5) detects the electromagnetic radiation (EMs) in synchronization with the detection modulation signal (Sd).

Systems and methods for hyperspectral imaging are described. In one implementation, a hyperspectral imaging system includes a sample holder configured to hold a sample, an illumination system, and a detection system. The illumination system includes a light source configured to emit excitation light having one or more wavelengths, and a first set of optical elements that include a first spatial light modulator (SLM), at least one lens, and at least one dispersive element. The illumination system is configured to structure the excitation light into a predetermined two-dimensional pattern at a conjugate plane of a focal plane in the sample, spectrally disperse the structured excitation light in a first lateral direction, and illuminate the sample in an excitation pattern with the one or more wavelengths dispersed in the first lateral direction.

In one aspect, presence and/or level of an analyte within a sample is determined by use of a construct comprising a magnetic moiety and a fluorescent moiety. In one embodiment, the construct is magnetically migrated to a transparent surface and then dragged along the surface. In one aspect, an evanescent field is applied and changes in the diffusional or rotational properties of the fluorescent moiety as it migrates in and out of the evanescent field are measured by changes in its fluorescent emission, providing a measure of the interaction between the construct and a component of the sample.

A structured illumination microscope includes: a first illumination optical system configured to irradiate, from a first direction, a sample with activating light for activating a fluorescent substance included in the sample; a second illumination optical system configured to irradiate, from a second direction that is different from the first direction, the sample with interference fringes of exciting light for exciting the fluorescent substance; a control unit configured to control a direction and a phase of the interference fringes; an imaging optical system configured to form an image of the sample irradiated with the interference fringes; an imaging element configured to take the image formed by the imaging optical system to generate a first image; and a demodulation unit configured to generate a second image by using a plurality of the first images generated by the imaging element.

Systems and methods for three-dimensional fluorescence polarization excitation that generates maps of positions and orientation of fluorescent molecules in three or more dimensions are disclosed.