A liquid supplier includes: a supply port which supplies a liquid to a space between an objective lens and an observation object; and a recovery port which recovers the liquid supplied from the supply port, wherein the supply port and the recovery port satisfy a condition where positions of the supply port and the recovery port differ from each other in a direction of an optical axis of the objective lens or a condition where positions of the supply port and the recovery port with respect to the optical axis differ from each other in a direction perpendicular to the optical axis of the objective lens or both conditions.

Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the assay chip. The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells. Each sensor may detect emission energy from a sample in a respective sample well. The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors.

A biosensor for base calling is provided. The biosensor comprises a sampling device, which includes a sample surface that has an array of pixel areas and a solid-state imager that has an array of sensors. Each sensor generates pixel signals in each base calling cycle. Each pixel signal represents light gathered in one base calling cycle from one or more clusters in a corresponding pixel area of the sample surface. The biosensor further comprises a signal processor configured for connection to the sampling device. The signal processor receives and processes the pixel signals from the sensors for base calling in a base calling cycle, and uses the pixel signals from fewer sensors than a number of clusters base called in the base calling cycle. The pixel signals from the fewer sensors include at least one pixel signal representing light gathered from at least two clusters in the corresponding pixel area.

Apparatus and methods for analyzing single molecule and performing nucleic acid sequencing. An apparatus can include an assay chip that includes multiple pixels with sample wells configured to receive a sample, which, when excited, emits emission energy; at least one element for directing the emission energy in a particular direction; and a light path along which the emission energy travels from the sample well toward a sensor. The apparatus also includes an instrument that interfaces with the assay chip. The instrument includes an excitation light source for exciting the sample in each sample well; a plurality of sensors corresponding the sample wells. Each sensor may detect emission energy from a sample in a respective sample well. The instrument includes at least one optical element that directs the emission energy from each sample well towards a respective sensor of the plurality of sensors.

To reduce optical noise in fluorescence measurement. A biochip 110 for fluorescence measurement includes a transparent substrate 111, multiple microlenses 112 dispersively formed on a first surface 111a of the transparent substrate 111, multiple protruding portions 113 formed corresponding one-to-one with the microlenses 112 on a second surface 111b of the transparent substrate 111, and a fluorescence measurement site 114 formed at a top portion of each protruding portion 113.

The present invention seeks to provide an easily portable means of visualizing biological samples by way of fluorescent emissions from fluorescently tagged antibodies associated with the biological entities; thereby acting as a diagnostic tool when appropriate antibodies and samples are applied to the sample plate. Current methods used to visualize biological entities by way of fluorescent emissions from fluorescently tagged antibodies associated with the biological samples involve the use of large bulky equipment that doesn't exist in a modular format—different components existing as disparate disjointed units that cannot be physically associated or linked with each other. This invention significantly decreases the size of the components needed to visualize biological samples by way of fluorescent emissions from fluorescently tagged antibodies and also modularizes the components such that they can be connected to each other to form the portable detection device.

Systems and methods for analyzing samples, such as tissue samples, and measuring the emissions when these samples are exposed to light are disclosed. Embodiments include illuminating multiple target locations on a sample with laser light, which may first be manipulated by a scanner, and receiving decaying emissions from the target location. At least some embodiments include the emissions traveling backwards along a substantial portion of the laser light pathway and being received by a detector. Additional embodiments include converting the received emissions into streak lines of position versus time, converting the streak lines to plots of signal strength versus time, and curve fitting the plots to determine representative decay times. In some embodiments, the decay times are presented as plots of position on the surface of the sample versus emission strength, which may be color coded. Some embodiment dwell on each target location for multiple scans of the laser.

A biological analysis system can include an excitation module and an emission module. The excitation module can include a collimator element for receiving excitation light from the excitation light source and transmitting collimated excitation light in a first direction, and a plurality of excitation mirrors arrayed along the excitation light path, each excitation mirror disposed at an acute angle relative to the first direction and configured to reflect collimated excitation light along a second direction. The emission module can be positioned to receive excitation light transmitted along the second direction and can include a sample block comprising a plurality of sample receptacles positioned to receive a beam of collimated excitation light, and a plurality of photodetectors configured to receive emission light transmitted from a respective sample receptacle in a direction transverse to the second direction of the excitation light path.

To reduce optical noise in fluorescence measurement. A biochip 110 for fluorescence measurement includes a transparent substrate 111, multiple microlenses 112 dispersively formed on a first surface 111a of the transparent substrate 111, multiple protruding portions 113 formed corresponding one-to-one with the microlenses 112 on a second surface 111b of the transparent substrate 111, and a fluorescence measurement site 114 formed at a top portion of each protruding portion 113.

Arrays of integrated analytical devices and their methods for production are provided. The arrays are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices allow the highly sensitive discrimination of optical signals using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices include an integrated diffractive beam shaping element that provides for the spatial separation of light emitted from the optical reactions.