Abstract: A system is described wherein multiple lasers are used to irradiate particles in a flow cytometer's flow stream. In certain embodiments, a light source having a first laser configured for continuous irradiation of a flow stream and one or more second lasers configured for irradiation of the flow stream in discrete intervals where each discrete interval of irradiation by the second laser is triggered by irradiation of one or more particles in the flow stream with the first laser. Methods for modulating the laser irradiation and measuring light intensity are also described. Also described is the computations and systems required to operate the one or more second lasers.

Abstract: A measurement system includes an optical source (e.g., laser) to irradiate a sample (e.g., a cell); a solid-state photon detector (SSPD) to receive resultant light from the sample; and a photon counter to count photons received by the SSPD. The photon counter can include a differentiator to provide a differentiated photon signal and a crossing detector configured to count photons based on a number of times the differentiated photon signal crosses a predetermined threshold level. In some examples, a pulse detector can provide a pulse-width signal from the SSPD output photon signal, and a pulse counter can count based on both a number of pulses and widths of the pulses. The SSPD can include a silicon photomultiplier (SiPM) array or a solid-state photomultiplier. Some examples use the measurement system to measure samples in fluids, e.g., in flow cytometers or multi-well plates.

Abstract: An example system can include a support and two or more sensor elements mounted to the support. Each sensor element can be electrically connected to a common electrical node and may include: a respective quench resistor connected to a respective internal node; and a respective photodiode (PD) connected to the respective internal node; a differentiating element fed by at least one of the photodiodes; a first readout electrode fed by the common electrical node; and a second readout electrode fed by the differentiating element. The common electrical node may be connected to at least one of the quench resistors or at least one of the photodiodes.

Abstract: A photon-accounting system for use with a flow cytometry system is disclosed which includes a signal shaping sub-system, including a differentiator configured to generate a differentiated output of photodiode signals into corresponding zero-crossings each associated with one of the received photons, a comparator configured to receive the differentiated signal and compare to a threshold to thereby generate a comparator output digital signal associated with the crossing of the differentiated signal about the threshold, a front-end synchronization system adapted to receive and synchronize the comparator generated digital signal to a clock, thereby generate synchronized photon data with the clock and associated with the asynchronized photodiode signal, and a timestamping system adapted to receive the synchronized data as a bit stream and generate a timestamp associated with each photon data.

Abstract: A measurement system includes an optical source (e.g., laser) to irradiate a sample (e.g., a cell); a solid-state photon detector (SSPD) to receive resultant light from the sample; and a photon counter to count photons received by the SSPD. The photon counter can include a differentiator to provide a differentiated photon signal and a crossing detector configured to count photons based on a number of times the differentiated photon signal crosses a predetermined threshold level. In some examples, a pulse detector can provide a pulse-width signal from the SSPD output photon signal, and a pulse counter can count based on both a number of pulses and widths of the pulses. The SSPD can include a silicon photomultiplier (SiPM) array or a solid-state photomultiplier. Some examples use the measurement system to measure samples in fluids, e.g., in flow cytometers or multi-well plates.

Abstract: A measurement system includes an optical source (e.g., laser) to irradiate a sample (e.g., a cell); a solid-state photon detector (SSPD) to receive resultant light from the sample; and a photon counter to count photons received by the SSPD. The photon counter can include a differentiator to provide a differentiated photon signal and a crossing detector configured to count photons based on a number of times the differentiated photon signal crosses a predetermined threshold level. In some examples, a pulse detector can provide a pulse-width signal from the SSPD output photon signal, and a pulse counter can count based on both a number of pulses and widths of the pulses. The SSPD can include a silicon photomultiplier (SiPM) array or a solid-state photomultiplier. Some examples use the measurement system to measure samples in fluids, e.g., in flow cytometers or multi-well plates.

Abstract: According to various aspects, a flow system for transporting microparticulate samples in a hydrodynamically planar flow in a selected flow direction includes a flow chamber extending in the flow direction, having first and second apertures on opposed surfaces of the flow chamber. A sheath-fluid channel has first and second branches to carry the sheath fluid into the flow chamber through the first aperture and having orientations separated by less than about 15° at the first aperture; and third and fourth branches to carry the sheath fluid through the second aperture and having orientations separated by less than about 15° at the second aperture. In some examples, guide channels extend from the apertures substantially perpendicular to the flow chamber at the apertures, and sheath-fluid channel supply sheath fluid to the guide channels. Flow systems can be used in image flow cytometers for observing microparticulate samples, e.g., using scanning irradiation.

Abstract: A photon-accounting system for use with a flow cytometry system is disclosed which includes a signal shaping sub-system, including a differentiator configured to generate a differentiated output of photodiode signals into corresponding zero-crossings each associated with one of the received photons, a comparator configured to receive the differentiated signal and compare to a threshold to thereby generate a comparator output digital signal associated with the crossing of the differentiated signal about the threshold, a front-end synchronization system adapted to receive and synchronize the comparator generated digital signal to a clock, thereby generate synchronized photon data with the clock and associated with the asynchronized photodiode signal, and a timestamping system adapted to receive the synchronized data as a bit stream and generate a timestamp associated with each photon data.

Abstract: An image flow cytometer for observing a microparticulate sample includes a flow chamber having a flow channel that permits the microparticulate sample to travel in a flow direction. An irradiation system scans an irradiation spot across a sensing area of the flow channel in a scan direction different from the flow direction. A detection system detects resultant light from the sensing area and provides a detection signal. An alignment system alters a location of the sensing area with respect to the flow chamber. A control unit causes the irradiation system to scan the irradiation spot during a first measurement interval and operates the alignment system to translate the location of the sensing area along the flow direction. The flow chamber can be mounted to a movable stage in some examples, and the alignment system can move the flow chamber substantially opposite the flow direction using the stage.

Abstract: A measurement system includes a system for causing relative motion between a sample and an irradiation spot. The sample includes fluorescent markers having respective wavelengths. A gating system provides a gating signal based at least in part on resultant light substantially at an irradiation wavelength. A detection system detects fluorescent light from the irradiated markers and provides detection signals representing the fluorescent light detected concurrently with a gate-open signal. In some examples, the detection system detects fluorescent light at multiple wavelengths and provides respective detection signals. A spectral discriminator arranged optically between the sample and the detection system receives the fluorescent light from the sample and provides respective fluorescent light at the wavelengths to the detection system. A flow cytometer can spectrally disperse resultant fluorescent light and measure the wavelengths separately.

Abstract: An example assembly includes a target holder that retains a target in a detection region. A reflective surface reflects at least part of a focused spot of light to provide resultant light. An irradiation system irradiates at least part of the detection region with the focused spot of light. A motion system causes motion of the focused spot of light relative to the reflective surface. A detection system detects the resultant light. An example device, e.g., a lab-on-chip, includes a substrate, a sample inlet, and a reflective grating. The grating is retains a fluidic sample in a detection region fluidically connected to the sample inlet. The detection region is operatively arranged with respect to the reflective grating so that at least a portion of light passing through the detection region towards the reflective grating also passes through the detection region after reflecting off the reflective grating.

Abstract: An image flow cytometer for observing a microparticulate sample includes a flow chamber having a flow channel that permits the microparticulate sample to travel in a flow direction. An irradiation system scans an irradiation spot across a sensing area of the flow channel in a scan direction different from the flow direction. A detection system detects resultant light from the sensing area and provides a detection signal. An alignment system alters a location of the sensing area with respect to the flow chamber. A control unit causes the irradiation system to scan the irradiation spot during a first measurement interval and operates the alignment system to translate the location of the sensing area along the flow direction. The flow chamber can be mounted to a movable stage in some examples, and the alignment system can move the flow chamber substantially opposite the flow direction using the stage.

Abstract: An image flow cytometer has a flow chamber with a flow channel formed therein to permit a microparticulate sample to flow through the flow channel. An irradiation optical system irradiates the sample in the channel with incident light in an irradiation spot smaller than a selected representative size, e.g., smaller than the sample. The system scans an irradiation position perpendicular to the flow direction of the sample. A detection optical system is opposed to the irradiation optical system through the flow chamber, or is off the optical axis of the incident light. The detection system detects a light intensity of resultant light from the flow chamber. A control unit detects the microparticulate sample according to a change of the light intensity of the resultant light detected by the detection optical system.