Quantum-Si Incorporated

Cellsbin, Inc.

Ali Kabiri

Gerard M Schmid

Jeremy Lackey

Jonathan Marc Rothberg

Jason W Sickler

Lawrence Camest West

Benjamin Cipriany

Brett J Gyarfas

Keith Glen Fife

Farshid Ghasemi

Kyle Preston

Paul E Glenn

James Beach

Todd Rearick

Jack L Jewell

Dajiang Yang

Bing Shen

Michael Ferrigno

Anthony Bellofiore

Eric A G Webster

Changhoon Choi

Adam Ezra Cohen

Sharath Hosali

Xin Ru Wang

Jonathan C Schultz

Xin Wang

Guojun Chen

Alexander Goryaynov

Eric Ag Webster

Brian Reed

Jonathan M Rothberg

Alexander Gondarenko

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.

Optical system and assay chip for probing, detecting and analyzing molecules

Described herein are techniques to reduce or remove the impact of secondary path photons and/or charge carriers on storage bins of an integrated device to improve noise performance, and thus, sample analysis. Some embodiments relate to optical rejection techniques such as including an optical barrier positioned to block at least some photons from reaching the storage bins. Some embodiments relate to electrical rejection techniques such as including an electrical barrier configured to block at least some charge carriers from reaching the storage bins along at least one secondary path. Some embodiments relate to an integrated device in which at least one storage bin is shaped and/or positioned relative to the photodetector to facilitate receipt of some charge carriers (e.g., fluorescent emission charge carriers) and/or photons and to impede receipt of other charge carriers (e.g., noise charge carriers) and/or photons.

Optical and electrical secondary path rejection

Apparatus and methods for improving optical signal collection in an integrated device are described. A microdisk can be formed in an integrated device and increase collection and/or concentration of radiation incident on the microdisk and re-radiated by the microdisk. An example integrated device that can include a microdisk may be used for analyte detection and/or analysis. Such an integrated device may include a plurality of pixels, each having a reaction chamber for receiving a sample to be analyzed, an optical microdisk, and an optical sensor configured to detect optical emission from the reaction chamber. The microdisk can comprise a dielectric material having a first index of refraction that is embedded in one or more surrounding materials having one or more different refractive index values.

Optical microdisks for integrated devices

Aspects of the technology described herein relate to improved semiconductor-based image sensor designs. In some embodiments, an integrated circuit may comprise a photodetection region and a drain region electrically coupled to the photodetection region, and the photodetection region may be configured to induce an intrinsic electric field in a direction from the photodetection region to the drain region(s). In some embodiments, a charge storage region and the drain region may be positioned on a same side of the photodetection region. In some embodiments, at least one drain layer may be configured to receive incident photons and/or charge carriers via the photodetection region. In some embodiments, an integrated circuit may comprise a plurality of pixels and a control circuit configured to control a transfer of charge carriers in the plurality of pixels.

Integrated sensor for lifetime characterization

System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device may include multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes a surface having a trench region recessed from a portion of the surface and an array of sample wells, disposed in the trench region. The integrated device also includes a waveguide configured to couple excitation energy to at least one sample well in the array and positioned at a first distance from a surface of the trench region and at a second distance from the surface in a region separate from the trench region. The first distance is smaller than the second distance. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device.

Photonic structures and integrated device for detecting and analyzing molecules

Apparatus and methods relating to photonic bandgap optical nanostructures are described. Such optical nanostructures may exhibit prohibited photonic bandgaps or allowed photonic bands, and may be used to reject (e.g., block or attenuate) radiation at a first wavelength while allowing transmission of radiation at a second wavelength. Examples of photonic bandgap optical nanostructures includes periodic and quasi-periodic structures, with periodicity or quasi-periodicity in one, two, or three dimensions and structural variations in at least two dimensions. Such photonic bandgap optical nanostructures may be formed in integrated devices that include photodiodes and CMOS circuitry arranged to analyze radiation received by the photodiodes.

Optical nanostructure rejecter for an integrated device and related methods

Some aspects relate to integrated devices for obtaining timing and/or spectral information from incident light. In some embodiments, a pixel may include one or more charge storage regions configured to receive charge carriers generated responsive to incident photons from a light source, with charge carriers stored in the charge storage region(s) indicative of spectral and timing information. In some embodiments, a pixel may include regions having different depths, each configured to generate charge carriers responsive to incident photons. In some embodiments, a pixel may include multiple charge storage regions having different depths, and one or more of the charge storage regions may be configured to receive the incident photons and generate charge carriers therein. In some embodiments, a pixel may include an optical sorting element configured to direct at least some incident photons to one charge storage region and other incident photons to another charge storage region.

Sensor for lifetime plus spectral characterization

One aspect provided herein is an analyte processing device, comprising one or more flow channels, wherein at least one flow channel of the one or more flow channels comprise an analyte processing area; one or more excitation sources in optical communication with the analyte processing area and comprising an optical path from the one or more excitation sources to the analyte processing area; and one or more photodetectors in optical communication with the analyte processing area, wherein the optical path comprises a light scattering control system.

Devices for biological analysis

Systems and methods for optical power distribution within an integrated device, in a substantially uniform manner, to a large number of sample wells and/or other photonic elements. The integrated device and related instruments and systems may be used to analyze samples in parallel. The integrated device may include a grating coupler configured to receive light from an excitation source and optically couple with multiple waveguides configured to couple with sample wells. Vertical extents of optical modes of individual waveguides may be modulated to adjust confinement of light within the waveguides. This modulation may enable more uniform distribution of excitation light to the sample wells, improve excitation efficiency, and prevent overpower on regions of the integrated device.

Waveguide excitation uniformity

An active-source-pixel, integrated device capable of performing biomolecule detection and/or analysis, such as single-molecule nucleic acid sequencing, is described. An active pixel of the integrated device includes a sample well into which a sample to be analyzed may diffuse, an excitation source for providing excitation energy to the sample well, and a sensor configured to detect emission from the sample. The sensor may comprise two or more segments that produce a set of signals that are analyzed to differentiate between and identify tags that are attached to, or associated with, the sample. Tag differentiation may be spectral and/or temporal based. Identification of the tags may be used to detect, analyze, and/or sequence the biomolecule.

Active-source-pixel, integrated device for rapid analysis of biological and chemical specimens

System and methods for analyzing single molecules and performing nucleic acid sequencing. An integrated device includes multiple pixels with sample wells configured to receive a sample, which when excited, emits radiation. The integrated device includes at least one waveguide configured to propagate excitation energy to the sample wells from a region of the integrated device configured to couple with an excitation energy source. A pixel may also include at least one element for directing the emission energy towards a sensor within the pixel. The system also includes an instrument that interfaces with the integrated device. The instrument may include an excitation energy source for providing excitation energy to the integrated device by coupling to an excitation energy coupling region of the integrated device. One of multiple markers distinguishable by temporal parameters of the emission energy may label the sample and configuration of the sensor within a pixel may allow for detection of a temporal parameter associated with the marker labeling the sample.

Integrated device with external light source for probing, detecting and analyzing molecules

Apparatus and techniques for electrokinetic loading of samples of interest into sub-micron-scale reaction chambers are described. Embodiments include an integrated device and related apparatus for analyzing samples in parallel. The integrated device may include at least one reaction chamber formed through a surface of the integrated device and configured to receive a sample of interest, such as a molecule of nucleic acid. The integrated device may further include electrodes patterned adjacent to the reaction chamber that produce one or more electric fields that assist loading the sample into the reaction chamber. The apparatus may further include a sample reservoir having a fluid seal with the surface of the integrated device and configured to hold a suspension containing the samples.

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Madison, CT, United States of America

Ali Kabiri