# US 2018/0321128 A1 · Fluid Sample Enrichment System and Method > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0321128 A1 - Document ID: US20180321128A1 - Status: Published application - Kind: A1 - Application number: 15/968,519 - Filed: 2018-05-01 - Published: 2018-11-08 - Earliest claimed: 2017-05-02 - Assignees: See-Through Scientific Limited - Applicants: See-Through Scientific Limited - Inventors: Oliver Harriman; Irwin Zaid - Web page: https://patentgrep.com/patent/US20180321128A1 ## CPC - G01N 15/1429: Signal processing - G01N 1/40: Concentrating samples - G01N 15/1404: Handling flow, e.g. hydrodynamic focusing - G01N 15/1434: Optical arrangements - G01N 15/147: {the analysis being performed on a sample stream} - G01N 15/1409: Handling samples, e.g. injecting samples - G01N 15/149: specially adapted for sorting particles, e.g. by their size or optical properties - G01N 2015/1006: {for cytology} - G01N 2015/1454: {using phase shift or interference, e.g. for improving contrast} - G03H 2001/005: {in microscopy, e.g. digital holographic microscope [DHM]} - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - G03H: HOLOGRAPHIC PROCESSES OR APPARATUS (holograms, e.g. point holograms, used as ordinary optical elements G02B5/32; producing stereoscopic or other three-dimensional effects G02B30/00; diffraction-grating systems G02B27/44; systems using moiré fringes G02B27/60; optical logic elements G02F3/00; stereo-photography G03B35/00; photosensitive materials or processes for photographic purposes G03C; {stereo-photographic or similar processes G03C9/00}; apparatus for processing exposed photographic materials G03D; analogue computers performing mathematical operations with the aid of optical elements G06E3/00; authentication by radiation, of concealed information carried by holograms or diffraction gratings G06K19/16; holographic storage G11B7/0065, G11C13/04; {stereoscopic or other three dimensional effects in television systems H04N13/00}) ## Abstract An enrichment system for enrichment of a sample comprising one or more microscopic particles of interest in a fluid carrier is disclosed. The enrichment system comprises a flow cell configured to receive a portion of the sample, a plurality of sample holding chambers and a waste, each connected to a flow cell, an imaging sensor configured to obtain an image of the microscopic particles in the fluid carrier in the flow cell and a controller configured to direct passage of the portion of the fluid sample in the flow cell, in dependence on the image obtained by the imaging sensor, to one of the holding chambers or to the waste. ## Claims ### Claim 1 An enrichment system for enrichment of a sample comprising one or more microscopic particles of interest in a fluid carrier, the enrichment system comprising: a flow cell configured to receive a portion of the sample; a plurality of sample holding chambers and a waste, each connected to a flow cell; an imaging sensor configured to obtain an image of the microscopic particles in the fluid carrier in the flow cell; and, a controller configured to direct passage of the portion of the fluid sample in the flow cell, in dependence on the image obtained by the imaging sensor, to one of the holding chambers or to the waste. ### Claim 2 (depends on 1) The enrichment system of claim 1, further comprising a buffer source connected to the flow cell, the buffer source being configured to deliver buffer to the flow cell to direct passage of the portion of the fluid sample from the flow cell to a holding chamber. ### Claim 3 (depends on 1) The enrichment system of claim 1, wherein the imaging sensor comprises a digital holographic microscope. ### Claim 4 (depends on 3) The enrichment system of claim 3, wherein the digital holographic microscope is a lensless digital holographic microscope and is configured to generate a hologram of substantially the entire portion of the sample in the flow cell. ### Claim 5 (depends on 1) The enrichment system of claim 1, wherein the controller is configured to execute a supervised learning system to classify particles in the image of the microscopic particles in the portion of the sample. ### Claim 6 (depends on 5) The enrichment system of claim 5, wherein the controller is configured to train and apply the supervised learning system directly on captured holograms. ### Claim 7 (depends on 1) The enrichment system of claim 1, wherein the holding chambers are pipettes. ### Claim 8 (depends on 1) The enrichment system of claim 1, further comprising a heat regulation system comprising a conductive thermal mass, a temperature sensor, a fan and a heat controller, the conductive thermal mass being thermally connected to the controller, the imaging sensor and the holding chambers, the heat controller being configured to receive temperature readings from the temperature sensor and to control speed of the fan to control temperature of the holding chambers. ### Claim 9 (depends on 1) The enrichment system of claim 1, wherein, one or more of the holding chambers and the flow cell are disposable consumable parts. ### Claim 10 (depends on 1) The enrichment system of claim 1, wherein the flow cell is optically transparent and is interposed between the imaging sensor and an illumination system. ### Claim 11 (depends on 1) The enrichment system of claim 1, wherein the plurality of holding chambers comprise first and second holding chambers. ### Claim 12 (depends on 11) The enrichment system of claim 11, wherein the first holding chamber and waste are connected to the flow cell on one side of the flow cell and the second holding chamber and buffer source are connected to the flow cell on a side of the flow cell opposite to that of the first holding chamber and waste. ### Claim 13 (depends on 11) The enrichment system of claim 11, wherein the first and second holding chambers and the waste are connected to the flow cell on a first side of the flow cell, the buffer being connected to the flow cell on a side opposite the first side. ### Claim 14 (depends on 11) The enrichment system of claim 11, wherein the plurality of holding chambers are arranged, during operation of the enrichment system, to rotate around their axes of symmetry. ### Claim 15 (depends on 14) The enrichment system of claim 14, further comprising spur gears mounted to, or high friction wheels in contact with, each of the holding chambers, the spur gears or wheels being controllable by the controller to rotate the holding chambers. ### Claim 16 (depends on 1) The enrichment system of claim 1, wherein the controller is arranged to identify presence of a bubble in the image of the portion of the sample in the flow cell and is arranged to control buffer to flow from the buffer source to the waste to displace the bubble. ### Claim 17 (depends on 1) The enrichment system of claim 1, wherein the flow cell is configured to produce a linear flow profile of the fluid passing through the flow cell. ### Claim 18 A method of fluid sample enrichment comprising: a) passing at least a portion of the fluid sample into a flow cell; b) imaging the portion of the fluid sample in the flow cell; c) controlling passage of the portion out of the flow cell in dependence on said imaging; and repeating steps a) to c) until a predetermined number or proportion of particles of interest remain in the portion, wherein said step of controlling includes: selecting one of a plurality of outlets from the flow cell in dependence on said imaging to selectively dispose of or retain the portion, retaining the portion if it comprises at least one particle of interest. ### Claim 19 (depends on 18) The method of claim 18, further comprising the step of d) diluting the retained portion after step c). ### Claim 20 The method of step 18, further comprising repeating steps a) to c) until a single particle is isolated.