# US 9,040,304 B2 · Multi-channel system and methods for sorting particles > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,040,304 B2 - Document ID: US9040304B2 - Status: Granted - Kind: B2 - Application number: 14/206,832 - Filed: 2014-03-12 - Published: 2014-08-07 - Granted: 2015-05-26 - Earliest claimed: 2003-03-28 - Assignees: Inguran, LLC - Applicants: Inguran, LLC - Inventors: Gary Durack; Jeffrey D. Wallace; Gary P. Vandre; Lon A. Westfall; Jeremy T. Hatcher; Niraj V. Nayak - Web page: https://patentgrep.com/patent/US9040304B2 ## CPC - C12N 5/0612: {sorting of gametes, e.g. according to sex or motility} - A01N 1/162: Temperature processes, e.g. following predefined temperature changes over time - C12N 5/06: {Animal cells or tissues; Human cells or tissues (preservation of excised living parts A01N1/10)} - C12N 5/061: {Sperm cells, spermatogonia} - C12Q 1/02: involving viable microorganisms - C12Q 3/00: Condition responsive control processes (apparatus therefor C12M1/36; controlling or regulating in general G05) - G01N 15/1404: Handling flow, e.g. hydrodynamic focusing - G01N 15/1459: {the analysis being performed on a sample stream} - G01N 15/1468: {with spatial resolution of the texture or inner structure of the particle} - G01N 15/147: {the analysis being performed on a sample stream} - G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)} - G01N 33/48: Biological material, e.g. blood, urine (G01N33/02, G01N33/26, G01N33/44, G01N33/46 take precedence); Haemocytometers (counting blood corpuscules distributed over a surface by scanning the surface G06M11/02) - G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)} - G01N 15/01: specially adapted for biological cells, e.g. blood cells (investigating sedimentation of particle suspensions in blood G01N15/05) - G01N 15/149: specially adapted for sorting particles, e.g. by their size or optical properties - G01N 21/63: optically excited - G01N 2015/1006: {for cytology} - G01N 2015/1406: {Control of droplet point} - G01N 2015/1415: {Control of particle position} - G01N 2021/6439: {with indicators, stains, dyes, tags, labels, marks} - Y10T 436/10: Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing - Y10T 436/115831: Condition or time responsive - Y10T 436/12: Condition responsive control - Y10T 436/25: including sample preparation - Y10T 436/2525: Stabilizing or preserving - Y10T 436/25375: Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] - Y10T 436/255: including use of a solid sorbent, semipermeable membrane, or liquid extraction - Y10T 436/2575: Volumetric liquid transfer - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - 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) - Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION ## Abstract A multi-channel system and methods for sorting particles according to one or more characteristics of the particles. The system includes multiple flow cytometry units, each unit can have a nozzle for producing a fluid stream containing a desired population of particles in a mixture of particles. Each of the units may be operable to sort said desired population of particles by interrogating the fluid stream with a beam of electromagnetic radiation and classifying particles based on one or more characteristics of the particles. The system also includes a common fluid delivery system for delivering sheath fluid to each flow cytometer unit for producing respective fluid streams. ## Claims ### Claim 1 A multi-channel system for sorting particles according to one or more characteristics of the particles, said system comprising: multiple flow cytometry units, each unit having a nozzle to produce a fluid stream containing a desired population of particles in a mixture of particles, wherein each of said units is operable to sort said desired population of particles by interrogating the fluid stream with a beam of electromagnetic radiation and classifying particles based on one or more characteristics of the particles; and a common fluid delivery system for delivering sheath fluid to each flow cytometer unit for producing respective fluid streams. ### Claim 2 (depends on 1) The multi-channel system of claim 1 wherein the particles are cells. ### Claim 3 (depends on 1) The multi-channel system of claim 1 wherein the particles are sperm cells. ### Claim 4 (depends on 1) The multi-channel system of claim 1 wherein one or more of the multiple flow cytometry units comprises a jet-in-air droplet sorting flow cytometry unit. ### Claim 5 (depends on 1) The multi-channel system of claim 1 wherein the multiple flow cytometry units are provided on an integrated platform. ### Claim 6 (depends on 5) The multi-channel system of claim 5 wherein the integrated platform comprises a common input for controlling operation of said units and a common processor for receiving and processing information from said units. ### Claim 7 (depends on 5) The multi-channel system of claim 5 wherein said integrated platform comprises a common source of electromagnetic radiation for producing the beam of electromagnetic radiation for each unit. ### Claim 8 (depends on 7) The multi-channel system of claim 7 wherein the common source of electromagnetic radiation comprises a single laser producing a single laser beam and further comprising a beam splitting system for splitting the single laser beam into multiple beams and directing the multiple beams into optics systems of respective flow cytometry units. ### Claim 9 (depends on 8) The multi-channel system of claim 8 wherein said single laser beam comprises a plurality of pulses. ### Claim 10 (depends on 9) The multi-channel system of claim 9 and wherein one or more of said flow cytometry units comprises: a flow channel for directing a fluid stream containing sample particles through a particle interrogation location; a beam guidance system operable to direct a portion of the electromagnetic radiation in a pulse to the interrogation location; a timing circuit operable to produce a timing signal indicative of the arrival of electromagnetic radiation at the interrogation location; a detector adapted to detect electromagnetic radiation from the interrogation location and operable to output a time-varying analog signal indicative of the intensity of the detected electromagnetic radiation; an analog to digital converter adapted to receive the time-varying analog signal as input and to sample the analog signal to produce a digitized output; and an electronic processor operable to analyze the digitized output from the analog to digital converter as a function of the timing signal. ### Claim 11 (depends on 5) The multi-channel system of claim 5, wherein the integrated platform comprises a common processor which performs at least one of: (1) receiving and processing information from the flow cytometry units in real time; and (2) receiving and processing information from the flow cytometry units to permit evaluation of the operation of one unit relative to another unit. ### Claim 12 (depends on 5) The multi-channel system of claim 5 wherein said integrated platform comprises a common processor operable to send control signals to the flow cytometry units in real time during a sorting process to adjust their operation as a function of information received by the common processor, and wherein the flow cytometry units are responsive to the control signals. ### Claim 13 (depends on 1) The multi-channel system of claim 1 wherein each flow cytometry unit comprises a sensor operable to generate a time-varying output signal indicative of at least one characteristic of the particles, and further comprising a common processor for receiving and processing information from the units and said information received by the common processor comprises the output signals from the respective sensors, and wherein the processor is operable to receive the output signals as a substantially continuous stream and to substantially continuously process the output signals in real time. ### Claim 14 (depends on 1) The multi-channel system of claim 1 wherein each flow cytometry unit comprises an epi-illumination optics system for interrogating a respective fluid stream. ### Claim 15 (depends on 1) The multi-channel system of claim 1 wherein at least one of said flow cytometry units comprises a photo-damage system. ### Claim 16 (depends on 1) The multi-channel system of claim 1 wherein at least one of said flow cytometry units comprises a fluid-switching sorting system. ### Claim 17 (depends on 1) The multi-channel system of claim 1 wherein said flow cytometry units are adapted to operate in parallel. ### Claim 18 (depends on 1) The multi-channel system of claim 1 wherein the multiple flow cytometry units comprise three or more flow cytometry units. ### Claim 19 (depends on 1) The multi-channel system of claim 1 wherein the multiple flow cytometry units comprise at least twelve flow cytometry units. ### Claim 20 A multi-channel method of sorting particles according to one or more characteristics of the particles, said method comprising: delivering sheath fluid to multiple flow cytometry units from a common fluid delivery system; generating fluid streams containing sheath fluid at each of said units, each fluid stream also containing a desired population of particles within a mixture of particles; interrogating each fluid stream with a beam of electromagnetic radiation; classifying particles based on one or more characteristics of the particles; and sorting the desired population of particles within a mixture of particles. ### Claim 21 (depends on 20) The method of claim 20 wherein said particles are cells. ### Claim 22 (depends on 20) The method of claim 20 wherein said particles are sperm cells. ### Claim 23 (depends on 20) The method of claim 20 wherein at least one of said multiple flow cytometry units comprises a jet-in-air droplet sorting flow cytometry unit. ### Claim 24 (depends on 20) The method of claim 20 further comprising sharing a common source of electromagnetic radiation in the form of a single laser beam, said method further comprising splitting the single laser beam into multiple beams and directing the multiple beams into optics systems of respective flow cytometry units. ### Claim 25 (depends on 24) The method of claim 24 further comprising reflecting a percentage of beam light of the single beam toward the optics system of one of said flow cytometry units, and passing a percentage of beam light of the single beam for transmission to the optics system of another of said flow cytometry units. ### Claim 26 (depends on 20) The method of claim 20 further comprising the step of removably mounting said flow cytometry units in a common housing. ### Claim 27 (depends on 20) The method of claim 20 further comprising a common source of electromagnetic radiation in the form of a shared laser; the method further comprising the steps of: emitting a plurality of electromagnetic radiation (EMR) pulses from a laser, wherein a peak power of each pulse exceeds an average power of the laser; directing each pulse into a beam splitting and guidance system to intermittently illuminate each fluid stream and the particles contained therein by directing a portion of the energy in the pulses along a beam path from the laser to an interrogation location associated with each of the flow cytometer units; detecting EMR from at least one interrogation location; generating a time-varying analog signal indicative of the intensity of the detected EMR from said interrogation location; generating a timing signal indicative of the arrival of a pulse at said interrogation location; converting the time-varying analog signal into a digital signal; and analyzing the digital signal to determine characteristics of the particles in the fluid stream flowing through the respective interrogation location. ### Claim 28 (depends on 20) The method of claim 20 further comprising collecting a population of desired particles sorted by each flow cytometry unit, and combining the population collected from one unit with a population collected from a different unit to produce a blended population of desired particles. ### Claim 29 (depends on 20) The method of claim 20 further comprising sharing a common processor for receiving and processing information from the units wherein the common processor receives and processes said information in real time; and receives and processes said information to permit evaluation of the operation of one unit relative to another unit.