# US 2020/0399583 A1 · Acoustic perfusion devices > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2020/0399583 A1 - Document ID: US20200399583A1 - Status: Published application - Kind: A1 - Application number: 16/885,883 - Filed: 2020-05-28 - Published: 2020-12-24 - Earliest claimed: 2012-03-15 - Assignees: FloDesign Sonics, Inc. - Applicants: FloDesign Sonics, Inc. - Inventors: Bart Lipkens; Rudolf Gilmanshin; Louis Masi; Benjamin Ross-Johnsrud; Erik Miller; Walter M. Presz, JR.; Thomas J. Kennedy, III - Web page: https://patentgrep.com/patent/US20200399583A1 ## CPC - C12M 47/02: {Separating microorganisms from the culture medium; Concentration of biomass (separating microorganisms from their culture media C12N1/02)} - B01D 17/04: Breaking emulsions - B01D 17/06: Separation of liquids from each other by electricity - B01D 21/283: {Settling tanks provided with vibrators} - B06B 1/0644: {using a single piezoelectric element (B06B1/0688 takes precedence)} - C07K 1/14: Extraction; Separation; Purification - C12M 29/10: {Perfusion} - C12M 29/18: {External loop; Means for reintroduction of fermented biomass or liquid percolate (loop type reactors for chemical or physical processes B01J19/2435)} - C12M 33/08: {by vibration} - C12M 35/04: {Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli} - C12M 41/12: {of temperature (controlling the temperature of chemical or physical processes B01J19/0013, heating or cooling apparatus for laboratory use B01L7/00)} - C12M 47/10: {Separation or concentration of fermentation products (bioreactors combined with means for distillation or extraction of liquid fuel C12M43/02)} - C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves - G10K 9/122: using piezoelectric driving means {(G10K9/121 takes precedence)} - G10K 15/00: Acoustics not otherwise provided for - G10K 15/043: {producing shock waves (G10K15/046, G10K15/06 take precedence; generating seismic energy G01V1/02)} - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} - B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28) - B06B: METHODS OR APPARATUS FOR GENERATING OR TRANSMITTING MECHANICAL VIBRATIONS OF INFRASONIC, SONIC, OR ULTRASONIC FREQUENCY, {e.g.} FOR PERFORMING MECHANICAL WORK IN GENERAL (for particular applications, see the relevant subclasses, e.g. B07B1/40, B23Q17/12, B24B31/06; measurement of mechanical vibrations G01H; in direction finding, locating, distance or velocity measuring G01S; {generating seismic energy G01V1/02}; control of mechanical vibrations in general G05D; sound-producing devices, e.g. bells, sirens, whistles G10K, {e.g. methods or devices for transmitting, conducting, or directing sound in general G10K11/00}; generation of electrical oscillations H03B; electromechanical resonators in general H03H; electromechanical transducers {for communication techniques, e.g. microphones, speakers} H04R) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - G10K: SOUND-PRODUCING DEVICES; METHODS OR DEVICES FOR PROTECTING AGAINST, OR FOR DAMPING, NOISE OR OTHER ACOUSTIC WAVES IN GENERAL; ACOUSTICS NOT OTHERWISE PROVIDED FOR ## Abstract Methods are disclosed for separating beads and cells from a host fluid. The method includes flowing a mixture containing the host fluid, the beads, and the cells through an acoustophoretic device having an ultrasonic transducer including a piezoelectric material driven by a drive signal to create a multi-dimensional acoustic standing wave. A drive signal is sent to drive the at least one ultrasonic transducer to create the multi-dimensional acoustic standing wave. A recirculating fluid stream having a tangential flow path is located substantially tangential to the standing wave and separated therefrom by an interface region. A portion of the cells pass through the standing wave, and the beads are held back from the standing wave in the recirculating fluid stream at the interface region. Also disclosed is an acoustophoretic device having a coolant inlet adapted to permit the ingress of a cooling fluid into the device for cooling the transducer. ## Claims ### Claim 1 An acoustic bead retention device, comprising: a chamber; at least one ultrasonic transducer coupled to the chamber; the at least one ultrasonic transducer configured to be excited to generate a multi-dimensional acoustic standing wave that is configured to retain beads and pass fluid in which the beads are entrained. ### Claim 2 (depends on 1) The device of claim 1, further comprising a recirculation path communicating with the acoustic chamber. ### Claim 3 (depends on 1) The device of claim 1, wherein the multi-dimensional acoustic standing wave is further configured to generate a pressure rise and an acoustic radiation force on the beads at an interface region of the multi-dimensional acoustic standing wave. ### Claim 4 (depends on 3) The device of claim 3, further comprising a locale adjacent to the interface region where the bead concentration is increased. ### Claim 5 (depends on 1) The device of claim 1, further comprising a locale in the multi-dimensional acoustic standing wave where the bead concentration is increased. ### Claim 6 (depends on 1) The device of claim 1, wherein the multi-dimensional acoustic standing wave is further configured to generate an acoustic radiation force with an axial force component and a lateral force component that are of the same order of magnitude. ### Claim 7 (depends on 1) The device of claim 1, further comprising a control system coupled to the at least one ultrasonic transducer to obtain feedback for control of the at least one ultrasonic transducer. ### Claim 8 (depends on 7) The device of claim 7, further comprising a flow rate monitor coupled to the control system to obtain feedback for control of the flow rate. ### Claim 9 (depends on 1) The device of claim 1, further comprising an inlet communicating with the acoustic chamber for providing media to the chamber to permit media exchange for or washing of the retained beads. ### Claim 10 (depends on 9) The device of claim 9, further comprising an outlet communicating with the chamber for withdrawing the retained beads. ### Claim 11 A method for separating biological material in a fluid, comprising: providing beads that are functionalized with a material with an affinity for the biological material to the fluid; flowing the fluid containing the biological material through an acoustic retention device, the device comprising: a chamber; at least one ultrasonic transducer coupled to the chamber; the at least one ultrasonic transducer configured to be excited to generate a multi-dimensional acoustic standing wave; and exciting the at least one ultrasonic transducer to generate the multi-dimensional acoustic standing wave; and retaining the beads with the multi-dimensional acoustic standing wave; and capturing the biological material with the beads. ### Claim 12 (depends on 11) The method of claim 11, further comprising recirculating the fluid containing the biological material to the chamber. ### Claim 13 (depends on 11) The method of claim 11, further comprising generating a pressure rise and an acoustic radiation force on the beads at an interface region of the multi-dimensional acoustic standing wave. ### Claim 14 (depends on 13) The method of claim 13, further comprising increasing bead concentration adjacent to the interface region. ### Claim 15 (depends on 11) The method of claim 11, further comprising increasing bead concentration in the multi-dimensional acoustic standing wave. ### Claim 16 (depends on 11) The method of claim 11, further comprising exciting the at least one ultrasonic transducer to generate the multi-dimensional acoustic standing wave with an axial force component and a lateral force component that are of the same order of magnitude. ### Claim 17 (depends on 11) The method of claim 11, further comprising: obtaining feedback from the at least one ultrasonic transducer; and controlling the at least one ultrasonic transducer in accordance with the feedback. ### Claim 18 (depends on 11) The method of claim 11, further comprising flowing media through the chamber while the beads with the captured biological material are retained to perform a media exchange for or washing of the biological material. ### Claim 19 (depends on 1) A method for providing a media exchange for cells or for washing cells, comprising: capturing the cells with beads that are functionalized with an affinity for the cells; retaining the beads with the captured cells using the acoustic bead retention device of claim 1; and flowing a fluid into the chamber and through the multi-dimensional acoustic standing wave. ### Claim 20 A method for retaining material in a fluid, comprising: generating a multi-dimensional acoustic standing wave with an acoustic transducer; trapping and clustering the material in the multi-dimensional acoustic standing wave to permit the material to grow in size and exit the multi-dimensional acoustic standing wave; and generating an acoustic edge effect with the multi-dimensional acoustic standing wave to form a barrier to entry to the multi-dimensional acoustic standing wave for the material.