# US 8,783,109 B2 · Ultrasonic analyte concentration and application in flow cytometry > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,783,109 B2 - Document ID: US8783109B2 - Status: Granted - Kind: B2 - Application number: 11/982,042 - Filed: 2007-10-31 - Published: 2010-01-07 - Granted: 2014-07-22 - Earliest claimed: 2004-07-29 - Assignees: Los Alamos National Sercurity, LLC - Applicants: Gregory Kaduchak; Greg Goddard; Gary Salzman; Dipen Sinha; John C. Martin; Christopher Kwiatkowski; Steven Graves - Inventors: Gregory Kaduchak; Greg Goddard; Gary Salzman; Dipen Sinha; John C. Martin; Christopher Kwiatkowski; Steven Graves - Web page: https://patentgrep.com/patent/US8783109B2 ## CPC - B01D 21/28: Mechanical auxiliary equipment for acceleration of sedimentation, e.g. by vibrators or the like - G01N 15/1459: {the analysis being performed on a sample stream} - G01N 2001/4094: {using ultrasound} - G01N 2015/1413: {Hydrodynamic focussing} - G01N 2015/142: {Acoustic or ultrasonic focussing} - Y10T 137/0324: With control of flow by a condition or characteristic of a fluid - Y10T 137/206: Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system] - 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) - 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 The present invention includes an apparatus and corresponding method for concentrating analytes within a fluid flowing through a tube using acoustic radiation pressure. The apparatus includes a function generator that outputs a radio frequency electrical signal to a transducer that transforms the radio frequency electric signal to an acoustic signal and couples the acoustic signal to the tube. The acoustic signal is converted within the tube to acoustic pressure that concentrates the analytes within the fluid. ## Claims ### Claim 1 A system, comprising: an inlet for accepting a fluid having particles therein; a substantially cylindrical chamber for flowing the fluid having particles therein; an acoustic radiation pressure applier configured to apply acoustic radiation pressure to the fluid, the acoustic radiation pressure being adapted to cause an effect on the particles within the fluid; and a function generator outputting a radio frequency electrical signal related to the acoustic radiation pressure applier to drive the acoustic radiation pressure applier, wherein the acoustic radiation pressure applier is configured to apply acoustic radiation pressure to the fluid by acoustically exciting the length of the cylindrical chamber. ### Claim 2 (depends on 1) The flow cytometer of claim 1 wherein said acoustic radiation pressure concentrates the particles. ### Claim 3 (depends on 1) The system of claim 1 wherein said acoustic radiation pressure positions the particles. ### Claim 4 (depends on 1) The flow cytometer of claim 1 wherein said acoustic radiation pressure fractionates the particles. ### Claim 5 (depends on 1) The system of claim 1 further comprising an acoustic signal producing transducer producing said acoustic radiation pressure. ### Claim 6 (depends on 1) The flow cytometer of claim 1 wherein said acoustic radiation pressure induces an outer boundary surface displacement. ### Claim 7 (depends on 1) The system of claim 1 further comprising an interrogation light source analyzing the particles. ### Claim 8 (depends on 7) The system of claim 7 further comprising collection optics receiving information from said interrogation light source. ### Claim 9 (depends on 7) The system of claim 7 wherein said interrogation light source is a laser. ### Claim 10 (depends on 7) The system of claim 7 wherein said interrogation light source is an arc lamp. ### Claim 11 (depends on 1) The system of claim 1 wherein said function generator is selected from any voltage source circuit capable of producing a variety of voltage waveforms of varying frequencies. ### Claim 12 (depends on 1) The system of claim 1 further comprising a power amplifier amplifying said output of said function generator. ### Claim 13 (depends on 1) The system of claim 1 wherein said flow cytometer does not contain a hydrodynamic sheath. ### Claim 14 (depends on 1) The system of claim 1 wherein the fluid comprises a dilute suspension of particles. ### Claim 15 (depends on 1) The system of claim 1 further comprising photomultiplier tubes configured for analyzing the particles, wherein analyzing the particles comprises: subjecting the particles to an interrogation light source; and collecting information from the interrogated particles; and identifying the information to determine molecular makeup of the particles. ### Claim 16 (depends on 1) The system of claim 1 further comprising a detector configured to collect Raman signals from the particles. ### Claim 17 A system, comprising: an inlet for accepting a fluid having particles therein; a substantially cylindrical chamber for flowing the fluid having particles therein; an acoustic radiation pressure applier configured to apply acoustic radiation pressure to the fluid, the acoustic radiation pressure being adapted to cause an effect on the particles within the fluid, and wherein the acoustic radiation pressure applier is configured to apply acoustic radiation pressure to the fluid by acoustically exciting the length of the cylindrical chamber; a monitoring transducer configured to monitor a frequency of the acoustic radiation pressure; an interrogation light source configured to illuminate the particles; and a photomultiplier tube configured collect information from the interrogated particles, the information comprising information to determine molecular makeup of the particles. ### Claim 18 (depends on 17) The system of claim 17 wherein said monitoring transducer monitors said outer boundary surface displacement. ### Claim 19 (depends on 17) The system of claim 17 wherein said monitoring transducer adjusts said acoustic radiation pressure to maintain resonant frequency. ### Claim 20 (depends on 17) The system of claim 17 wherein said monitoring transducer adjusts the frequency of said acoustic radiation pressure to adjust for a temperature fluctuation. ### Claim 21 (depends on 17) The system of claim 17 wherein said monitoring transducer is selected from the group consisting of a piezoceramic, piezosalt, piezopolymer, piezocrystal, magnetostrictive, and electromagnetic transducer. ### Claim 22 (depends on 17) The system of claim 17 further comprising a detector configured to collect Raman signals from the particles. ### Claim 23 A method of imparting movement to particles in a fluid comprising: supplying a fluid having particles therein to a flow cytometer comprising a substantially cylindrical chamber; applying acoustic radiation pressure to the fluid, wherein said acoustic radiation pressure causes an effect on the particles within the fluid, and wherein applying acoustic radiation pressure to the fluid comprises acoustically exciting the length of the cylindrical chamber; and outputting a radio frequency electrical signal. ### Claim 24 (depends on 23) The method of claim 23 further comprising concentrating the particles. ### Claim 25 (depends on 23) The method of claim 23 further comprising collecting magnetic moment signals from the particles. ### Claim 26 (depends on 23) The method of claim 23 wherein collecting magnetic moment signal comprises determining the molecular makeup of the particles. ### Claim 27 (depends on 23) The method of claim 23 further comprising positioning the particles with said acoustic radiation pressure. ### Claim 28 (depends on 23) The method of claim 23 further comprising fractionating the particles. ### Claim 29 (depends on 23) The method of claim 23 further comprising analyzing the particles. ### Claim 30 (depends on 29) The method of claim 29 wherein analyzing the particles comprises: subjecting the particles to an interrogation light source; and collecting information from the interrogated particles. ### Claim 31 (depends on 23) The method of claim 23 further comprising inducing an outer boundary surface displacement. ### Claim 32 (depends on 23) The method of claim 23 further comprising monitoring the outer boundary surface displacement. ### Claim 33 (depends on 23) The method of claim 23 further comprising adjusting the acoustic radiation pressure for an ambient temperature fluctuation. ### Claim 34 (depends on 23) The method of claim 23 further comprising amplifying the output of the radio frequency electrical signal. ### Claim 35 (depends on 23) The method of claim 23 further comprising moving the particles to a nodal position. ### Claim 36 (depends on 23) The method of claim 23 not using a hydrodynamic sheath. ### Claim 37 (depends on 23) The method of claim 23 further comprising analyzing the particles, wherein analyzing the particles comprises: subjecting the particles to an interrogation light source; and collecting information from the interrogated particles; and identifying the information to determine molecular makeup of the particles. ### Claim 38 (depends on 23) The method of claim 23 further comprising collecting Raman signals from the particles. ### Claim 39 A method of analyzing particles in a fluid comprising: supplying a fluid having particles therein to a flow cytometer comprising a substantially cylindrical chamber; applying acoustic radiation pressure to the fluid, wherein said acoustic radiation pressure causes an effect on the particles within the fluid, and wherein applying acoustic radiation pressure to the fluid comprises acoustically exciting the length of the cylindrical chamber; analyzing the particles, wherein analyzing the particles comprises: subjecting the particles to an interrogation light source; and collecting information from the interrogated particles; and identifying the information to determine molecular makeup of the particles. ### Claim 40 (depends on 39) The method of claim 39 further comprising collecting Raman signals from the particles. ### Claim 41 A method of imparting movement to particles in a fluid comprising: supplying a fluid having particles therein to a flow cytometer comprising a substantially cylindrical chamber; applying acoustic radiation pressure to the fluid, wherein said acoustic radiation pressure causes an effect on the particles within the fluid, and wherein applying acoustic radiation pressure to the fluid comprises acoustically exciting the length of the cylindrical chamber; adjusting the acoustic radiation pressure to maintain a resonant frequency; and collecting Raman signals from the particles. ### Claim 42 (depends on 41) The method of claim 41 further comprising tuning a drive frequency to the resonance frequency by varying the drive frequency. ### Claim 43 (depends on 41) The method of claim 41 further comprising analyzing the particles, wherein analyzing the particles comprises: subjecting the particles to an interrogation light source; and collecting information from the interrogated particles; and identifying the information to determine molecular makeup of the particles. ### Claim 44 A method of analyzing particles in a fluid comprising: supplying a fluid having particles therein to a flow cytometer comprising a substantially cylindrical chamber; applying acoustic radiation pressure to the fluid, wherein said acoustic radiation pressure causes an effect on the particles within the fluid, and wherein applying acoustic radiation pressure to the fluid comprises acoustically exciting the length of the cylindrical chamber; and collecting Raman signals from the particles.