Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

Ultrasonic analyte concentration and application in flow cytometry

Patent ·
OSTI ID:1149911

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.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC52-06NA25396
Assignee:
Los Alamos National Security, LLC (Los Alamos, NM)
Patent Number(s):
8,783,109
Application Number:
11/982,042
OSTI ID:
1149911
Country of Publication:
United States
Language:
English

References (190)

Microparticle manipulation in millimetre scale ultrasonic standing wave chambers journal August 1998
Positioning of small particles by an ultrasound field excited by surface waves journal April 2004
Cell–cell contact and membrane spreading in an ultrasound trap journal April 2004
Concentration and Fractionation of Small Particles in Liquid by Ultrasound journal May 1995
Comparative analysis of whole blood lysis methods for flow cytometry journal June 1997
Diazo Coupling Method for Covalent Attachment of Proteins to Solid Substrates journal March 2006
Manipulation of Fluid Objects with Acoustic Radiation Pressure journal January 2006
Positioning, displacement, and localization of cells using ultrasonic forces journal January 2005
Compact acoustic levitation device for studies in fluid dynamics and material science in the laboratory and microgravity journal November 1985
Ultrasonic particle-concentration for sheathless focusing of particles for analysis in a flow cytometer journal January 2006
Design, modeling and characterization of microfluidic devices for ultrasonic manipulation journal February 2007
Selective Retention of Viable Cells in Ultrasonic Resonance Field Devices journal February 1996
Enhanced immunofluorescence measurement resolution of surface antigens on highly autofluorescent, glutaraldehyde-fixed cells analyzed by phase-sensitive flow cytometry journal December 1999
Data Analysis for a Dual-Channel Virus Counter journal April 2005
Microchip-Based Cell Lysis and DNA Extraction from Sperm Cells for Application to Forensic Analysis journal March 2006
Time-resolved flow cytometry for the measurement of lanthanide chelate fluorescence: II. Instrument design and experimental results journal July 1994
High throughput particle analysis: Combining dielectrophoretic particle focussing with confocal optical detection journal February 2006
A micro-particle positioning technique combining an ultrasonic manipulator and a microgripper journal June 2006
Fractionation of cell mixtures using acoustic and laminar flow fields journal January 2004
Synthesis, Characterization, and Application of Eu(III), Tb(III), Sm(III), and Dy(III) Lanthanide Chelate Nanoparticle Labels journal April 2005
Force field particle filter, combining ultrasound standing waves and laminar flow journal May 2001
Separation of a biocatalyst with ultrafiltration or filtration after bioconversion journal March 1997
Acoustic separation in a laminar flow conference January 1994
Micro particle trapping by opposite phases ultrasonic travelling waves journal July 1998
Lanthanide-based luminescence probes and time-resolved luminescence bioassays journal May 2006
Separation devices based on forced coincidence response of fluid‐filled pipes journal June 1992
Electroacoustic production of murine hybridomas journal May 1990
Experimental study of streaming flows associated with ultrasonic levitators journal November 1994
Classification of Spectroscopically Encoded Resins by Raman Mapping and Infrared Hyperspectral Imaging journal March 2006
Enhanced sedimentation of mammalian cells following acoustic aggregation journal August 1989
Quantum Dot-Encoded Mesoporous Beads with High Brightness and Uniformity:  Rapid Readout Using Flow Cytometry journal April 2004
Major signal increase in fluorescence microscopy through dark-state relaxation journal December 2006
Near-Infrared Photo- and Electroluminescence of Alkoxy-Substituted Poly p-phenylene) and Nonconjugated Polymer/Lanthanide Tetraphenylporphyrin Blends journal July 2004
Generalized rainbows and unfolded glories of oblate drops: organization for multiple internal reflections and extension of cusps into Alexander's dark band journal January 1994
Effect of Process Parameters on Ultrasonic Separation of Dispersed Particles in Liquid journal May 1999
Particle separation using acoustic radiation force and elecrostatic force
  • Yasuda, Kenji; Umemura, Shin‐ichiro; Takeda, Kazuo
  • The Journal of the Acoustical Society of America, Vol. 99, Issue 4, p. 1965-1970 https://doi.org/10.1121/1.415382
journal April 1996
Improved quartz crystal microbalance technique journal August 1984
Ultrasonic Micromanipulator Using Visual Feedback journal May 1996
Acoustic control of suspended particles in micro fluidic chips journal January 2004
E6 diffraction catastrophe of the primary rainbow of oblate water drops: observations with white-light and laser illumination journal January 1994
Linear and nonlinear frequency shifts in acoustical resonators with varying cross sections
  • Hamilton, Mark F.; Ilinskii, Yurii A.; Zabolotskaya, Evgenia A.
  • The Journal of the Acoustical Society of America, Vol. 110, Issue 1, p. 109-119 https://doi.org/10.1121/1.1379080
journal July 2001
Manipulation of cells using an ultrasonic pressure field journal June 2005
Development of a novel compact sonicator for cell disruption journal February 2005
Ultrasonic waves for fabricating lattice structure in composite materials
  • Saito, Mitsunori; Itagaki, Kazuhiro; Imanishi, Yoshihiro
  • SPIE's International Symposium on Optical Science, Engineering, and Instrumentation https://doi.org/10.1117/12.363793
conference September 1999
Sub-micron particle manipulation in an ultrasonic standing wave: Applications in detection of clinically important biomolecules journal January 2000
Precise Measurements Of Particle Entrainment In A Standing-Wave Acoustic Field Between 20 And 3500 Hz journal December 2000
Cavitation bubble-driven cell and particle behavior in an ultrasound standing wave
  • Kuznetsova, Larisa A.; Khanna, Sanjay; Amso, Nazar N.
  • The Journal of the Acoustical Society of America, Vol. 117, Issue 1, p. 104-112 https://doi.org/10.1121/1.1835503
journal January 2005
Acoustic radiation force on a spherical particle in a viscous heat-conducting fluid. I. General formula journal February 1997
Particle separation using ultrasound can be used with human shed mediastinal blood journal January 2005
Continuous cell washing and mixing driven by an ultrasound standing wave within a microfluidic channel journal January 2004
Use of acoustic radiation pressure to concentrate small particles in an air flow conference January 2002
Deoxyribonucleic acid concentration using acoustic radiation force
  • Yasuda, Kenji; Kiyama, Masaharu; Umemura, Shin‐ichiro
  • The Journal of the Acoustical Society of America, Vol. 99, Issue 2, p. 1248-1251 https://doi.org/10.1121/1.414635
journal February 1996
Manipulation of in vitro toxicant sensors in an ultrasonic standing wave journal February 2004
On the drift of aerosol particles in sonic fields journal September 1992
Zeptomole detection sensitivity of prostate-specific antigen in a rapid microtitre plate assay using time-resolved fluorescence journal January 2000
Mathematical modeling of the movement of suspended particles subjected to acoustic and flow fields journal June 2005
Batch and semicontinuous aggregation and sedimentation of hybridoma cells by acoustic resonance fields journal March 1995
Light-scattering properties of individual erythrocytes journal January 1999
Theory of long wavelength acoustic radiation pressure journal October 1991
Acoustic streaming generated by standing waves in two-dimensional channels of arbitrary width
  • Hamilton, Mark F.; Ilinskii, Yurii A.; Zabolotskaya, Evgenia A.
  • The Journal of the Acoustical Society of America, Vol. 113, Issue 1, p. 153-160 https://doi.org/10.1121/1.1528928
journal January 2003
Acoustically aided separation of oil droplets from aqueous emulsions journal August 2004
Increasing the luminescence of lanthanide complexes journal January 2006
Plasma preparation from whole blood using ultrasound journal June 2000
Ultrasound, a new separation technique to harvest microalgae journal March 2003
A new immobilisation method to arrange particles in a gel matrix by ultrasound standing waves journal February 2005
Individual Escherichia coli cells studied from light scattering with the scanning flow cytometer journal January 2000
Resonator frequency shift due to ultrasonically induced microparticle migration in an aqueous suspension: Observations and model for the maximum frequency shift
  • Kwiatkowski, Christopher S.; Marston, Philip L.
  • The Journal of the Acoustical Society of America, Vol. 103, Issue 6, p. 3290-3300 https://doi.org/10.1121/1.423080
journal June 1998
Angular distribution of light scattered by single biological cells and oriented particle agglomerates journal January 2003
Modelling of particle paths passing through an ultrasonic standing wave journal April 2004
Ultrasonic deposition of cells on a surface journal April 2004
Single-collector experiments and modeling of acoustically aided mesh filtration journal January 2005
Comparative study of five commercial reagents for preparing normal and leukaemic lymphocytes for immunophenotypic analysis by flow cytometry journal August 1999
New types of microspheres and microsphere-related materials for medical diagnostics
  • Slomkowski, Stanislaw; Basinska, Teresa; Miksa, Beata
  • Polymers for Advanced Technologies, Vol. 13, Issue 10-12, p. 905-918 https://doi.org/10.1002/pat.283
journal October 2002
Transport and harvesting of suspended particles using modulated ultrasound journal November 1991
A Novel Ultrasonic Resonance Field Device for the Retention of Animal Cells journal July 1994
Ultrasonic manipulation of locomotive microorganisms and evaluation of their activity journal December 2002
Seven-Color Time-Resolved Fluorescence Hybridization Analysis of Human Papilloma Virus Types journal November 1997
Trapping of microparticles in the near field of an ultrasonic transducer journal March 2005
Side drift of aerosols in two-dimensional resonant acoustic levitators journal November 1997
On the Possibility of Long-Wavelength Long-Lifetime High-Quantum-Yield Luminophores journal January 2001
Fluorescence background discrimination by prebleaching. journal January 1979
Virus removal in a membrane separation process journal January 1998
A computer-controlled system for the measurement of complete admittance spectra of piezoelectric resonators journal September 1990
Identification of cell asymmetry and orientation by light scattering. journal July 1977
Design and characterization of a compact dual channel virus counter journal January 2005
Ultrasonic separations in analytical biotechnology journal December 1997
Dual-laser, differential fluorescence correction method for reducing cellular background autofluorescence journal November 1986
Monodisperse Mesoporous Silica Microspheres Formed by Evaporation-Induced Self Assembly of Surfactant Templates in Aerosols journal September 2002
Single fiber model of particle retention in an acoustically driven porous mesh journal March 2003
Layered piezoelectric resonators with an arbitrary number of electrodes (general one‐dimensional treatment)
  • Nowotny, Helmut; Benes, Ewald; Schmid, Michael
  • The Journal of the Acoustical Society of America, Vol. 90, Issue 3, p. 1238-1245 https://doi.org/10.1121/1.401915
journal September 1991
Spatial light-scattering analysis as a means of characterizing and classifying non-spherical particles journal February 1998
Preparation of three terbium complexes with p-aminobenzoic acid and investigation of crystal structure influence on luminescence property journal October 2004
Fractionation of mixed particulate solids according to compressibility using ultrasonic standing wave fields journal October 1995
Contactless micromanipulation of small particles by an ultrasound field excited by a vibrating body journal May 2005
Blood Concentration by Superposition of Higher Harmonics of Ultrasound journal May 1997
Microfluidic tools for biological sample preparation conference January 2002
Acoustic agglomeration of a glycol fog aerosol: Influence of particle concentration and intensity of the sound field at two frequencies journal June 1995
Ultrasonic four‐wave mixing mediated by an aqueous suspension of microspheres: Theoretical steady‐state properties journal September 1995
Hydrodynamic orientation of sperm heads for flow cytometry journal July 1978
Resolution of dimly fluorescent particles: A practical measure of fluorescence sensitivity journal October 1998
Acoustic radiation force on a spherical particle in a viscous heat-conducting fluid. III. Force on a liquid drop journal February 1997
Micromanipulation using a focused ultrasonic standing wave field journal January 2000
Standing‐wave acoustic trap for nonintrusive positioning of microparticles journal October 1995
Optimization of high-sensitivity fluorescence detection journal September 1990
Ultrasonic Micromanipulation of Small Particles in Liquid journal May 1994
A laminar flow expansion chamber facilitating downstream manipulation of particles concentrated using an ultrasonic standing wave journal July 1998
The Small-Angle Light Scattering of Biological Cells: Theoretical Considerations journal August 1970
Trapping of heavy gases in stationary ultrasonic fields journal September 2002
Carrier Medium Exchange through Ultrasonic Particle Switching in Microfluidic Channels journal March 2005
Impedance spectroscopy flow cytometry: On-chip label-free cell differentiation journal January 2005
Cellular platforms for HTS: three case studies journal March 2002
Transport analysis and model for the performance of an ultrasonically enhanced filtration process journal June 2005
A novel nozzle for more efficient sperm orientation to improve sorting efficiency of X and Y chromosome-bearing sperm journal December 1998
Inorganic phosphors as new luminescent labels for immunocytochemistry and time-resolved microscopy journal January 1990
Oscillational instabilities in single‐mode acoustic levitators journal January 1990
Book Reviews journal April 1989
Acoustic radiation force on a spherical particle in a viscous heat-conducting fluid. II. Force on a rigid sphere journal February 1997
Cell discrimination by multiangle light scattering. journal January 1976
Free Flow Acoustophoresis:  Microfluidic-Based Mode of Particle and Cell Separation journal July 2007
Continuous separation of lipid particles from erythrocytes by means of laminar flow and acoustic standing wave forces journal January 2005
Strategy for selection of methods for separation of bioparticles from particle mixtures journal January 2006
Evaluation of SDF-1/CXCR4-induced Ca2+ signaling by fluorometric imaging plate reader (FLIPR) and flow cytometry journal December 2002
Using acoustic radiation force as a concentration method for erythrocytes
  • Yasuda, Kenji; Haupt, Stephan Shuichi; Umemura, Shin-ichiro
  • The Journal of the Acoustical Society of America, Vol. 102, Issue 1, p. 642-645 https://doi.org/10.1121/1.421009
journal July 1997
Ultrasonic separation in microfluidic capillaries conference January 2003
Ultrasonic trapping of paramecia and estimation of their locomotive force journal October 1997
Coincidence in high-speed flow cytometry: Models and measurements journal January 1991
Hydrodynamic orientation of cells. journal July 1977
Ruthenium(II) complex with a notably long excited state lifetime journal January 2000
Particle Characterization and Separation by a Coupled Acoustic−Gravity Field journal July 2001
Ueber longitudinale Schwingungen und Klangfiguren in cylindrischen Flüssigkeitssäulen journal January 1874
Acoustic Radiation Pressure of Plane Compressional Waves journal July 1953
Separation of lipids from blood utilizing ultrasonic standing waves in microfluidic channels journal January 2004
PDMS-based opto-fluidic micro flow cytometer with two-color, multi-angle fluorescence detection capability using PIN photodiodes journal March 2004
Analytical scale ultrasonic standing wave manipulation of cells and microparticles journal March 2000
The mean force acting on a small body in an axisymmetric sound field in a real medium journal January 1987
Particle column formation in a stationary ultrasonic field journal January 1992
A means for orienting flat cells in flow systems journal July 1978
Continuous particle size separation and size sorting using ultrasound in a microchannel journal January 2006
SPART analyzer: its application to aerodynamic size distribution measurement journal January 1979
Non-destructive, non-contact handling method for biomaterials in micro-chamber by ultrasound journal June 2000
Single particle high resolution spectral analysis flow cytometry journal January 2006
Extension of acoustic levitation to include the study of micron‐size particles in a more compressible host liquid journal May 1982
Resolving leukocytes using axial light loss journal July 1989
Progress in Lanthanides as Luminescent Probes journal July 2005
An analytical system based on a compact flow cytometer for DNA fragment sizing and single-molecule detection journal January 2004
A numerically stable global matrix method for cylindrically layered shells excited by ring forces journal June 1994
Formation and growth of ice particles in stationary ultrasonic fields journal September 1998
Flow cytometry to evaluate Theileria sergenti parasitemia using the fluorescent nucleic acid stain, SYTO16 journal January 2000
Operating Characteristics of Acoustically Driven Filtration Processes for Particulate Suspensions journal January 2000
Ultrasonic particle concentration in a line-driven cylindrical tube journal June 2005
Acoustic Radiation Pressure on a Rigid Sphere in a Viscous Fluid journal December 1994
Physical enviroment of 2-D animal cell aggregates formed in a short pathlength ultrasound standing wave trap journal March 2005
Acoustically driven collection of suspended particles within porous media journal March 1997
Continuous Flow Microfluidic Device for Rapid Erythrocyte Lysis journal November 2004
Modelling in the design of a flow-through ultrasonic separator journal March 2000
Acoustic micromanipulation using a multi-electrode transducer conference January 1996
Control of a Standing Wave Field Using a Line-Focused Transducer for Two-Dimensional Manipulation of Particles journal May 1998
Upper sound pressure limits on particle concentration in fields of ultrasonic standing-wave at megahertz frequencies journal January 1992
Enhanced synchronized ultrasonic and flow-field fractionation of suspensions journal March 1994
Acoustic concentration of particles in piezoelectric tubes: Theoretical modeling of the effect of cavity shape and symmetry breaking
  • Kogan, Shulim; Kaduchak, Gregory; Sinha, Dipen N.
  • The Journal of the Acoustical Society of America, Vol. 116, Issue 4, p. 1967-1974 https://doi.org/10.1121/1.1785613
journal October 2004
Modelling of layered resonators for ultrasonic separation journal May 2002
Migration of suspended particles in plane stationary ultrasonic field journal January 1981
Hyperbolic umbilic and E6 diffraction catastrophes associated with the secondary rainbow of oblate water drops: observations with laser illumination journal January 1994
Micro-organism manipulation and microparticle arrangement by the use of ultrasonic standing waves conference November 2001
Pulsed laser fluorescence spectrometer journal October 1987
Tensile strength and visible ultrasonic cavitation of superfluid4He journal November 1976
Acoustic Positioning for Space Processing of Materials Science Samples in Mirror Furnaces conference January 1983
Time-resolved flow cytometry for the measurement of lanthanide chelate fluorescence: I. Concept and theoretical evaluation journal July 1994
On the Acoustic Radiation Pressure on Spheres journal November 1934
The selection of layer thicknesses to control acoustic radiation force profiles in layered resonators journal January 2003
Blue LED Excitable Temperature Sensors Based on a New Europium(III) Chelate journal February 2008
Microparticle concentration in short path length ultrasonic resonators: Roles of radiation pressure and acoustic streaming journal October 2004
A differential amplifier circuit for reducing noise in axial light loss measurements journal July 1983
Single particle aerodynamic relaxation time analyzer journal June 1977
Field-assisted extraction of cells, particles and macromolecules journal February 2002
Retention and Viability Characteristics of Mammalian Cells in an Acoustically Driven Polymer Mesh journal January 2004
A silicon microfluidic ultrasonic separator journal October 2003
Separation of dispersed phases from liquids in acoustically driven chambers journal February 1993
Scanning flow cytometry for individual particle analysis journal January 2000
Acoustic radiation potential on a sphere in plane, cylindrical, and spherical standing wave fields journal March 1985
Single half-wavelength ultrasonic particle filter: Predictions of the transfer matrix multilayer resonator model and experimental filtration results
  • Hawkes, Jeremy J.; Coakley, W. Terence; Gröschl, Martin
  • The Journal of the Acoustical Society of America, Vol. 111, Issue 3, p. 1259-1266 https://doi.org/10.1121/1.1448341
journal March 2002
The effect of centreline particle concentration in a wave tube journal January 1996
Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis journal March 2007
Mean force on a small sphere in a sound field in a viscous fluid journal January 2000
Dynamics of suspended particles in a two-dimensional high-frequency sonic field journal June 1995
Acoustic filtration and sedimentation of soot particles journal December 1997
Measurement of Mammalian Erythrocyte Indices from Light Scattering with Scaning Flow Cytometer conference January 2003
The use of ultrasonic standing waves to enhance optical particle sizing equipment journal March 2000
Quantum mechanical representation of acoustic streaming and acoustic radiation pressure journal July 2001
Experimental and theoretical study of light scattering by individual mature red blood cells by use of scanning flow cytometry and a discrete dipole approximation journal January 2005