Ultrasonic analyte concentration and application in flow cytometry

• US 7,340,957 B2
• Filed: 11/02/2004
• Issued: 03/11/2008
• Est. Priority Date: 07/29/2004
• Status: Active Grant

• Current Assignee: TRIAD National Security, LLC
• Original Assignee: Los Alamos National Security LLC (Government of the United States of America)
• Inventors: Kaduchak, Gregory, Goddard, Greg, Martin, John C., Salzman, Gary, Sinha, Dipen, Graves, Steven, Kwiatkowski, Christopher
• Primary Examiner(s): Williams; Hezron
• Assistant Examiner(s): MILLER, ROSE MARY
• Application Number:
  US10/979,065
• Publication Number:
  US 20060021437A1
• Time in Patent Office: 1,225 Days
• Field of Search: 735/705
• US Class Current: 73/570.5
• CPC Class Codes: B01D 21/28 Mechanical auxiliary equipment for acceleration of sedimentation, e.g. by vibrators or the like
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2001/4094 using ultrasound
• CPC Class Codes: G01N 2015/1413 Hydrodynamic focussing
• CPC Class Codes: G01N 2015/142 Acoustic or ultrasonic focussing
• CPC Class Codes: Y10T 137/0324 With control of flow by a condition or characteristic of a fluid
• CPC Class Codes: Y10T 137/206 Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]

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

1. An apparatus for concentrating analyte within a fluid using acoustic radiation pressure, said apparatus comprising:

a function generator to output a radiofrequency electrical signal;

a single acoustic signal producing transducer; and

a tube comprising an inherently axially symmetric geometry;

said single acoustic signal producing transducer acoustically coupled to said tube and used to transform said radiofrequency electrical signal to an acoustic signal;

said tube converting said acoustic signal to said acoustic radiation pressure within said tube, and said acoustic pressure concentrating the analytes within said tube.

2. The apparatus of claim 1 wherein said tube comprises an elastic material.

3. The apparatus of claim 1 wherein said geometry of said driving transducer is cylindrical.

4. The apparatus 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.

5. The apparatus of claim 1 further including a power amplifier to amplify said output of said function generator.

6. The apparatus of claim 1 further including a monitoring transducer to monitor said acoustic radiation pressure to maintain resonant frequency and compensate for ambient temperature fluctuations.

7. The apparatus of claim 6 wherein said second transducer is selected from the group consisting of piezoceramic, piezosalt, piezopolymer, piezocrystal, magnetostrictive, and electromagnetic transducers.

8. A method for concentrating analyte within a fluid using acoustic radiation pressure, the method comprising:

producing the acoustic radiation pressure in a tube comprising an inherently axially symmetric geometry using a single acoustic signal producing transducer;

flowing a fluid with the analyte through the tube;

driving the transducer and inducing an outer boundary surface displacement; and

concentrating the analyte within the tube.

9. The method of claim 8 further including:

monitoring the outer boundary surface displacement;

and adjusting the acoustic radiation pressure to maintain a resonant frequency and adjust for ambient temperature changes via a monitoring transducer.

10. A flow cytometer for the analysis of analytes, comprising:

a tube having an inlet for accepting a fluid sample stream of the analytes;

an acoustic signal producing transducer coupled to said tube, wherein said acoustic signal producing transducer produces an acoustic signal to said tube to induce within said tube acoustic radiation pressure capable inducing an outer boundary surface displacement to concentrate the analytes within the fluid sample stream;

optical equipment for analyzing the analytes wherein said optical equipment comprises a light source to create light scatter along with several wavelength bands of fluorescence for analyzing the analytes; and

collection optics to receive the light scatter and the several wavelength bands of fluorescence created to determine molecular makeup of the analytes.

11. The flow cytometer of claim 10 wherein said tube comprises an inherently axially symmetric geometry.

12. The flow cytometer of claim 10 wherein said tube is cylindrical.

13. The flow cytometer of claim 10 wherein said function generator is selected from any voltage source circuit capable of producing a variety of voltage waveforms of varying frequencies.

14. The flow cytometer of claim 10 further including a power amplifier to amplify the output of said function generator.

15. The flow cytometer of claim 10 further including a monitoring transducer to monitor the acoustic radiation pressure to maintain resonant frequency and compensate for ambient temperature fluctuations.

16. The flow cytometer of claim 15 wherein said monitoring transducer is selected from the group consisting of piezoceramic, piezosalt, piezopolymer, piezocrystal, magnetostrictive, and/or electromagnetic transducers.

17. The flow cytometer of claim 10 wherein said light source is a laser.

18. The flow cytometer of claim 10 wherein said light source is an arc lamp.

19. A method of flow cytometry, comprising:

supplying a fluid stream with analytes to an inlet of a tube;

subjecting the tube to acoustic radiation pressure to induce an outer boundary surface displacement to concentrate the analytes within the fluid stream; and

analyzing the analytes via a flow cytometer.

20. The method of claim 19 further comprising monitoring the outer boundary surface displacement and adjusting the acoustic radiation pressure to maintain a resonant frequency and adjust for ambient temperature changes.

21. A method of flow cytometry comprising:

supplying a fluid stream with analytes to an inlet of a tube;

subjecting the tube to acoustic radiation pressure to induce an outer boundary surface displacement to concentrate the analytes within the fluid stream; and

analyzing the analytes with optical equipment, wherein analyzing the analytes includes subjecting the analytes to a light source that creates light scatter and several bands of fluorescence, and collecting the light scatter and wavelength bands of fluorescence with an optical detector, and identifying the collected wavelength bands to determine molecular makeup of the analytes.

22. The method of claim 21 wherein analyzing the analytes comprises collecting magnetic moment signals and determining the molecular makeup of the analytes.

23. A flow cytometer for analysis of analytes comprising:

a tube having an inlet for accepting a fluid stream with analytes;

a single acoustic signal producing transducer acoustically coupled to said tube;

said single driving transducer producing an acoustic signal that induces acoustic radiation pressure in said tube to produce an outer boundary surface displacement to concentrate the analytes within the fluid stream; and

a flow cytometer fluidly connected to said tube for analyzing the analytes.

24. The flow cytometer of claim 23 further comprising a monitoring transducer for monitoring said outer boundary surface displacement, and adjusting said acoustic radiation pressure to maintain a resonant frequency and adjust for ambient temperature changes.

25. The flow cytometer of claim 23 wherein said tube comprises an inherently axially symmetric geometry.

26. The flow cytometer of claim 25 wherein said tube comprises a cylindrical shape.