Photo-acoustic detection device and method

• US 7,968,347 B2
• Filed: 07/11/2007
• Issued: 06/28/2011
• Est. Priority Date: 07/11/2006
• Status: Active Grant

• Current Assignee: Curators of the University of Missouri (University of Missouri)
• Original Assignee: Curators of the University of Missouri (University of Missouri)
• Inventors: Weight, Ryan M., Sutovsky, Peter, Viator, John A., Dale, Paul S.
• Primary Examiner(s): WALLENHORST, MAUREEN
• Application Number:
  US11/827,346
• Publication Number:
  US 20080014574A1
• Time in Patent Office: 1,448 Days
• Field of Search: 436/63, 436/64, 436/52, 436/164, 436/86, 436/518, 436/524, 436/531, 436/534, 435/4, 435/287.1, 435/7.1, 435/29, 435/288.7, 738/612.5, 738/612.6, 356/73, 356/445
• US Class Current: 436/164
• CPC Class Codes: G01N 21/1702 with opto-acoustic detection, e.g. for gases or analysing solids

Abstract

An example method for detecting an analyte in a sample of a bodily fluid comprises the steps of exposing the bodily fluid sample to electromagnetic energy to cause a thermoelastic expansion in the analyte, and detecting a photoacoustic signal in the sample that results from the thermoelastic expansion.

Claims

1. An in vitro method for detecting an analyte in a sample of a bodily fluid comprising the steps of:

extracting a bodily fluid sample from a subject;

exposing the bodily fluid sample as it flows through a test chamber to a pulsed laser beam to cause a thermoelastic expansion in the analyte, and capturing the entire cross sectional flow of said bodily fluid sample in said test chamber with said beam; and

,

detecting a photoacoustic signal in the sample that results from said thermoelastic expansion.

2. A method for detecting an analyte as defined by claim 1 wherein said thermoelastic expansion results from said analyte absorbing at least a portion of light from said laser beam, and wherein said photoacoustic signal comprises an acoustic wave resulting from said thermoelastic expansion.

3. A method for detecting an analyte as defined by claim 1 wherein said laser beam comprises a laser with a pulse duration of less than a microsecond, wherein said bodily fluid comprises one or more of blood, bile, sperm, urine or saliva, and wherein said analyte comprises one of a protein or a pathogen, and further including the step of suspending said bodily fluid sample in a saline solution prior to the step of exposing said sample to said pulsed laser.

4. A method for detecting an analyte as defined by claim 1 wherein said test chamber includes an acoustic sensor configured to detect said photoacoustic signal after said thermoelastic expansion occurs in said test chamber, and wherein the step of exposing said sample to said laser beam comprises directing said beam into said test chamber.

5. A method for detecting an analyte as defined by claim 1 and further comprising the step of adding target particles to said bodily fluid sample having a diameter of less than 0.01 millimeter, said particles configured to respond to said laser beam, and said particles configured to adhere to said analyte.

6. A method for detecting an analyte as defined by claim 5 wherein said target particles comprises microspheres having antibodies selected to adhere to said analyte, said microspheres configured to absorb said laser beam.

7. A method for detecting an analyte as defined by claim 1 wherein the step of detecting said photoacoustic signal comprises detecting a deflection in a diaphragm that is in fluid contact with said bodily fluid sample, said deflection resulting when an acoustic wave contacts said diaphragm.

8. A method for detecting an analyte as defined by claim 1 wherein said photoacoustic signal comprises a pressure wave traveling through said bodily fluid sample.

9. A method for detecting an analyte as defined by claim 1 wherein the step of detecting said photoacoustic signal further includes using the magnitude of said signal to estimate one or more of analyte size, density, and concentration.

10. A method for detecting an analyte as defined by claim 1 wherein the laser beam has a wavelength that is smaller than the analyte.

11. A method for detecting an analyte as defined by claim 1 and further comprising the step of causing the fluid sample to flow through the pulsing beam at a velocity selected to cause an analyte in the fluid to be excited more than once by said pulsing beam as it passes through said pulsing beam.

12. An in vitro method for detecting one or more circulating cancer cells comprising the steps of:

separating white blood cells from a quantity of blood;

suspending said white blood cells in a carrier liquid to create a test sample;

causing said test sample to flow through a test chamber at a first velocity wherein a laser beam captures the entire cross section of said flowing test sample and wherein said beam induces a thermoelastic expansion of said one or more cancer cells in said test sample, said beam transmitted through a test chamber transparent sidewall, said first velocity selected to cause said one or more cancer cells in said test sample to be excited by said beam more than once as it passes through said test chamber; and

,

using an acoustic sensor to detect an acoustic signal that results from said thermoelastic expansion in said test sample, said sensor arranged on a sidewall of said test chamber not in the direct path of said beam.

13. A method for detecting one or more circulating cancer cells as defined by claim 12 and further including the steps of:

adhering a plurality of microsphere targets to each of said one or more cancer cells;

wherein said laser has a pulse duration of less than about 1 microsecond into said test sample through said transparent test chamber sidewall; and

,

wherein said acoustic signal comprises an acoustic wave traveling through said sample; and

,

wherein said acoustic sensor includes a diaphragm in fluid contact with said test sample in said test chamber, said diaphragm deflected when said acoustic wave strikes it.

14. An in vitro method for detecting an analyte in a sample of a bodily fluid comprising the steps of:

extracting a bodily fluid sample from a subject;

exposing the bodily fluid sample as it flows through a test chamber that is at least partially transparent to a pulsed laser beam that captures the entire cross sectional width of said test chamber to cause a thermoelastic expansion in the analyte; and

,

detecting a photoacoustic signal in the sample that results from said thermoelastic expansion by measuring an electrical perturbation that results when a piezoelectric layer is deflected.

15. A method for detecting an analyte as defined by claim 14 wherein said bodily fluid comprises blood, wherein said analyte comprises a pathogen, wherein the step of extracting a bodily fluid sample comprises extracting a quantity of blood from the subject, and wherein the method further comprises the steps of further preparing said bodily fluid sample prior to flowing through said test chamber through the steps of:

isolating white blood cells in said quantity of blood; and

,

suspending said white blood cells from said quantity of blood in a carrier liquid.

16. A method for detecting an analyte as defined by claim 14 and further comprising the steps of:

further preparing said bodily fluid sample before the step of exposing it to a pulsed laser beam by including a carrier saline solution with it;

causing said bodily fluid sample to flow from a reservoir through a conduit and into said test chamber where said beam captures the entire cross section of said flowing sample, said test chamber including at least a first and a second sidewall, said first sidewall being narrower than said second sidewall, said laser directed through said first sidewall; and

using a sensor to detect said photoacoustic signal, said sensor arranged on said second sidewall.

17. A method for detecting an analyte as defined by claim 14 and wherein the step of detecting further comprises the steps of:

using a sensor that is arranged on a test chamber sidewall to detect said photoacoustic signal, said sensor positioned on a sidewall to avoid directly receiving said beam; and

,

wherein the test chamber has generally funnel shaped entrance and exit ports with a cylindrical throat section therebetween, said beam directed across the entire cross section of said throat section.