Methods and apparatuses for label-free particle analysis

• US 9,778,193 B2
• Filed: 08/15/2014
• Issued: 10/03/2017
• Est. Priority Date: 08/22/2013
• Status: Active Grant

• Current Assignee: Kinetic River Corp.
• Original Assignee: Kinetic River Corp.
• Inventors: Vacca, Giacomo
• Primary Examiner(s): Geisel, Kara E
• Assistant Examiner(s): BRYANT, REBECCA CAROLE
• Application Number:
  US14/461,293
• Publication Number:
  US 20150056645A1
• Time in Patent Office: 1,145 Days
• CPC Class Codes: G01N 15/1434 Optical arrangements
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1438 Using two lasers in succession
• CPC Class Codes: G01N 2021/653 Coherent methods [CARS]
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G01N 2201/06113 Coherent sources; lasers
• CPC Class Codes: G01N 2201/0697 Pulsed lasers

Abstract

An apparatus to provide a label-free or native particle analysis comprises a light generating system producing first light pulses at a first wavelength and second light pulses at a second wavelength; and a flow cell coupled to the light generating system to convey particles for analysis. The light generating system is configured to chirp at least one of the first light pulses and the second light pulses to analyze the particles.

Claims

1. An apparatus comprising:

a light generating system configured to produce a first set of light pulses in a first wavelength region and a second set of light pulses in a second wavelength region, wherein the first and the second wavelength regions do not substantially overlap;

a first optical system coupled to the light generating system, the first optical system comprising a first dispersion control module configured to positively chirp the first set of light pulses and a second dispersion module configured to negatively chirp the second set of light pulses;

a second optical system coupled to the first optical system, the second optical system comprising optics configured to combine the first set of chirped light pulses and the second set of chirped light pulses into a set of combined light pulses, wherein each of the combined light pulses comprises a first pulse from the first set of chirped light pulses and a second pulse from the second set of chirped light pulses; and

a flow cell coupled to the second optical system and configured to convey, in a flow, particles for analysis, wherein at least one of the particles is exposed to a plurality of the combined light pulses.

2. The apparatus of claim 1, further comprising a synchronization system configured to provide synchronization timing signals to the light generating system, wherein the synchronization timing signals are configured to establish a fixed phase relationship between the first set of light pulses and the second set of light pulses.

3. The apparatus of claim 1, wherein, for each of the combined light pulses, the first pulse from the first set of chirped light pulses is at least partially spatially and temporally overlapping with the second pulse from the second set of chirped light pulses.

4. The apparatus of claim 1, further comprising:

a third optical system coupled to the flow cell, the third optical system configured to collect an interaction light signal resulting from an interaction of the plurality of the combined light pulses with the at least one of the particles; and

an analysis system comprising spectrally dispersive means, the analysis system configured to measure a plurality of spectral components of the interaction light signal.

5. An apparatus comprising:

a light generating system configured to produce a first set of light pulses in a first wavelength region and a second set of light pulses in a second wavelength region, wherein the first and the second wavelength regions do not substantially overlap;

a first optical system coupled to the light generating system, the first optical system comprising a first dispersion control module configured to positively chirp the first set of light pulses and a second dispersion module configured to negatively chirp the second set of light pulses;

a second optical system coupled to the first optical system, the second optical system comprising optics configured to combine the first set of chirped light pulses and the second set of chirped light pulses into a set of combined light pulses, wherein each of the combined light pulses comprises a first pulse from the first set of chirped light pulses and a second pulse from the second set of chirped light pulses; and

a sample holder coupled to the second optical system and configured to hold sample for analysis, wherein at least a portion of the sample is exposed to a plurality of the combined light pulses.

6. The apparatus of claim 5, further comprising a synchronization system configured to provide synchronization timing signals to the light generating system, wherein the synchronization timing signals are configured to establish a fixed phase relationship between the first set of light pulses and the second set of light pulses.

7. The apparatus of claim 5, wherein, for each of the combined light pulses, the first pulse from the first set of chirped light pulses is at least partially spatially and temporally overlapping with the second pulse from the second set of chirped light pulses.

8. The apparatus of claim 5, further comprising:

a third optical system coupled to the sample holder, the third optical system configured to collect an interaction light signal resulting from an interaction of the plurality of the combined light pulses with the at least a portion of the sample; and

an analysis system comprising spectrally dispersive means, the analysis system configured to measure a plurality of spectral components of the interaction light signal.

9. An apparatus comprising:

a light generating system configured to produce a first set of light pulses in a first wavelength region and a second set of light pulses in a second wavelength region, wherein the first and the second wavelength regions do not substantially overlap, and wherein the light generating system is internally configured to positively chirp the first set of light pulses and negatively chirp the second set of light pulses;

a first optical system coupled to the light generating system, the first optical system comprising optics configured to combine the first set of chirped light pulses and the second set of chirped light pulses into a set of combined light pulses, wherein each of the combined light pulses comprises a first pulse from the first set of chirped light pulses and a second pulse from the second set of chirped light pulses; and

a sample holder coupled to the first optical system and configured to hold particles for analysis, wherein at least one of the particles is exposed to a plurality of the combined light pulses.

10. The apparatus of claim 9, wherein the light generating system comprises temporally dispersive means to positively chirp the first set of light pulses and negatively chirp the second set of light pulses.

11. An apparatus comprising:

a light generating system configured to produce a first set of amplified light pulses in a first wavelength region and a second set of amplified light pulses in a second wavelength region, wherein the first and the second wavelength regions do not substantially overlap;

a first optical system coupled to the light generating system, the first optical system comprising a first dispersion control module configured to positively chirp the first set of amplified light pulses and a second dispersion module configured to negatively chirp the second set of amplified light pulses;

a second optical system coupled to the first optical system, the second optical system comprising optics configured to combine the first set of chirped amplified light pulses and the second set of chirped amplified light pulses into a set of combined light pulses, wherein each of die combined light pulses comprises a first pulse from the first set of chirped amplified light pulses and a second pulse from the second set of chirped amplified light pulses; and

a flow cell coupled to the first optical system and configured to convey, in a flow, particles for analysis, wherein at least one of the particles is exposed to at least one of the combined light pulses.

12. An apparatus comprising:

a light generating system configured to produce a first set of amplified light pulses in a first wavelength region and a second set of amplified light pulses in a second wavelength region, wherein the first and the second wavelength regions do not substantially overlap;

a first optical system coupled to the light generating system, the first optical system comprising a first dispersion control module configured to positively chirp the first set of amplified light pulses and a second dispersion module configured to negatively chirp the second set of amplified light pulses;

a second optical system coupled to the first optical system, the second optical system comprising optics configured to combine the first set of chirped amplified light pulses and the second set of chirped amplified light pulses into a set of combined light pulses, wherein each of the combined light pulses comprises a first pulse from the first set of chirped amplified light pulses and a second pulse from the second set of chirped amplified light pulses; and

a sample holder coupled to the first optical system and configured to hold a sample for analysis, wherein at least a portion of the sample is exposed to at least one of the combined light pulses.