Optical space-time coding technique in microfluidic devices

• US 9,074,978 B2
• Filed: 07/12/2012
• Issued: 07/07/2015
• Est. Priority Date: 07/12/2011
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Lo, Yu-Hwa, Wu, Tsung-Feng, Mei, Zhe
• Primary Examiner(s): Alsomiri, Isam
• Assistant Examiner(s): Abraham, Samantha K
• Application Number:
  US13/548,160
• Publication Number:
  US 20130016335A1
• Time in Patent Office: 1,090 Days
• Field of Search: 356/28
• US Class Current: 1/1
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1486 Counting the particles
• CPC Class Codes: G01N 2015/1493 Particle size
• CPC Class Codes: G01P 5/001 Full-field flow measurement, e.g. determining flow velocity and direction in a whole region at the same time, flow visualisation
• CPC Class Codes: G01P 5/20 using particles entrained by a fluid stream G01P5/22 takes precedence
• CPC Class Codes: G01P 5/26 by measuring the direct influence of the streaming fluid on the properties of a detecting optical wave

Abstract

Techniques, devices and systems are disclosed for characterizing particles in a fluid sample by optical space-time coding. In one aspect, a microfluidic device for optical detection of particles includes a substrate, a microfluidic channel formed on the substrate and structured to carry a fluid sample containing particles, in which the microfluidic channel is structured to transmit a probe light, and a mask formed on one side of the microfluidic channel and structured to include a pattern of openings along the microfluidic channel, in which at least two of the openings have varying dimensions across the microfluidic channel, and in which the pattern of openings encodes a waveform on the probe light that transmits through the microfluidic channel to allow optical detection of a position of a particle in the microfluidic channel.

Claims

1. A microfluidic device for optical detection of particles, comprising:

a substrate;

a microfluidic channel formed on the substrate and structured to carry a fluid sample containing particles, the microfluidic channel structured to transmit a probe light; and

a mask formed on one side of the microfluidic channel and structured to include a pattern of openings along the microfluidic channel, wherein at least two of the openings have varying longitudinal and transverse dimensions with respect to a fluid flow direction across the microfluidic channel, and wherein the pattern of openings encodes a waveform on the probe light that transmits through the microfluidic channel to allow optical detection of a position of a particle in at least two dimensions in the microfluidic channel.

2. The device of claim 1, further comprising:

a light source that generates the probe light through the pattern of openings to illuminate the fluid sample, wherein each particle scatters the light beam to produce an optical scattering signal at each position that the particle flows along the pattern of openings of the microfluidic channel; and

an optical detector arranged in a location relative to the pattern of openings to receive the optical scattering signal and produce a scattering signal waveform including signal peaks corresponding to the openings of the pattern of openings, respectively.

3. The device of claim 2, further comprising:

a processing unit communicatively coupled to the optical detector that processes the scattering signal waveform to determine the position of the particle.

4. The device of claim 3, wherein the processing unit determines the position of the particle based on the width of at least two signal peaks of the scattering signal waveform corresponding to the at least two openings of the pattern of openings with unequal widths.

5. The device of claim 3, wherein the processing unit determines a velocity of the particle based on the position of the particle.

6. The device of claim 3, wherein the processing unit determines a multidimensional positional distribution of the particle in the microfluidic channel.

7. The device of claim 3, wherein the processing unit determines fluid dynamic properties of the particle in the microfluidic channel including at least one of inertial focusing, Dean'"'"'s flow, or flow confinement.

8. The device of claim 2, wherein the location of the optical detector is between 5 to 10 degrees relative to the pattern of openings to receive a forward scattering (FS) signal.

9. The device of claim 2, wherein the location of the optical detector is between 45 to 60 degrees relative to the pattern of openings to receive a large angle scattering (LAS) signal.

10. The device of claim 2, wherein the location of the optical detector is substantially 90 degrees relative to the pattern of openings to receive a side scattering (SS) signal.

11. The device of claim 2, wherein the light source includes at least one of a semiconductor laser diode or a mercury arc lamp.

12. The device of claim 2, wherein the optical detector includes a silicon PIN photodiode.

13. The device of claim 1, wherein the pattern of openings comprises four trapezoidal shapes.

14. The device of claim 1, wherein the device determines at least one of size, shape, and granularity of the particles of the fluid sample.

15. The device of claim 1, wherein the fluid sample is blood sample.

16. The device of claim 15, wherein the blood sample prepared without the use of centrifugation, addition of anticoagulation agents, antibody labeling, filtering, and pipetting.

17. The device of claim 16, wherein the processing unit determines the quantity of neutrophil cells from among the other cells of the blood sample based on the size distribution of the cells of the blood sample.

18. A method of determining a position of particle in a microfluidic channel, comprising:

transferring a fluid sample containing particles through a microfluidic channel having an pattern of apertures spatially arranged on a surface of the channel, wherein at least two of the apertures have varying longitudinal and transverse dimensions with respect to a fluid flow direction across the microfluidic channel;

transmitting a light beam through the pattern of apertures to illuminate the fluid sample, wherein each particle scatters the light beam to produce an optical scattering signal at each position along the pattern of apertures;

detecting the optical scattering signal with an optical detector configured at a scattering angle formed between the optical detector and the pattern of apertures, wherein the detected optical scattering signal produces a scattering signal waveform; and

processing the scattering signal waveform to determine the position of the particle in at least two dimensions.

19. The method of claim 18, further comprising determining the velocity of the particle based on the determined position of the particle.

20. The method of claim 18, further comprising determining a multidimensional positional distribution of the particle in the microfluidic channel.

21. The method of claim 18, further comprising determining fluid dynamic properties of the particle in the microfluidic channel including at least one of inertial focusing, Dean'"'"'s flow, or flow confinement.

22. The method of claim 18, further comprising determining at least one of size, shape, and granularity of the particles of the fluid sample.

23. The method of claim 22, wherein the fluid sample is blood sample.

24. The method of claim 23, further comprising quantifying the number of neutrophil cells from among the other cells of the blood sample based on a distribution of cell size.

25. A microfluidic device, comprising:

a microfluidic channel structured to carry a fluid sample containing particles along a fluid flow direction from an inlet region to an outlet region, the microfluidic channel including a pattern of openings spatially arranged on a surface of the channel, wherein at least two openings of the pattern of openings have unequal widths in a longitudinal dimension and a transverse dimension along the fluid flow direction;

a light source that generates a light beam through the pattern of openings to illuminate the fluid sample, wherein each particle scatters the light beam to produce an optical scattering signal at each position that the particle flows along the pattern of openings of the microfluidic channel;

an optical detector arranged in a location relative to the pattern of openings to receive the optical scattering signal and produce a scattering signal waveform, the waveform including a signal peak corresponding to each opening of the pattern of openings; and

a data processing and storage unit communicatively coupled to the optical detector, the data processing and storage unit to convert the scattering signal waveform from an analog signal format to a digital signal representation and to store the digital signal representation in a data storage.

26. The microfluidic device of claim 25, further comprising an input/output (I/O) unit communicatively coupled to the data processing and storage unit to interface with an external computer system that can retrieve the digital signal representation from the data storage to the external computer system.

27. The microfluidic device of claim 26, wherein the external computer system includes at least one of a personal computer, tablet, or smartphone device.