# US 7,411,672 B2 · Method and apparatus for chemical imaging in a microfluidic circuit

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- Number: US 7,411,672 B2
- Document ID: US7411672B2
- Status: Granted
- Kind: B2
- Application number: 11/824,878
- Filed: 2007-07-03
- Published: 2007-11-08
- Granted: 2008-08-12
- Earliest claimed: 2004-06-30
- Assignees: ChemImage Corporation
- Inventors: David Tuschel; Thomas Voigt
- Web page: https://patentgrep.com/patent/US7411672B2

## CPC

- G01N 21/05: Flow-through cuvettes (G01N21/09 takes precedence; handling fluid samples G01N1/10)
- G01N 21/31: Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry {(G01N21/72 takes precedence)}
- G01N 21/3577: for analysing liquids, e.g. polluted water
- G01N 21/64: Fluorescence; Phosphorescence
- G01N 21/65: Raman scattering
- B01L 3/5027: {by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip}
- G01J 3/0227: {using notch filters}
- G01J 3/4406: {Fluorescence spectrometry}
- G01N 21/03: Cuvette constructions
- G01N 2021/0325: {Cells for testing reactions, e.g. containing reagents}
- G01N 2021/0346: {Capillary cells; Microcells}
- G01N 2021/651: {Cuvettes therefore}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N)

## Abstract

The disclosure generally relates to a system for detecting a change in an attribute of a substance. The system may include a photon source for producing a first of a plurality of photons which interact with the substance while an attribute of the substance changes to produce a second plurality of photons. The system may also include a filter for receiving the collected photons and providing filtered photons; a photon detector for receiving the filtered photons and obtaining therefrom a spectrum of the substance; and a processor for detecting an aspect of the filtered photons wherein the aspect of the filtered photons is the function of the attribute of the substance.

## Claims

### Claim 1

A system for determining a change in an attribute of a substance, the system comprising: a microfluidic circuit having a plurality of input channels integral thereto, wherein said substance is provided through a first one of said plurality of input channels; a photon source for providing a first plurality of photons through a second one of said plurality of input channels so as to internally illuminate a portion of said microfluidic circuit containing said substance, wherein said first plurality of photons interact with the substance while an attribute of the substance changes to thereby produce a second plurality of photons; an optical lens for collecting said second plurality of photons; a filter for receiving the collected photons and providing therefrom filtered photons having one or more predetermined wavelengths; and a processor for determining an aspect of the filtered photons wherein the aspect of the filtered photons is a function of the attribute of the substance, to thereby determine a change in the attribute of the substance.

### Claim 2 (depends on 1)

The system of claim 1 wherein the attribute is selected from the group consisting of a physical property, a chemical property, an electrical property, a magnetic property, an optical property, and a biological property.

### Claim 3 (depends on 2)

The system of claim 2 wherein the substance is a single molecule or a group of molecules.

### Claim 4 (depends on 1)

The system of claim 1 wherein the attribute is at least one of the following: a physical structure; a physical orientation; a chemical structure; a chemical composition; a chemical state; and an index of refraction.

### Claim 5 (depends on 1)

The system of claim 1 wherein the substance is selected from the group consisting of a cell, an element, a compound, a molecule, a reactant, a solvent, a solute, a fluid, and a biological substance.

### Claim 6 (depends on 1)

The system of claim 1 wherein said photon source is selected from the group consisting of a laser and a light emitting diode.

### Claim 7 (depends on 6)

The system of claim 6 wherein the first plurality of photons has a wavelength in one of the following wavelength ranges: the infrared wavelength range; the near infrared wavelength range; the ultraviolet wavelength range; the X-ray wavelength range; and the visible wavelength range.

### Claim 8 (depends on 1)

The system of claim 1 wherein said filter is selected from the group consisting of a notch filter, a bandpass filter, a spectral filter, a tunable filter, a liquid crystal tunable filter, and an acousto-optical tunable filter.

### Claim 9 (depends on 1)

The system of claim 1 wherein the interaction of the first plurality of photons with the substance is selected from the group consisting of scattering, emission, reflection, and refraction.

### Claim 10 (depends on 1)

The system of claim 1 wherein said processor comprises software programmed to determine the aspect of the filtered photons.

### Claim 11 (depends on 1)

The system of claim 1 wherein said processor comprises firmware programmed to determine the aspect of the filtered photons.

### Claim 12 (depends on 1)

The system of claim 1, further comprising a photon detector for receiving the filtered photons and for providing therefrom a spectral image of the substance.

### Claim 13 (depends on 12)

The system of claim 12, wherein the spectral image is one of the following: a Raman spectral image; a luminescence spectral image; a near infrared spectral image; an infrared spectral image; and an ultraviolet spectral image.

### Claim 14 (depends on 1)

The system of claim 1, wherein said optical lens, said filter, and said processor are external to said microfluidic circuit.

### Claim 15 (depends on 1)

The system of claim 1, wherein said aspect of the filtered photons is at least one of the following: a wavelength; a frequency; a phase; a polarization; and an intensity.

### Claim 16 (depends on 1)

The system of claim 1, further comprising an illumination source placed external to said microfluidic circuit so as to externally illuminate said portion of said microfluidic circuit with a third plurality of photons, wherein said third plurality of photons interact with the substance while said attribute of the substance changes to thereby produce a fourth plurality of photons, wherein said optical lens is configured to collect said fourth plurality of photons, and wherein said filter is configured to receive said collected fourth plurality of photons and provide therefrom said filtered photons to said processor.

### Claim 17 (depends on 16)

The system of claim 16, wherein said illumination source is different from said photon source.

### Claim 18 (depends on 16)

The system of claim 16, wherein a wavelength of said third plurality of photons is different from a wavelength of said first plurality of photons.

### Claim 19 (depends on 16)

The system of claim 16, wherein the third plurality of photons has a wavelength in one of the following wavelength ranges: the infrared wavelength range; the near infrared wavelength range; the ultraviolet wavelength range; the X-ray wavelength range; and the visible wavelength range.

### Claim 20 (depends on 12)

The system of claim 12, wherein said photon detector is selected from the group consisting of a charge-coupled device, a complementary metal oxide semiconductor array, and a focal plane array.

### Claim 21

A method for determining a change in an attribute of a substance provided through a first one of a plurality of input channels within a microfluidic circuit, the method comprising: illuminating the substance with a first plurality of photons provided through a second one of said plurality of input channels so as to internally illuminate a portion of said microfluidic circuit containing said substance, wherein said first plurality of photons interact with the substance while an attribute of the substance changes to thereby produce a second plurality of photons; collecting said second plurality of photons; receiving the collected photons and providing therefrom filtered photons having one or more predetermined wavelengths; and determining an aspect of the filtered photons wherein the aspect of the filtered photons is a function of the attribute of the substance, to thereby determine a change in the attribute of the substance.

### Claim 22 (depends on 21)

The method of claim 21 wherein the attribute is selected from the group consisting of a physical property, a chemical property, property, an electrical property, a magnetic property, an optical property, and a biological property.

### Claim 23 (depends on 21)

The method of claim 21 wherein the substance is a single molecule or a group of molecules.

### Claim 24 (depends on 21)

The method of claim 21 wherein the attribute is at least one of the following: a physical structure; a physical orientation; a chemical structure; a chemical composition; a chemical state; and an index of refraction.

### Claim 25 (depends on 21)

The method of claim 21 wherein the substance is selected from the group consisting of a cell, an element, a compound, a molecule, a reactant, a solvent, a solute, a fluid, and a biological substance.

### Claim 26 (depends on 21)

The method of claim 21 wherein the first plurality of photons has a wavelength in one of the following wavelength ranges: the infrared wavelength range; the near infrared wavelength range; the ultraviolet wavelength range; the X-ray wavelength range; and the visible wavelength range.

### Claim 27 (depends on 21)

The method of claim 21 wherein the interaction of the first plurality of photons with the substance is selected from the group consisting of scattering, emission, reflection, and refraction.

### Claim 28 (depends on 21)

The method of claim 21, further comprising:
detecting the filtered photons to provide therefrom a spectral image of the substance.

### Claim 29 (depends on 28)

The method of claim 28 wherein the spectral image is one of the following: a Raman spectral image, a luminescence spectral image, a near infrared spectral image, an infrared spectral image, and an ultraviolet spectral image.

### Claim 30

A system comprising:
a microfluidic circuit having a plurality of input channels integral thereto, wherein a first substance is provided through a first one of said plurality of input channels and a second substance is provided through a second one of said plurality of input channels;
a first photon source for providing a first plurality of photons through a third one of said plurality of input channels so as to internally illuminate a portion of said microfluidic circuit containing a mixture of said first and said second substances, wherein said first plurality of photons interact with said mixture while an attribute of at least one of said first and said second substances changes to thereby produce a second plurality of photons;
an optical lens for collecting said second plurality of photons;
a filter for receiving the collected photons and providing therefrom filtered photons having one or more predetermined wavelengths; and
a processor for determining an aspect of the filtered photons wherein the aspect of the filtered photons is a function of the attribute of at least one of said first and said second substances, to thereby determine a change in said attribute.

### Claim 31 (depends on 30)

The system of claim 30, wherein said attribute is at least one of the following:
a physical property, a chemical property, an electrical property, a magnetic property, an optical property, and a biological property.

### Claim 32 (depends on 30)

The system of claim 30, further comprising:
a second photon source placed external to said microfluidic circuit so as to externally illuminate said portion of said microfluidic circuit with a third plurality of photons, wherein a wavelength of said third plurality of photons is different from a wavelength of said first plurality of photons, and wherein said third plurality of photons interact with the mixture while said attribute of at least one of said first and said second substances changes to thereby produce a fourth plurality of photons,
wherein said optical lens is configured to collect said fourth plurality of photons, and wherein said filter is configured to receive said collected fourth plurality of photons and provide therefrom said filtered photons to said processor.
