# US 12,181,395 B2 · Optical systems and methods of probing biological fluids

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- Number: US 12,181,395 B2
- Document ID: US12181395B2
- Status: Granted
- Kind: B2
- Application number: 18/205,154
- Filed: 2023-06-02
- Published: 2024-09-12
- Granted: 2024-12-31
- Earliest claimed: 2023-03-10
- Assignees: Solaris BioSciences, Inc.
- Applicants: Solaris BioSciences, Inc.
- Inventors: Nabil Lawandy
- Web page: https://patentgrep.com/patent/US12181395B2

## CPC

- G01N 11/00: Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
- G01N 21/6428: {Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53)}
- G01N 2011/008: {optical properties}
- 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)

## Abstract

A system and method for determining a viscosity of a fluid medium containing a fluorescent species, including a light source exciting the fluorescent species at an excitation area of the fluid medium to produce a fluorescent signal and photobleaching the fluorescent species, and the fluorescent species diffusing in and out of the excitation area of the fluid medium at a rate determined by an excitation geometry of the light source, a diffusivity of the fluorescent species, and the viscosity of the fluid medium; and a detector detecting the fluorescent signal over time to generate a fluorescence decay curve of the fluorescent species in the fluid medium, where the viscosity of the fluid medium is determined based on a numerical comparison of the fluorescence decay curve of the fluorescent species in the fluid medium with a fluorescence decay curve of the fluorescent species in a reference medium of known viscosity.

## Claims

### Claim 1

A system for determining a viscosity of a fluid medium containing a fluorescent species capable of emitting a fluorescent signal, the system comprising:
a light source providing radiation of a fixed intensity and having an excitation geometry when directed at the fluid medium, the light source capable of exciting the fluorescent species at an excitation area of the fluid medium to produce the fluorescent signal and photobleaching the fluorescent species, and the fluorescent species diffusing in and out of the excitation area of the fluid medium at a rate determined by the excitation geometry of the light source, a diffusivity of the fluorescent species, and the viscosity of the fluid medium; and
a detector capable of detecting the fluorescent signal over time to generate a fluorescence decay curve of the fluorescent species in the fluid medium,
wherein the viscosity of the fluid medium is determined based on a numerical comparison of the fluorescence decay curve of the fluorescent species in the fluid medium with a fluorescence decay curve of the fluorescent species in a reference medium of known viscosity.

### Claim 2 (depends on 1)

The system of claim 1, further comprising a filter utilized in connection with the detector.

### Claim 3 (depends on 1)

The system of claim 1, further comprising a beam splitter disposed such that both the radiation of the light source and the fluorescent signal pass through the beam splitter, the beam splitter directing the fluorescent signal to the detector.

### Claim 4 (depends on 1)

The system of claim 1, further comprising one or more lenses disposed on an optical pathway with the light source or the detector.

### Claim 5 (depends on 1)

The system of claim 1, wherein the detector is a photosensor.

### Claim 6 (depends on 5)

The system of claim 5, wherein the photosensor is a photodiode, a photocell, or a photomultiplier.

### Claim 7 (depends on 1)

The system of claim 1, wherein the fluid medium is serum, plasma, blood, urine, ocular fluid, or spinal fluid.

### Claim 8 (depends on 7)

The system of claim 7, wherein the fluid medium is serum or plasma and wherein the fluorescent species is bilirubin bound to albumin.

### Claim 9 (depends on 7)

The system of claim 7, wherein the fluid medium is plasma or serum obtained from a pinprick of blood subjected to a microcapillary separation to separate a hematocrit from the blood.

### Claim 10 (depends on 7)

The system of claim 7, wherein the fluid medium is urine and wherein the fluorescent species is urobilin or urochrome.

### Claim 11 (depends on 1)

The system of claim 1, wherein the fluorescent species is a photobleachable dye.

### Claim 12 (depends on 11)

The system of claim 11, wherein the photobleachable dye is fluorescein.

### Claim 13

A method for determining a viscosity of a fluid medium containing a fluorescent species capable of emitting a fluorescent signal, the method comprising:
directing a light source at the fluid medium, the light source providing radiation of a fixed intensity and having an excitation geometry when directed at the fluid medium, to excite the fluorescent species at an excitation area of the fluid medium to produce the fluorescent signal and photobleach the fluorescent species, the fluorescent species diffusing in and out of the excitation area of the fluid medium at a rate determined by the excitation geometry of the light source, a diffusivity of the fluorescent species, and the viscosity of the fluid medium;
detecting the fluorescent signal with a detector over time to generate a fluorescence decay curve of the fluorescent species in the fluid medium; and
determining the viscosity of the fluid medium based on a numerical comparison of the fluorescence decay curve of the fluorescent species in the fluid medium with a fluorescence decay curve of the fluorescent species in a reference medium of known viscosity.

### Claim 14 (depends on 13)

The method of claim 13, wherein the fluid medium is serum, plasma, blood, urine, ocular fluid, or spinal fluid.

### Claim 15 (depends on 14)

The method of claim 14, wherein the fluid medium is serum or plasma and wherein the fluorescent species is bilirubin bound to albumin.

### Claim 16 (depends on 14)

The method of claim 14, wherein the fluid medium is plasma or serum obtained from a pinprick of blood subjected to a microcapillary separation to separate a hematocrit from the blood.

### Claim 17 (depends on 14)

The method of claim 14, wherein the fluid medium is urine and wherein the fluorescent species is urobilin or urochrome.

### Claim 18 (depends on 13)

The method of claim 13, wherein the fluorescent species is a photobleachable dye.

### Claim 19 (depends on 18)

The method of claim 18, wherein the photobleachable dye is fluorescein.

### Claim 20

A system for determining a viscosity of a fluid medium containing a fluorescent species capable of emitting a fluorescent signal, the system consisting of:
a light source providing radiation of a fixed intensity and having an excitation geometry when directed at the fluid medium, the light source capable of exciting the fluorescent species at an excitation area of the fluid medium to produce the fluorescent signal and photobleaching the fluorescent species, and the fluorescent species diffusing in and out of the excitation area of the fluid medium at a rate determined by the excitation geometry of the light source, a diffusivity of the fluorescent species, and the viscosity of the fluid medium;
a detector capable of detecting the fluorescent signal over time to generate a fluorescence decay curve of the fluorescent species in the fluid medium; and
optionally, one or more of:
a filter utilized in connection with the detector;
a beam splitter disposed such that both the radiation of the light source and the fluorescent signal pass through the beam splitter, the beam splitter directing the fluorescent signal to the detector; and
one or more lenses disposed on an optical pathway with the light source or the detector,
wherein the viscosity of the fluid medium is determined based on a numerical comparison of the fluorescence decay curve of the fluorescent species in the fluid medium with a fluorescence decay curve of the fluorescent species in a reference medium of known viscosity.