# US 2010/0297635 A1 · Collection and measurement of exhaled particles

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- Number: US 2010/0297635 A1
- Document ID: US20100297635A1
- Status: Published application
- Kind: A1
- Application number: 12/680,428
- Filed: 2008-10-01
- Published: 2010-11-25
- Earliest claimed: 2007-10-02
- Assignees: Pexa AB
- Inventors: Anna-Carin Olin; Ann-Charlotte Almstrand; Jukka Lausmaa; Evert Ljungstrom
- Web page: https://patentgrep.com/patent/US20100297635A1

## CPC

- G01N 15/0255: {with mechanical, e.g. inertial, classification, and investigation of sorted collections (with centrifuges G01N15/042)}
- A61B 5/411: {Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance}
- A61B 5/097: Devices for facilitating collection of breath or for directing breath into or through measuring devices
- G01N 33/497: of gaseous biological material, e.g. breath
- G01N 2015/0261: {using impactors}
- 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)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)

## Abstract

Particles are exhaled in the breath of animals. The nature and amounts of the particles can be indicative of certain medical conditions. They can therefore be collected, sorted according to size or mass and used in the diagnosis of one or more medical conditions. The invention provides a method and system for collecting and sorting exhaled particles and a method for diagnosis using said exhaled particles.

## Claims

### Claim 1

A method for determining the medical condition of a subject, said method comprising the steps of:
a. collecting particles exhaled by said subject;
b. sorting said particles according to their mass or size; and
c. analysing the chemical content of said particles;
thereby allowing the medical condition of said subject to be determined.

### Claim 2 (depends on 1)

A method according to claim 1, wherein said step b comprises
i. sorting said particles according to their mass or size to obtain a particle distribution profile of said particles;
ii. comparing the particle distribution profile of the particles exhaled by said subject with a reference particle distribution profile;
iii. noting similarities and/or deviations between the particle distribution profile of the subject and the reference particle distribution profile; and
iv. assigning the deviations or similarities between the particle distribution profile of the subject and the reference particle distribution profile to one or more medical conditions in the subject.

### Claim 3 (depends on 1)

A method according to claim 1, wherein the medical condition is selected from the group consisting of Asthma bronchiale, Cystic fibrosis, Chronic Obstructive pulmonary disease (COPD), Interstitial lung-disease, Sarcoidosis, Pulmonary engagement in systemic disease such as systemic lupus erythromatodes (SLE), Pulmonary infections such as pneumonia, bacterial colonization or viral infections-Heart failure, Hypercholesterolemia, Diabetes (insulin is found in the particles), Metabolic syndrome, Increased genetic susceptibility to disease or exposure.

### Claim 4 (depends on 2)

A method according to claim 2, wherein the medical condition is selected from the group consisting of Asthma bronchiale, Cystic fibrosis, Chronic obstructive pulmonary disease (COPD), Interstitial lung-disease, Sarcoidosis, Pulmonary engagement in systemic disease such as systemic lupus erythromatodes (SLE), Pulmonary infections such as pneumonia, bacterial colonization or viral infections.

### Claim 5 (depends on 2)

A method according to claim 2, wherein the reference particle distribution profile is obtained from a subject not having a given medical condition, and step iii. comprises noting deviations between the particle distribution profile of the subject and the reference particle distribution profile.

### Claim 6 (depends on 2)

A method according to claim 2, wherein the reference particle distribution profile is from a patient having a given medical condition, and step iii. involves comprises noting similarities between the particle distribution profile of the subject and the patient, leading to the determination of said given medical condition in the subject.

### Claim 7

A method for providing a particle distribution profile of exhaled breath particles, said method comprising the steps of:
a. collecting particles exhaled by a subject; and
b. sorting said particles at a temperature such that the size distribution of the exhaled aerosol is not changed either by evaporation or condensation of water vapour according to their size or mass, to obtain a particle distribution profile of said particles.

### Claim 8 (depends on 7)

A method according to claim 7, wherein particles are sorted according to their mass using an inertial impactor (10).

### Claim 9 (depends on 8)

A method according to claim 8, wherein the impactor (10) has an inlet (12) and an outlet (14), said impactor (10) comprising a plurality of stages (20, 30, 40, 50 . . . ) arranged such that a gas stream (A) comprising particles (P) enters the impactor (10) via the inlet (12) and passes through each stage (20, 30, 40, 50 . . . ) in turn before exiting the impactor (10) via said outlet (14);
wherein each stage (20, 30, 40, 50 . . . ) is separated from adjacent stages by a partition (21, 31, 41, 51 . . . ) having an orifice (22, 32, 42, 52 . . . ) which directs the gas stream (A) towards collection plates (33, 43, 53 . . . ), the major face of each collection plate (33, 43, 53 . . . ) being arranged substantially perpendicular to the direction of flow of the gas stream (A);
whereby exhaled particles are passed through said inertial impactor (10) in a gas stream (A); such that the primary gas stream (A) is directed towards each collection plates (23, 33, 43, 53 . . . ) in each stage (20, 30, 40, 50 . . . ) in turn; such that at least a first collection plate (33) located in a first stage (30) collects particles of a first mass and at least a second collection plate (43) located in a second stage (40) collects particles of a second mass.

### Claim 10 (depends on 9)

A method according to claim 9, wherein particles are sorted according to their size using a particle counter (116).

### Claim 11 (depends on 1)

A method according to claim 1, wherein, after being sorted according to their size or mass, particles are analysed by at least one analysis technique selected from the group consisting of: time-of-flight secondary ion mass spectrometry (TOF-SIMS), matrix assisted laser desorption ionization mass spectrometry (MALDI-MS), biochemical assays or protocols based on labelled antibodies, quantitative PCR analysis, scanning electron microscopy (SEM), gas-chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS), surface plasmon resonance (SPR), fluorescence spectroscopy, TOC (total organic content) analysis, elemental analysis and inductively coupled plasma mass spectrometry (ICP-MS), with or without being first washed off the collection plates.

### Claim 12

A system (100) for collecting and sorting exhaled particles, said system comprising:
a. a reservoir (114) which is located in a thermostatted compartment (120) having the purpose of maintaining the aerosol size distribution, said reservoir (114) having a first opening (112) and a second opening (113);
b. a two-way mouthpiece (110) which is kept at a temperature such that the size distribution of the exhaled aerosol is not changed either by evaporation or condensation of water vapour and connected to the first opening (112) of the reservoir (114);
c. an inertial impactor (10) which is located in a thermostatted compartment (120) having the purpose of maintaining the aerosol size distribution, said reservoir (114), said impactor (10) having an inlet (12) and an outlet (14), said impactor (10) comprising a plurality of stages (20, 30, 40, 50 . . . ) arranged such that a gas stream (A) comprising particles (P) enters the impactor (10) via the inlet (12) and passes through each stage (20, 30, 40, 50 . . . ) in turn before exiting the impactor (10) via said outlet (14);
wherein each stage (20, 30, 40, 50 . . . ) is separated from adjacent stages by a partition (21, 31, 41, 51 . . . ) having an orifice (22, 32, 42, 52 . . . ) which directs the primary gas stream (A) towards collection plates (33, 43, 53 . . . ), the major face of each collection plate (33, 43, 53 . . . ) being arranged substantially perpendicular to the direction of flow of the gas stream (A); the inlet (12) of the inertial impactor being connected to the first opening (112) of the reservoir (114).

### Claim 13 (depends on 12)

A system (100) according to claim 12, wherein each stage (20, 30, 40, 50 . . . ) comprises a collection plate (33, 43, 53 . . . ) adapted to detect an analyte which is different to a collection plate (33, 43, 53 . . . ) in another stage (20, 30, 40, 50 . . . ).

### Claim 14 (depends on 12)

A collection plate (33, 43, 53 . . . ) adapted for use in the system (100) of claim 12, in which at least one surface thereof is modified by coating with a substance, such as e.g. a hydrophobic substance or an antibody.

### Claim 15 (depends on 14)

A collection plate (33, 43, 53 . . . ) according to claim 14, comprising electrical connections which enable a change in the electric current or capacitance of the collection plate (33, 43, 53 . . . ) to be detected in response to binding of particles to said collection plate.
