# US 5,349,538 A · Method for determining the distribution of constituent subpopulations within a population of particles having overlapping subpopulations

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- Number: US 5,349,538 A
- Document ID: US5349538A
- Status: Granted
- Kind: A
- Application number: 08/017,618
- Filed: 1993-02-12
- Granted: 1994-09-20
- Earliest claimed: 1991-02-05
- Assignees: Edward Lawrence Carver, Jr.
- Inventors: Edward L. Carver, Jr.; Richard D. DeVeaux; David C. DeCava
- Web page: https://patentgrep.com/patent/US5349538A

## CPC

- G06F 17/18: for evaluating statistical data {, e.g. average values, frequency distributions, probability functions, regression analysis (forecasting specially adapted for a specific administrative, business or logistic context G06Q10/04)}
- G01D 1/14: giving a distribution function of a value, i.e. number of times the value comes within specified ranges of amplitude
- G01N 15/02: Investigating particle size or size distribution (by measuring osmotic pressure G01N7/10; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10)
- G16H 10/20: for electronic clinical trials or questionnaires
- G16H 10/40: for data related to laboratory analysis, e.g. patient specimen analysis
- G01N 15/1456: {without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals}
- G01N 2015/1488: {Methods for deciding}
- G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N)
- G01D: MEASURING NOT SPECIALLY ADAPTED FOR A SPECIFIC VARIABLE; ARRANGEMENTS FOR MEASURING TWO OR MORE VARIABLES NOT COVERED IN A SINGLE OTHER SUBCLASS; TARIFF METERING APPARATUS; MEASURING OR TESTING NOT OTHERWISE PROVIDED FOR
- 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)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA

## Abstract

A method and apparatus for determining the parameters (i.e., proportion, mean, and standard deviation) of constituent subpopulations within a sample population of particles which contains overlapping populations. The invention includes the use of the EM algorithm, an iterative process which estimates the probability that a particle belongs to any given overlapping subpopulation.

## Claims

### Claim 1

A method for measuring and determining the parameters of constituent subpopulations of particles within a sample containing a population of particles including overlapping subpopulations of particles, comprising the following steps:
detecting the differences in at least one physical characteristic of the particles and generating first signals indicative of the differences;
measuring at least one characteristic of the first signals indicative of the differences in the at least one physical characteristic of the particles being measured, and generating second signals indicative of the at least one measured characteristic of the first signals; and
generating the parameters of each subpopulation of particles by estimating the probability that a particle belongs to a given subpopulation based on the second signals.

### Claim 2 (depends on 1)

A method as defined in claim 1, wherein the step of generating parameters of each subpopulation of particles employs the EM algorithm to estimate the probability that a particle belongs to a given subpopulation of particles and to generate the parameters based thereon.

### Claim 3 (depends on 1)

A method as defined in claim 1, wherein the constituent subpopulations of particles are subpopulations of blood cells within a sample of blood, and the parameters generated are indicative of the subpopulation of blood cells.

### Claim 4 (depends on 1)

A method as defined in claim 1, wherein the physical characteristics in which the differences are detected are selected from the group including the diameter, volume, optical density, physical density, and fluorescent intensity of the particles.

### Claim 5 (depends on 1)

A method as defined in claim 1, further comprising the step of amplifying the first signals prior to measuring at least one characteristic of the first signals.

### Claim 6 (depends on 1)

A method as defined in claim 1, further comprising the step of digitizing the second signals prior to generating the parameters of each subpopulation based on the second signals.

### Claim 7 (depends on 1)

A method as defined in claim 1, further comprising the step of forming at least one histogram based on the second signals prior to generating the parameters of each subpopulation based on the second signals.

### Claim 8 (depends on 1)

A method as defined in claim 1, wherein the at least one physical characteristic of the particles is selected from the group including electrical, optical, and chemical characteristics.

### Claim 9

A method of measuring the distribution of various subpopulations of blood cells that are present in a sample population of blood cells, comprising the following steps:
determining the number of subpopulations of blood cells in the sample population;
separately characterizing each of the subpopulations of blood cells based on a physical property of the blood cells, and selecting an equation describing the distribution of particles within each subpopulation of blood cells;
measuring each of the particles in the sample population of blood cells for the physical property; and
generating the parameters of each subpopulation of blood cells based on a statistical estimation of the probability that a particle belongs to a given subpopulation of blood cells.

### Claim 10 (depends on 9)

A method as defined in claim 9, wherein the parameters of subpopulations of blood cells are selected from the group including the proportion, mean and standard deviation of each subpopulation of blood cells.

### Claim 11 (depends on 9)

A method as defined in claim 9, wherein the step of separately characterizing each of the subpopulations of blood cells is based on a physical property selected from the group including the size, density and opacity of the blood cells.

### Claim 12 (depends on 9)

A method as defined in claim 9, wherein the step of generating the parameters of each subpopulation employs the EM algorithm to estimate the probability that a particle belongs to a given subpopulation of blood cells and to generate the parameters based thereon.

### Claim 13 (depends on 9)

A method as defined in claim 9, further comprising the step of displaying the parameters of each subpopulation on a visual electronic display.

### Claim 14 (depends on 9)

A method as defined in claim 9, wherein the blood cells are white blood cells and the parameters generated are indicative of the subpopulations of white blood cells.

### Claim 15 (depends on 9)

A method as defined in claim 9, further comprising the step of detecting abnormalities in a patient's blood based on the generated parameters of the subpopulations of blood cells.