# US 12,112,834 B2 · System and method for non-invasive quantification of blood biomarkers

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- Number: US 12,112,834 B2
- Document ID: US12112834B2
- Status: Granted
- Kind: B2
- Application number: 18/358,655
- Filed: 2023-07-25
- Published: 2024-03-07
- Granted: 2024-10-08
- Earliest claimed: 2022-09-06
- Assignees: Refana, Inc.
- Applicants: Refana Inc.
- Inventors: Marcelo Adorni Pereira
- Web page: https://patentgrep.com/patent/US12112834B2

## CPC

- G16B 40/10: Signal processing, e.g. from mass spectrometry [MS] or from PCR
- G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)}
- G06F 18/214: Generating training patterns; Bootstrap methods, e.g. bagging or boosting
- G06F 18/23: Clustering techniques
- G06N 20/00: Machine learning
- G01N 2800/60: Complex ways of combining multiple protein biomarkers for diagnosis
- G06N 3/09: Supervised learning
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- 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)
- G06F: ELECTRIC DIGITAL DATA PROCESSING (computer systems based on specific computational models G06N)
- G06N: COMPUTING ARRANGEMENTS BASED ON SPECIFIC COMPUTATIONAL MODELS

## Abstract

A system, method for determining blood biomarkers implemented by a processor and memory circuitry (PMC) and a program storage device and computer program product which includes providing near infra-red spectrogram data i of a patient's living tissue; using one or more pre-trained prediction models comprising a selected number of prediction routes, and determining prediction data on a selected group of biomarkers; determining one or more biomarkers associated with a number of groups, and determining an average concentration data of said biomarkers in accordance with output data of a number of prediction routes associated with said number of groups; and generating output data indicative of estimated levels of a selected set of biomarkers for said patient.

## Claims

### Claim 1

A method for determining levels of blood biomarkers implemented by a processor and memory circuitry (PMC), comprising:
(a) providing near infra-red spectrogram data of a patient's living tissue;
(b) using one or more pre-trained prediction models comprising a selected number of prediction routes for processing the near infra-red spectrogram data, and determining accordingly prediction data on a selected group of biomarkers;
(c) determining one or more biomarkers associated with a number of groups, and determining for the one or more biomarkers an average concentration data of said one or more biomarkers in accordance with output data of a number of prediction routes associated with said number of groups; and
(d) generating output data indicative of estimated levels of a selected set of biomarkers for said patient.

### Claim 2 (depends on 1)

The method of claim 1, wherein said providing spectrogram data comprises providing spectrogram data in a range between 600 nm and 2700 nm.

### Claim 3 (depends on 1)

The method of claim 1, wherein said providing spectrogram data comprises obtaining a spectrometric reading of said patient's skin.

### Claim 4 (depends on 1)

The method of claim 1, wherein said selected number of prediction routes comprises prediction routes pre-trained for predicting data on selected groups of biomarkers, being different between said prediction routes.

### Claim 5 (depends on 4)

The method of claim 4, wherein said selected groups of biomarkers comprise a selected number of groups, each group comprising two or more biomarkers characterized by typical concentration above a first threshold, and one or more biomarkers characterized by typical concentration below a second threshold.

### Claim 6

A program storage device readable by machine, tangibly embodying a program of instructions executable by the machine to perform a method for determining levels of blood biomarkers, comprising:
(a) providing spectrogram data indicative of near infra-red absorption of a patient's tissue;
(b) using one or more pre-trained prediction models comprising a selected number of prediction routes for processing the spectrogram data, and determining prediction data on a selected group of biomarkers accordingly;
(c) determining one or more biomarkers associated with a number of groups and for the one or more biomarkers associated with a number of groups, determining an average concentration data of in accordance with the prediction data of a number of prediction routes associated with said number of groups; and
generating output data indicative of estimated levels of a selected set of biomarkers for said patient.

### Claim 7 (depends on 6)

The program storage device of claim 6, wherein said selected groups of biomarkers comprise a selected number of groups, each group comprising two or more biomarkers characterized by typical concentration above a first threshold, and one or more biomarkers characterized by typical concentration below a second threshold.

### Claim 8

A computer program product comprising a computer useable medium having computer readable program code embodied therein for determining levels of blood biomarkers, the computer program product comprising:
computer readable program code for causing the computer to provide spectrogram data indicative of near infra-red absorption of a patient's tissue;
computer readable program code for causing the computer to use one or more pre-trained prediction models comprising a selected number of prediction routes to process the spectrogram data and to determine prediction data on a selected group of biomarkers;
computer readable program code for causing the computer to determine one or more biomarkers associated with a number of groups and to determine an average concentration data of said one or more biomarkers in accordance with the prediction data being output of a number of prediction routes associated with said number of groups; and
computer readable program code for causing the computer to generate output data indicative of estimated levels of a selected set of biomarkers for said patient.

### Claim 9 (depends on 8)

The computer program product of claim 8, wherein said selected groups of biomarkers comprise a selected number of groups, each group comprising two or more biomarkers characterized by typical concentration above a first threshold, and one or more biomarkers characterized by typical concentration below a second threshold.

### Claim 10

A system for non-invasive determining of levels of blood biomarkers comprising:
a processor and memory circuitry (PMC), wherein the PMC comprises a pre-stored prediction model, and is configured to:
(a) obtain spectrogram data indicative of near infra-red absorption of a patient's tissue;
(b) use one or more pre-trained prediction models comprising a selected number of prediction routes comprising prediction routes pre-trained for predicting data on selected groups of biomarkers, being different between said prediction routes, and determining prediction data on a selected group of biomarkers;
(c) determine one or more biomarkers associated with a number of groups and determine for each of the one or more biomarkers an average concentration data of said one or more biomarkers in accordance with the prediction data being output of a number of prediction routes associated with said number of groups; and
(d) generate output data indicative of estimated levels of a selected set of biomarkers for said patient.

### Claim 11 (depends on 10)

The system of claim 10, further comprising at least one spectrometer connectable to said PMC for transmission of communication signals, said at least one spectrometer being configured for obtaining spectrogram data from biological tissue.

### Claim 12 (depends on 11)

The system of claim 11, wherein said at least one spectrometer is configured to obtain spectrogram data from a skin portion of an individual.

### Claim 13 (depends on 11)

The system of claim 11, wherein said at least one spectrometer is configured to obtain spectrogram data comprising a spectral range between 600 nm and 2700 nm.

### Claim 14 (depends on 10)

The system of claim 10, wherein said selected number of prediction routes comprise prediction routes pre-trained for predicting data on a selected groups of biomarkers, being different between said prediction routes.

### Claim 15 (depends on 14)

The system of claim 14, wherein said selected groups of biomarkers comprise a selected number of groups, each group comprising two or more biomarkers characterized by typical concentration above a first threshold, and one or more biomarkers characterized by typical concentration below a second threshold.
