IP Library › Granted Patent US 12,736,546
Granted Patent B2
US 12,736,546 · App. 17/296,499 · Granted Sep 15, 2026

Methods, systems, and a kit for diagnosis, detection, monitoring and treatment of traumatic brain injury

Inventors: Balwant Rai (Dragor, DK); Jasdeep Kaur (Dragor, DK)
Assignee: RapidDx, Inc.
G01N33/6896G01N33/534G01N2800/2871
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Quick Facts
Patent No.
US 12,736,546
App. No.
17/296,499
Granted
Sep 15, 2026
Kind
B2
Abstract

Methods and systems for diagnosis, detection, monitoring, and treatment of traumatic brain injury are described. The methods and systems include detection of salivary biomarkers associated with brain injury in a human subject, one application of which is to determine whether the subject has sustained a concussion or a more severe traumatic brain injury (TBI). Detection of the salivary biomarkers can also provide a basis to determine that a subject can safely return to play in an athletic event and can provide a basis to evaluate the efficacy of particular treatments. The methods and systems may be implemented, for example, by means of a kit.

Claims (59)

1 . A system for detecting traumatic brain injury (TBI) of at least mild severity (mTBI) in a human subject, comprising:

(a) at least one binding agent specific to a Ubiquitin Carboxy-Terminal Hydrolase L1 (UCH-L1) biomarker or UCH-L1 in combination with one or more biomarker selected from the group consisting of Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), and Interleukin 8 (IL-8);

(b) a measurable label that indicates a proportional reaction based on the level of biomarker present in a saliva sample from the subject; and

(c) a measurement device operable to provide a visible indication of the measurable label to provide a qualitative or quantitative level of one or more biomarkers in the saliva sample indicative that the subject has TBI,

wherein the system detects when the one or more biomarkers are at the following concentrations in the saliva sample and such detection is indicative that the subject should be evaluated for possible TBI:

(i) NSE concentrations of between 0.8 pg/ml and 2.1 pg/ml;

(ii) GFAP concentrations of between 0.7 pg/ml and 2.5 pg/ml;

(iii) UCH-L1 concentrations of between 0.8 pg/ml and 65 pg/ml; and

(iv) IL-8 concentrations of between 450 pg/ml and 950 pg/ml.

2 . The system of claim 1 , wherein the binding agent comprises an antibody binding agent.

3 . The system of claim 2 , further comprising at least one lateral flow substrate with the binding agent affixed thereto.

4 . The system of claim 3 , wherein the measurement device provides a visual indication of the measurable label.

5 . The system of claim 4 , wherein the visual indication is a fluorescent indication.

6 . The system of claim 1 , wherein the at least one binding agent is specific to the biomarkers IL-8 and UCH-L1.

7 . The system of claim 1 , wherein the at least one binding agent is specific to the biomarkers NSE and UCH-L1.

8 . The system of claim 1 , wherein the at least one binding agent is specific to the biomarkers GFAP and UCH-L1.

9 . The system of claim 1 , wherein a combination of any two of the biomarkers is effective at detecting TBI in adolescent, youth, and older populations aged six through at least ninety years.

10 . The system of claim 1 , wherein the system detects that the subject can return to play (RTP) within about twenty minutes to about two weeks following a suspected TBI.

11 . The system of claim 10 , wherein the system detects that the subject can return to play (RTP) within about four to eight hours following the suspected TBI.

12 . The system of claim 11 , wherein the system detects that the subject can return to play (RTP) within about six hours following the suspected TBI.

13 . The system of claim 1 , wherein the system is capable of differentiating differentiates TBI from injuries unrelated to TBI.

14 . The system of claim 1 , wherein the measurement device detects that the level of the one or more biomarkers in the saliva sample is at or above a reference level.

15 . The system of claim 14 , wherein the indication that the level of the one or more biomarkers in the saliva sample is at or above the reference level is indicative that the subject should not return to play (RTP).

16 . The system of claim 1 , wherein the system is an in vitro system.

17 . The system of claim 1 , wherein the system is a point-of-care test platform.

18 . The system of claim 17 , wherein the point-of-care test platform is a kit.

19 . The system of claim 17 , wherein the system includes a mouth guard appliance and the mouth guard appliance includes the at least one binding agent.

20 . A system for detection of possible mild traumatic brain injury (mTBI) or more severe traumatic brain injury (TBI) in a human subject within 6 hours after a head injury event, the system comprising:

(a) at least one binding agent specific to a Ubiquitin Carboxy-Terminal Hydrolase L1 (UCH-L1) biomarker or UCH-L1 in combination with one or more biomarker, the one or more biomarker being selected from the group consisting of Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), and Interleukin 8 (IL-8);

(b) a measurable label that indicates a proportional reaction based on the level of biomarker present in a saliva sample from the subject; and

(c) a measurement device which provides a visible indication of the measurable label when the one or more biomarker in the subject's saliva sample is at or above the following concentrations:

(i) NSE at or above about 1 pg/ml;

(ii) GFAP at or above of about 1 pg/ml;

(iii) UCH-L1 at or above about 10 pg/ml; and

(iv) IL-8 at or above about 400 pg/ml,

whereby, appearance of the indication means that the subject should be evaluated for possible mTBI or TBI.

21 . The system of claim 20 wherein the visible indication is provided when the one or more biomarker in the subject's saliva sample is at or above the following concentrations:

(i) NSE at or above about 1.5 pg/ml;

(ii) GFAP at or above of about 1.8 pg/ml;

(iii) UCH-L1 at or above about 13.6 pg/ml; and

(iv) IL-8 at or above about 624 pg/ml.

22 . The system of claim 21 wherein the visible indication is provided when the one or more biomarker in the subject's saliva sample is at or above the following concentrations within about 1 to about 6 hours after the head injury:

(i) NSE at or above about 1.8 pg/ml;

(ii) GFAP at or above of about 1.9 pg/ml;

(iii) UCH-L1 at or above about 54 pg/ml; and

(iv) IL-8 at or above about 709 pg/ml.

23 . The system of claim 20 , wherein the binding agent comprises an antibody binding agent.

24 . The system of claim 23 , wherein the measurement device comprises a lateral flow substrate with the binding agent affixed thereto.

25 . The system of claim 24 , wherein a visual indication of the measurable label is provided on the lateral flow substrate when the one or more biomarker is captured by the binding agent and is present in an amount at or above the concentration.

26 . The system of claim 25 , wherein the visual indication is a fluorescent indication.

27 . The system of claim 20 , wherein the at least one binding agent is specific to the biomarkers IL-8 and UCH-L1.

28 . The system of claim 27 , wherein the system consisting of the at least one binding agent specific to the biomarkers IL-8 and UCH-L1 detects mTBI in a subject with a correlation of at least about 0.92 within one hour after the head injury event.

29 . The system of claim 20 , wherein the at least one binding agent is specific to the biomarkers NSE and UCH-L1.

30 . The system of claim 29 , wherein the system consisting of the at least one binding agent specific to the biomarkers NSE and UCH-L1 detects mTBI in a subject with a correlation of at least about 0.89 within one hour after the head injury event.

31 . The system of claim 20 , wherein the at least one binding agent is specific to the biomarkers GFAP and UCH-L1.

32 . The system of claim 31 , wherein the system consisting of the at least one binding agent specific to the biomarkers GFAP and UCH-L1 detects mTBI in a subject with a correlation of at least about 0.89 within one hour after the head injury event.

33 . The system of claim 20 , wherein a combination of any two of the biomarkers is effective at detecting TBI in adolescent, youth, and older populations aged six through at least ninety years.

34 . The system of claim 20 , wherein the system provides the indication within about twenty minutes to about two weeks following the head injury event and the indication means that the subject should not return to play (RTP).

35 . The system of claim 20 , wherein the system provides the indication within about one hour following the head injury event and the indication means that the subject should not return to play (RTP).

Assignments (7)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2026
From: RAI, BALWANT; KAUR, JASDEEP
To: RAPIDDX, INC.
Reel/Frame 075254/0225 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2026
From: RAI, BALWANT; KAUR, JASDEEP
To: RAPIDDX, INC.
Reel/Frame 075254/0348 →
CHANGE OF NAME Recorded Apr 7, 2026
From: BASELINE BIOSCIENCE INC.
To: RAPIDDX INC.
Reel/Frame 075654/0540 →
CORRECTION BY DECLARATION Recorded Dec 29, 2023
From: BASELINE BIOSCIENCE, INC.; BASELINE DESIGN INNOVATIONS INC.
To: BASELINE BIOSCIENCE, INC.; BASELINE DESIGN INNOVATIONS INC.
Reel/Frame 066368/0935 →
SECURITY INTEREST Recorded Jun 22, 2023
From: BASELINE, INC.
To: AVIDBANK
Reel/Frame 064031/0213 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 28, 2022
From: BASELINE GLOBAL, INC.
To: BASELINE BIOSCIENCE, INC.
Reel/Frame 058813/0070 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2021
From: RAI, BALWANT, DR.; KAUR, JASDEEP
To: BASELINE GLOBAL, INC.
Reel/Frame 056333/0699 →
Priority Claims (1)
IN 201811044520 · Nov 26, 2018 · national
Continuity (1)
Related Publication 20230135030A1 · May 4, 2023
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