The Next Generation of Brain Health Diagnostics

Unlocking the power of cellular saliva to detect brain injury at the point of care.

Our Breakthrough Innovations

Cellular Biomarkers in Saliva

For years, the challenge in saliva diagnostics has been the low and highly variable biomarker concentration in the saliva fluid.

We have fundamentally changed saliva diagnostics by showing that Saliva contains live cells expressing disease biomarkers.

Our patented saliva assay measures cellular and fluid biomarkers, yielding >100 times higher and 7-fold less variable biomarker concentration than the standard fluid assays. This breakthrough allows BrainGuardian™ to detect the saliva-based TBI biomarker using a rapid lateral flow test — no laboratory equipment required.

Standard saliva specimen (low biomarker concentration, no rapid test) versus saliva specimen with cells (high biomarker concentration, rapid test possible)

Standard saliva fluid yields low biomarker concentration (pg/ml). Cellular saliva yields high concentration (ng–μg/ml), enabling a rapid visual test.

Cellular composition of human saliva — Hematoxylin and Eosin stain, original magnification x100

Original magnification ×100

Cellular composition of human saliva — Hematoxylin and Eosin stain, original magnification x400, showing epithelial cells (E), granulocytes (G), monocytes (M), and lymphocytes

Original magnification ×400

Cellular composition of human saliva. Hematoxylin & Eosin stain. Adult human saliva contains approximately 2 million cells/ml comprising epithelial cells (E), granulocytes (G), monocytes (M) and lymphocytes.

S. Southern, J Hum Virol. (1998) 1(5):328-37. Milk-borne transmission of HIV. Characterization of productively infected cells in breast milk and interactions between milk and saliva.

Southern, S. et al. (2002). Cellular Mechanism for Milk-Borne Transmission of HIV and HTLV. In: Advances in Experimental Medicine and Biology, vol 503. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0559-4_21

Our Breakthrough Innovations

The first digital IHC assay for biomarkers in saliva cells and fluid

Digital IHC assay of saliva with cells - four panels: a) digitized IHC slide with saliva microarray, b) Mucin1 in epithelial cells, c) segmented image, d) staining intensity map

Digital IHC assay of saliva with cells. a, Digitized IHC slide with saliva microarray (4 fields). Field 4 (green frame) was selected for image analysis. b, Mucin1 in epithelial cells (red immunostain). c, Segmented image: magenta — epithelial cells, dark blue — non-epithelial cells, cyan — saliva fluid. d, Staining intensity map: white — Mucin1 signal.

Accuracy and reliability of the saliva IHC assay - standard calibration curve over 40-fold concentration range with R-squared 0.9723 and mean CV 16 percent

Accuracy and reliability of the saliva IHC assay. Accuracy 97%, CV 16%. a, Image analysis of Muc1 signal (magnification ×200). b, Standard calibration curve for the Muc1 IHC assay shows a 40-fold linear dynamic range.

Hamamatsu Hamamatsu NanoZoomer S210 whole-slide scanner for digital pathology
Hamamatsu Advantage

Region of Interest profiles for microarray slide images

Saliva microarray slide with Region of Interest profiles for the Hsp27 biomarker

Southern SO, inventor; Gaia Medical Institute, assignee. Health test for a broad spectrum of health problems. United States patent 0705097 (2020).

Our Breakthrough Innovations

The first image analysis algorithm for saliva — AI powered by Visiopharm

a. Conventional RGB APP

Conventional RGB algorithm segmentation result showing scattered magenta epithelial cells and dark blue non-epithelial cells in a clinical saliva specimen from dementia

b. Visiopharm AI APP

Visiopharm AI-powered segmentation showing accurate classification of epithelial cells (magenta) and non-epithelial cells (dark blue) in the same clinical saliva specimen
Visiopharm Comparison of RGB vs AI segmentation: 70 percent area decrease from missed epithelial cells with RGB APP; no significant difference in saliva fluid area; 400 percent area increase from false non-epithelial cells with RGB APP

c. Visiopharm LayerData output

Segmentation Area (Epi Cells) Area (Fluid) Area (Non Epi Cells) Area Cells Area Epi Ratio Area Total
RGB APP 6,478,072.00 86,060,279.00 5,732,000.00 12,210,072.00 0.065920921 98,270,351.00
AI APP 21,271,059.78 75,899,350.52 1,100,524.41 22,371,584.19 0.216453215 98,270,934.71

Source path: C:\ProgramData\Visiopharm\Database

Visiopharm AI-powered digital pathology. a, Conventional RGB APP incorrectly classified saliva epithelial cells (magenta) and non-epithelial cells (dark blue) in a digital image of a clinical saliva specimen from dementia. b, Visiopharm AI APP provided 100% accurate segmentation of epithelial and non-epithelial cells in the same saliva specimen. c, Visiopharm LayerData shows area of saliva epithelial cells, non-epithelial cells and saliva fluid using the RGB and AI APPs.

Our Breakthrough Innovations

Our saliva IHC assay unlocks actionable insights to advance disease diagnostics, drug discovery and in vitro oral drug response modeling

IHC assay of dementia biomarker in clinical saliva samples - four panels: a-b show high biomarker expression in saliva from Neurocognitive Disorder due to mild TBI (NCDT), c-d show baseline expression in healthy control

IHC assay of dementia biomarker in clinical saliva samples. a-b, Neurocognitive Disorder due to mild traumatic brain injury (NCDT). Saliva epithelial cells express and secrete high level of the biomarker (arrow). c-d, Healthy control. Baseline expression of the biomarker in epithelial cells (arrow). Original magnifications: ×100 (a, c) and ×400 (b, d).

References

  • Southern SO, inventor; Gaia Medical Institute, assignee. Health test for a broad spectrum of health problems. United States patent 12360122 (2025).
  • Southern SO, Peacock WF, Puccio AM. Chapter 23 — Saliva biomarkers of traumatic brain injury. In: Wu AHB, Peacock WF, eds. Biomarkers for Traumatic Brain Injury. Academic Press; 2020:333–353.
Saliva IHC assay in vitro drug safety test - three panels: A baseline biomarker expression before drug spike, B-C elevated biomarker level at 2 and 8 hours after drug spike in primary culture of normal human saliva

Saliva IHC assay — in vitro drug safety test. Stress Response biomarker panel was measured in a primary culture of normal human saliva. a, Baseline biomarker expression level before drug spike. b-c, Elevated biomarker level 2 and 8 hours after the drug spike. Original magnification: ×400 (b, d).

References

  • Southern SO. Milk-borne transmission of HIV. Characterization of productively infected cells in breast milk and interactions between milk and saliva. J Hum Virol. Jul-Aug 1998;1(5):328–37.
  • Southern SO, inventor; Gaia Medical Institute, assignee. Health test for a broad spectrum of health problems. United States patent 8771962 (2014).
  • Southern SO, inventor; Gaia Medical Institute, assignee. Systems and methods for analyzing persistent homeostatic perturbations. Patent number 8518649 (2013).
BREAKTHROUGH INNOVATIONS

Objective discovery of TBI biomarkers in saliva

The traditional way to identify a disease biomarker has been to measure of the components of the injured tissue leaking into blood and other body fluids (e.g., troponin after heart attack or GFAP/UCHL-1 after TBI).

We used our new method STRESS RESPONSE PROFILING (SRP) (US Patent 8,518,649) for a large-scale data mining of systemic response to TBI to objectively discover new TBI biomarkers in saliva.

Sarka O. Southern, W. Frank Peacock, and Ava M. Puccio. "Saliva biomarkers of traumatic brain injury." Biomarkers for Traumatic Brain Injury. Academic Press, 2020. pp. 333-353.

Iceberg diagram showing the small known part of TBI injury versus the much larger, unknown part, with TBI biomarkers in saliva highlighted in the unknown part

Stress Response Profiling (SRP) measures the systemic biological response to TBI using an array of 100 surrogate biomarkers that monitor activation of principal homeostatic pathways with known links to cellular and molecular responses to TBI. The SRP method for biomarker discovery has been successfully applied to other diseases such as dementia, showing that it is innovative in a broad sense. The table below shows the 11 systemic responses to TBI mapped to their homeostatic pathways and corresponding SRP biomarkers.

Stress Response Profiling table showing 11 systemic responses to TBI, their corresponding homeostatic pathways, and a heatmap of 100 SRP biomarkers
INTELLECTUAL PROPERTY PORTFOLIO

Nine issued patents protect the company’s foundational technology

United States patent certificate with ribbon
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9. Health test for a broad spectrum of health problem US Patent 12360122. Issued July 15, 2025
Key IP: Saliva based diagnostic biomarkers for TBI and dementia
8. Systems and methods for analyzing persistent homeostatic perturbations US Patent 10802028, October 13, 2020
Key IP: Saliva assay of dehydration biomarkers
7. Health test for a broad spectrum of health problems US Patent 0705097, July 7, 2020
Key IP: Digital biomarker immunoassays using image analysis
6. Health test for a broad spectrum of health problems US Patent 10317416, June 11, 2019
Key IP: Biomarker analysis using saliva with cells
5. Health test for a broad spectrum of health problems European patent EP 2660 596 B1, November 30, 2018
Key IP: Methods and devices for saliva diagnostics
4. Health test for a broad spectrum of health problems US Patent 9874573, January 18, 2018
Key IP: Saliva biomarkers for dehydration, heart failure and kidney disease
3. Health test for a broad spectrum of health problems US Patent 9176149, November 3, 2015
Key IP: Methods for biomarker immunoassays using microscopy slides
2. Health test for a broad spectrum of health problems US Patent number 8771962, July 8, 2014
Key IP: Methods and devices for identifying panels of saliva biomarkers associated with a medical condition or disorder
1. Systems and methods for analyzing persistent homeostatic perturbations US Patent 8518649, August 27, 2013
Key IP: The Stress Response Profiling method for objective discovery of disease biomarkers
THE BrainGuardian™ ADVANTAGE

Why This Test Is Different

No TBI
Left Behind

Blood tests and CT scan are positive only in TBI with brain bleed.

BrainGuardian provides a solution for the “Silent Majority” with undiagnosed TBI. It is the one-stop solution for the entire TBI spectrum, from sport concussions to TBI with or without a brain bleed.

Extended Diagnostic
Window

Blood tests can detect TBI biomarkers for up to 24 hours after injury.

BrainGuardian detects saliva biomarker of TBI from 1 hour up to 9 days after injury — critical for patients with delayed-onset symptoms.

Noninvasive Saliva
Collection

Point-of-Care ready for
Any Environment

BrainGuardian uses a simple, non-invasive saliva swab for a rapid "Yes/No" answer on the sideline, in the clinic, at home or on the battlefield—no needles or specialized imaging required. No medical training required. Safe for children.

Unmatched
IP protection

9 issued US and international patents: Synergistic Ecosystem of 3 functional clusters.

Cluster A: Continuous Discovery Engine (Platform IP).

Cluster B: Diagnostic Mechanics (Method IP).

Cluster C: Clinical Products (Application IP) specific revenue streams —saliva tests for TBI and dementia.

Head-to-Head

The Only Rapid, Consumer-Ready Solution

Others require a lab, a blood draw, and equipment. We just need a saliva swab.

Feature BrainGuardian™ Abbott i-STAT GE CT Scan
Detects sport concussion Yes Not indicated Not indicated
Diagnostic window 1 hour to 9 days 12–24 hours 1–24 hours
Sample type Saliva (noninvasive) Blood draw None (radiation)
Time to result 15 minutes 15–60 min 30–60 min
Cost $30–$50 $309+ $300–$4,800
Safe for children Yes Not indicated Radiation concerns
Point-of-care setting Professional & consumer Professional only Hospital only
CLINICAL VALIDATION

Validated by the Key Opinion Leaders in TBI diagnostics

Three independent NIH-funded studies at leading U.S. academic centers have validated our saliva TBI biomarker.

94%
Accuracy across 3 NIH studies
100%
Sensitivity — no missed concussion
2,128
Prospective saliva samples

N=1,059 men and women age 8–70 (mTBI and controls) were enrolled in sport concussion clinics and Emergency Departments at the University of Pittsburgh UPMC; Children’s Hospital of Philadelphia (CHOP), University of Pennsylvania, Ben Taub Hospital and Texas Children’s Hospital, Baylor College of Medicine in Houston, University of California San Diego, and University of Arkansas.

TBI cases included sport concussion, fall, motor vehicle crash, and assault. Controls included mild traumatic orthopedic injury (broken bones, no head injury), uninjured ER patients, healthy non-athletes and athletes (uninjured players and preseason athletes) — providing strong specificity data for the FDA.

See Who’s Behind the Science

Our clinical pathways are guided by Key Opinion Leaders who set the standard of care for concussion in the U.S.

Meet the Team