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For disease detection, every molecule counts.

Our molecular counting platform can help quantify nearly undetectable DNA changes, unlocking improvements to non-invasive prenatal screening and liquid biopsy.

Our molecular counting platform can help quantify nearly undetectable DNA changes, unlocking improvements to non-invasive prenatal screening and liquid biopsy.

The Challenge
Some genetic nuances are nearly undetectable in cell-free DNA

Cell-free DNA (cfDNA) are fragments of genetic material that are shed into the bloodstream. Some conditions are easier to detect and quantify with cfDNA as they involve drastic genetic changes and/or are more abundant in the bloodstream. However, other conditions shed tiny and/or sparse DNA fragments into the blood. These conditions can benefit from quantification at the molecular level to confer meaningful observations.

Prenatal

Traditional non-invasive prenatal screening focuses on assessing a fetus’ risk for larger chromosomal changes (e.g., an extra chromosome such as trisomy 21). But several common and severe conditions are the result of much smaller genetic changes that are not as abundant in the maternal bloodstream. Sickle cell disease, for example, is an inherited condition caused by a base pair alteration within a single gene. 

Identifying these tiny changes within cfDNA is complex because the fragments are small and sparse compared to the wildtype variations and vast maternal DNA in the background.

Oncology

It is important to monitor how a patient’s tumor changes over time. Scans are non-invasive and widely used but can present logistical, cost, and radiation challenges. Liquid biopsy tests are a rapidly growing mechanism to non-invasively look at circulating tumor DNA (ctDNA; a type of cfDNA).

Some small but meaningful tumor changes can be challenging to detect as they may be hard to physically see (on scans) or only reflect minimal changes to the amount of ctDNA in the blood (liquid biopsy). Currently available liquid biopsy products for monitoring focus on qualitative measurements that primarily work when the tumor can be surgically removed (minimal residual disease detection), resulting in an unmet medical need when surgical removal is difficult.

Tiny-scale changes call for tiny-scale quantification

BillionToOne’s proprietary molecular counting technology, or Quantitative Counting Templates (QCTs), quantifies DNA fragments (molecules) to detect conditions caused by tiny DNA variations that can be sparse in the bloodstream. These include pregnancy-related DNA that code for recessively inherited conditions such as sickle cell disease and cystic fibrosis and ctDNA in the case of cancer.

How It Works
molecular counting

An accurate count of disease-related DNA fragments (molecules) in a blood sample can tell us about the status of a patient’s cancer or a fetus’ risk for genetic conditions. Because some fragments are tiny and/or sparse, they must be amplified. However, amplification can confound the challenge of detecting disease as it can be noisy and molecules amplify at different rates. Adding QCTs prior to amplification provides a measurement tool that allows for better quantification after this step to determine how many disease molecules were in the initial sample to begin with. 

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add

Add a specific number of traceable, synthetic DNA fragments called QCTs (n1) into the patient’s blood sample, which contains an unknown number of DNA fragments of interest ( m1) among a vast background of the patient’s genome.

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amplify

Using PCR, the DNA fragments
of interest are amplified at the
same, unknown rate as QCTs.

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count

Count the number of QCTs ( n2) in the amplified sample and divide it by the number added to the original sample. This is the amplification multiplier (x).

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compute

Apply the multiplier (x) from the QCTs
amplification to solve for the number of
DNA fragments of interest in the original
sample ( m1). This involves proprietary
machine learning-enabled bioinformatics
and computation methods.

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A patient's blood stream cell-free DNA

Our molecular counting technology makes our commercially available non-invasive prenatal test, UNITY Screen™, possible. UNITY is the only NIPT that can assess fetal risk for recessive conditions and aneuploidies from a single maternal blood draw.
We are also actively looking for research collaboration partners for our new research liquid biopsy products, Northstar Select™ and Northstar Response™.

Our Proprietary Technology Platforms

  • QCT technology

    Quantitative counting templates for flexible, accurate and high throughput combined sequencing and counting of DNA molecules.
  • Dilution tagging technology

    Application of statistical compression algorithms during physical DNA sample preparation. Compresses DNA samples with high dynamic range while preserving initial signal. Enables low cost sequencing of DNA samples with rare sequences without loss of quantitative information.
  • Spike-in technology

    Synthetic DNA controls custom made for each assay and added to every patient sample. These DNA controls enable per patient correction factors when determining copy number of targeted genes.
  • qSanger technology

    Combines spike-in technology with custom-built, proprietary signal processing and applies it to Sanger sequencing and capillary electrophoresis, bringing the power of quantitation to previously qualitative technologies. This approach brings NGS-level precision to easy-to-deploy technologies and enables their use as low-cost, high-throughput, diagnostic tools.

Publications

UNITY Aneuploidy NIPT Clinical Validity

Published in Annals of Gynecology and Obstetrics Research

May 21, 2024

Performance Characteristics of a Next Generation Sequencing-Based cfDNA Assay for Common Aneuploidies in a General Risk Population

  • 99.7% sensitivity & 99.9% specificity
  • Results applicable to a general obstetric population: 80% of patients in the study were <35 years of age
Read Article for Performance Characteristics of a Next Generation Sequencing-Based cfDNA Assay for Common Aneuploidies in a General Risk Population
performance-characteristics-of-a-next-generation-sequencing-based-cfdna-assay-for-10032 (2)

UNITY Fetal Risk Screen Clinical Validity and Utility

Published in Prenatal Diagnosis

September 6, 2023

Performance of single-gene noninvasive prenatal testing for autosomal recessive conditions in a general population setting

  • 528 neonatal outcomes, with at least 75 for each condition
  • 99.8% NPV and 96% assay sensitivity
  • All cases identified as 9 in 10 risk were confirmed to have an affected child via neonatal outcomes
Read Article for Performance of single-gene noninvasive prenatal testing for autosomal recessive conditions in a general population setting
Prenatal Diagnosis - 2023 - Wynn Copy Thumbnail conv 1

Validation for Red Blood Cell Fetal Antigen NIPT

Published in Scientific Reports

August 7, 2023

Validation of a Non-invasive Prenatal Test for Fetal RhD, C, c, E, Kell and FyA Antigens

  • The assay correctly determined fetal antigen status for 1061 preclinical samples with an analytical sensitivity of 100% (95% CI: 99-100%) and analytical specificity of 100% (95% CI: 99-100%)
  • A clear separation between antigen detected and not detected was demonstrated for 15,939 clinical plasma samples in a general population setting, with an estimated clinical sensitivity of 99.6%-100%
  • This assay had excellent performance for fetal fractions as low as 1.1% and as early as 10 weeks of gestation, without the need for a sample from the biological partner
Read Article for Validation of a Non-invasive Prenatal Test for Fetal RhD, C, c, E, Kell and FyA Antigens
s41598-023-39283-3 conv 1

Clinical Validity and Utility for UNITY Carrier Screen with sgNIPT

Published in Genetics in Medicine

December 1, 2022

Maternal carrier screening with single-gene NIPS provides accurate fetal risk assessments for recessive conditions

  • Single-gene NIPT had a 93.3% clinical sensitivity in 191 cases with outcome data compared to ~35% of traditional carrier screening
  • PPV was 48.3% vs traditional carrier screening (25%); NPV was >99.4%
  • Full 9151 sample set had an estimated end-to-end 90% sensitivity and 99.8% specificity for carrier screening with single- gene NIPT
Read Article for Maternal carrier screening with single-gene NIPS provides accurate fetal risk assessments for recessive conditions
Maternal carrier screening with single-gene NIPS provides accura

Sickle Cell Disease Validation

Published in American Journal of Hematology

April 16, 2022

Validation of single-gene noninvasive prenatal testing for sickle cell disease

  • Single-gene NIPT accurately identified all affected pregnancies as high risk at a greater than 9 in 10 risk
  • Single-gene NIPT accurately identified all unaffected pregnancies as low or decreased risk
Read Article for Validation of single-gene noninvasive prenatal testing for sickle cell disease
First page of article: Validation of single-gene noninvasive prenatal testing for sickle cell disease

Single-gene NIPT Health Economics

Published in Journal of Medical Economics

March 23, 2022

Reflex single-gene non-invasive prenatal testing is associated with markedly better detection of fetuses affected with single-gene recessive disorders at lower cost

  • Carrier screening with reflex to single-gene NIPT resulted in an estimated $37.6M saving per 100,000 pregnancies compared to traditional carrier screening in a model comparison
  • The cost to detect one affected pregnancy by carrier screening with reflex to single-gene NIPT was 62% lower than traditional carrier screening
Read Article for Reflex single-gene non-invasive prenatal testing is associated with markedly better detection of fetuses affected with single-gene recessive disorders at lower cost
First page of article Reflex single-gene non-invasive prenatal testing is associated with markedly better detection of fetuses affected with single-gene recessive disorders at lower cost

Single-Gene NIPT Analytical Validation

Published in Nature Scientific Reports

October 7, 2019

A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT

  • Proof of concept for QCT platform necessary for the technology of single-gene NIPT
  • Analytical validity of single-gene NIPT with an estimated sensitivity of >98% and specificity of >99%
Read Article for A novel high-throughput molecular counting method with single base-pair resolution enables accurate single-gene NIPT
First page of article: A novel high-throughput molecular counting method with single base pair resolution enables accurate single-gene NIPT

Liquid biopsy

Published in AACR 2022 Poster Session

April 10, 2022

Novel methylation-based, tissue-free ctDNA assay accurately quantifies longitudinal tumor burden changes for precision treatment monitoring

Read Article for Novel methylation-based, tissue-free ctDNA assay accurately quantifies longitudinal tumor burden changes for precision treatment monitoring

Liquid biopsy

Published in AACR 2023 Poster Session

April 18, 2023

Methylated ctDNA dynamics correspond with clinical tumor load in metastatic lung cancer patients on therapy

Read Article for Methylated ctDNA dynamics correspond with clinical tumor load in metastatic lung cancer patients on therapy