Cellular liquid biopsy · Barcelona
Isolating fetal cells from a tube of maternal blood.
We are developing a method that isolates whole fetal cells from a routine maternal blood draw, giving access to the fetal genome without amniocentesis or chorionic villus sampling.
The same principle could separate other rare cells defined by what they transcribe, such as circulating tumor cells, pathogens or immune subsets. Prenatal diagnosis is where we are proving it first.
The gap
Today, certainty still requires an invasive procedure.
Prenatal genetic testing is split between two imperfect options. One is accurate but carries risk. The other is safe but reads a fragmented, blurred signal.
Invasive sampling
Amniocentesis and chorionic villus sampling give access to the intact fetal genome, but require entering the uterus and carry a small procedure-related risk of pregnancy loss.
Cell-free DNA
Liquid biopsy as practiced today reads short DNA fragments of trophoblast origin, diluted in maternal plasma. While informative, the signal is mixed, incomplete and interpreted as a probability, not a diagnosis.
Single-gene disease
Cell-free DNA screening for single-gene conditions covers a limited set of genes and returns a risk estimate. For families at known risk, a definitive answer still requires an invasive procedure.
Clinical value
What a whole fetal cell lets a clinician read.
In maternal plasma, fetal DNA fragments sit in a background of maternal DNA. When the mother carries the same variant as the fetus, the two cannot be cleanly told apart, and confirmation means amniocentesis or chorionic villus sampling. An isolated fetal cell contains only the fetal genome. HELENA is designed to read it directly.
| Clinical situation | Cell-free DNA today | An isolated fetal cell |
|---|---|---|
| Both parents carry a recessive conditionCystic fibrosis, spinal muscular atrophy, β-thalassemia, sickle cell disease · 1 in 4 risk per pregnancy | Risk estimate for selected genes | Both fetal alleles read directly |
| The mother carries the variantX-linked conditions such as Duchenne muscular dystrophy | Maternal background masks the fetal result | Fetal genotype without maternal signal |
| Repeat expansions and large rearrangementsFragile X syndrome | Short fragments cannot size the repeat or span the change | Intact genomic DNA suited to long-read sequencing |
| An unexpected ultrasound findingWhere the cause could be any of many genes | Targeted panels; a broad search usually means amniocentesis | Broad analysis, such as an exome, from a blood draw |
These are the clinical questions HELENA is being developed to answer. They describe intended use, not demonstrated clinical performance.
Technology
Selection by the cell's own transcript.
Our platform targets a specific mRNA inside the cell and uses amplification to magnetically charge the cell. Cells are separated by their transcripts, not by what happens to be on their surface.
- 01
A transcript no maternal cell carries
Fetal erythroblasts express fetal hemoglobin. The HBG2 mRNA is present in them and absent from the mother's cells, which makes it a discriminating target rather than a shared surface marker.
- 02
Amplification inside the cell
An isothermal reaction amplifies the target within the cell itself, at a constant temperature and without breaking the cell open. The cell keeps its structure and its genome through the chemistry.
- 03
The amplified target becomes the handle
Biotin molecules are built into the amplified product. A cell that amplified carries many of them; a cell that did not carries none. Magnetic beads then bind only the former.
- 04
Separation by magnetic field
Excess biotin and unbound beads are washed out, so no cell is dragged along without having amplified. A magnetic field then retains the labeled cells while everything else is drawn off.
- 05
Cells that are still worth reading
What is recovered is a cell, not a signal. Its DNA and morphology are preserved, so it is suitable for long-read sequencing and downstream characterization.
Lead application
HELENA: non-invasive access to the fetal genome.
Human ErythrobLast Enrichment for Non-invasive Analysis. Our first application isolates fetal erythroblasts from maternal peripheral blood and pairs them with a bioinformatic pipeline built to call congenital anomalies from whole-cell sequence data, including monogenic conditions that current non-invasive testing does not reach.
1 in 1,639
Non-fetal cells showing signal in the in-cell reaction: the measured specificity of the amplification step.
>14,000×
Sequencing depth of fetal hemoglobin cDNA in the isolated fraction, against 120× in cord blood.
Y chromosome
Fetal sequence confirmed in isolated fractions from male pregnancies, verifying fetal origin independently.
Frozen samples
The method works on frozen blood, decoupling sample collection from processing across sites.
No magnet
Magnet above
Magnet belowFetal hemoglobin cDNA is absent from the supernatant after magnetic separation, and amplification-specific sequences appear only in the isolated fraction. This is direct evidence that the reaction took place inside the cells that were captured. Isolated material has been validated by long-read sequencing.
All human samples were obtained under institutional review board–approved protocols, following standardized collection and processing procedures, with de-identified clinical data and in accordance with the Declaration of Helsinki.
Platform
One chemistry, addressed by primer design.
Because targeting is defined by the primer set rather than by an antibody, the same workflow might reach any rare cell that can be distinguished by what it transcribes. Prenatal medicine is where we are proving it first.
| Application | Target | Stage |
|---|---|---|
| Non-invasive prenatal diagnosisHELENA, fetal erythroblasts | Fetal hemoglobin transcript | Lead program |
| Circulating tumor cellsWhole cells for mutational profiling | Tumor-specific transcripts | Exploratory |
| Rare pathogen detectionIsolation from complex clinical samples | Pathogen-specific sequences | Exploratory |
| Immune cell subsetsPopulations without distinguishing surface markers | Lineage-defining transcripts | Exploratory |
Development & regulatory
Where we are, and the route we are taking.
Proof of concept is established and documented. The program is now in protocol optimization and product formatting, on a defined path toward conformity assessment under the European In Vitro Diagnostic Regulation.
Quality system
An ISO 13485 quality management system will be established ahead of clinical validation, together with the technical documentation required under the IVDR.
Classification & notified body
The device classification and the corresponding conformity-assessment route are being defined with regulatory counsel, for confirmation with a notified body before validation begins.
Clinical partnerships
Clinical validation will be conducted with hospital partners in Catalonia. Partners will be named once agreements allow it.
Intellectual property
The core method is protected by an international patent application owned by Bioliquid Diagnostics, S.L.
Team
Small, experienced, and built for this specific problem.
Research is carried out by scientists trained at UCSF, UPF and the CRG. Strategy is set by two promoting partners who bring clinical science in reproductive medicine and twenty-five years of in vitro diagnostics leadership.
Strategic committee
More than twenty-five years in senior leadership across the in vitro diagnostics industry. Most recently EVP and Head of EMEA at Ortho Clinical Diagnostics, through its combination with Quidel to form QuidelOrtho, and previously EVP and Head of EMEA at Accelerate Diagnostics and SVP at Siemens Healthineers. Founder and Managing Partner of Bluemedtech, a strategic advisory practice for diagnostics and AI companies.
Gynecologist and researcher in reproductive medicine at IVIRMA Barcelona and the gynecology research group of the Vall d'Hebron Research Institute, with a visiting research period at UCSF. His published work includes the isolation of rare circulating cells from peripheral blood, the problem at the heart of Bioliquid.
Operating team
PhD in Biomedicine from Universitat Pompeu Fabra, followed by five years as a postdoctoral researcher at UCSF, where he held an independent PBBR research award, and previously at the Centre for Genomic Regulation in Barcelona. First author of work on kinetochore–microtubule attachment published in Current Biology. He leads protocol development and analytical validation.
MD and PhD from Universitat Autònoma de Barcelona, with a clinical and research background in ophthalmology across leading Barcelona centers. At Bioliquid she leads non-dilutive funding strategy, the interface with regulatory counsel, and coordination with clinical partners.
A deliberately lean structure through the development phase: execution by a small, experienced team, with direction from people who have built, led and validated diagnostics businesses.
Contact
Talk to us.
Spain