By Dr. David Rubert, Xpedite Diagnostics · 6 min read
A diagnostic gap the size of a continent
Sickle cell disease (SCD) is the most common inherited haemoglobinopathy in the world, and its burden is profoundly uneven. The Global Burden of Disease 2021 analysis estimated 7.74 million people living with SCD, up 41% since 2000, with roughly 80% of that burden, and of the deaths, concentrated in sub-Saharan Africa [1]. Yet the tools that establish an exact molecular diagnosis, and the reference data that make those tools interpretable, sit almost entirely elsewhere.
That imbalance is not only clinical; it is genomic. African populations are the most genetically diverse on Earth and remain the most under-represented in reference databases: one landmark study identified more than three million previously undescribed variants from just 426 African individuals [2]. Variants that are diagnostically important in these populations can therefore be absent from the very panels used to interpret them.
Prof. Hugues Abriel, Professor of Molecular Medicine at the Institute of Biochemistry and Molecular Medicine (IBMM), University of Bern, set out to address that gap by moving the analysis to the sample, rather than the sample to the analysis.
From ion channels to nanopores
Abriel's laboratory works on ion-channel physiology and the wider class of monogenic disorders, inherited epilepsies, cardiac arrhythmias, cystic fibrosis, where single-gene resolution is what settles a diagnosis. His interest in portable sequencing is long-standing.
'I have been following the development of Oxford Nanopore since more than 20 years.' — Prof. Hugues Abriel
The attraction, for fieldwork, is a combination of properties: a small instrument footprint, low capital cost, and long read lengths that resolve both single-nucleotide variants and structural variants in a single assay. During a 2021 sabbatical, Abriel ran an early MinION in medical-genetics laboratories in Fez, Morocco, and Kinshasa, DRC, the groundwork for a more ambitious question: could an entire medical-genetics workflow run outside conventional infrastructure?
A laboratory in three suitcases
In practice, "portable" required some honesty about scope.
'At the beginning, I thought everything would fit in one suitcase. You need at least three.' — Prof. Hugues Abriel
The platform was developed jointly with Xpedite Diagnostics as an integrated, extraction-to-sequencing system: nucleic acid extraction and amplification chemistry, a compact MIC PCR cycler, a MinION MK1D sequencer, and a single laptop driving both amplification and sequencing. It runs the full path, sample input (fresh blood, dried blood spots, or buccal swabs), DNA extraction, targeted PCR, nanopore sequencing, and variant calling, without shipping samples to a central facility. Abriel put the fully assembled system at 'about 40,000 EUR, with everything', with a MinION MK1D starter configuration near EUR 5,000.
Why sickle cell disease?
SCD is an autosomal recessive disorder of HBB, encoding β-globin. The canonical allele is HBB rs334 (c.20A>T; p.Glu7Val, legacy nomenclature p.Glu6Val / E6V), producing haemoglobin S (HbS). On deoxygenation, HbS polymerises, deforming erythrocytes into the sickle morphology and driving chronic haemolytic anaemia; homozygosity (HbSS) carries a high risk of early-childhood mortality where care is limited [3]. Crucially, compound genotypes, HbS combined with HbC, or with a β-thalassemia allele, produce clinically distinct phenotypes. This is precisely where a genotyping assay that interrogates only rs334 can mislead, and where full-gene sequencing earns its place.
A first test, close to home
The programme's first field exercise deliberately used a simpler readout. Working with the Swiss Association of Sickle Cell Disease Patients, the team moved the platform from Bern to the association's April 2025 annual meeting in Lausanne (≈100 km) and processed samples on site. This stage genotyped rather than sequenced, using a CE-marked IVD loop-mediated isothermal amplification (LAMP) assay (LaCAR MDx Hb S/C) that resolves the HbS and HbC alleles and their zygosity from buccal swabs and dried blood spots, in about three hours. Across 27 participants, the on-site workflow returned concordant genotypes for nearly all samples, with a single pipetting error. The results are available as a medRxiv preprint.
Dakar: a diagnosis in 36 hours
The sequencing deployment followed. The team carried three cases to Dakar, the Xpedite Diagnostics platform, a reagent case under cold-chain control, and a consumables case, and installed the workflow at the Children's Hospital in Dakar with a University of Dakar team spanning biochemistry, paediatric genetics, and medical genetics. The initial test cohort was ten patients with anaemias of uncertain molecular diagnosis, in whom SCD was suspected but unconfirmed.
From 200 µL of blood per patient, the team performed on-site DNA extraction (Xpedite kit), amplified the HBB coding region (three exons, ≈1 kb), prepared multiplexed nanopore libraries, and sequenced overnight, read depths in the thousands, analysed by local bioinformaticians. In one patient, sequencing resolved two variants in trans: the HbS allele (rs334) on one chromosome and, in exon 2, a nonsense variant introducing a premature termination codon, a β⁰ (null) allele, on the other. The resulting HbS/β⁰-thalassemia compound heterozygosity is clinically comparable to HbSS, and would not have been captured by an assay targeting rs334 alone.
'We obtained what we call diagnostic-grade sequences from 10 patients with these anaemias within 36 hours.' — Prof. Hugues Abriel
The workflow operated autonomously with a vehicle battery a viable power source.
What the missing suitcase taught them
The next leg was not completed, and Abriel presented that outcome as openly as the success. On transfer to Kinshasa, and onward to Kindu, a site in central DRC with no genetics laboratory, only two of the three cases arrived. The reagent case, under cold-chain control, was held at Dakar airport.
'So logistics matter a lot. We could not perform the experiment in Kinshasa and in Kindu.' — Prof. Hugues Abriel, University of Bern
The lesson is consistent across the programme: the sequencing chemistry and instrumentation are field-viable; the limiting variables are cold-chain reagent stability, customs documentation (evidence of non-infectious, non-toxic status), and operator preparedness.
From breakthrough to system change
The near-term roadmap extends the panel from HBB to a multiplex of HBB, HBA1, and HBA2, adding alpha-thalassemia, and scales the amplicon approach toward long-range PCR products of 40–45 kb, bringing larger loci such as CFTR into range, with adaptive sampling on genomic DNA as a longer-term objective. Wilson disease, inherited epilepsies, arrhythmias, and oncology applications are all candidates. Abriel noted that the DRC operates a network of roughly ten genetics centres:
'The dream would be to have in each of these centres one of such mobile minimal medical-genetics labs.' — Prof. Hugues Abriel
Equally deliberate is the governance model. Samples are analysed in-country, reference data reside locally rather than on external servers, and personnel exchange runs in both directions, a design that consciously avoids the extractive "helicopter science" pattern in which data leave the continent and expertise does not stay. A portable instrument is the visible part of the story; the durable part is the capacity built around it.
Related Xpedite products
The DNA extraction step in the Dakar workflow used an Xpedite SwiftX™ kit, and the field platform was co-developed as the Xpedite Mobile Laboratory. For blood-derived genomic DNA, the relevant product is the SwiftX™ Blood Genomic Kit (magnet-based extraction from fresh, whole, or dried blood; no centrifuge or chaotropic reagents).
About the speaker. Prof. Hugues Abriel (MD; PhD, physiology) is Professor of Molecular Medicine at the Institute of Biochemistry and Molecular Medicine, University of Bern, and the initiator of the PORTA-HBB portable genetic-testing programme.
PORTA-HBB is a research programme; the field results described here are from early deployments. Xpedite extraction products are for research use only (RUO). The LaCAR MDx Hb S/C assay is CE-marked for in vitro diagnostic use.
References
- GBD 2021 Sickle Cell Disease Collaborators. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021. The Lancet Haematology. 2023. DOI: 10.1016/S2352-3026(23)00118-7.
- Choudhury A, et al. High-depth African genomes inform human migration and health. Nature. 2020;586(7831):741–748. DOI: 10.1038/s41586-020-2859-7.
- Hoffbrand AV, Steensma DP. Hoffbrand's Essential Haematology. 8th ed. Hoboken, NJ: Wiley; 2020.