In the liquid biopsy field, much attention is focused on the analytical end of the workflow: detecting increasingly small amounts of tumor-derived material, distinguishing biological signal from background cell-free DNA, and developing sequencing and computational methods that can translate those signals into clinically useful results.
But there is another layer to the technology that happens before the patient sample reaches the laboratory instrument: the synthesis of the oligonucleotides used to interrogate it.
That manufacturing layer is becoming particularly relevant as developers pursue increasingly complex assays for minimal residual disease (MRD) and multicancer early detection (MCED). A recent review highlighted the growing use of liquid-biopsy multiomics and artificial intelligence in MRD and MCED development, reflecting the increasing complexity of these approaches.
Integrated DNA Technologies (IDT) recently highlighted this issue when it announced expanded DNA synthesis capabilities spanning yield, sequence complexity, and scale. The company said the expansion will allow production of low-yield, high-diversity oligonucleotides while complementing its established high-yield, high-fidelity synthesis capabilities.
More targets, more complexity
For assay developers, “high diversity” can mean working with large collections of distinct oligonucleotide sequences rather than producing relatively small numbers of a single sequence. Depending on the assay architecture, these sequences can serve as probes, primers, capture reagents, or other components used to interrogate genomic material.
MRD assays illustrate why that matters. Following treatment, residual malignant cells may be present at very low levels, making analytical sensitivity and specificity critical considerations. Different MRD technologies use different strategies to identify residual disease, including tumor-informed approaches that track patient-specific tumor alterations and tumor-naive approaches that detect cancer-associated signals without requiring a matched tumor sample.
MCED assays pose a different challenge. A test intended to screen for signals associated with multiple cancer types potentially has to account for substantially greater biological and genomic diversity than an assay directed at a single known tumor.
In both cases, expanding the number and diversity of molecular targets can place greater demands on the underlying oligonucleotide supply chain. It is not enough for sequences to be designed computationally. They must also be synthesized with appropriate quality, consistency, and yield, and eventually supplied at a scale compatible with the intended workflow.
Scaling the molecules behind the assay
IDT's expanded offering will help address this range of synthesis requirements.
The company said its expanded capabilities are intended to give customers a path from rapid production of high-diversity designs during early development through more dependable scale-up for larger programs. IDT is also establishing a pilot laboratory at its Innovation Nexus in Sunnyvale, CA, to accelerate development and optimization of new synthesis solutions.
The company previously expanded its Coralville, IA, synthesis capacity by more than threefold.
The broader implication for molecular diagnostics is that assay scalability is not solely an analytical problem. As MRD and MCED programs move toward larger studies and potentially broader clinical deployment, the ability to manufacture the molecular components of those assays reproducibly and at scale becomes part of the development equation.
IDT's announcement does not establish that DNA synthesis is currently the limiting factor for MRD or MCED. But it does highlight an often-overlooked component of the liquid-biopsy ecosystem: before a highly sensitive molecular assay can be validated, deployed, and scaled, someone has to reliably manufacture the molecules that make the assay work.
This article was created with the assistance of Generative AI and has undergone editorial review before publishing.
