#	Pagina
attuale pagina	/open-h2020/projects/219296/results.html

Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - CONAN II (CONAN II - COmplete Nucleic acid ANalysis at genome scale at ultra-high throughput Phase 2)

Teaser

Summary

Depixus is developing an innovative new biotechnology for â€˜complete nucleic acid analysisâ€™ called SIMDEQ (SIngle molecule Magnetic DEtection and Quantification). SIMDEQ is being developed not only for standard DNA sequencing, but to also
reveal previously undecipherable layers of information contained within the many subtle chemical signatures (epigenetic base modifications) that are found on both DNA and RNA. The emerging picture is that these base modifications form a
â€˜second genomeâ€™ that plays many vital roles in biology â€“ from early embryonic development, to pathogenic defence mechanisms, and the evolution of many cancers. Current sequencing technologies have very limited abilities to read these
modifications. This SIMDEQ technology can analyse individual nucleic acid molecules (DNA or RNA). Our current prototype instruments are highly robust and can be used to generate accurate genetic and epigenetic data, but have limited sample
throughput. This CONAN 2 proposal describes an ambitious project that focusses on the development of a high-throughput system, known as â€˜SIMDEQ Digitalâ€™, based on a CMOS chip (like those in digital cameras) on which many millions of
electronically addressable micron-scale wells are fabricated. The basic concepts underpinning SIMDEQ Digital have been well validated during the H2020 SME Phase 1 project, and the goal of CONAN 2 is to industrialise advanced MEMS and
CMOS technologies to develop a fully-functional system suitable for commercialisation. The release of SIMDEQ technology will not only allow Depixus to compete in the existing sequencing industry, but also to open new markets for genetic and
epigenetic analysis, EU-wide and globally. Early access to this technology will provide great business opportunities especially for European SMEs, who will help pioneer an entirely new â€œcomplete genomicsâ€ ecosystem.

Work performed

Most aspects of the project have proceeded according to schedule during the first year of activity. A project this complex requires careful planning and design work, and thus a great deal of the early efforts were devoted to hiring staff and completing basic planning and design tasks. While 3 staff had been hired during the course of CONAN 1 and other subsequent activities prior to CONAN 2 kickoff,, 7 additional new scientists and engineers were required to work on the project in our U.K. office, and human resources in our Paris office were also assigned to particular tasks. All-in-all approximately 20 staff have contributed to the project during its first year.

During the initial planning stages of the project, efforts were expended on 7 of the 8 work packages as described in detail below. In terms of specific tasks, all 8 of the 8 deliverables scheduled to be released in the first year have been uploaded into the platform on schedule (or very close to it) and 5 of the 6 scheduled milestone have been achieved (also registered on the H2020 platform). Further details on these deliverables can be found in the summaries of individual work packages below.

During the first year of this project, we have closely monitored and amended the project risk register. The project has experienced some mild to moderate delays, but these were largely anticipated in the register, and mitigation strategies have been deployed when possible. In some cases, this has resulted in slight shifting of priorities for certain aspects of the project; due to the extremely short timeline for such a complex project this may result some of the originally planned tasks to be delayed beyond the endpoint of the grant period. In these cases, these project tasks will simply be shifted into the commercialization phase of our overall development plan (and paid for with funding from investors rather than H2020). Meanwhile, surface chemistry issues were identified as a significant technical challenge not fully appreciated in the initial project plan, and we have therefore devoted a considerable amount of effort towards addressing these issues. We have not created a new Work Package for these tasks, but rather expanded the existing tasks of MEMS development and Biochemical testing (T3.3 and T7.3)

Final results

In our original proposal we pointed out that while DNA sequencing has become increasingly efficient, accurate and cheap, advancement in this field is stalling, with users lacking the fundamental capability to uncover deeper layers of information from their genomics samples. We identified this as a large untapped future market, and we still believe this to be the case. Regarding the specific markets for RNA sequencing and DNA/RNA epityping, we have every reason to believe that their growth trajectories will be similar to that of DNA sequencing over the last 20 years. We have slightly shifted our short-term focus however, to emphasize the power of DNA and RNA fragment identification/fingerprinting combined with epigenetic testing, but not necessarily required full DNA or RNA sequencing. We therefore devoted increased development efforts to producing the software tools necessary to realize these capabilities for our instrument.

The expected results by the end of the project remain largely unaltered since the commencement of the project:
*The project has focussed on the development of a digital high-throughput SIMDEQ system (SIMDEQ Digital) based on detection using a complementary metalâ€“oxideâ€“semiconductor (CMOS) chip.
*This project has been a major catalyst for Depixus to receive further equity funding of â‚¬20m-â‚¬40m in support of the companyâ€™s wider activities (which we are currently in the process of securing this financing, and expect to complete the current fundraising round by Q1 2020).
*The project has created more than 10 jobs already and we expect an additional 75-100 new employees to join the company within the next 24 months. T

In addition to the user benefits discussed above, we proposed that SIMDEQ Digital will also have the following wide-ranging societal and environmental benefits
* There will be a major impact on advances in medical sciences and, subsequently, on health.
* The novel data generated by SIMDEQ Digital will also have the capacity to improve public health surveillance and infectious disease outbreak investigation.
* Enabling epigenetics technology will accelerate advances in environmental sciences.
* SIMDEQ Digital dispenses with large inefficient detection systems, and thus uses considerably less energy, requires less expensive laboratory space, and consumes lower amounts of chemical reagents and plastic consumables.

Conclusions.

The project is proceeding largely as anticipated, and we have addressed technical and market challenges by making some course corrections to our original R&D plan. We anticipate that at the end of the project, we will be well positioned (both financially and from the perspective of TRL) to enter immediately into the commercialization phase of this innovative technology platform.