Semiconductor companies are developing proprietary diagnostic detection technologies that have potential for significant disruption in the medical technology sector, specifically relating to the field of in vitro diagnostics (IVDs).
IVDs are tests that can detect diseases, conditions or infections. Some tests are used in laboratories or other health professional settings.
Other tests exist for consumers to use at home. IVDs are increasingly employing molecular technologies which detect specific sequences in a patient’s genetic material (typically DNA or RNA) that may or may not be associated with disease.
Many physicians prescribing certain pharmaceutical treatments, such as the latest generation of oncology drugs, rely upon knowledge of a patient’s DNA in order decide whether that treatment will be effective.
So-called ‘personalised medicine’ – using an individual's genetic profile to guide optimal drug prescribing decisions – has been advanced through data from the Human Genome Project.
The mainstream medical field is progressing rapidly towards this much-heralded era of personalised medicine because of the huge potential clinical value that it offers.
Following completion of the $2.7bn Human Genome Project, it was estimated in 2001 that the personalised medicine era would be enabled once the cost of sequencing a human genome had reached a threshold $1,000.
DNA sequencing technology firm Illumina says it has successfully demonstrated the ability to sequence a human genome in a single day below this $1,000 barrier with its HiSeq X Ten sequencing platform.
The diagnostic requirements and perceived challenges of personalised medicine are well understood by the healthcare industry.
Diagnostic tests need to analyse multiple indicators of disease – so-called biomarkers – in a single test format. Frequent monitoring of patient response to drug therapy and disease progression places an additional burden on already overstretched healthcare budgets.
Another dimension to personalised medicine is the need to understand an individual patient’s predisposition towards particular drug therapies, so that harmful side effects of potent drugs can be avoided. The outcome of these requirements is an increase in the breadth and depth of testing.
Current limitations in the personalised medicine field
Significant limitations are emerging in the ability of conventional molecular diagnostic technologies to adequately serve current and future requirements of personalised medicine. The cost of performing molecular diagnostic tests may be prohibitively expensive to some payers. Also, turnaround time of these tests further diminishes the clinical value. This scenario is occurring against the emerging requirements identified above for routine patient monitoring practices to establish patient response to therapy.
Access to routine diagnostic testing for healthcare professionals is paramount to the success of personalised medicine. Specifically, this means affordable diagnostic systems that provide actionable information derived from easy-to-use devices.
Wider access to diagnostic testing will be facilitated in part by the introduction of disruptive technologies. Given the limitations of lab-based existing diagnostic platforms, mainstream adoption of diagnostic technologies presents a significant challenge.
The issue is multi-dimensional with technical, clinical and commercial considerations. The value of introducing disruptive technologies in this area is exemplified by the plummeting cost of genome sequencing in recent years from the $2.7bn of the Human Genome Project to $1,000 today.
Diagnostic companies will struggle to meet these new requirements with incumbent technology platforms.
For example, current molecular platform technologies such as polymerase chain reaction (PCR) can only detect a relatively small number of disease biomarkers.
Furthermore, considerable characterisation and validation of the biomarker is required prior to testing. Existing diagnostic systems may lack the required sensitivity to detect very low copy numbers of certain biomarkers.
Step forward semiconductor organisations
The last few years have seen the emergence of semiconductor-based diagnostic technologies in parallel with the maturing of the personalised medicine field.
Examples of companies in this space include Ion Torrent, DNA Electronics and Oxford Nanopore.
The semiconductor-based trend appears to continue with the development of novel diagnostic technologies by large semiconductor players described above.
Technologies developed by companies such as Panasonic, Hitachi, Samsung, Sony and Intel demonstrate considerable potential to enable the democratisation of diagnostic testing.
Their proprietary technologies cover a wide area of the diagnostics space including DNA microarrays, single-molecule DNA sequencing, PCR and isothermal PCR. Each identified development represents a core detection technology around which a diagnostic platform could be created.
Semiconductor characteristics could shift the value proposition in diagnostics
The majority of IVD tests are performed using instrumentation in large reference laboratories. These instrument platforms represent a significant development cost and need to be applicable to a wide panel of tests. This latter requirement often entails a trade-off involving reduced test sensitivity.
Semiconductor-based design platforms have the potential to address the technical, clinical and commercial bottlenecks that need to be removed to facilitate the routine use of diagnostic technologies. Diagnostic technology platforms that are enabled by semiconductor developments have the potential to yield fundamentally different diagnostic system architectures.
This is exemplified in a Samsung PCR patent, which demonstrates a shift of functionality to the consumable, potentially resulting in an instrument of vastly reduced complexity. The elimination of a large instrument could shift the current value proposition in diagnostics (repeat consumables for an installed base of high-cost lab-based instruments) and enable the technology democratisation required for routine diagnostic testing in personal medicine.
Technical considerations are addressed by the exploitation of ‘ground-up’ semiconductor fabrication methods that enable greater consumable functionality and lead to radically different diagnostic system architectures.
Consumables with additional functionality fabricated within them enable smaller and less complex instruments. This leads to improved ease-of-use by non-skilled staff and thus greater availability of diagnostic testing for routine use. Clinical considerations are addressed by the use of existing life science techniques such as PCR, ensuring parity between tests used on existing diagnostic platforms and those tests carried out on new platforms.
Commercial considerations such as cost are readily addressed by semiconductor-based developments. By its nature, semiconductor manufacturing is organised around vast economies of scale. Manufacturers would be able to utilise significant existing semiconductor manufacturing facilities. The exploitation of Moore’s Law could also mean significant cost savings in the longer term as manufacturers use their experience of the consumer electronics industry with aggressive price pressures.
This is an opportune moment for semiconductor companies to gain a foothold in the personalised medicine field through the potential to enable fundamentally different diagnostic system architectures. These novel platforms and systems could shift the current value proposition in diagnostics. The forecast market size for personalised medicine is significant with diagnostic testing a key enabler in this area.
Nick Rollings is principal engineer in the medical technology division at Cambridge Consultants and Dr James Blakemore is senior market strategy consultant in the medtech consulting group at Cambridge Consultants.