Point of Care Sepsis Diagnostic Development Milestone Hit

The first stage of the Magna Parva led RAPPID point of care (PoC) diagnostic platform development (part funded by Innovate UK), has come to an end demonstrating that the device is capable of both simple “bed-side” blood sample preparation and rapid multiplexed detection of our first application; infectious markers found in sepsis patients.

A Potentially Life Threatening Condition

Sepsis is a life threatening condition that arises when the body’s response to an infection injures its own tissues and organs. An estimated 18 million people worldwide are affected by sepsis annually, however if it is caught early, it can be treated, but for every hour that sepsis remains undiagnosed, the risk of death increases by 8%. In the UK the economic burden is huge costing the UK/US ~£20Bn annually, currently there is no clinically useful diagnostic for sepsis and with it being responsible for more deaths than breast and bowel cancer combined, that huge gap in the market needs to be filled.

RAPPID Diagnostic Tool

RAPPID is a fully-integrated, rapid multiplexed pathogen/biomarker immunodiagnostic device for rapid detection (<15 min) of infectious diseases. The RAPPID’s diagnostic tool is being developed as a specific application version to enable point of care detection of sepsis. The technology will accept blood samples as collected by a doctor/nurse in which the blood cells will be removed and the remaining plasma concentrated for subsequent immunosensor detection, all within a single, automated, self-contained process. At the current development stage the sample preparation and biosensor are in two separate subsystems.
The assay element will allow rapid identification of the pathogen(s) responsible for the underlying infection, as well as measure levels of several key host markers. This enables identification of patient position within the complex disease cycle allowing targeted therapy and monitoring of response to treatment.
In turn, this will allow for the most appropriate treatments to be started at the earliest possible opportunity, leading to improved patient outcomes.
An improved quality of life and cost savings are brought about by reductions in spending on unnecessary medications.

 Technical Challenges

In order for the hardware to be used as a point of care diagnostic, we needed to miniaturize the sample preparation processes from large laboratory sized equipment to a low cost small consumable still capable of accepting a ~5ml blood sample and able to deliver a concentrated 50ml output to the biosensor element.
The RAPPID diagnostic tool needs to be an easy to use tool so all members of staff are able to use it efficiently. We were required to develop a tool that is simple to use, portable and provides results in less than 15 minutes. The resulting system was designed to have a single button interface.
Our project partners Cardiff University and Gwent Group worked on the assay and the extending of the shelf life of the biosensor consumable product i.e. the antibodies used for the detection system. This enabled the antibodies to remain active following the initial drying steps and extended the shelf life of the antibody consumable chip to at least 6 months at 37oC.

Putting RAPPID to the Test

The prototype hardware and preliminary testing also demonstrated successful results.
The sample preparation prototype was constructed in order to test the miniature, consumable centrifuge/concentrator with blood samples. The blood samples were metered into the processing module using a syringe pump and the centrifuge separated the plasma from cellular material. The diluted plasma was then concentrated by vacuum boiling and extracted by pipette for analysis. 40 samples were collected from patients and 15 samples were analysed using the biosensor. The Surface Plasma Resonance Biosensor prototype developed with help from Chelsea Technologies was then tested with clinical samples with the results showing that it is able to detect applicable markers from serum of sepsis patients.
Further larger scale clinical studies will need to be performed in order to demonstrate unequivocally that the device delivers clinical benefit in terms of patient outcome and health economics.

First Stage Development Success

A platform SPR immunoassay biosensor capable of reading multiple ‘assay spots’ on an optical grating has been developed in this project. The biosensor has achieved the detection of Pathogens and Biomarkers with clinical samples. A separate sample preparation system capable of producing serum from whole blood has been produced, within the current development this has not yet been integrated with the biosensor, but with further development this is possible. Both subsystems have high utility in their own right, both within and outside of the healthcare sector in addition to the potential final integrated system for both Sepsis detection and for other infectious disease applications.
The main goal of the current development was to deliver a diagnostic device for Sepsis; however during this process several other exploitable markets are also being explored. This will provide a number of opportunities for the RAPPID diagnostic tool to apply its technologies in new areas.

Platform Applications

As the development process took place three platform technologies have been developed. The Instrument Biosensor, PoC Sample Prep and Integrated System are all individually exploitable and all suited to a range of markets and fields like Biodefense, Agri-Food, Life Science and Veterinary; making this development extremely versatile. The manufacture sample processing technology is already being developed for another application as the front end of a ‘one-stop’ ‘sample-to-result’ tumour profiling device, which will generate results directly from human tissue samples within 30 minutes. The technology will accept fresh or formalin-fixed tissue, homogenise the sample, lyse the tumour cells, extract and purify nucleic acids for upstream molecular detection, all within a single, automated self-contained disposable consumable.

The SBRI programme uses the power of government procurement to drive innovation. It provides opportunities for innovative companies to engage with the public sector and gain contracts to solve specific problems. Competitions for new technologies and ideas are run on specific topics and aim to engage a broad range of organisations. SBRI enables the public sector to engage with industry during the early stages of development, supporting projects through the stages of feasibility and prototyping.

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