Core structure of penicillins (top) and cephalosporins (bottom). Beta-lactam ring in red.

The main objective of COBIOPHAD is the development of an integrated biophotonic device based on compact disc technology to address the most prevalent drug hypersensitivity to beta-lactams antibiotics (BLCs). The system will be developed in a low cost and rapid point-of-care format, and will integrate multiple key enabling technologies – advanced materials, optics, electronics, bio-analytical tools, manufacturing systems, and cloud-based data networking. The project targets a highly sensitive, selective, and multiplexed in vitro medical diagnostic device to contribute to the sustainability of healthcare systems and the life quality of millions of European citizens suffering drug allergies.

The use of in vitro diagnostic tests (IVD) for the detection of specific IgEs associated to BLC hypersensitivity is a highly demanded solution to substitute the invasive and risky in vivo tests (gold reference). The current IVDs, developed with bulky auto-analysers and based on classical technologies, show low sensitivity (lower than 40%; detection limits > 0.2 kU/L), analyze only five BLCs and give false-positive and -negative results. For these reasons, the integration of innovative technologies for the development of reliable and cost-effective IVD is the solution proposed by the COBIOPHAD consortium.

Mass consumer electronic technologies offer huge advantages to serve as basis of health devices. Amongst them, the compact disc incorporates a potential analytical platform (disc) and a detector (disc player) with competitive performances and costs. Proofs demonstrating the viability of this concept have been shown.

The following steps are considered for integration in a final device: blood sample purification, IgE pre-concentration, specific and sensitive bio-recognition, optical detection, and data management.

The biophotonic system will be characterized by the following specifications:

• Sensitivity (80%) and detection limit below 0.1 kU/L. This will be achieved by integrating a high sensitive detection technique, a functional analytical platform, and a reliable assay.
• High specificity (around 98%) due to selective assays simultaneously determining responses of different BLCs.
• Multiplexing capability (high number of samples per disc and BLCs per sample), rapid (30 minutes maximum total analysis time) in vitro diagnosis of the main allergenic BLCs. As a result, the envisioned system is a hundred times more efficient when compared to current tests.
• Low-cost device with a manufacturing price of 300 € for the detector, 1 € per disc and 0.3 €/allergen in reagents, at least ten-times lower than the current IVD tests.
• High scalability covering a broad range of scenarios, i.e. from 1-2 samples per disc for Emergency and Critical care units to 10 samples per disc recommended in Allergy Departments. Upon request, samples can be tested to either one drug or to the complete BLC family within a single run.
• Robustness of operation in point-of-care settings, achieved by combining centrifugal disc and detection drive.
• Operational autonomy: Due to the compact format, the device can be fully autonomously operated in clinical or mobile lab environment and does not require any additional medical equipment. The integration of advanced microstructures and microfluidics on a disc allows a high degree of operational flexibility, i.e. variable rotation rate, type and volume of sample (starting with 100 µL of whole blood).
• External communication and the end-user’s interface. Developments in telecommunication and in (digital) information technology enable eHealth solution providers to deliver remote clinical care.
• Reliable, validated in an operational environment and certified pre-commercial implementation.

COBIOPHAD will lead an important technological goal within the drug allergy diagnosis market. Hardware, software, (bio)-chemicals, and methodologies of high commercial value will be exploited by the European SMEs. The device will demonstrate superior performance for in vitro diagnosis of drug hypersensitivity to BLC antibiotics when compared to current methods.