Laser Multiplexed Biosensor

Project Information

GLAM

Grant agreement ID: 634928

DOI

10.3030/634928

Project closed

EC signature date 8 April 2015

Start date 1 May 2015

End date 30 April 2019

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost

€ 4 835 584,25

EU contribution

€ 4 835 584,00

Coordinated by

ACONDICIONAMIENTO TARRASENSE ASSOCIACION
Spain

Periodic Reporting for period 3 - GLAM (Laser Multiplexed Biosensor)

Reporting period: 2018-05-01 to 2019-04-30

Summary of the context and overall objectives of the project

Current diagnostic technologies are expensive and sophisticated with a need of specific equipment and trained technicians. In addition, they deliver data within days, usually more than two weeks, which compromises personalized medicine and affects both patient and relatives’ quality of life. Moreover, diagnostic outcomes are often not consistent nor robust enough because often only one biomarkers is analyzed. Accordingly, there is a clear requirement for new methods to allow an easy, fast, ultra-sensitive, multiplexed, and reliable detection of soluble biomarkers. The aim of GLAM project is to provide an innovative device to fulfill these requirements using soluble biomarkers for personalized medicine.
Biomarker analysis is made from patient urine, which is directly applied to a microring chip. At the same time, a real-time biophotonic measurement provides ultra-sensitivity, simplicity, speed, and large multiplexing necessary for the GLAM device. End users will be clinical personnel who will be able to get diagnostic inputs within few minutes allowing oncologists to stratify patients, profile prognosis, monitor treatments, and take appropriate decisions.
Moreover, Glam Biosensor will directly impact on several beneficiaries, starting with the users by providing technology approaches for contributing to the user health. Additional benefits also include: economic benefits for the health sector in terms of cost reduction which lead to an improved performance are also foreseen. Finally, GLAM biosensor is also a very versatile diagnostic device, that could be used with other biofluids.
The objective of GLAM has been to develop a new diagnostic tool to detect multiplexed biomarkers from biofluids, specifically urine and focusing on bladder cancer, enabling oncologists to take better treatment decisions. GLAM developed a prototype device based on novel label-free photonic biosensors with ultra-sensitivity, simplicity of use, portability, multiplexing and low cost by simply applying a drop of urine and reading several biomarker levels. GLAM technology will make the device also usable, in a future, with other biofluids and might also help physicians in personalized medicine in many other biomarkers driven diseases, aside of cancer.
GLAM project allowed to develop new technologies in photonic biosensing (some of them are new developments that have been patent protected by the consortium). GLAM has also generated new monoclonal antibodies against specific bladder cancer biomarkers. This tools have been used for both the device and to set up specific sandwich ELISAs, allowing the analysis of urine from bladder cancer patients. For biosensing, GLAM has adapted particular biochemical protocols for antibody functionalization in photonic microrings. The final biosensor prototype has been characterized using preclinical and clinical urine samples, proving its applicability (this has also been published in upfront scientific journals).

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The selection of biomarkers has been made, which led to the correct start of next tasks. The 10 most promising biomarkers were listed, ranked, selected, and recombinant biomarkers have been produced. Antibodies against all biomarkers were obtained, validated and used in later phases of the project to both set up the biosensor device and determine biomarker levels in clinical samples.
An analytical theoretical framework was developed and numerical tools were used to provide guidelines for the design of the microrings and waveguide. The optical performance of the microrings was checked to select the best configuration. Futhermore, several functionalization protocols have been tested to efficiently and selectively immobilize antibodies at the surface of the microrings. Both “passive” and “active” sensing experiment were realized.
In the GLAM sensor prototype, several microring resonator configurations were implemented. Using this technology it was possible to quantify the biomarker S100A4 in urine, with a sensitivity below 1nM (better than most immunochemical assays). The prototype has been used to prove that a beatnote could be generated and detected by relatively inexpensive readout electronics.
A development demonstrator has been setup based on the expected value of 3 GHz. It consists of a processing platform, an acquisition module and means prepared to graphically present the value of the beat frequency in real-time, as well as over a time period, thus presenting the attached biomarker concentration.
For clinical validation, a set of patients with different clinical stages of bladder cancer, were recruited. More than 200 urines have been analyzed for several biomarker level using the selected antibodies in conventional immunochemical tests. Results showed a promising expression pattern that might be very useful for bladder cancer patient prognosis and therapy monitoring.
Altogether, the mentioned results allowed to continue with the exploitation and dissemination plans. First, a new patent application has been submitted with the main aim to protect the newly developed technology. Additionally, new contacts with potential licensees of the technology have been reinforced and the consortium keeps business conversations with some of them. In parallel, preliminary outcomes, side-ground developments, and final results have been disseminated thorough the project development in scientific seminars, congresses, forums, and journals.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

GLAM device is based on an innovative concept for the detection of soluble biomarker levels: the combined use of a cartridge containing multiplexed novel active laser microring resonators functionalized with biomarker detecting antibodies, and ultra-resolution detection nanophotonic methodology. Altogether, the use of these two aspects will result in a novel, miniaturized, ultrasensitive, robust, reliable, fast, and cost-effective device, capable of multiplexed biomarker level determination.
Optical micro-resonators of circular, ring, or spherical shape have been investigated for several years to be used as the heart of optical label free detection-based devices. Such microresonators can yield ultra-sensitive detection of single proteins.
GLAM project capitalizes on the unprecedented sensitivity achieved using laser microring resonators to detect key biomarkers in tumor development and treatment. Proof of concept of the new technologies and materials have been carried out using preclinical and clinical analysis of bladder cancer patients warranting personalized medicine.
In terms of commercial impact, GLAM consortium keeps high level contacts with diagnostic and medical device companies to set up business agreements to commercialize it. We are working to identify the best partner and the best business deal that might allow final development to commercialization and marketing this innovative biosensor device.
A second goal is to broaden its applicability to other chronic diseases. Basically, the GLAM biosensor device is like a technological platform that might be applied for the detection and monitoring of virtually any biomarker that can be detected in any bodyfluid using a specific monoclonal antibody. In this sense, the same concept could be applicable to other bodyfluids and other life-threatening diseases.

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