Project: Development of an Innovative Miniature Bio-chip Reader for Whole Blood Diagnostic Analysis

Laboratories have at their disposal a wide range of advanced technologies for the implementation of laboratory diagnosis. _x000D_However, the specific sector of immuno-analysis is still very much in demand for « Physician Office Laboratory » (POL) or point-of-care (POC) tools that offer a similar level of performance to those of the laboratory systems. A great deal of interest has been shown in such near-patient solutions as a means of assisting the clinician in making real-time clinical decisions that can affect both patient treatment and decision making. _x000D__x000D_Cardiac markers help to categorize myocardial infarction (MI) or other heart diseases such as congestive heart failure (CHF). MI is part of a spectrum that is referred to as the acute coronary syndrome. According to the WHO, MI is a leading cause of mortality and morbidity in the world: more than 1 800 000 cases of MI are reported each year in Europe and approximately 1.3M in the United States in 2007._x000D_Cardiac marker testing allows the clinician to make the earlier diagnosis of acute myocardial infarction and helps in predicting which patients are likely to experience complications, avoiding the inadvertent discharge of acute myocardial infarction patients from the emergency unit._x000D__x000D_The same is true for systemic infections for which the Procalcitonine marker makes it possible to provide an early diagnosis of severe bacterial infections which in turn paves the way for fast and targeted antibiotic treatment._x000D_A number of POC tests are available for MI (Troponine T or I) but none of them meet today’s laboratory testing standards, particularly “rapid tests”, mostly based on lateral flow techniques. _x000D_Indeed, it is now recommended (1) to set the cut-off for Troponine testing below 0.04ng/ml to enable earlier detection of myocardial infarction in relation to its initial onset and to detect a higher percentage of emergency department chest pain patients who are at risk for short-term major adverse cardiac events._x000D_To address this need, several quantitative point of care systems for immuno-analysis have been developed and have become available in the market over recent years (Inverness-Biosite TRIAGE / Roche Cardiac Reader / Abbott I-STAT, etc.), but they still lack sensitivity and precision._x000D__x000D_Because of the lack of appropriate diagnostic tools and standardized diagnostic processes, it is reported that 40% of patients entering emergency departments (E.D.) and suffering from heart failure are not properly diagnosed._x000D_The use of more sensitive POC systems and the development of better markers will help to reduce this rate. The CO challenge is hence to develop such advanced systems._x000D__x000D_For this purpose, CEZANNE, a French research-intensive SME, specialized in innovation in medical diagnosis, asked the German SME MILDENDO, which manufactures biochips and the Fraunhofer Research Institute (Germany), specialized in the processing of polymers with special physical properties for high-tech (particularly biotech) applications, to work on an innovative Point of care device. The specific goal of the project is to develop an immuno-assay biochip producing fluorescence combined with a data reader. The new automatic miniature device will be capable of precisely and more rapidly analysing all blood, thanks to a unique approach combining homogeneous assays and FRET (Fluorescence Resonance Energy Transfer). _x000D_Among the possible applications for this new concept, the Ps have chosen to adapt the biochip to the analysis of the reference cardiac marker of myocardial infarction (Troponine), for which timing and precision of the analysis are prevalent._x000D_These are two of the most representative cases of immunological analysis for emergencies. _x000D_The immunoassay biochip will be read by a miniature photon-counting fluorimeter that CEZANNE plans to embed first on a POL instrument (the KRYPTOR-POL) and, in a second step, on a POC device (the KRYPTOR-POC). The goal is to dispose of two complementary platforms, one used in clinics for multiple testing, and the second for single testing at local practices. Both will share the same fluorescence reader allowing the measurement on both systems of the same immunoassay biochip with the same performance. Only the POL device development is concerned with this project, but the later POC system will be quickly developed based on the bricks composing the POL system._x000D__x000D_Once the first two markers have been developed (Troponine and Procalcitonine), CEZANNE plans to develop additional innovative markers on the KRYPTOR-POL and -POC platforms. _x000D_Moreover, the 33-month project will benefit from the results of an ongoing FP6 STREP project called POC4LIFE aimed at demonstrating the feasibility of using multiplexed FRET analysis on a point of care diagnosis platform ( CHIPOC work programme will hence benefit from strong foundations._x000D__x000D_

Acronym CHIPOC (Reference Number: 4847)
Duration 01/06/2009 - 01/02/2012
Project Topic Development of an innovative diagnostic chip that produces fluorescence (« bio-chip ») combined with a miniature diagnostic platform. The new miniature device will be capable to precisely and rapidly analysing whole blood assays.
Project Results
(after finalisation)
We made the proof that the TRACE technology used in the Kryptor analyzer could be downsized to a POC system._x000D_The project reached the proof of concept phase. We could realize a demonstrator and run performance tests._x000D_The preliminary results are very satisfying and within the expected range of precision. Nevertheless one function of the complete process (blood filtration with a membrane) did not reach the expectations._x000D_The decision switching to development was not made, COly due to the fact that another POC system (with lower performance) was developed inside the group. The performances were judged good enough for going to market, preventing the Eurostar project going to further step for economical reasons. Nevertheless, the project can be restarted if a need for better performances is identified._x000D_
Network Eurostars
Call Eurostars Cut-Off 2

Project partner

Number Name Role Country
3 CEZANNE Coordinator France
3 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Partner Germany
3 MILDENDO GmbH Partner Germany