The diagnosis of infectious diseases frequently not only depends on the reliable identification of the pathogenic species that has caused them, but also on obtaining rapid results in order to immediately initiate appropriate therapy or further diagnostic measures. Tests are normally carried out in central laboratories, samples need to be sent to the laboratories and the results are rarely immediate. As part of the BMBF-funded project “ResCheck”, QIAGEN Lake Constance GmbH has joined forces with several partners with the aim of developing a microfluidic “lab-on-a-disk” diagnostic system and improve the medical provision at the “point of need”.
Infections of the respiratory system are the most common diseases worldwide and can be triggered by a broad range of different pathogens. The diseases are usually diagnosed on the basis of individual symptoms, but this does not always allow conclusions to be drawn on the pathogens that might have caused the disease. The investigation of laboratory parameters is usually required for patients with complex or serious medical conditions and patients that have acquired an infection during a hospital stay.
Many tests are highly complex and can only be performed in specifically equipped medical laboratories and by expert personnel. Samples have to be sent to these laboratories, which is a process that often requires complex sample logistics. Moreover, the transport of patient samples to the laboratory, registration of the samples and allocation of the samples to the respective analysis stations in the laboratory prolong the time to diagnosis. “In order to improve medical care, we are working on the development of systems for point-of-need diagnostics which provide quick and reliable results in a clinic or a GP’s practice and no longer require samples to be sent to central laboratories,” said Dr. Jörg Schickedanz, General Manager at QIAGEN Lake Constance GmbH. The Stockach-based subsidiary of the global biotechnology company QIAGEN specialises in the development and production of highly sensitive testing and diagnosis platforms for point-of-need testing. The huge advantage of point-of-need diagnostics is that tests can be carried out in the hospital departments, medical practices and pharmacies where the results are required.
The new system is based on QIAGEN Lake Constance’s “LabPlayer”, a device for performing and analysing different tests with minimal effort at the site where samples are taken. Originally developed for the rapid and reliable detection of hazardous substances in biological material in the field, the benefits of the LabPlayer for application in point-of-need diagnostic settings soon became clear. “It was obvious that we had to develop the platform further and adapt it to routine human application,” Dr. Schickedanz said.
The “LabPlayer“ is a device similar to a CD player. Used with the “LabDisk” which is inserted into the device, the LabPlayer is a kind of miniature laboratory – a mobile “lab-on-a-disk” diagnostic system. The LabDisk is a system consisting of a polymer disk with channels and chambers that contain all test reagents required, all brought together on a tiny surface area. The rotation of the LabDisk inside the LabPlayer generates defined centrifugal forces which make the sample fluid move through the microchannels and the different compartments of the LabDisk.
This process, which is referred to as “centrifugal microfluidics”, integrates all necessary analysis steps in a format that is easy to handle. “The device performs all steps fully automatically, starting with the preparation of the samples, i.e. cell disruption, extraction, purification and concentration, to the detection of the target molecule,” said Schickedanz explaining how the microfluidic system works. Target molecules may be pathogen-specific nucleic acids or antigens which are detected with a reporter substance at the end of the analysis process. The reporter substance may be a fluorescent dye that can be visualised using extremely effective miniaturised detectors.
Sample material like sputum, blood or urine is applied manually to the LabDisk before the fully automated analysis is started by pressing a button. “The analysis takes between 20 and 90 minutes; immunoassays take around 20 minutes and the amplification of nucleic acids takes up to 90 minutes,” Dr. Schickedanz explains. The results are displayed on a touch screen, but can, if required, also be transferred to laboratory and hospital information systems (LIS and HIS) using standardised interfaces and be integrated into electronic patient records. “The new diagnostic system will be as good as the gold standards of classical laboratory medicine applications in terms of reproducibility, specificity and other technical validation parameters, but it will be considerably faster and easier to operate,” said Dr. Schickedanz. The easy handling of the device might make it suitable for performing complex detection technologies – the amplification of nucleic acids, for example – at the point of need in a hospital or a GP’s practice. “We’re talking about diagnostics of the future,” said Schickedanz fully confident that the procedure will at some stage be possible. At present, the LabPlayer is only available as a prototype and needs to be developed further before it is ready to go into serial production. The system is an open platform that can be used for a broad range of different applications. The BMBF-funded project ResCheck runs until 2014.
“The microfluidic design of the LabDisk is quite flexible. It can be used with specific reagents and theoretically be adapted to almost any application,” said Schickedanz highlighting the advantages of the system. In principle, the LabDisk can be used for the detection of immunological parameters such as antigens and antibodies, nucleic acid-based parameters such as the DNA and RNA of pathogens, including their resistance genes. However, Schickedanz is sure that the system can be used for many other things. “I believe that the system can also be used for applications other than human diagnostics, in food testing or environmental analysis, to name but two examples.”
Under the BMBF-funded project ResCheck (funding number 16SV5433K in the “Mobile Diagnostics” programme), QIAGEN Lake Constance is working with several cooperation partners. QIAGEN Lake Constance is in charge of developing the LabPlayer – both hard- and software – and of overall system integration. The ‘Klinikum rechts der Isar’ in Munich and the Institute of Organic Chemistry at the University of Tübingen are in charge of immunoassay development, scientists at the European QIAGEN headquarters in Hilden are working with the Institute of Virology at the University Göttingen on the development of nucleic acid-based tests for the detection of pathogens, the Federal Institute for Materials Research and Testing is developing calibration materials and strategies, the company Conworx from Berlin is in charge of integrating the system into hospital IT systems, MVZ Dr. Stein + Kollegen in Mönchengladbach and MVZ Clotten in Freiburg provide sample material and HSG-IMIT in Freiburg develops and produces microfluidics components for the LabDisk.
QIAGEN Lake Constance GmbH
Dr. Jörg Schickedanz
Senior Director Head of PON Instrumentation
Tel.: +49 7771 9166 260
Fax: +49 7771 9166 760