IMEC, a leading European
research center in nanotechnology, the Institüt für Mikrotechnik Mainz
(IMM), one of the leading European research centers in microfluidics, and their
partners within the European Sixth Framework Project MASCOT achieve a major
milestone in the development of a lab-on-chip for the detection and therapy
evaluation of breast cancer. This is the first time that a lab-on-chip system
including many complex sample preparation steps and multiplexed detection was
conceived and is being implemented. All modules for sample preprocessing and
detection are ready for further miniaturization and integration in a single
lab-on-chip platform. The system will be clinically validated in a breast cancer
therapy study in Oslo.
Circulating tumor diagnostics is a promising methodology to individually follow
up cancer patients in an early or advanced phase during therapy, thereby improving
the medical doctor's therapy decisions. In the case of breast cancer, 5 ml of
blood contains only 2 to 3 tumor cells. To detect cancer from blood, these rare
circulating tumor cells need to be isolated, enriched and their genetic content
has to be identified. Current diagnostics performed in medical laboratories
are labor intensive, expensive and time-consuming. They require many sample
preprocessing steps in different medical instruments so that the full analysis
takes more than a day. A lab-on-chip system however can bring huge advantages
both to the patient and the healthcare system. They enable a fast, easy-to-use,
cost-effective test method which can be performed at regular times in a doctor’s
office or even near the patient’s bed. Lab-on-chip systems are a labor-saving
and minimally invasive solution for cancer cell detection, therapy selection
The project partners developed a modular platform where each module has its
specific task and autonomy and as such can also be used for many different medical
applications. The first module is the incubation module performing the mixing
of the blood sample with functionalized magnetic beads which specifically bind
the tumor cells. The second module is used for tumor cell isolation and counting
using a combination of dielectrophoresis and magnetic sensing with single cell
sensitivity. In the third module, the amplification module, the cell wall of
the tumor cells is destroyed and the genetic material (i.e. the mRNA) is extracted
and amplified based on multiplex ligation dependent probe amplification (MLPA).
Within this module, specific assays amplify about 20 markers that are expressed
in breast carcinoma cells. In the final detection module, the amplified genetic
material is detected using an array of electrochemical sensors. The different
building blocks have been developed and validated on spiked blood samples. The
modules are now ready for further hetero-integration into a single lab-on-chip.
By miniaturizing and merging the microfluidic and electronic functionalities
the reliability and accuracy of the patient’s analysis will be improved.
The clinical use of the system will be evaluated to compare it to more conventional
approaches in a breast cancer therapy follow-up study.
Within the framework of the MASCOT project, IMEC collaborates with the Institut
für Mikrotechnik Mainz (Germany), AdnaGenAG (Germany), Universitat Rovira
i Virgili in Sweden, NorwegianRadium Hospital (Norway), MRC Holland (The Netherlands),
and FuijerebioDiagnosticsAB (Spain). The project’s aim is to develop an
integrated microsystem for the magnetic isolation and analysis of single circulating
tumor cells for oncology diagnostics and therapy follow-up. MASCOT was partly
funded by the European Commission (IST-027652).