Microfluidic impedimetric biosensor system for simultaneous and label-free on-site detection of blood coagulation status

• Applicants: Professorin Dr. Meltem Avci-Adali; Dr.-Ing. Can Dincer
• Subject Area: Microsystems ; Biomedical Systems Technology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446617142

This project aims to implement a microfluidic impedimetric sensor using aptamers for simultaneous and label-free on-site detection of blood coagulation status. For this purpose, aptamers for fibrinogen, plasmin, and beta-thromboglobulin will be selected and validated regarding their specificity, affinity, and system applicability. A previously selected thrombin aptamer will be used to immediately start with impedimetric biosensor development. To achieve a high sensitivity by overcoming the issues with the ion strength of the sample, different nanogap biosensors integrated with multiplexed microfluidics will be fabricated and characterized. Herein, the influence of nanogap design, various electrode materials and microfluidic designs will be studied. Finally, the developed biosensor will be applied for multiplexed on-site blood coagulation testing in whole blood samples of healthy donors and its performance will be verified using standard techniques.In clinical coagulation diagnostics, there is a great and urgent need for bed-side testing devices to determine the coagulation status, especially during or after extracorporeal procedures such as cardiac surgery or dialysis. Infrequent or inaccurate measurements can lead to bleeding complications or life-threatening thrombosis. The conventional coagulation tests are either associated with long turnaround times or require sample preparation, costly equipment, and skilled staff. So, they are mainly not appropriate for on-site use. Furthermore, in many cases, clinical findings, based on a single biomarker, are not enough for an accurate diagnosis. Thus, it is highly desirable to measure various biomarkers simultaneously.Impedimetric biosensors enable the label-free detection of biomolecular interactions by applying a small sinusoidal voltage over a frequency range to an electrochemical system and measuring the resulting response. Their low system complexity and high miniaturization capability favor them for the development of handheld devices. However, current impedimetric sensors suffer mainly from the influence of the ion strength of the sample solution. With our nanogap IDA sensor the influence of the sample solution can be minimized.Aptamers can recognize their target molecules due to their 3D structure with a high specificity and affinity and they have numerous advantages, including high stability, chemical synthesizability, sensitivity, and selectivity. Therefore, in this project, aptamers are selected for the assessment of coagulation status and the functionalized biosensor will be evaluated using whole fresh human blood to implement a quadruplex panel for on-site diagnosis.The successful proof-of-concept of such a microfluidic impedimetric biosensor using aptamers would be a game-changer in the blood coagulation testing and beyond as it could also be applied in many other application fields and pave the way for the real-time and online monitoring of various biomarkers in future.

• DFG Programme: Research Grants
• International Connection: Austria
• Partner Organisation: Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Cooperation Partner: Dr.-Ing. Stefan Partel