High-Tc SQUID readout of magnetic nanoparticles

Molecular diagnostics with high-Tc SQUID readout of magnetic nanoparticles

Infectious disease is responsible for roughly one quarter of deaths worldwide; it causes more than half the deaths in many third-world countries. Early diagnostics can significantly improve these numbers. MedTech West is developing a rapid high-throughput and ultra-sensitive biomolecular diagnostic tool. The system can ultimately be used by untrained personnel for disease identification and staging in a clinical setting.

Our technique is based on several cutting-edge technologies: micro-cryocooler systems, high-Tc SQUIDs, and biofunctionalized magnetic nanoparticles. Because the readout is magnetic, screening can be performed on “raw” samples including whole blood, saliva, urine, etc. We therefore eliminate the need for expensive labs and personnel required by more sensitive diagnostic techniques like ELISA. Furthermore, we obtain improved sensitivity and specificity when compared to standard rapid-screening methods like cultures and staining.  In the future, care centers will be able to identify pathogens at the earliest stages of infection, thereby improving patient outcomes and reducing transmission.

Our Approach

Immunoassays are a type of biomolecular detection technique that rely on a specific binding reaction between a target molecule (called an antigen) and a tag (an antibody). The “gold standard” in immunoassay techniques is ELISA whose detection method requires subsequent binding reactions (typically on the surface of a well) and optical readout. More recently, magnetic immunoassays based on biofunctionalized magnetic nanoparticles (MNPs) have been developed that replace the optical readout (that requires a transparent medium) with a magnetic detection scheme. MNPs are advantageous because they eliminate the need for well-surface binding and intermediate washing steps (that may cause contamination and/or loss of target) while enabling detection in liquids with arbitrary optical properties (e.g. whole blood, urine, etc.). Perhaps most importantly, MNP-based immunoassays drastically increase biomolecular sensitivity because of the high surface area available for binding reactions between the target molecules and their tags: whereas an ELISA well surface may have a surface area of ~1 cm2, an equivalent volume of MNPs has a surface area of ~1 m2 (10 000x bigger). Our MNP-based immunoassay system combines ultra-sensitive magnetic sensors (high-Tc SQUIDs) with MEMS technology for a rapid and high-throughput diagnostic system that can be used by untrained personnel for fast and accurate disease diagnosis and monitoring.

Current Developments

We have demonstrated both frequency- and time-domain MNP-based detection of the prostate-specific antigen, a commonly used marker for prostate cancer screening. We have also employed a MEMS chip for micro-droplet liquid handling with our high-Tc SQUID readout of the MNPs. Our system thus combines the high sensitivity of frequency-domain recordings with the high temporal resolution of time-domain detection and the high throughput capability of MEMS sample handling. Diagnostics and monitoring of disease are target application areas, but infectious disease research that includes biomolecular dynamics and biophysics can also benefit. The integration of the full system translates into simplicity for users: the final system will house a cooler and electronics system for high-Tc SQUID-based magnetic readout and sample handling will be automated with MEMS. Outputs can be as detailed as full magnetic susceptibility and relaxometry curves or as simple as a “yes/no” response to a question of infection.

Outlook

The final system will accept arbitrary liquid samples like whole blood, urine, etc., thus eliminating the need for expensive laboratories, trained personnel, and the possibility of false-negatives and contamination induced by multiple purification and washing steps. Clinicians can thus obtain rapid and extremely accurate diagnostic and prognostic information without having to send samples “to the lab”.

Research team

MedTech West partner

Dr. Justin F. Schneiderman, Department of Clinical Neuroscience and Rehabilitation, University of Gothenburg.

Clinical partners

Prof. Dag Winkler, Department of Microtechnology and Nanoscience, MC2, Chalmers University of Technology.

Dr. Alexei Kalabukhov, Department of Microtechnology and Nanoscience, MC2, Chalmers University of Technology.

Dr. Fredrik Öisjöen, Department of Microtechnology and Nanoscience, MC2, Chalmers University of Technology.

Dr. Aldo Jesorka, Department of Microtechnology and Nanoscience, MC2, Chalmers University of Technology.

Dr. Anke Sans - Velasco, Department of Microtechnology and Nanoscience, MC2, Chalmers University of Technology.

Contact

For more information on this project, contact Henrik Mindedal at henrik.mindedal@medtechwest.se

 

References

Öisjöen, F., Schneiderman, J.F., Prieto Astalan, A., Kalabukhov, A., Johansson, C., & Winkler, D. A new approach for bioassays based on frequency- and time-domain measurements of magnetic nanoparticles. Biosensors and Bioelectronics, 2010, 25(5) p 1008-1013. http://dx.doi.org/10.1016/j.bios.2009.09.013

Schaller, V., Sanz-Velasco, A., Kalabukhov, A., Schneiderman, J.F., Öisjöen, F., Jesorka, A., Prieto Astalan, A., Krozer, A., Rusu, C., Enoksson, P., & Winkler, D. Towards an electrowetting-based digital microfluidic platform for magnetic immunoassays. Lab on a Chip, 2009, 9(23), p 3433-3436. DOI: 10.1039/B912646E

Öisjöen, F., Schneiderman, J.F., Astalan, A.P., Kalabukhov, A., Johansson, C., & Winkler, D. The need for stable, mono-dispersed, and biofunctional magnetic nanoparticles for one-step magnetic immunoassays. Journal of Physics: Conference Series, 2010, 200(12), p 122006. http://dx.doi.org/10.1088/1742-6596/200/12/122006

Oisjoen, F., Schneiderman, J.F., Zaborowska, M., Shunmugavel, K., Magnelind, P., Kalaboukhov, A., Petersson, K., Astalan, A.P., Johansson, C., & Winkler, D. Fast and sensitive measurement of specific antigen-antibody binding reactions with magnetic nanoparticles and HTS SQUID. IEEE Transactions on Applied Superconductivity, 2009, 19(3), p 848-852. http://dx.doi.org/10.1109/TASC.2009.2019246