Global Medical Discovery features paper: Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of Circulating Tumor Cells

Significance Statement

To advance cancer studies and enable oncologists to make more accurate diagnosis, prognosis, and develop personalized therapies, Prof. John X.J. Zhang and Dr. Peng Chen led a team of bioengineers from the Thayer School of Engineering at Dartmouth and the University of Texas at Austin in developing an innovative system that combines inkjet-printing, microfluidic technology, and immunoassay for capturing and manipulating circulating tumor cells (CTCs). This miniaturized bio-analytical system can be further integrated with fluorescent microscope for cancer cell imaging, with fluorescent in-situ hybridization (FISH) and PCR for molecular level cancer studies. It opens up a great many possibilities to optimize cancer diagnostic and tumor management.

“This work provides a new angle, other than traditional tissue biopsy and medical imaging, to approach cancer. A fast, simple and less painful blood test may eventually provide equivalently accurate disease information about individual cancer patient in a timely manner, ” said Zhang. circulating tumor cells detach from primary tumor site, shed into the blood circulation system, and may initiate the deadly cancer metastasis process. Through efficient detection of these cells, especially at an early stage, physicians will be able to design the best diagnosis and treatment strategy for each individual cancer patient.

Immunomagnetic assay has been successfully used to separate rare circulating tumor cells from blood. However, traditional immunomagnetic assay is often limited in the low magnetic field gradient and low density of effective magnetic traps. In this work, Dr. Chen developed a novel method using inkjet-printing technology to fabricate microscale magnetic structures that can be easily deposited on an arbitrary substrate.

This inkjet-printing technology is a versatile but cost-effective approach for rapid prototyping with high accuracy and flexibility. Such microscale magnets, when placed in an external magnetic field, largely enhance the magnetic field and the attractive force applied on the target circulating tumor cells, and hence facilitates the detection. In our experiments with COLO205 (a human colorectal cancer cell line) as the separation target, the inkjet-printed micro-magnets integrated assay increased the system sensitivity by 26% compared with using normal glass slide as the substrate.

Dr. Chen’s research is focused on developing miniaturized high-performance bio-analytical systems for point-of-care and globally relevant medical diagnostic applications. “This project is to implement advanced engineering fabrication, sensing, and manipulating techniques with multiplexing immunoassay to separate these rare circulating tumor cells from whole blood.” Zhang said. “The ultimate goal is to deliver a highly sensitive, reliable, affordable, and portable cancer screening platform with high throughput. The next step – bringing the technology from lab bench to clinics is a big challenging step, but is also the most rewarding step.

This work has the potential to revolutionize cancer risk assessment, cancer management, and increase the cure rate for cancers such as breast cancer, lung cancer, and prostate cancer.” This paper is published on Annals of Biomedical Engineering (DOI: 10.1007/s10439-015-1427-z).

      

About The Author

Dr. Peng Chen received his PhD degree in Biomedical Engineering from the University of Texas at Austin. He is now working as a postdoc research associate at the Center for Applied NanoBioscience and Medicine at the University of Arizona. His research interests include (1) miniaturized microfluidic system for detection and analysis of rare circulating tumor cells (CTCs), and (2) vertical flow paper based microfluidic device as point-of-need multiplex diagnostic and surveillance tool for bio-threat detection. He has published 10 peer-reviewed journal papers and 10 conference proceedings. He now serves the editorial board of Scientific Reports (Nature publishing group). Email: pengchen@email.arizona.edu

About The Author

Prof. John Zhang, Ph.D., is a Professor at Thayer School of Engineering at Dartmouth, and a Fellow of American Institute for Medical and Biological Engineering (AIMBE). He received his Ph.D. from Stanford University, and was a Research Scientist at MIT. His key contribution is in developing miniature medical systems to improve global health, through innovations in bio-inspired nanomaterials, lab-on-chip design, and advanced nanofabrication technologies for probing complex biological networks critical to human development and diseases such as cancer. He received the Wallace Coulter Foundation Early Career Award for developing handheld microphotonic imaging scanners and microsystems for early oral cancer detection; NSF CAREER award for the invention of plasmonic scanning probes design for controlled perturbation and imaging at sub-cellular level; and DARPA Young Faculty Award for patterning plasmonic surface on MEMS for biomarker sensing applications. He has published over 120 peer reviewed papers and proceedings, presented over 45 invited seminars worldwide, and filed over 60 US and international patents. He is an alumnus of NAE Frontiers of Engineering programs, an Associate Editor for Biomedical Microdevices, IEEE/ASME Journal of Microelectromechanical Systems, and has published a textbook for undergraduates titled “Molecular Sensors and Nanodevices: Principles, Designs and Applications in Biomedical Engineering”. Email: john.zhang@dartmouth.edu

Reference

Ann Biomed Eng. 2016;44(5):1710-20.

Peng Chen¹, Yu-Yen Huang², Gauri Bhave¹, Kazunori Hoshino³, Xiaojing Zhang^4,5

Show Affiliations

¹Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.

²Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA.

³Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA.

⁴Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.

⁵Thayer School of Engineering, Dartmouth College, Hanover, NH, 03755, USA. john.zhang@dartmouth.edu.

We report an inkjet-printed microscale magnetic structure that can be integrated on regular glass slides for the immunomagnetic screening of rare circulating tumor cells . circulating tumor cells detach from the primary tumor site, circulate with the bloodstream, and initiate the cancer metastasis process. Therefore, a liquid biopsy in the form of capturing and analyzing circulating tumor cells may provide key information for cancer prognosis and diagnosis. Inkjet printing technology provides a non-contact, layer-by-layer and mask-less approach to deposit defined magnetic patterns on an arbitrary substrate. Such thin film patterns, when placed in an external magnetic field, significantly enhance the attractive force in the near-field close to the circulating tumor cells to facilitate the separation. We demonstrated the efficacy of the inkjet-print micromagnet array integrated immunomagnetic assay in separating COLO205 (human colorectal cancer cell line) from whole blood samples. The micromagnets increased the capture efficiency by 26% compared with using plain glass slide as the substrate.

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