Inkjet-Print Micromagnet Array on Glass Slides for Immunomagnetic Enrichment of Circulating Tumor Cells

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 the 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).