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

Abstract

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 (CTCs). CTCs 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 CTCs 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 CTCs 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.

Microfluidics cell sample preparation for analysis: Advances in efficient cell enrichment and precise single cell capture

“…Immunomagnetic assay has shown clinical significance in cancer diagnosis and prognosis. [104][105][106][107][108][109] The generation and fine-tuning of the magnetic field play essential roles in such assay toward effective singlecell-based analyses.…”

Printed Microfluidics

“…The low cost of the screen‐printed electrodes in the examples above is important; traditionally, DEP electrodes have been formed using expensive cleanroom‐based techniques, but experiments with cells often limit devices to a single use before disposal . A third method for cell trapping in printed microfluidic devices was reported by Chen et al, who isolated circulating tumour cells (CTCs) from whole blood using an inkjet‐printed CFM device (Figure c) (CFM, IJP). To form these devices, a Dimatix printer was used to deposit clusters of magnetic nanoparticles onto glass slides (each cluster comprising a micromagnet).…”

“…The NPs specifically bind CTCs, which are pulled toward the micromagnets relative to other cell types such as red blood cells (RBCs, red) and white blood cells (WBCs, purple) inside the channel. Reproduced with permission . Copyright 2016, Biomedical Engineering Society.…”

Circulating Tumor Cells: From Theory to Nanotechnology-Based Detection

“… Kim et al (2013) presented a microseparator for the isolation of CTCs using immunomagnetic nanobeads with bound EpCAM antibodies, revealing that the CTC microseparator isolated approximately 90% of spiked CTCs in human peripheral blood and purified to approximately 97%. In another micromagnet array, which was fabricated integrating inkjet-printing technology combined with immunomagnetic microchip, the whole blood sample is labeled with MNPs and separated due to the magnetic momentum when the mixture flows through the microchannel ( Figure 2A ) ( Chen et al, 2015 ). Immunomagnetic nanospheres (IMNs) fabricated by a convenient and highly controllable layer-by-layer assembly method successfully captured more than 94% of tumor cells in whole blood via only a 5 min incubation ( Wen et al, 2014 ).…”