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Su et al. J Cancer Metastasis Treat 2020;6:19 I http://dx.doi.org/10.20517/2394-4722.2020.48 Page 15 of 21

A B C

D
E

Figure 9. Principle of MNP-enhanced NMR bioassay. When monodispersed MNPs cluster upon binding to targets, the self-assembled
clusters become more efficient at dephasing nuclear spins of many surrounding water protons, leading to a decrease in T2 relaxation
time. The bottom panel shows an example of the proximity assay measured by the DMR system. Avidin was added to a solution of
biotinylated magnetic nanoparticles, causing T2 to decrease from 40 to 14 ms (A); schematic diagram of the DMR system (B); the
microcoil generates rf pulses (C); the microfluidic network (D); schematic of the NMR electronics (E) [89] (reprinted with permission
from Springer Nature)

A

B

n

Figure 10. Schematic of the μNMR system. TCO-labeled antibodies are added to whole blood. Red blood cells are then lysed and the
cells spun down before reaction with tetrazine-modified MNPs. The process of labeling antibodies and targeting nanoparticles requires
less than 30 min. Biomarker measurements are then taken using the μNMR device (A); Biomarker expression, as assessed by μNMR,
showed that significant percentages of cancer patients (n = 58) were negative for EpCAM (34.4%), HER-2 (32.7%), MUC-1 (32.7%),
and EGFR (31.0%). Combining these markers, however, enabled identification of nearly all cancer patients (99.2%) (B) [95] . Reprinted
with permission from Elsevier. μNMR: micro nuclear magnetic resonance; EpCAM: epithelial cell adhesion molecule; HER-2: human
epidermal growth factor receptor 2; MUC-1: mucin 1; EGFR: epidermal growth factor receptor