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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 9 of 21

















































               Figure 4. Real-time GMR sensor for multiplexed detection of the biomarkers (A,B); Calibration curves of multiplexed IL6, CA125 II, and
               Human HE4 assays (C-E) [61]  (reprinted with permission from Elsevier). GMR: giant magnetoresistance; IL6: interleukin 6; CA125: cancer
               antigen 125; HE4: epididymis protein 4

               MR sensors for liquid biopsy
               Immunoassay-based liquid biopsy
               The elevated or reduced concentration of protein biomarkers in blood, saliva, or tissue can serve as
                                      [60]
               indicators of cancer status . Since single biomarker detection can lead to false positive or false negative
               cases, multiplexed detection systems are required to achieve specific and sensitive cancer diagnosis, which
               can be achieved in MR sensors. During multiplexed detection, densely packed MR sensors are fabricated
               on a single chip with simultaneous signal readout. The sensors can be divided into different groups which
                                                                                                        [61]
               are functionalized with different capture antibodies that are specific to various biomarkers. Klein et al.
               developed a multiplexed GMR sensing system that can detect three ovarian cancer biomarkers at the
               same time. The detection limit for cancer antigen 125 (CA125 II), human epididymis protein 4 (HE4),
               and interleukin 6 (IL6) are 3.7 U/mL, 7.4 pg/mL, and 7.4 pg/mL, respectively [Figure 4]. Another GMR
                                               [62]
               sensing system reported by Gao et al.  shows the capability of detecting 12 tumor biomarkers at the same
               time in only 15 min. It was shown that the analytical sensitivity was either comparable or better than the
               commercially available single-analyte immunoassays. Besides the aforementioned work, various kinds of
                                                                                                       [63]
               biomarkers have been validated in the GMR sensor system such as urinary endoglin for prostate cancer ,
                                                 [64]
                                                                    [65]
               eotaxin, and tumor necrosis factor alpha . Recently, Zhu et al.  proposed to replace the traditional MNPs
               with 2D MoS -Fe O  nanostructures (MOFE). With the addition of layered MoS materials, the loading
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