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Page 10 of 21 Su et al. J Cancer Metastasis Treat 2020;6:19 I http://dx.doi.org/10.20517/2394-4722.2020.48

density of MNPs are increased, resulting in higher sensor signal. With the integration of the MOFE probes,
the GMR system was capable of detecting as few as 100 exomes.

Besides GMR sensing platforms, magnetic tunneling junction (MTJ) sensors have also been demonstrated
[66]
as a proof-of-concept for the detection of liver cancer biomarkers . The CoFeB/MgO/CoFeB MTJ
exhibited a MR ratio of 122% and a sensitivity of 0.95%/Oe at room temperature. Three concentrations
of alpha-fetoprotein were successfully detected. However, there has not been any further research in
multiplexed cancer biomarker detection with MTJ sensors to the authors’ best knowledge. The lack of
experimental results for MTJ-based liquid biopsies can be attributed to the following reasons: (1) the
complex stack structures of MTJs can result in large variations of performance between different MTJ
devices, making it hard to generate calibration curves for different biomarkers; (2) the top electrodes of
the MTJs tend to increase the distance between the sensor and the magnetic tags, leading to a decrease in
sensor signal; and (3) it is hard to realize linear transfer curves in MTJ sensors, which further complicates
the process of correlating sensor signal to the analyte concentrations.

DNA-based liquid biopsy
Besides antibody-antigen-based liquid biopsy, DNA is another important analyte for cancer detection.
The ability of DNA detection has been demonstrated for both MTJ and GMR sensors. A proof-of-
[67]
concept detection of DNA was achieved in a MTJ sensor with a Al O barrier . Later, a quantitative
3
2
detection of DNA was achieved by integrating 64 MgO MTJs on a single chip. However, there was not
much work on MTJ-based DNA detection related to cancer detection. On the contrary, GMR sensors have
been extensively studied as potential candidates for DNA-based liquid biopsies. Nesvet et al. reported
[68]
the integration of methylation specific PCR to melting curve analysis on GMR sensors to enhance the
sensitivity for methylation detection. By measuring the difference of melting point between the DNA
probes that targeted on methylated or unmethylated cytosineguanine dinucleotides (CpG) sites, the system
was able to detect the methylated DNA with an analytical LOD down to 0.1%. It was also shown by the same
group that this melting curve approach can simultaneously profile five mutation and four methylation sites
[70]
in human melanoma cell lines . The detection of cell-free (cfDNA) was demonstrated by Dias et al. .
[69]
The capture DNA probes were firstly spotted manually on the GMR chip, followed by the integration of
a microfluidic channel. The magnetically labeled target DNA fragments (ALU115 and ALU247) was then
introduced to the sensor surface through the microfluidic channel. A detection limit of picomolar range
was achieved upon optimization.

POC devices
Ever since the discovery of MR sensors as a potential biosensor, MR-based POC devices have had a very
exciting past showing a very promising future. Nevertheless, this topic has been subjected to extensive
reviews [48,71,72] . There have been two decades of research on improving the sensitivity of the GMR sensor,
which was inevitably followed by untiring attempts from several groups worldwide to develop GMR-based
POC devices that have proved extremely successful in rapid detection of multivariate pathogens. A research
group from Stanford University has developed a device, named Eigen Lifescience, along with a customized
App, all fit in the size of a smartphone. This smartphone-shaped device operating on the basis of GMR-
based biosensor has been reported to be capable of diagnosing several harmful pathogens such as Hepatitis
[68]
[73]
B virus and detecting DNA hypermethylation from melanoma cancer cells as well as prostate cancer
antigen , protein signatures in mouse lymphoma , HIV and leukocytosis , RNA sequencing , and
[76]
[77]
[74]
[75]
[78]
lung cancer . A research group from the University of Minnesota has developed another handheld device
for GMR-based biosensing that has been commercialized. The device, better known as Z-Lab [Figure 5],
[50]
[61]
has been reported to diagnose several diseases such as ovarian cancer and H1N1 influenza virus ,
which has also been very recently reported to be detected wash-free by the same device . Drew A. Hall’s
[51]
group from the University of California, San Diego has worked hard to improve the electronic circuitry