Biomedical Engineering Reference
In-Depth Information
9.1
Introduction
Robust, sensitive, and easy-to-use biosensors for the detection and quantification
of rare biomarkers will have significant applications in both basic research and
clinical practice. If made available, these platforms could aid in understanding of
fundamental biology, in accurately detecting diseases at their early stage, and in
evaluating and monitoring the efficacy of therapy [
1
-
3
]. To realize such sensors,
the underlying detection technology should ideally (1) enable high sensitivity and
accuracy, with minimal false positives and negatives; (2) support short assay time
with minimal sample processing; and (3) allow for multiplexed detection in a single
parent sample [
4
]. Different types of sensing platforms, fulfilling some of these
requirements, have been developed based on optical [
5
,
6
], electronic [
7
,
8
], or
mass-based [
9
] detection. These systems, however, often require lengthy sample
purification, large sample volumes, or long assay time, which can potentially limit
their clinical utility and adaption.
Biosensors based on magnetic detection have recently emerged as a promising
diagnostic platform. Due to the intrinsically negligible magnetic susceptibilities of
biological entities, magnetic detection experiences little interference from native
biological samples; even optically turbid samples will often appear transparent
to magnetic fields. Biomarkers of interests, when magnetically labeled, however,
can attain a high contrast against the biological background. Recent progresses
in the synthesis of magnetic nanoparticles (MNPs) have further advanced the
magnetic detection technology. With their size scale similar to that of biologi-
cal molecules, MNPs can efficiently and abundantly bind to biological targets,
amplifying analytical signals [
10
-
13
]. Various detection technologies have been
developed based on this magnetic-tagging concept. These include techniques that
use magnetometers, such as superconducting quantum interference device (SQUID)
[
14
-
16
], magnetoresistive sensors [
17
-
20
], and Hall sensors [
21
], all of which
directly measure the magnetic fields arising from the magnetically labeled targets.
We have recently developed a new magnetic sensing platform, diagnostic
magnetic resonance (DMR) [
22
]. Contrary to directly measuring the magnetic
moments of the labeled targets, the DMR uses nuclear magnetic resonance (NMR)
as the detection mechanism. When placed in NMR magnetic fields, MNPs create
local magnetic fields and change the relaxation rate of surrounding water molecules
[
23
]. The detection offers an intrinsic signal amplification mechanism, as more
than millions of water molecules can be affected by a single MNP. Moreover,
since the signal is generated from the entire sample volume, the assay procedure
is significantly simpler than the direct magnetic detection in which MNP-labeled
targets have to be closely positioned to the sensing elements.
By optimizing MNPs and miniaturizing NMR detectors, the DMR detection
sensitivities for various target types have been considerably improved over the last
few years. These developments enable rapid and multiplexed detection on a wide
range of targets in microliter sample volumes, including nucleic acids [
24
], proteins
[
22
], drugs, bacteria [
25
], and tumor cells [
26
-
28
]. With the recent integration
