TY - JOUR
AU1 - Kricka, Larry, J
AU2 - Park, Jason, Y
AB - There is a strong consensus that an ideal diagnostic test should be rapid, noninvasive, reagentless, inexpensive, and suitable for application at the point of care. For most tests, this ideal is a distant prospect. One recent success has been reflectance spectrophotometry, which is now used for transcutaneous bilirubin measurements in neonates (BiliCheck™; http://bilichek.respironics.com). Another is the noninvasive measurement of blood oxygen saturation using red and infrared absorption measurements (e.g., 660 and 920 nm). However, early hope for a broad range of infrared-based noninvasive testing has been dashed. Although successful for oxygen saturation, the expansion of the scope of this technology to the main prize, namely blood glucose, has not been successful, and in fact has been the source of major controversy. In view of the slow progress in reagentless noninvasive technologies, efforts have continued in ways to reduce the number of steps, reagents, and manipulations in more conventional assays, particularly for disposable assays intended for point of care, where speed, error-free operation, and ease of use are paramount. In the current range of point-of-care tests, 2 endpoints dominate. The first and earliest point-of-care tests were portable tablet- and powder-based colorimetric assays that were available in the early twentieth century. The second generation of point-of-care test devices was based on electrochemical measurements using a meter. Many assays have been effectively reduced to a single-addition-and-read format; for multistep point-of-care assays, such as immunoassays, assay simplification has been achieved using self-contained cartridges that enable reagent and sample manipulations, as exemplified by lateral flow devices. Magnetism is emerging as a possible source of point-of-care assay innovation (1). The exploitation of magnetism in clinical assays is not new. Magnetic particles are commonly used as solid phases for immobilizing reagents to facilitate separation after incubation or washing steps, but can also used as components of a detection technology. Magnetic particles have been used to measure clot formation times by monitoring the effect of a magnetic field on the motion of magnetic particles mixed with a blood sample in a small chamber on a credit card–sized cassette. Interestingly, another type of coagulation assay measures changes in viscosity by magnetoelastic sensors in an essentially particle-free and reagent-free manner. Magnetic labels have also been used in immunoassay (magneto-immunoassay) and in polynucleotide assays. These labels include superparamagnetic iron oxide nanoparticles detected using a superconducting quantum interference device (SQUID),1 and paramagnetic materials and dextran-coated nanoscale superparamagnetic particles detected using a magnetic permeability detector. A recent series of studies has fueled interest in magnetoresistance in bioassays and has demonstrated the feasibility of a disposable assay system based on giant magnetoresistance (GMR) (2)(3). GMR is the change in resistance to current flow that occurs in a conductor when exposed to an external magnetic field. It is best known as the key technology in computer hard disk drives and magnetic-based memory. In fact, GMR has become the standard of hard disk drive technology and has been cited as essential for miniaturized memory of portable devices such as the iPod™ digital music player from Apple™. Over the past decade, the principle of magnetoresistance has been used to develop prototypes for analytical devices (4). This type of technology is attractive in bioanalysis because it facilitates miniaturization of the detection device, and no additional reagents are needed to detect the magnetic label. Biological samples contain very little magnetic material, so background is minimal. In addition, the engineering processes that allow for the nearly flawless manufacturing of hard drives that fit in the palm of the hand would seem to be well suited for manufacturing similar-sized, hand-held, wearable or implantable biosensors. Several groups have created biosensor prototypes using GMR. The first biosensor system to use GMR was called BARC® (Bead-Array Counter), which detected magnetic microbeads (4). In its initial format, the BARC assay used DNA recognition sequences to accumulate magnetic beads on the GMR sensor; the magnetoresistance sensor then detected the presence of the magnetic beads. Prototypes for detection of a multitude of analytes have followed (1). The biosensor formats for GMR encompass a range of magnetic particles ranging in size from nanometers to microns, and these particles are detected by GMR-sensor pads with micron- to millimeter-dimensioned footprints. The GMR advance in the recent articles is not necessarily in detection technology, but in the progress toward practical application (2)(3). In this series of articles, the sample handling and sensor modules have been separated. Although at first glance a minor change, this step may make this technique more economically viable because the complicated sensor electronics are reusable and the contamination-prone sample-handling module is disposable. Currently, a “simulated” 20- by 3-mm sample stick is being used that has 14 20-nm-thick, 0.04-mm2 test locations fabricated from a NiFe alloy. The sample stick is read in the same way that a credit card is read by a credit card reader. The detection limit corresponds to 800 1-μm-diameter magnetic beads at an individual location. The analogy with a credit card and credit card reader has led to the intriguing concept of a “wellness card” that has an array of test locations that are read with a card swipe. Other magnetic effects are also being explored for point-of-care testing applications. A type of miniaturized, portable MRI instrument, called a relaxometer, is being developed to detect magnetic resonance signals from solutions of superparamagnetic iron oxide nanoparticles. These nanoparticles can be configured such that their change from dispersed to clustered states upon specific binding with antigen alters the spin–spin, or T2, relaxation time of the protons in the surrounding water, allowing for the detection of specific binding events and biomolecular analytes. Signal acquisition takes less than a few minutes. Examples of detection include Mycobacterium avium spp in milk at 15.5 cfu, circulating tumor cell surface protein profiling, small molecule analytes at single nanomolar concentrations, and antibody and proteins at subpicomolar concentrations (5). Royal Philips Electronics has developed a handheld multianalyte immunoassay analyzer (Magnotech) for point-of-care testing based on an integrated disposable biosensor cartridge that can measure picomolar concentrations of analytes in 5 min or less (http://www.apptech.philips.com/healthcare/projects/magnetic_biosensors.html). This system uses a cartridge preloaded with ligand-coated magnetic nanoparticles and requires addition of only a single drop of blood or saliva. The nanoparticles automatically disperse and bind to analyte molecules in the sample, and an electromagnet facilitates rapid contact between the magnetic nanoparticles, including the captured analyte, with the biosensor surface. Next, a second magnetic field repels unbound magnetic nanoparticles away from the biosensor surface, enabling measurement of the bound analyte molecules using frustrated total internal reflection. The plastic cartridge has no moving parts or embedded electronics and is disposable. The analyzer unit contains all of the electromagnets and the optical detection system, control electronics, software, and the read-out display. To date, proof-of-concept sandwich assays for cardiac troponin I and parathyroid hormone and inhibition assays for morphine have been completed. These new detection technologies based on magnetoresistance and magnetism have considerable promise in terms of their miniaturization, throughput, and parallel processing; however, their success will depend on many additional factors. The first hurdle will be that these new technologies, like so many before them, must be substantially better than currently available methodologies. If the end goal of the new technologies is a new pregnancy test, the prospect of success is probably quite limited in view of the maturity and the user-friendly nature of current pregnancy test technologies (e.g., Unipath digital pregnancy testing, http://www.clearblueeasy.com/). The key to the success of any new technology for point-of-care testing is to provide bioanalytical information that cannot be obtained currently in a setting that requires an immediate turnaround time. Success will also be inevitably linked to the future role and scope of point-of-care in health care. Author Contributions: Both authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors’ Disclosures of Potential Conflicts of Interest:Upon manuscript submission, both authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: L.J. Kricka, T2 Biosystems. Stock Ownership: None declared. Honoraria: None declared. Research Funding: None declared. Expert Testimony: None declared. Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript. 1 " Nonstandard abbreviations: SQUID, superconducting quantum interference device; GMR, giant magnetoresistance. References 1 Tamanaha CR, Mulvaney SP, Rife JC, Whitman LJ. Magnetic labeling, detection, and system integration. Biosens Bioelectron 2008 ; 24 : 1 -13. Crossref Search ADS PubMed 2 Nording J, Millen RL, Bullen HA, Porter MD. Giant magnetoresistance sensors. 1. Internally calibrated readout of scanned magnetic arrays. Anal Chem 2008 ; 80 : 7930 -7939. Crossref Search ADS PubMed 3 Millen RL, Nordling J, Bullen HA, Porter MD. Giant magnetoresistive sensors. 2. Detection of biorecognition events at self-referencing and magnetically tagged arrays. Anal Chem 2008 ; 80 : 7940 -7946. Crossref Search ADS PubMed 4 Baselt DR, Lee GU, Natesan M, Metzger SW, Sheehan PE, Colton RJ. A biosensor based on magnetoresistance technology. Biosens Bioelectron 1998 ; 13 : 731 -739. Crossref Search ADS PubMed 5 Koh I, Hong R, Weissleder R, Josephson L. Sensitive NMR sensors detect antibodies to influenza. Angew Chem Int Ed 2008 ; 47 : 4119 -4121. Crossref Search ADS © 2009 The American Association for Clinical Chemistry This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Magnetism and Magnetoresistance: Attractive Prospects for Point-of-Care Testing?
JF - Clinical Chemistry
DO - 10.1373/clinchem.2009.123927
DA - 2009-06-01
UR - https://www.deepdyve.com/lp/oxford-university-press/magnetism-and-magnetoresistance-attractive-prospects-for-point-of-care-1y0Fl2IPb2
SP - 1058
VL - 55
IS - 6
DP - DeepDyve
ER -