An integrated and sensitive detection platform for magneto-resistive biosensors

Boer, B.M. de; Kahlman, J.A.H.M.; Jansén, Tove; Duric, H.; Veen, Jan van der

doi:10.1016/j.bios.2006.09.020

Cited by 112 publications

(73 citation statements)

References 8 publications

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“…Several research groups are investigating MNT (4-6)-based analyte quantification as a highly sensitive alternative to optical biosensors and biochips (7)(8)(9)(10). By labeling the target analyte of interest with MNTs (see Fig.…”

mentioning

confidence: 99%

Multiplex protein assays based on real-time magnetic nanotag sensing

Osterfeld

Heng

Gaster

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

274

232

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Magnetic nanotags (MNTs) are a promising alternative to fluorescent labels in biomolecular detection assays, because minute quantities of MNTs can be detected with inexpensive giant magnetoresistive (GMR) sensors, such as spin valve (SV) sensors. However, translating this promise into easy to use and multilplexed protein assays, which are highly sought after in molecular diagnostics such as cancer diagnosis and treatment monitoring, has been challenging. Here, we demonstrate multiplex protein detection of potential cancer markers at subpicomolar concentration levels and with a dynamic range of more than four decades. With the addition of nanotag amplification, the analytic sensitivity extends into the low fM concentration range. The multianalyte ability, sensitivity, scalability, and ease of use of the MNT-based protein assay technology make it a strong contender for versatile and portable molecular diagnostics in both research and clinical settings.A consensus is emerging that early detection and personalized treatment in clinics based on genetic and proteomic profiles of perhaps 4-20 biomarkers are the key to improving the survival rate of patients with complex diseases, such as cancer, autoimmune disorders, infectious diseases, and cardiovascular diseases (1-3). Although the tools for large-scale biomarker discovery with hundreds to thousands of biomarkers are available, there are few biomolecular detection tools capable of multiplex and sensitive detection of protein biomarkers that can be readily adopted in clinical settings for biomarker validation and for personalized diagnosis and treatment. This need, we believe, can be fulfilled by the magnetic nanotag (MNT)-based biomolecular assay technology reported here. We demonstrate the feasibility and implementation of this technology with multiple potential cancer markers.Several research groups are investigating MNT (4-6)-based analyte quantification as a highly sensitive alternative to optical biosensors and biochips (7-10). By labeling the target analyte of interest with MNTs (see Fig. 1), analyte detection and quantification can occur when the analyte binds to capture probes on the surface of giant magnetoresistive (GMR) sensors (11-15) such as spin valve (SV) sensors (16), which have been developed and optimized for use in hard disk drives on a scale of hundreds of millions of units annually with great economy and reliability. Such sensors, when modified for use in biological applications, were previously shown to be capable of detecting as few as 10 MNTs (13, 16). ResultsGiven the recent efforts to develop methods for early cancer detection via quantification of cancer-related cytokines, we chose the following analytes for our MNT-based protein assays: cancer embryonic antigen (CEA), eotaxin, granulocyte colonystimulating factor (G-CSF), interleukin-1-alpha (IL-1␣), interleukin-10 (IL-10), IFN gamma (IFN-␥), lactoferrin, and tumor necrosis factor alpha (TNF-␣). Fig. 1 outlines the detection scheme in which analyte is captured on the sensor surface and qu...

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mentioning

confidence: 99%

Multiplex protein assays based on real-time magnetic nanotag sensing

Osterfeld

Heng

Gaster

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

274

232

View full text Add to dashboard Cite

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“…Moreover, to further simplify the treatment, we will only consider a DC external magnetic field applied in the y-direction H app y . These effects have been central for the use of frequency mixing detection schemes [16][17][18] that are, hence, not considered in the present work. We generally allow the magnetic bead susceptibility to be complex such that v ¼ v 0 À iv 00 , where v 0 and v 00 are the in-phase and out-of-phase magnetic susceptibilities, respectively.…”

Section: Theory a Sensor Construction Elementsmentioning

confidence: 99%

“…This implies that these methods will also to some extent be affected by external magnetic fields. Lock-in techniques and various frequency mixing techniques [16][17][18] are often used to filter away the signal not due to the magnetic beads. However, it is still desired to minimize the signal due to externally applied magnetic fields.…”

Section: Introductionmentioning

confidence: 99%

Planar Hall effect bridge geometries optimized for magnetic bead detection

Østerberg

Rizzi

Henriksen

et al. 2014

Journal of Applied Physics

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Articles you may be interested inNovel designs of planar Hall effect bridge sensors optimized for magnetic bead detection are presented and characterized. By constructing the sensor geometries appropriately, the sensors can be tailored to be sensitive to an external magnetic field, the magnetic field due to beads being magnetized by the sensor self-field or a combination thereof. The sensors can be made nominally insensitive to small external magnetic fields, while being maximally sensitive to magnetic beads, magnetized by the sensor self-field. Thus, the sensor designs can be tailored towards specific applications with minimal influence of external variables. Three different sensor designs are analyzed theoretically. To experimentally validate the theoretical signals, two sets of measurements are performed. First, the sensor signals are characterized as function of an externally applied magnetic field. Then, measurements of the dynamic magnetic response of suspensions of magnetic beads with a nominal diameter of 80 nm are performed. Furthermore, a method to amplify the signal by appropriate combinations of multiple sensor segments is demonstrated. V C 2014 AIP Publishing LLC.

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“…Giant magnetoresistance (GMR) sensors have been widely used to detect SPBs in magnetic microsystems because they are sensitive to lowmagnetic fields, compact in size, can be fabricated in a large scale and easily integrated with existing semiconductor electronics. 8 Rectangular, [8][9][10] meander, 11 horseshoe, 12 and spiral 13 shaped GMR sensors have been used with tapered current lines, large external electromagnets, complementary GMR sensor bound biomolecules as well as various combinations of these, to trap and detect biomolecular tagged SPBs. Given that only a few biomolecular tagged SPBs are used in magnetic microsystems, tapered current lines, large external electromagnets, and complementary labels do not allow precise control and manipulation of SPBs.…”

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confidence: 99%

A giant magnetoresistance ring-sensor based microsystem for magnetic bead manipulation and detection

Gooneratne

Giouroudi

Cai

et al. 2011

Journal of Applied Physics

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In this paper a novel spin valve giant magnetoresistance (GMR) ring-sensor integrated with a microstructure is proposed for concentrating, trapping, and detecting superparamagnetic beads (SPBs). Taking advantage of the fact that SPBs can be manipulated by an external magnetic field, a unique arrangement of conducting microrings is utilized to manipulate the SPBs toward the GMR sensing area in order to increase the reliability of detection. The microrings are arranged and activated in such a manner so as to enable the detection of minute concentrations of SPBs in a sample. Precise manipulation is achieved by applying current sequentially to the microrings. The fabricated ring-shaped GMR element is located underneath the innermost ring and has a magnetoresistance of approximately 5.9%. By the performed experiments it was shown that SPBs could be successfully manipulated toward the GMR sensing zone.

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An integrated and sensitive detection platform for magneto-resistive biosensors

Cited by 112 publications

References 8 publications

Multiplex protein assays based on real-time magnetic nanotag sensing

Multiplex protein assays based on real-time magnetic nanotag sensing

Planar Hall effect bridge geometries optimized for magnetic bead detection

A giant magnetoresistance ring-sensor based microsystem for magnetic bead manipulation and detection

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