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Hall D.A.,Stanford University | Gaster R.S.,Stanford University | Lin T.,Stanford University | Osterfeld S.J.,Magarray, Inc. | And 3 more authors.
Biosensors and Bioelectronics | Year: 2010

Giant magnetoresistive biosensors are becoming more prevalent for sensitive, quantifiable biomolecular detection. However, in order for magnetic biosensing to become competitive with current optical protein microarray technology, there is a need to increase the number of sensors while maintaining the high sensitivity and fast readout time characteristic of smaller arrays (1-8 sensors). In this paper, we present a circuit architecture scalable for larger sensor arrays (64 individually addressable sensors) while maintaining a high readout rate (scanning the entire array in less than 4. s). The system utilizes both time domain multiplexing and frequency domain multiplexing in order to achieve this scan rate. For the implementation, we propose a new circuit architecture that does not use a classical Wheatstone bridge to measure the small change in resistance of the sensor. Instead, an architecture designed around a transimpedance amplifier is employed. A detailed analysis of this architecture including the noise, distortion, and potential sources of errors is presented, followed by a global optimization strategy for the entire system comprising the magnetic tags, sensors, and interface electronics. To demonstrate the sensitivity, quantifiable detection of two blindly spiked samples of unknown concentrations has been performed at concentrations below the limit of detection for the enzyme-linked immunosorbent assay. Lastly, the multiplexing capability and reproducibility of the system was demonstrated by simultaneously monitoring sensors functionalized with three unique proteins at different concentrations in real-time. © 2010 Elsevier B.V.


Gaster R.S.,Stanford University | Xu L.,Stanford University | Han S.-J.,IBM | Wilson R.J.,Stanford University | And 4 more authors.
Nature Nanotechnology | Year: 2011

Monitoring the kinetics of protein interactions on a high-density sensor array is vital to drug development and proteomic analysis. Label-free kinetic assays based on surface plasmon resonance are the current gold standard, but they have poor detection limits, suffer from non-specific binding, and are not amenable to high-throughput analyses. Here, we show that magnetically responsive nanosensors that have been scaled to over 100,000sensors per cm2 can be used to measure the binding kinetics of various proteins with high spatial and temporal resolution. We present an analytical model that describes the binding of magnetically labelled antibodies to proteins that are immobilized on the sensor surface. This model is able to quantify the kinetics of antibody-antigen binding at sensitivities as low as 20zeptomoles of solute. © 2011 Macmillan Publishers. All rights reserved.


Hall D.A.,Stanford University | Gaster R.S.,Stanford University | Osterfeld S.J.,Magarray, Inc. | Murmann B.,Stanford University | Wang S.X.,Stanford University
Biosensors and Bioelectronics | Year: 2010

Giant magnetoresistive biosensors possess great potential in biomedical applications for quantitatively detecting magnetically tagged biomolecules. Magnetic sensing does not suffer from the high background levels found in optical sensing modalities such as the enzyme linked immunosorbent assay translating into a technology with higher sensitivity. However, to reveal the full potential of these sensors and compensate for non-idealities such as temperature dependence, digital correction and calibration techniques are not only useful but imperative. Using these calibration techniques to correct for process variations and dynamic changes in the sensing environment (such as temperature and magnetic field), we are able to obtain extremely sensitive and, more importantly, reproducible results for quantifiable biomolecular reorganization. The reproducibility of the system was improved by over 3× using digital correction techniques and the sensors are made temperature independent by using a novel background correction technique. © 2010 Elsevier B.V.


PubMed | Stanford University and Magarray, Inc.
Type: | Journal: Scientific reports | Year: 2016

Giant magnetoresistive (GMR) biosensors consisting of many rectangular stripes are being developed for high sensitivity medical diagnostics of diseases at early stages, but many aspects of the sensing mechanism remain to be clarified. Using e-beam patterned masks on the sensors, we showed that the magnetic nanoparticles with a diameter of 50 nm located between the stripes predominantly determine the sensor signals over those located on the sensor stripes. Based on computational analysis, it was confirmed that the particles in the trench, particularly those near the edges of the stripes, mainly affect the sensor signals due to additional field from the stripe under an applied field. We also demonstrated that the direction of the average magnetic field from the particles that contributes to the signal is indeed the same as that of the applied field, indicating that the particles in the trench are pivotal to produce sensor signal. Importantly, the same detection principle was validated with a duplex protein assay. Also, 8 different types of sensor stripes were fabricated and design parameters were explored. According to the detection principle uncovered, GMR biosensors can be further optimized to improve their sensitivity, which is highly desirable for early diagnosis of diseases.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 2.82M | Year: 2013

DESCRIPTION provided by applicant This project seeks to optimize a promising magneto nanosensor technology for use in cancer diagnosis By adapting a common technology from the computer disk drive industry this simple device enables researchers to simultaneously detect multiple proteins or biomarkers at ultra low concentrations in biological fluids The abundance and change over time of several of these biomarkers when taken together can be a powerful diagnostic tool At this time the tools required to measure these biomarkers such as mass spectrometry or ELISA immunoassays are slow expensive difficult to use and often not very reproducible In addition many interesting biomarkers are present at such low concentrations that they simply cannot be detected with any but the most sophisticated and involved methods The technology under development combines the advantages of high sensitivity ease of use rapid quantification and low cost These drastic improvements are possible in part due to the use of extremely sensitive giant magnetoresistive GMR sensors and also because there are no natural magnetic signal sources in a blood sample which results in a very low background signal Additionally these sensors have been modified to detect only those magnetic nanoparticle labels which are actually bound to the sensors unbound labels floating nearby are almost completely ignored That means that unlike most other assay technologies it is not necessary to remove the excess labels to determine the result This allows the assay to be partially or completely wash free which again greatly increases the sensitivity and ease of use Furthermore no laser or complex optics are required because the signal is a simple change in electrical resistance of the sensor This means that the ancillary instrumentation can be very simple and cost efficient With an initial focus on lung cancer where there are no effective methods for early detection of the disease researchers are attempting to validate a panel of six biomarkers that have been associated with asymptomatic lung cancer The long term goal is to have a diagnostic test that allows doctors to diagnose patients when they are still in Stage I and face survival rates of as opposed todayandapos s situation where most patients donandapos t get diagnosed until they reach Stage IIIB or IV and face less than a chance of survival PUBLIC HEALTH RELEVANCE PROJECT NARRATIVE Researchers are using a promising magneto nanosensor technology to develop a novel diagnostic test for early detection of lung cancer This simple blood test would greatly improve patient survival by making it possible to diagnose lung cancer in its early stages when it has a much better chance of being successfully treated


Provided are high-throughput detection systems. The systems include a magnetic sensor device, a magnetic field source and a reservoir plate that includes a plurality of fluid reservoirs. The magnetic sensor device includes a support with two or more elongated regions each having a magnetic sensor array disposed at a distal end. Also provided are methods in which the subject high-throughput detection systems find use.


Patent
Magarray, Inc. and Stanford University | Date: 2014-05-07

Methods for analyte detection with magnetic sensors are provided. Aspects of the methods include producing a magnetic sensor device having a magnetically labeled analyte from a sample, such as a serum sample, bound to a surface of a magnetic sensor thereof; and obtaining a signal, e.g., a real-time signal, from the magnetic sensor to determine whether the analyte is present in the sample. Also provided are devices, systems and kits that find use in practicing the methods of the invention. The methods, devices, systems and kits of the invention find use in a variety of different applications, including detection of biomarkers, such as disease markers.


Patent
Magarray, Inc. | Date: 2014-03-13

Provided are magnetic sensors, which include a magnetic tunnel junction (MTJ) magnetoresistive element, a first electrode contacting at least a portion of a surface of the MTJ magnetoresistive element and extending beyond an edge of the surface of the MTJ magnetoresistive element, and a second electrode contacting at least a portion of an opposing surface of the MTJ magnetoresistive element and extending beyond an edge of the opposing surface of the MTJ magnetoresistive element, where facing surfaces of the extending portions of the first and second electrodes are non-overlapping. Also provided are devices, systems and methods in which the subject magnetic sensors find use.


Patent
Magarray, Inc. | Date: 2016-05-10

Provided are magnetic sensors, which include a magnetic sensor element having a sensor surface modification and an inter-element area adjacent to the magnetic sensor element and having an inter-element area surface modification, where the sensor surface modification and the inter-element area surface modification provide a binding surface in the inter-element area. Also provided are devices, systems and methods in which the subject magnetic sensors find use.


Provided are high-throughput detection systems. The systems include a magnetic sensor device, a magnetic field source and a reservoir plate that includes a plurality of fluid reservoirs. The magnetic sensor device includes a support with two or more elongated regions each having a magnetic sensor array disposed at a distal end. Also provided are methods in which the subject high-throughput detection systems find use.

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