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1
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Dabla PK, Dabas A. Transformative impact of point-of-care testing in critical care. World J Crit Care Med 2025; 14:100623. [DOI: 10.5492/wjccm.v14.i2.100623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 01/06/2025] [Accepted: 01/14/2025] [Indexed: 02/27/2025] Open
Abstract
The advent of point-of-care testing (POCT) has revolutionized the approach to patient management, especially for pediatric care. POCT provides rapid, on-the-spot biochemical and microbiological evaluations, bypassing delays typically associated with central laboratory testing, enabling swift clinical decision-making. Additionally, POCT has proven to be a valuable prognostic tool for monitoring electrolyte, lactate, creatinine levels, often a marker of severe illness and poor outcomes. POCT enables its faster identification, allowing for prompt interventions. This capability is essential in managing conditions like sepsis, where timely treatment can significantly impact survival rates. However, the implementation of POCT is not without its challenges. Variability in sample handling, particularly with heparinized syringes, can affect the accuracy of certain measurements, such as potassium levels. The absence of comprehensive follow-up data and cost-effectiveness analyses in some studies indicate the need for continued research to optimize the use of POCT. In conclusion, POCT is a transformative tool in critical care, offering prompt and reliable assessments that significantly enhance patient management. As technology advances, the integration of POCT into emergency departments and intensive critical care units holds great promise for improving the quality of healthcare and patient survival rates.
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Affiliation(s)
- Pradeep K Dabla
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Education and Research, Associated Maulana Azad Medical College, New Delhi 110002, Delhi, India
| | - Aashima Dabas
- Department of Pediatrics, Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi 110002, Delhi, India
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2
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Magneto-nanosensor smartphone platform for the detection of HIV and leukocytosis at point-of-care. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2018; 16:10-19. [PMID: 30502420 DOI: 10.1016/j.nano.2018.11.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 10/08/2018] [Accepted: 11/01/2018] [Indexed: 11/23/2022]
Abstract
The advent of personalized medicine has brought an increased interest in personal health among general consumers. As a result, there is a great need for user-centric point-of-care (POC) health devices. Such devices are equally pertinent in developing countries or resource-limited settings for performing diagnostic tests. However, current POC tests for diseases such as human immunodeficiency virus (HIV) or leukocytosis do not provide adequate levels of sensitivity or do not exist at all. Here, we extend our mobile magneto-nanosensor platform to point-of-care HIV and leukocytosis detection. The platform can be multiplexed, and the circuitry enables portability and sensitivity in the POC setting. A smartphone application simplifies operation and provides guidance to facilitate self-testing. Commercially available POC test kits typically provide only qualitative or semi-quantitative results of a single analyte. The magneto-nanosensor platform can provide users with pleasant user-experience while demonstrating robust sensitive and specific multiplexed quantification and detection of common diseases.
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3
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Uhlirova D, Stankova M, Docekalova M, Hosnedlova B, Kepinska M, Ruttkay-Nedecky B, Ruzicka J, Fernandez C, Milnerowicz H, Kizek R. A Rapid Method for the Detection of Sarcosine Using SPIONs/Au/CS/SOX/NPs for Prostate Cancer Sensing. Int J Mol Sci 2018; 19:E3722. [PMID: 30467297 PMCID: PMC6320840 DOI: 10.3390/ijms19123722] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 11/16/2018] [Accepted: 11/18/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Sarcosine is an amino acid that is formed by methylation of glycine and is present in trace amounts in the body. Increased sarcosine concentrations in blood plasma and urine are manifested in sarcosinemia and in some other diseases such as prostate cancer. For this purpose, sarcosine detection using the nanomedicine approach was proposed. In this study, we have prepared superparamagnetic iron oxide nanoparticles (SPIONs) with different modified surface area. Nanoparticles (NPs) were modified by chitosan (CS), and sarcosine oxidase (SOX). SPIONs without any modification were taken as controls. Methods and Results: The obtained NPs were characterized by physicochemical methods. The size of the NPs determined by the dynamic light scattering method was as follows: SPIONs/Au/NPs (100⁻300 nm), SPIONs/Au/CS/NPs (300⁻700 nm), and SPIONs/Au/CS/SOX/NPs (600⁻1500 nm). The amount of CS deposited on the NP surface was found to be 48 mg/mL for SPIONs/Au/CS/NPs and 39 mg/mL for SPIONs/Au/CS/SOX/NPs, and repeatability varied around 10%. Pseudo-peroxidase activity of NPs was verified using sarcosine, horseradish peroxidase (HRP) and 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate. For TMB, all NPs tested evinced substantial pseudo-peroxidase activity at 650 nm. The concentration of SPIONs/Au/CS/SOX/NPs in the reaction mixture was optimized to 0⁻40 mg/mL. Trinder reaction for sarcosine detection was set up at 510 nm at an optimal reaction temperature of 37 °C and pH 8.0. The course of the reaction was linear for 150 min. The smallest amount of NPs that was able to detect sarcosine was 0.2 mg/well (200 µL of total volume) with the linear dependence y = 0.0011x - 0.0001 and the correlation coefficient r = 0.9992, relative standard deviation (RSD) 6.35%, limit of detection (LOD) 5 µM. The suggested method was further validated for artificial urine analysis (r = 0.99, RSD 21.35%, LOD 18 µM). The calculation between the detected and applied concentrations showed a high correlation coefficient (r = 0.99). NPs were tested for toxicity and no significant growth inhibition was observed in any model system (S. cerevisiae, S. aureus, E. coli). The hemolytic activity of the prepared NPs was similar to that of the phosphate buffered saline (PBS) control. The reaction system was further tested on real urine specimens. Conclusion: The proposed detection system allows the analysis of sarcosine at micromolar concentrations and to monitor changes in its levels as a potential prostate cancer marker. The whole system is suitable for low-cost miniaturization and point-of-care testing technology and diagnostic systems. This system is simple, inexpensive, and convenient for screening tests and telemedicine applications.
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Affiliation(s)
- Dagmar Uhlirova
- Department of Research and Development, Prevention Medicals, Tovarni 342, 742 13 Studenka-Butovice, Czech Republic.
| | - Martina Stankova
- Department of Research and Development, Prevention Medicals, Tovarni 342, 742 13 Studenka-Butovice, Czech Republic.
| | - Michaela Docekalova
- Department of Research and Development, Prevention Medicals, Tovarni 342, 742 13 Studenka-Butovice, Czech Republic.
| | - Bozena Hosnedlova
- Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1946/1, 612 42 Brno, Czech Republic.
| | - Marta Kepinska
- Department of Biomedical and Environmental Analyses, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
| | - Branislav Ruttkay-Nedecky
- Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1946/1, 612 42 Brno, Czech Republic.
| | - Josef Ruzicka
- Department of Research and Development, Prevention Medicals, Tovarni 342, 742 13 Studenka-Butovice, Czech Republic.
| | - Carlos Fernandez
- School of Pharmacy and Life Sciences, Robert Gordon University, Garthdee Road, Aberdeen AB10 7QB, UK.
| | - Halina Milnerowicz
- Department of Biomedical and Environmental Analyses, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
| | - Rene Kizek
- Department of Research and Development, Prevention Medicals, Tovarni 342, 742 13 Studenka-Butovice, Czech Republic.
- Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1946/1, 612 42 Brno, Czech Republic.
- Department of Biomedical and Environmental Analyses, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.
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4
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Kim K, Hall DA, Yao C, Lee JR, Ooi CC, Bechstein DJB, Guo Y, Wang SX. Magnetoresistive biosensors with on-chip pulsed excitation and magnetic correlated double sampling. Sci Rep 2018; 8:16493. [PMID: 30405155 PMCID: PMC6220270 DOI: 10.1038/s41598-018-34720-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 10/04/2018] [Indexed: 11/09/2022] Open
Abstract
Giant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20 ms, approximately 50× faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92 ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings.
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Affiliation(s)
- Kyunglok Kim
- Department of Electrical Engineering, Stanford University, Stanford, CA, United States
| | - Drew A Hall
- Department of Electrical and Computer Engineering, University of California San Diego, La Jolla, CA, United States
| | - Chengyang Yao
- Department of Electrical Engineering, Stanford University, Stanford, CA, United States
| | - Jung-Rok Lee
- Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul, South Korea
| | - Chin C Ooi
- Department of Chemical Engineering, Stanford University, Stanford, CA, United States
| | - Daniel J B Bechstein
- Department of Mechanical Engineering, Stanford University, Stanford, CA, United States
| | - Yue Guo
- Department of Electrical Engineering, Stanford University, Stanford, CA, United States
| | - Shan X Wang
- Department of Electrical Engineering, Stanford University, Stanford, CA, United States.
- Department of Materials Science and Engineering, Stanford University, Stanford, CA, United States.
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5
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Klein T, Wang W, Yu L, Wu K, Boylan KLM, Vogel RI, Skubitz APN, Wang JP. Development of a multiplexed giant magnetoresistive biosensor array prototype to quantify ovarian cancer biomarkers. Biosens Bioelectron 2018; 126:301-307. [PMID: 30445305 DOI: 10.1016/j.bios.2018.10.046] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 10/21/2018] [Accepted: 10/22/2018] [Indexed: 11/28/2022]
Abstract
In this work, we developed benchtop and handheld Giant Magnetoresistive (GMR) biosensing systems that serve as platforms for detecting a wide variety of protein biomarkers for human diseases. System development included spintronic and nanomagnetic materials, biomolecular chemistry, electronic circuitry, analog and digital signal processing, firmware programming, user interface programming on both PC and Android smartphone, communications over both USB and Bluetooth, and mechanical integration. In this work, we demonstrated the benchtop GMR biosensing system in the context of ovarian cancer assay development. The prototype system delivered the required performance in terms of high-sensitivity multiplex assays in a portable format with enough flexibility to serve as a platform for ovarian cancer and many other diseases. We achieved multiplex detection of cancer antigen 125 (CA125 II), human epididymis protein 4 (HE4), and interleukin 6 (IL6), with limits of detection (LOD) as low as 3.7 U/mL, 7.4 pg/mL, and 7.4 pg/mL, respectively.
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Affiliation(s)
- Todd Klein
- Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455, USA
| | - Wei Wang
- Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455, USA
| | - Lina Yu
- Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455, USA
| | - Kai Wu
- Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455, USA
| | - Kristin L M Boylan
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
| | - Rachel Isaksson Vogel
- Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Amy P N Skubitz
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Jian-Ping Wang
- Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
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6
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Chen Y, Ding X, Zhang Y, Natalia A, Sun X, Wang Z, Shao H. Design and synthesis of magnetic nanoparticles for biomedical diagnostics. Quant Imaging Med Surg 2018; 8:957-970. [PMID: 30505724 DOI: 10.21037/qims.2018.10.07] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Sensitive and quantitative characterization of clinically relevant biomarkers can facilitate disease diagnosis and treatment evaluation. Magnetic nanomaterials and their biosensing strategies have recently received considerable attention. Magnetic signals experience little interference from native biological background as most biological molecules have negligible magnetic susceptibilities and thus appear transparent to external magnetic fields. Because of this unique property, magnetic sensing can be applied to both in vivo deep tissue imaging as well as ex vivo point-of-care diagnostics. To exploit this mode of magnetic detection, new advancements in both magnetic material syntheses and sensing technologies have been made. This review focuses on recent developments of magnetic nanomaterials as image contrast agents and diagnostic sensors. These developments have not only enabled precise control of magnetic nanomaterial properties but also expanded the reach of magnetic detection for biomedical diagnostics.
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Affiliation(s)
- Yuan Chen
- Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117599, Singapore.,Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore
| | - Xianguang Ding
- Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore
| | - Yan Zhang
- Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117599, Singapore.,Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore
| | - Auginia Natalia
- Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore
| | - Xuecheng Sun
- Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore
| | - Zhigang Wang
- Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore
| | - Huilin Shao
- Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore 117599, Singapore.,Biomedical Institute for Global Health Research and Technology, National University of Singapore, Singapore 117599, Singapore.,Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.,Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
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7
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Wang W, Luo J, Wang S. Recent Progress in Isolation and Detection of Extracellular Vesicles for Cancer Diagnostics. Adv Healthc Mater 2018; 7:e1800484. [PMID: 30009550 DOI: 10.1002/adhm.201800484] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 06/20/2018] [Indexed: 12/21/2022]
Abstract
Extracellular vesicles (EVs) are emerging as one of the many new and promising biomarkers for liquid biopsy of cancer due to their loading capability of some specific proteins and nucleic acids that are closely associated with cancer states. As such, the isolation and detection of cancer-derived EVs offer important information in noninvasive diagnosis of early-stage cancer and real-time monitoring of cancer development. In light of the importance of EVs, over the last decade, researchers have made remarkable innovations to advance the development of EV isolation and detection methods by taking advantage of microfluidics, biomolecule probes, nanomaterials, surface plasmon, optics, and so on. This review introduces the basic properties of EVs and common cancer-derived EV ingredients, and provides a comprehensive overview of EV isolation and detection strategies, with emphasis on liquid biopsies of EVs for cancer diagnostics.
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Affiliation(s)
- Wenshuo Wang
- CAS Key Laboratory of Bio-Inspired Materials and Interfacial Science; Technical Institute of Physics and Chemistry; Chinese Academy of Sciences; Beijing 100190 P. R. China
- University of Chinese Academy of Sciences; Beijing 100049 P. R. China
| | - Jing Luo
- CAS Key Laboratory of Bio-Inspired Materials and Interfacial Science; Technical Institute of Physics and Chemistry; Chinese Academy of Sciences; Beijing 100190 P. R. China
- University of Chinese Academy of Sciences; Beijing 100049 P. R. China
| | - Shutao Wang
- CAS Key Laboratory of Bio-Inspired Materials and Interfacial Science; Technical Institute of Physics and Chemistry; Chinese Academy of Sciences; Beijing 100190 P. R. China
- University of Chinese Academy of Sciences; Beijing 100049 P. R. China
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8
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Lee JR, Appelmann I, Miething C, Shultz TO, Ruderman D, Kim D, Mallick P, Lowe SW, Wang SX. Longitudinal Multiplexed Measurement of Quantitative Proteomic Signatures in Mouse Lymphoma Models Using Magneto-Nanosensors. Theranostics 2018; 8:1389-1398. [PMID: 29507628 PMCID: PMC5835944 DOI: 10.7150/thno.20706] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Accepted: 12/12/2017] [Indexed: 01/23/2023] Open
Abstract
Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis. Here, we present a technique based on magneto-nanosensors to longitudinally monitor the protein profiles in individual mice of lymphoma models using a small volume of a sample for multiplex assays. Methods: Drug-sensitive and -resistant cancer cell lines were used to develop the mouse models that render different outcomes upon the drug treatment. Two groups of mice were inoculated with each cell line, and treated with either cyclophosphamide or vehicle solution. Serum samples taken longitudinally from each mouse in the groups were measured with 6-plex magneto-nanosensor cytokine assays. To find the origin of IL-6, experiments were performed using IL-6 knock-out mice. Results: The differences in serum IL-6 and GCSF levels between the drug-treated and untreated groups were revealed by the magneto-nanosensor measurement on individual mice. Using the multiplex assays and mouse models, we found that IL-6 is secreted by the host in the presence of tumor cells upon the drug treatment. Conclusion: The multiplex magneto-nanosensor assays enable longitudinal proteomic studies on mouse tumor models to understand tumor development and therapy mechanisms more precisely within a single biological object.
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Affiliation(s)
- Jung-Rok Lee
- Division of Mechanical and Biomedical Engineering, Ewha Womans University, Seoul, South Korea
| | - Iris Appelmann
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH Aachen, Aachen, Germany
| | - Cornelius Miething
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
- Department of Internal Medicine, Medical Center - University of Freiburg, Freiburg, Germany
| | - Tyler O. Shultz
- Department of Materials Science and Engineering, Stanford University, Stanford, California, USA
| | - Daniel Ruderman
- Ellison Institute of Transformative Medicine of USC, USC Keck School of Medicine, Los Angeles, California, USA
| | - Dokyoon Kim
- Department of Materials Science and Engineering, Stanford University, Stanford, California, USA
| | - Parag Mallick
- Department of Medicine, Department of Radiology, Stanford University, Stanford, California, USA
| | - Scott W. Lowe
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Shan X. Wang
- Department of Materials Science and Engineering, Stanford University, Stanford, California, USA
- Department of Medicine, Department of Radiology, Stanford University, Stanford, California, USA
- Department of Electrical Engineering, Stanford University, Stanford, California, USA
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9
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Liu P, Lin X, Xu Y, Zhang B, Si Z, Cao K, Wei J, Zhao W. Optically Tunable Magnetoresistance Effect: From Mechanism to Novel Device Application. MATERIALS (BASEL, SWITZERLAND) 2017; 11:E47. [PMID: 29283394 PMCID: PMC5793545 DOI: 10.3390/ma11010047] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Revised: 12/16/2017] [Accepted: 12/16/2017] [Indexed: 02/05/2023]
Abstract
The magnetoresistance effect in sandwiched structure describes the appreciable magnetoresistance effect of a device with a stacking of two ferromagnetic layers separated by a non-magnetic layer (i.e., a sandwiched structure). The development of this effect has led to the revolution of memory applications during the past decades. In this review, we revisited the magnetoresistance effect and the interlayer exchange coupling (IEC) effect in magnetic sandwiched structures with a spacer layer of non-magnetic metal, semiconductor or organic thin film. We then discussed the optical modulation of this effect via different methods. Finally, we discuss various applications of these effects and present a perspective to realize ultralow-power, high-speed data writing and inter-chip connection based on this tunable magnetoresistance effect.
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Affiliation(s)
- Pan Liu
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
| | - Xiaoyang Lin
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
- Beihang-Geortek Joint Microelectronics Institute, Qingdao Research Institute, Beihang University, Qingdao 266000, China.
| | - Yong Xu
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
- Institut Jean Lamour, CNRS UMR 7198, Université de Lorraine, 54506 Vandœuvre-lès-Nancy, France.
| | - Boyu Zhang
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
| | - Zhizhong Si
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
| | - Kaihua Cao
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
| | - Jiaqi Wei
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
| | - Weisheng Zhao
- Fert Beijing Research Institute, School of Electrical and Information Engineering, Big Data and Brain Computing Center (BDBC), Beihang University, Beijing 100191, China.
- Beihang-Geortek Joint Microelectronics Institute, Qingdao Research Institute, Beihang University, Qingdao 266000, China.
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10
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Magnetic impedance biosensor: A review. Biosens Bioelectron 2017; 90:418-435. [DOI: 10.1016/j.bios.2016.10.031] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Revised: 10/12/2016] [Accepted: 10/18/2016] [Indexed: 01/15/2023]
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11
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Lee JR, Haddon DJ, Gupta N, Price JV, Credo GM, Diep VK, Kim K, Hall DA, Baechler EC, Petri M, Varma M, Utz PJ, Wang SX. High-Resolution Analysis of Antibodies to Post-Translational Modifications Using Peptide Nanosensor Microarrays. ACS NANO 2016; 10:10652-10660. [PMID: 27636738 PMCID: PMC5367622 DOI: 10.1021/acsnano.6b03786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Autoantibodies are a hallmark of autoimmune diseases such as lupus and have the potential to be used as biomarkers for diverse diseases, including immunodeficiency, infectious disease, and cancer. More precise detection of antibodies to specific targets is needed to improve diagnosis of such diseases. Here, we report the development of reusable peptide microarrays, based on giant magnetoresistive (GMR) nanosensors optimized for sensitively detecting magnetic nanoparticle labels, for the detection of antibodies with a resolution of a single post-translationally modified amino acid. We have also developed a chemical regeneration scheme to perform multiplex assays with a high level of reproducibility, resulting in greatly reduced experimental costs. In addition, we show that peptides synthesized directly on the nanosensors are approximately two times more sensitive than directly spotted peptides. Reusable peptide nanosensor microarrays enable precise detection of autoantibodies with high resolution and sensitivity and show promise for investigating antibody-mediated immune responses to autoantigens, vaccines, and pathogen-derived antigens as well as other fundamental peptide-protein interactions.
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Affiliation(s)
- Jung-Rok Lee
- Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
| | - D. James Haddon
- Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California 94305, United States
| | - Nidhi Gupta
- Intel Corporation, Santa Clara, California 95052, United States
| | - Jordan V. Price
- Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California 94305, United States
- Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, California 94720, United States
| | - Grace M. Credo
- Intel Corporation, Santa Clara, California 95052, United States
| | - Vivian K. Diep
- Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California 94305, United States
| | - Kyunglok Kim
- Department of Electrical Engineering, Stanford University, Stanford, California 94305, United States
| | - Drew A. Hall
- Department of Electrical Engineering, Stanford University, Stanford, California 94305, United States
- Department of Electrical and Computer Engineering, University of California, San Diego, California 92093, United States
| | - Emily C. Baechler
- Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, United States
| | - Michelle Petri
- Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States
| | - Madoo Varma
- Intel Corporation, Santa Clara, California 95052, United States
| | - Paul J. Utz
- Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California 94305, United States
- Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, California 94305, United States
| | - Shan X. Wang
- Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States
- Department of Electrical Engineering, Stanford University, Stanford, California 94305, United States
- Corresponding Author.
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12
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Choi J, Gani AW, Bechstein DJ, Lee JR, Utz PJ, Wang SX. Portable, one-step, and rapid GMR biosensor platform with smartphone interface. Biosens Bioelectron 2016; 85:1-7. [DOI: 10.1016/j.bios.2016.04.046] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 04/14/2016] [Accepted: 04/18/2016] [Indexed: 10/21/2022]
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13
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Ferromagnetic Multilayers: Magnetoresistance, Magnetic Anisotropy, and Beyond. MAGNETOCHEMISTRY 2016. [DOI: 10.3390/magnetochemistry2020022] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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14
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Young CC, Blackley BW, Porter MD, Granger MC. Frequency-Domain Approach To Determine Magnetic Address-Sensor Separation Distance Using the Harmonic Ratio Method. Anal Chem 2016; 88:2015-20. [PMID: 26879366 PMCID: PMC4758469 DOI: 10.1021/acs.analchem.5b04271] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
In this work, we describe an approach to determine the distance separating a magnetic address from a scanning magnetoresistive sensor, a critical adjustable parameter for certain bioassay analyses where magnetic nanoparticles are used as labels. Our approach is leveraged from the harmonic ratio method (HRM), a method used in the hard drive industry to control the distance separating a magnetoresistive read head from its data platter with nanometer resolution. At the heart of the HRM is an amplitude comparison of a signal's fundamental frequency to that of its harmonics. When the signal is derived from the magnetic field pattern of a periodic array of magnetic addresses, the harmonic ratio contains the information necessary to determine the separation between the address array and the read head. The elegance of the HRM is that there is no need of additional components to the detection platform to determine a separation distance; the streaming "bit signal" contains all the information needed. In this work, we demonstrate that the tenets governing HRM used in the hard drive industry can be applied to the bioanalytical arena where submicrometer to 100 μm separations are required.
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Affiliation(s)
- Colin C. Young
- Department of Chemical Engineering, University of Utah
- Nano Institute of Utah, University of Utah, University of Utah
| | - Benjamin W. Blackley
- Department of Chemical Engineering, University of Utah
- Nano Institute of Utah, University of Utah, University of Utah
| | - Marc D. Porter
- Department of Chemical Engineering, University of Utah
- Departments of Chemistry, Bioengineering, and Pathology, University of Utah
- Nano Institute of Utah, University of Utah, University of Utah
| | - Michael C. Granger
- Department of Chemical Engineering, University of Utah
- Nano Institute of Utah, University of Utah, University of Utah
- Department of Surgery, School of Medicine, University of Utah
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15
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Henriksen AD, Ley MWH, Flyvbjerg H, Hansen MF. Configurational Statistics of Magnetic Bead Detection with Magnetoresistive Sensors. PLoS One 2015; 10:e0141115. [PMID: 26496495 PMCID: PMC4619777 DOI: 10.1371/journal.pone.0141115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 10/04/2015] [Indexed: 11/18/2022] Open
Abstract
Magnetic biosensors detect magnetic beads that, mediated by a target, have bound to a functionalized area. This area is often larger than the area of the sensor. Both the sign and magnitude of the average magnetic field experienced by the sensor from a magnetic bead depends on the location of the bead relative to the sensor. Consequently, the signal from multiple beads also depends on their locations. Thus, a given coverage of the functionalized area with magnetic beads does not result in a given detector response, except on the average, over many realizations of the same coverage. We present a systematic theoretical analysis of how this location-dependence affects the sensor response. The analysis is done for beads magnetized by a homogeneous in-plane magnetic field. We determine the expected value and standard deviation of the sensor response for a given coverage, as well as the accuracy and precision with which the coverage can be determined from a single sensor measurement. We show that statistical fluctuations between samples may reduce the sensitivity and dynamic range of a sensor significantly when the functionalized area is larger than the sensor area. Hence, the statistics of sampling is essential to sensor design. For illustration, we analyze three important published cases for which statistical fluctuations are dominant, significant, and insignificant, respectively.
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Affiliation(s)
- Anders Dahl Henriksen
- Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech, Building 345 East, DK-2800 Kongens Lyngby, Denmark
| | | | - Henrik Flyvbjerg
- Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech, Building 345 East, DK-2800 Kongens Lyngby, Denmark
| | - Mikkel Fougt Hansen
- Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech, Building 345 East, DK-2800 Kongens Lyngby, Denmark
- * E-mail:
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16
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Henriksen AD, Wang SX, Hansen MF. On the importance of sensor height variation for detection of magnetic labels by magnetoresistive sensors. Sci Rep 2015. [PMID: 26195089 PMCID: PMC4508666 DOI: 10.1038/srep12282] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Magnetoresistive sensors are widely used for biosensing by detecting the signal from magnetic labels bound to a functionalized area that usually covers the entire sensor structure. Magnetic labels magnetized by a homogeneous applied magnetic field weaken and strengthen the applied field when they are over and outside the sensor area, respectively, and the detailed origin of the sensor signal in experimental studies has not been clarified. We systematically analyze the signal from both a single sensor stripe and an array of sensor stripes as function of the geometrical parameters of the sensor stripes as well as the distribution of magnetic labels over the stripes. We show that the signal from sensor stripes with a uniform protective coating, contrary to conventional wisdom in the field, is usually dominated by the contribution from magnetic labels between the sensor stripes rather than by the labels on top of the sensor stripes because these are at a lower height. We therefore propose a shift of paradigm to maximize the signal due to magnetic labels between sensor stripes. Guidelines for this optimization are provided and illustrated for an experimental case from the literature.
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Affiliation(s)
- Anders Dahl Henriksen
- Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech, Building 345 East, DK-2800 Kongens Lyngby, Denmark
| | - Shan Xiang Wang
- 1] Department of Materials Science and Engineering, Stanford University, California 94305, USA [2] Department of Electrical Engineering, Stanford University, California 94305, USA
| | - Mikkel Fougt Hansen
- Department of Micro- and Nanotechnology, Technical University of Denmark, DTU Nanotech, Building 345 East, DK-2800 Kongens Lyngby, Denmark
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17
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Hong Y, Lee HJ, Kim SG, Kim BH, Yun GH, Yook JG. A Label-Free Biosensing Platform Using a PLL Circuit and Biotin-Streptavidin Binding System. IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS 2015; 9:345-352. [PMID: 25314705 DOI: 10.1109/tbcas.2014.2349074] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
This paper proposes a novel RF biosensor that utilizes a frequency synthesizer associated with a microstrip open-loop resonator for label-free biomolecular detection. The RF biosensor consists mainly of a resonance-assisted transducer and a phase locked loop (PLL) circuit. In this work, the performance of the RF biosensor is validated using the well-known biotin-streptavidin binding system. When biotin is bound to streptavidin, the input impedance of the resonator is varied, resulting in a change in the oscillation frequency. The concentration of the streptavidin is ultimately detected by a voltage signal of the PLL's loop filter with simple measurement equipment. According to the experimental results, the RF biosensor has revealed excellent sensitivity ( ~ 61 kHz/ngml(-1)) and a low detection limit ( ~ 1 ng/ml), as well as a rapid response. These results demonstrate that the RF biosensor can be an effective sensing platform for label-free detection in a biomolecular binding system.
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18
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Li F, Kosel J. An efficient biosensor made of an electromagnetic trap and a magneto-resistive sensor. Biosens Bioelectron 2014; 59:145-50. [DOI: 10.1016/j.bios.2014.03.035] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 03/06/2014] [Accepted: 03/07/2014] [Indexed: 10/25/2022]
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19
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Juárez-Aguirre R, Domínguez-Nicolás SM, Manjarrez E, Tapia JA, Figueras E, Vázquez-Leal H, Aguilera-Cortés LA, Herrera-May AL. Digital signal processing by virtual instrumentation of a MEMS magnetic field sensor for biomedical applications. SENSORS 2013; 13:15068-84. [PMID: 24196434 PMCID: PMC3871138 DOI: 10.3390/s131115068] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Revised: 10/24/2013] [Accepted: 10/28/2013] [Indexed: 11/16/2022]
Abstract
We present a signal processing system with virtual instrumentation of a MEMS sensor to detect magnetic flux density for biomedical applications. This system consists of a magnetic field sensor, electronic components implemented on a printed circuit board (PCB), a data acquisition (DAQ) card, and a virtual instrument. It allows the development of a semi-portable prototype with the capacity to filter small electromagnetic interference signals through digital signal processing. The virtual instrument includes an algorithm to implement different configurations of infinite impulse response (IIR) filters. The PCB contains a precision instrumentation amplifier, a demodulator, a low-pass filter (LPF) and a buffer with operational amplifier. The proposed prototype is used for real-time non-invasive monitoring of magnetic flux density in the thoracic cage of rats. The response of the rat respiratory magnetogram displays a similar behavior as the rat electromyogram (EMG).
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Affiliation(s)
- Raúl Juárez-Aguirre
- Micro and Nanotechnology Research Center, Universidad Veracruzana, Calzada Ruiz Cortines 455, Boca del Río 94294, Veracruz, Mexico; E-Mails: (R.J.-A.); (S.M.D.-N.)
| | - Saúl M. Domínguez-Nicolás
- Micro and Nanotechnology Research Center, Universidad Veracruzana, Calzada Ruiz Cortines 455, Boca del Río 94294, Veracruz, Mexico; E-Mails: (R.J.-A.); (S.M.D.-N.)
- Depto. Control Automático, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. Zacatenco 07360, D.F., Mexico
| | - Elías Manjarrez
- Institute of Physiology, Benemérita Universidad Autónoma de Puebla, 14 Sur 6301, Colonia San Manuel, Puebla 72570, Puebla, Mexico; E-Mails: (E.M.); (J.A.T.)
| | - Jesús A. Tapia
- Institute of Physiology, Benemérita Universidad Autónoma de Puebla, 14 Sur 6301, Colonia San Manuel, Puebla 72570, Puebla, Mexico; E-Mails: (E.M.); (J.A.T.)
| | - Eduard Figueras
- Microelectronic Institute of Barcelona IMB-CNM, CSIC, Bellaterra 08193, Spain; E-Mail:
| | - Héctor Vázquez-Leal
- Electronic Instrumentation and Atmospheric Sciences School, Universidad Veracruzana, Gonzalo Aguirre Beltran S/N, Xalapa 91000, Veracruz, Mexico; E-Mail:
| | - Luz A. Aguilera-Cortés
- Depto. Ingeniería Mecánica, DICIS, Universidad de Guanajuato/Carretera Salamanca-Valle de Santiago km 3.5+1.8 km, Salamanca 36885, Guanajuato, Mexico; E-Mail:
| | - Agustín L. Herrera-May
- Micro and Nanotechnology Research Center, Universidad Veracruzana, Calzada Ruiz Cortines 455, Boca del Río 94294, Veracruz, Mexico; E-Mails: (R.J.-A.); (S.M.D.-N.)
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +52-229-775-2000 (ext. 11956); Fax: +52-229-921-6532
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20
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Lee JR, Magee DM, Gaster RS, LaBaer J, Wang SX. Emerging protein array technologies for proteomics. Expert Rev Proteomics 2013; 10:65-75. [PMID: 23414360 DOI: 10.1586/epr.12.67] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Numerous efforts have been made to understand fundamental biology of diseases based on gene expression. However, the relationship between gene expression and onset of disease often remains obscure. The great advances in protein microarrays allow us to investigate this unclear question through protein profiles, which are regarded as more reliable than gene expressions to serve as the harbinger of disease onset or as the biomarker of disease treatment monitoring. The authors review two relatively new platforms of protein arrays, along with an introduction to the common basis of protein array technologies. Immobilization of proteins on the surface of arrays and neutralizing reactive areas after the immobilization are key practical issues in the field of protein array. One of the emerging protein array technologies is the magneto-nanosensor array, where giant magnetoresistive sensors are used to quantitatively measure the analytes of interest, which are labeled with magnetic nanoparticles. Similar to giant magnetoresistive sensors, several different ways of utilizing magnetic properties for biomolecular detection have been developed and are reviewed here. Another emerging protein array technology is nucleic acid programmable protein arrays, which have thousands of protein features directly expressed by nucleic acids on the array surface. The authors anticipate that these two emerging protein array platforms can be combined to produce synergistic benefits and open new applications in proteomics and clinical diagnostics.
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Affiliation(s)
- Jung-Rok Lee
- Department of Mechanical Engineering, Stanford University, 476 Lomita Mall, Room 208, Stanford, CA 94305, USA
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21
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Chang AY, Lu MSC. A CMOS magnetic microbead-based capacitive biosensor array with on-chip electromagnetic manipulation. Biosens Bioelectron 2013; 45:6-12. [DOI: 10.1016/j.bios.2013.01.033] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2012] [Revised: 01/06/2013] [Accepted: 01/16/2013] [Indexed: 10/27/2022]
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22
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Hall DA, Gaster RS, Makinwa K, Wang SX, Murmann B. A 256 pixel magnetoresistive biosensor microarray in 0.18μm CMOS. IEEE JOURNAL OF SOLID-STATE CIRCUITS 2013; 48:1290-1301. [PMID: 24761029 PMCID: PMC3993911 DOI: 10.1109/jssc.2013.2245058] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/19/2023]
Abstract
Magnetic nanotechnologies have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors coupled with magnetic nanotags (MNTs) possess great promise as ultra-sensitive biosensors for diagnostics. We report an integrated sensor interface for an array of 256 GMR SV biosensors designed in 0.18 μm CMOS. Arranged like an imager, each of the 16 column level readout channels contains an analog front- end and a compact ΣΔ modulator (0.054 mm2) with 84 dB of dynamic range and an input referred noise of 49 nT/√Hz. Performance is demonstrated through detection of an ovarian cancer biomarker, secretory leukocyte peptidase inhibitor (SLPI), spiked at concentrations as low as 10 fM. This system is designed as a replacement for optical protein microarrays while also providing real-time kinetics monitoring.
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Affiliation(s)
| | | | - Kofi Makinwa
- Delft University of Technology, Delft, The Netherlands
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23
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Gu H, Zhang X, Wei H, Huang Y, Wei S, Guo Z. An overview of the magnetoresistance phenomenon in molecular systems. Chem Soc Rev 2013; 42:5907-43. [DOI: 10.1039/c3cs60074b] [Citation(s) in RCA: 83] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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24
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Freitas PP, Cardoso FA, Martins VC, Martins SAM, Loureiro J, Amaral J, Chaves RC, Cardoso S, Fonseca LP, Sebastião AM, Pannetier-Lecoeur M, Fermon C. Spintronic platforms for biomedical applications. LAB ON A CHIP 2012; 12:546-557. [PMID: 22146898 DOI: 10.1039/c1lc20791a] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
Since the fundamental discovery of the giant magnetoresistance many spintronic devices have been developed and implemented in our daily life (e.g. information storage and automotive industry). Lately, advances in the sensors technology (higher sensitivity, smaller size) have potentiated other applications, namely in the biological area, leading to the emergence of novel biomedical platforms. In particular the investigation of spintronics and its application to the development of magnetoresistive (MR) biomolecular and biomedical platforms are giving rise to a new class of biomedical diagnostic devices, suitable for bench top bioassays as well as point-of-care and point-of-use devices. Herein, integrated spintronic biochip platforms for diagnostic and cytometric applications, hybrid systems incorporating magnetoresistive sensors applied to neuroelectronic studies and biomedical imaging, namely magneto-encephalography and magneto-cardiography, are reviewed. Also lab-on-a-chip MR-based platforms to perform biological studies at the single molecule level are discussed. Overall the potential and main characteristics of such MR-based biomedical devices, comparing to the existing technologies while giving particular examples of targeted applications, are addressed.
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Affiliation(s)
- P P Freitas
- Instituto de Engenharia de Sistemas e Computadores-Microsistemas e Nanotecnologias, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
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25
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Loureiro J, Andrade PZ, Cardoso S, da Silva CL, Cabral JM, Freitas PP. Magnetoresistive chip cytometer. LAB ON A CHIP 2011; 11:2255-61. [PMID: 21562656 DOI: 10.1039/c0lc00324g] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Although conventional state-of-the-art flow cytometry systems provide rapid and reliable analytical capacities, they are bulky, expensive and complex. To overcome these drawbacks modern flow cytometers have been developed with enhanced portability for on-site measurements. Unlike external fluorescent/optical detectors, magnetoresistive sensors are micro-fabricated, can be integrated within microfluidic channels, and can detect magnetically labelled cells. This work describes the real-time detection of single magnetically labelled cells with a magnetoresistive based cell cytometer. For Kg1-a cells magnetically labelled with 50 nm CD34 microbeads (Milteny) flowing through a 150 μm wide, 14 μm high microchannel, with speeds around 1 cm s(-1), bipolar signals with an average amplitude of 10-20 μV were observed corresponding to cell events. The number of cells counted by the spin valve cytometer has been compared with that obtained with a hemocytometer. Both methods agree within the respective error bars.
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Affiliation(s)
- J Loureiro
- INESC-MN Instituto de Engenharia de Sistemas e Computadores-Microsistemas e Nanotecnologias, Rua Alves Redol no. 9, 1000-029, Lisbon, Portugal.
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26
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Luppa PB, Müller C, Schlichtiger A. Point-of-care testing (POCT): Current techniques and future perspectives. Trends Analyt Chem 2011; 30:887-898. [PMID: 32287536 PMCID: PMC7125710 DOI: 10.1016/j.trac.2011.01.019] [Citation(s) in RCA: 326] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Point-of-care testing (POCT) is a laboratory-medicine discipline that is evolving rapidly in analytical scope and clinical application. In this review, we first describe the state of the art of medical-laboratory tests that can be performed near the patient. At present, POCT ranges from basic blood-glucose measurement to complex viscoelastic coagulation assays. POCT shortens the time to clinical decision-making about additional testing or therapy, as delays are no longer caused by transport and preparation of clinical samples, and biochemical-test results are rapidly available at the point of care. Improved medical outcome and lower costs may ensue. Recent, evolving technological advances enable the development of novel POCT instruments. We review the underlying analytical techniques. If new instruments are not yet in practical use, it is often hard to decide whether the underlying analytical principle has real advantage over former methods. However, future utilization of POCT also depends on health-care trends and new areas of application. But, even today, it can be assumed that, for certain applications, near-patient testing is a useful complement to conventional laboratory analyses.
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Affiliation(s)
- Peter B. Luppa
- Corresponding author. Tel.: +49 89 4140 4759; Fax: +49 89 4140 4875.
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27
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Gaster RS, Hall DA, Wang SX. nanoLAB: an ultraportable, handheld diagnostic laboratory for global health. LAB ON A CHIP 2011; 11:950-956. [PMID: 21264375 DOI: 10.1039/c0lc00534g] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Driven by scientific progress and economic stimulus, medical diagnostics will move to a stage in which straightforward medical diagnoses are independent of physician visits and large centralized laboratories. The future of basic diagnostic medicine will lie in the hands of private individuals. We have taken significant strides towards achieving this goal by developing an autoassembly assay for disease biomarker detection which obviates the need for washing steps and is run on a handheld sensing platform. By coupling magnetic nanotechnology with an array of magnetically responsive nanosensors, we demonstrate a rapid, multiplex immunoassay that eliminates the need for trained technicians to run molecular diagnostic tests. Furthermore, the platform is battery-powered and ultraportable, allowing the assay to be run anywhere in the world by any individual.
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Affiliation(s)
- Richard S Gaster
- Department of Bioengineering, Stanford University, Stanford, California 94305, USA
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28
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Beveridge JS, Stephens JR, Williams ME. The use of magnetic nanoparticles in analytical chemistry. ANNUAL REVIEW OF ANALYTICAL CHEMISTRY (PALO ALTO, CALIF.) 2011; 4:251-73. [PMID: 21417723 DOI: 10.1146/annurev-anchem-061010-114041] [Citation(s) in RCA: 101] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Magnetic nanoparticles uniquely combine superparamagnetic behavior with dimensions that are smaller than or the same size as molecular analytes. The integration of magnetic nanoparticles with analytical methods has opened new avenues for sensing, purification, and quantitative analysis. Applied magnetic fields can be used to control the motion and properties of magnetic nanoparticles; in analytical chemistry, use of magnetic fields provides methods for manipulating and analyzing species at the molecular level. In this review, we describe applications of magnetic nanoparticles to analyte handling, chemical sensors, and imaging techniques.
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Affiliation(s)
- Jacob S Beveridge
- Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16803, USA.
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29
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Anandakumar S, Rani VS, Oh S, Sinha B, Takahashi M, Kim C. Translocation of bio-functionalized magnetic beads using smart magnetophoresis. Biosens Bioelectron 2010; 26:1755-8. [DOI: 10.1016/j.bios.2010.08.033] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2010] [Revised: 08/04/2010] [Accepted: 08/12/2010] [Indexed: 10/19/2022]
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30
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Hall DA, Wang SX, Murmann B, Gaster RS. Portable Biomarker Detection with Magnetic Nanotags. THE ... MIDWEST SYMPOSIUM ON CIRCUITS AND SYSTEMS CONFERENCE PROCEEDINGS : MWSCAS. MIDWEST SYMPOSIUM ON CIRCUITS AND SYSTEMS 2010:1779-1782. [PMID: 22495252 DOI: 10.1109/iscas.2010.5537639] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
This paper presents a hand-held, portable biosensor platform for quantitative biomarker measurement. By combining magnetic nanoparticle (MNP) tags with giant magnetoresistive (GMR) spin-valve sensors, the hand-held platform achieves highly sensitive (picomolar) and specific biomarker detection in less than 20 minutes. The rapid analysis and potential low cost make this technology ideal for point-of-care (POC) diagnostics. Furthermore, this platform is able to detect multiple biomarkers simultaneously in a single assay, creating a promising diagnostic tool for a vast number of applications.
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Affiliation(s)
- Drew A Hall
- Stanford University Department of Electrical Engineering Stanford, CA, USA {drewhall, sxwang, murmann}@stanford.edu
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31
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Li Y, Srinivasan B, Jing Y, Yao X, Hugger MA, Wang JP, Xing C. Nanomagnetic Competition Assay for Low-Abundance Protein Biomarker Quantification in Unprocessed Human Sera. J Am Chem Soc 2010; 132:4388-92. [DOI: 10.1021/ja910406a] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Yuanpeng Li
- Department of Electrical and Computer Engineering, and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
| | - Balasubramanian Srinivasan
- Department of Electrical and Computer Engineering, and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
| | - Ying Jing
- Department of Electrical and Computer Engineering, and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
| | - Xiaofeng Yao
- Department of Electrical and Computer Engineering, and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
| | - Marie A. Hugger
- Department of Electrical and Computer Engineering, and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
| | - Jian-Ping Wang
- Department of Electrical and Computer Engineering, and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
| | - Chengguo Xing
- Department of Electrical and Computer Engineering, and Department of Medicinal Chemistry, University of Minnesota, Minneapolis, Minnesota 55455
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32
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GMR biosensor arrays: a system perspective. Biosens Bioelectron 2010; 25:2051-7. [PMID: 20207130 DOI: 10.1016/j.bios.2010.01.038] [Citation(s) in RCA: 123] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2009] [Revised: 12/01/2009] [Accepted: 01/31/2010] [Indexed: 11/20/2022]
Abstract
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 4s). 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.
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33
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Hall DA, Gaster RS, Osterfeld SJ, Murmann B, Wang SX. GMR biosensor arrays: correction techniques for reproducibility and enhanced sensitivity. Biosens Bioelectron 2010; 25:2177-81. [PMID: 20219342 DOI: 10.1016/j.bios.2010.01.039] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2009] [Revised: 12/11/2009] [Accepted: 01/31/2010] [Indexed: 11/25/2022]
Abstract
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 x using digital correction techniques and the sensors are made temperature independent by using a novel background correction technique.
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Affiliation(s)
- D A Hall
- Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA
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34
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Germano J, Martins VC, Cardoso FA, Almeida TM, Sousa L, Freitas PP, Piedade MS. A portable and autonomous magnetic detection platform for biosensing. SENSORS 2009; 9:4119-37. [PMID: 22408516 PMCID: PMC3291901 DOI: 10.3390/s90604119] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/24/2009] [Revised: 05/19/2009] [Accepted: 05/22/2009] [Indexed: 11/24/2022]
Abstract
This paper presents a prototype of a platform for biomolecular recognition detection. The system is based on a magnetoresistive biochip that performs biorecognition assays by detecting magnetically tagged targets. All the electronic circuitry for addressing, driving and reading out signals from spin-valve or magnetic tunnel junctions sensors is implemented using off-the-shelf components. Taking advantage of digital signal processing techniques, the acquired signals are processed in real time and transmitted to a digital analyzer that enables the user to control and follow the experiment through a graphical user interface. The developed platform is portable and capable of operating autonomously for nearly eight hours. Experimental results show that the noise level of the described platform is one order of magnitude lower than the one presented by the previously used measurement set-up. Experimental results also show that this device is able to detect magnetic nanoparticles with a diameter of 250 nm at a concentration of about 40 fM. Finally, the biomolecular recognition detection capabilities of the platform are demonstrated by performing a hybridization assay using complementary and non-complementary probes and a magnetically tagged 20mer single stranded DNA target.
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Affiliation(s)
- José Germano
- INESC-ID Instituto de Engenharia de Sistemas e Computadores-Investigação e Desenvolvimento, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
| | - Verónica C. Martins
- INESC-MN Instituto de Engenharia de Sistemas e Computadores-Microsistemas e Nanotecnologias ans IN-Institute of Nanoscience and Nanotechnology and IN-Institute of Nanoscience and Nanotechnology, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
- Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
| | - Filipe A. Cardoso
- INESC-MN Instituto de Engenharia de Sistemas e Computadores-Microsistemas e Nanotecnologias ans IN-Institute of Nanoscience and Nanotechnology and IN-Institute of Nanoscience and Nanotechnology, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
- Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
| | - Teresa M. Almeida
- INESC-ID Instituto de Engenharia de Sistemas e Computadores-Investigação e Desenvolvimento, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
- Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
| | - Leonel Sousa
- INESC-ID Instituto de Engenharia de Sistemas e Computadores-Investigação e Desenvolvimento, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
- Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
- Author to whom correspondence should be addressed; E-mail: ; Tel.: +351 213100320; Fax: +351 21 3145843
| | - Paulo P. Freitas
- INESC-MN Instituto de Engenharia de Sistemas e Computadores-Microsistemas e Nanotecnologias ans IN-Institute of Nanoscience and Nanotechnology and IN-Institute of Nanoscience and Nanotechnology, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
- Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
| | - Moisés S. Piedade
- INESC-ID Instituto de Engenharia de Sistemas e Computadores-Investigação e Desenvolvimento, Rua Alves Redol, 9, 1000-029 Lisbon, Portugal
- Instituto Superior Técnico, TU Lisbon, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
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35
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Femtomolar limit of detection with a magnetoresistive biochip. Biosens Bioelectron 2009; 24:2690-5. [DOI: 10.1016/j.bios.2009.01.040] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2008] [Revised: 01/10/2009] [Accepted: 01/28/2009] [Indexed: 10/21/2022]
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36
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Fu A, Hu W, Xu L, Wilson RJ, Yu H, Osterfeld SJ, Gambhir SS, Wang SX. Protein-functionalized synthetic antiferromagnetic nanoparticles for biomolecule detection and magnetic manipulation. ACTA ACUST UNITED AC 2009. [PMID: 19156803 DOI: 10.1002/ange.200803994] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Direct protein functionalization provides synthetic antiferromagnetic nanoparticles with high chemical specificity and multifunctionality. These nanoparticle-protein conjugates function as improved magnetic labels for biological detection experiments, and exhibit tunable responses to a small external magnetic field gradient, thus allowing the observation of distinctive single nanoparticle motion.
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Affiliation(s)
- Aihua Fu
- Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
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37
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Fu A, Hu W, Xu L, Wilson RJ, Yu H, Osterfeld SJ, Gambhir SS, Wang SX. Protein-functionalized synthetic antiferromagnetic nanoparticles for biomolecule detection and magnetic manipulation. Angew Chem Int Ed Engl 2009; 48:1620-4. [PMID: 19156803 DOI: 10.1002/anie.200803994] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Direct protein functionalization provides synthetic antiferromagnetic nanoparticles with high chemical specificity and multifunctionality. These nanoparticle-protein conjugates function as improved magnetic labels for biological detection experiments, and exhibit tunable responses to a small external magnetic field gradient, thus allowing the observation of distinctive single nanoparticle motion.
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Affiliation(s)
- Aihua Fu
- Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
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38
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Srinivasan B, Li Y, Jing Y, Xu Y, Yao X, Xing C, Wang JP. A Detection System Based on Giant Magnetoresistive Sensors and High-Moment Magnetic Nanoparticles Demonstrates Zeptomole Sensitivity: Potential for Personalized Medicine. Angew Chem Int Ed Engl 2009; 48:2764-7. [DOI: 10.1002/anie.200806266] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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39
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Srinivasan B, Li Y, Jing Y, Xu Y, Yao X, Xing C, Wang JP. A Detection System Based on Giant Magnetoresistive Sensors and High-Moment Magnetic Nanoparticles Demonstrates Zeptomole Sensitivity: Potential for Personalized Medicine. Angew Chem Int Ed Engl 2009. [DOI: 10.1002/ange.200806266] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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40
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Koets M, van der Wijk T, van Eemeren J, van Amerongen A, Prins M. Rapid DNA multi-analyte immunoassay on a magneto-resistance biosensor. Biosens Bioelectron 2009; 24:1893-8. [DOI: 10.1016/j.bios.2008.09.023] [Citation(s) in RCA: 97] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2008] [Revised: 09/19/2008] [Accepted: 09/23/2008] [Indexed: 12/01/2022]
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41
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Li Y, Jing Y, Yao X, Srinivasan B, Xu Y, Xing C, Wang JP. Biomarkers identification and detection based on GMR sensor and sub 13 nm magnetic nanoparticles. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2009; 2009:5432-5435. [PMID: 19963642 DOI: 10.1109/iembs.2009.5332479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
In this paper, we present a ultra high sensitive (Zeptomole, 10(-21)) technique to enable the detection of any potential low abundance biomarkers. We demonstrated for the first time the detection of sub 13nm high-moment magnetic nanoparticle and the implementation of a novel magnetoresistive (GMR) biosensor concept with higher sensitivity and 10 times lower external field in real biomarker sensing schemes. A potential lung cancer biomarker, interleukin-6 (IL-6), was successfully detected with extremely low concentration (as few as only 200 pieces of IL-6). Together with other features of GMR sensor systems like low-cost, portability, easy-to-use, our demonstrated device may lead to future family-based personalized medicine for cancer prevention.
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Affiliation(s)
- Yuanpeng Li
- Department of Electrical and Computer Engineering, Minneapolis, MN 55455, USA
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42
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Attomolar protein detection in complex sample matrices with semi-homogeneous fluidic force discrimination assays. Biosens Bioelectron 2009; 24:1109-15. [DOI: 10.1016/j.bios.2008.06.010] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2008] [Revised: 06/08/2008] [Accepted: 06/09/2008] [Indexed: 11/22/2022]
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43
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Multiplex protein assays based on real-time magnetic nanotag sensing. Proc Natl Acad Sci U S A 2008; 105:20637-40. [PMID: 19074273 DOI: 10.1073/pnas.0810822105] [Citation(s) in RCA: 189] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
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.
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44
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Janssen XJA, Schellekens AJ, van Ommering K, van Ijzendoorn LJ, Prins MWJ. Controlled torque on superparamagnetic beads for functional biosensors. Biosens Bioelectron 2008; 24:1937-41. [PMID: 19022651 DOI: 10.1016/j.bios.2008.09.024] [Citation(s) in RCA: 73] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2008] [Revised: 09/12/2008] [Accepted: 09/24/2008] [Indexed: 10/21/2022]
Abstract
We demonstrate that a rotating magnetic field can be used to apply a controlled torque on superparamagnetic beads which leads to a tunable bead rotation frequency in fluid. Smooth rotation is obtained for field rotation frequencies many orders of magnitude higher than the bead rotation frequency. A quantitative model is developed, based on results from a comprehensive set of experiments at different field strengths and frequencies. At low frequencies (<10Hz), rotation is due to a small permanent magnetic moment in the bead. At high frequencies (kHz-MHz), the torque results from a phase lag between the applied field and the induced magnetic moment, caused by the non-zero relaxation time of magnetic nanoparticles in the bead. The control of torque and rotation will enable novel functional assays in bead-based biosensors.
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Affiliation(s)
- X J A Janssen
- Eindhoven University of Technology, Eindhoven, The Netherlands
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45
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Sensitive and rapid immunoassay for parathyroid hormone using magnetic particle labels and magnetic actuation. J Immunol Methods 2008; 338:40-6. [DOI: 10.1016/j.jim.2008.07.001] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2008] [Revised: 05/23/2008] [Accepted: 07/01/2008] [Indexed: 11/19/2022]
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46
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Lateral flow (immuno)assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal Bioanal Chem 2008; 393:569-82. [PMID: 18696055 DOI: 10.1007/s00216-008-2287-2] [Citation(s) in RCA: 947] [Impact Index Per Article: 55.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2008] [Revised: 07/01/2008] [Accepted: 07/03/2008] [Indexed: 10/21/2022]
Abstract
Lateral flow (immuno)assays are currently used for qualitative, semiquantitative and to some extent quantitative monitoring in resource-poor or non-laboratory environments. Applications include tests on pathogens, drugs, hormones and metabolites in biomedical, phytosanitary, veterinary, feed/food and environmental settings. We describe principles of current formats, applications, limitations and perspectives for quantitative monitoring. We illustrate the potentials and limitations of analysis with lateral flow (immuno)assays using a literature survey and a SWOT analysis (acronym for "strengths, weaknesses, opportunities, threats"). Articles referred to in this survey were searched for on MEDLINE, Scopus and in references of reviewed papers. Search terms included "immunochromatography", "sol particle immunoassay", "lateral flow immunoassay" and "dipstick assay".
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47
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48
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De Palma R, Reekmans G, Liu C, Wirix-Speetjens R, Laureyn W, Nilsson O, Lagae L. Magnetic Bead Sensing Platform for the Detection of Proteins. Anal Chem 2007; 79:8669-77. [DOI: 10.1021/ac070821n] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Randy De Palma
- IMEC, NEXT, Kapeldreef 75, B-3001 Leuven, Belgium, Physical and Quantum Chemistry, Catholic University Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium, and Fujirebio Diagnostics, Majnabbe Terminal, SE-414 55 Gothenburg, Sweden
| | - Gunter Reekmans
- IMEC, NEXT, Kapeldreef 75, B-3001 Leuven, Belgium, Physical and Quantum Chemistry, Catholic University Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium, and Fujirebio Diagnostics, Majnabbe Terminal, SE-414 55 Gothenburg, Sweden
| | - Chengxun Liu
- IMEC, NEXT, Kapeldreef 75, B-3001 Leuven, Belgium, Physical and Quantum Chemistry, Catholic University Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium, and Fujirebio Diagnostics, Majnabbe Terminal, SE-414 55 Gothenburg, Sweden
| | - Roel Wirix-Speetjens
- IMEC, NEXT, Kapeldreef 75, B-3001 Leuven, Belgium, Physical and Quantum Chemistry, Catholic University Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium, and Fujirebio Diagnostics, Majnabbe Terminal, SE-414 55 Gothenburg, Sweden
| | - Wim Laureyn
- IMEC, NEXT, Kapeldreef 75, B-3001 Leuven, Belgium, Physical and Quantum Chemistry, Catholic University Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium, and Fujirebio Diagnostics, Majnabbe Terminal, SE-414 55 Gothenburg, Sweden
| | - Olle Nilsson
- IMEC, NEXT, Kapeldreef 75, B-3001 Leuven, Belgium, Physical and Quantum Chemistry, Catholic University Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium, and Fujirebio Diagnostics, Majnabbe Terminal, SE-414 55 Gothenburg, Sweden
| | - Liesbet Lagae
- IMEC, NEXT, Kapeldreef 75, B-3001 Leuven, Belgium, Physical and Quantum Chemistry, Catholic University Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium, and Fujirebio Diagnostics, Majnabbe Terminal, SE-414 55 Gothenburg, Sweden
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49
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De Palma R, Reekmans G, Laureyn W, Borghs G, Maes G. The Optimization of Magnetosandwich Assays for the Sensitive and Specific Detection of Proteins in Serum. Anal Chem 2007; 79:7540-8. [PMID: 17713969 DOI: 10.1021/ac0713407] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Over the past decade, the use of magnetic particles (MPs) as labels in magnetic biosensors has attracted increasing interest because it provides a highly sensitive platform that can meet the diagnostic needs that are currently not met by existing technologies. However, preparing magnetic biosensors for a specific diagnostic application is a challenging task, and the (bio)chemical aspects are often neglected. Hence, one of the major remaining bottlenecks in the development of magnetic biosensors is the lack of an optimized magnetosandwich assay for the highly sensitive and specific detection of proteins in complex sample matrices. Therefore, in this article, we report on the impact of several different aspects of magnetosandwich assay development, that is, surface chemistry, MP size, rinsing procedure, sample matrix, and blocking procedure on the total-assay performance using quartz crystal microbalance and optical microscopy analysis. The optimization focused on the diagnostically relevant protein S100betabeta, a marker for stroke and minor head injury. It was observed that small MPs in combination with a strong rinsing and a BSA/Tween-20 blocking allows for the most specific and sensitive detection of S100betabeta in serum over a wide concentration range.
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