Quantification of protein interactions and solution transport using high-density GMR sensor arrays
TL;DR: An analytical model is presented that describes the binding of magnetically labeled antibodies to proteins that are immobilized on the sensor surface and is able to quantify the kinetics of antibody-antigen binding at sensitivities as low as 20 zeptomoles of solute.
Abstract: Giant magnetoresistive nanosensors are used to quantify the binding kinetics of proteins at the surface of the sensor array, thus offering a sensitive assay for applications in antibody and drug development, and clinical diagnostics.
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TL;DR: Magnetoresponsive Therapy Nohyun Lee, Dongwon Yoo, Daishun Ling,†,‡,⊥ Mi Hyeon Cho, Taeghwan H Yeon,*,†,† and Jinwoo Cheon.
Abstract: Magnetoresponsive Therapy Nohyun Lee, Dongwon Yoo, Daishun Ling,†,‡,⊥ Mi Hyeon Cho, Taeghwan Hyeon,*,†,‡ and Jinwoo Cheon* †Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul 151-742, Korea ‡School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742, Korea Department of Chemistry, Yonsei University, Seoul 120-749, Korea School of Advanced Materials Engineering, Kookmin University, Seoul 136-702, Korea Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
777 citations
TL;DR: A comprehensive overview of sensor technology exploiting optical whispering gallery mode (WGM) resonances by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes.
Abstract: We present a comprehensive overview of sensor technology exploiting optical whispering gallery mode (WGM) resonances. After a short introduction we begin by detailing the fundamental principles and theory of WGMs in optical microcavities and the transduction mechanisms frequently employed for sensing purposes. Key recent theoretical contributions to the modeling and analysis of WGM systems are highlighted. Subsequently we review the state of the art of WGM sensors by outlining efforts made to date to improve current detection limits. Proposals in this vein are numerous and range, for example, from plasmonic enhancements and active cavities to hybrid optomechanical sensors, which are already working in the shot noise limited regime. In parallel to furthering WGM sensitivity, efforts to improve the time resolution are beginning to emerge. We therefore summarize the techniques being pursued in this vein. Ultimately WGM sensors aim for real-world applications, such as measurements of force and temperature, or alternatively gas and biosensing. Each such application is thus reviewed in turn, and important achievements are discussed. Finally, we adopt a more forward-looking perspective and discuss the outlook of WGM sensors within both a physical and biological context and consider how they may yet push the detection envelope further.
715 citations
TL;DR: An overview of recent advances in cancer biomarker detection is provided and several representative examples using different approaches for each biomarker demonstrate that the multidisciplinary technology-based cancer diagnostics are becoming an increasingly relevant alternative to traditional techniques.
Abstract: The early detection of cancer can significantly reduce cancer mortality and saves lives. Thus, a great deal of effort has been devoted to the exploration of new technologies to detect early signs of the disease. Cancer biomarkers cover a broad range of biochemical entities, such as nucleic acids, proteins, sugars, small metabolites, and cytogenetic and cytokinetic parameters, as well as entire tumour cells found in the body fluid. They can be used for risk assessment, diagnosis, prognosis, and for the prediction of treatment efficacy and toxicity and recurrence. In this review, we provide an overview of recent advances in cancer biomarker detection. Several representative examples using different approaches for each biomarker have been reviewed, and all these cases demonstrate that the multidisciplinary technology-based cancer diagnostics are becoming an increasingly relevant alternative to traditional techniques. In addition, we also discuss the unsolved problems and future challenges in the evaluation of cancer biomarkers. Clearly, solving these hurdles requires great effort and collaboration from different communities of chemists, physicists, biologists, clinicians, material-scientists, and engineering and technical researchers. A successful outcome will result in the realization of point-of-care diagnosis and individualized treatment of cancers by non-invasive and convenient tests in the future.
707 citations
TL;DR: Silicon nanowire field-effect transistors can be readily used as high-throughput biosensors to quantify protein interactions, and an analytical model is developed to calibrate the sensor response and quantify the molecular binding affinities of two representative protein-ligand binding pairs.
Abstract: Monitoring the binding affinities and kinetics of protein interactions is important in clinical diagnostics and drug development because such information is used to identify new therapeutic candidates. Surface plasmon resonance is at present the standard method used for such analysis, but this is limited by low sensitivity and low-throughput analysis. Here, we show that silicon nanowire field-effect transistors can be used as biosensors to measure protein–ligand binding affinities and kinetics with sensitivities down to femtomolar concentrations. Based on this sensing mechanism, we develop an analytical model to calibrate the sensor response and quantify the molecular binding affinities of two representative protein–ligand binding pairs. The rate constant of the association and dissociation of the protein–ligand pair is determined by monitoring the reaction kinetics, demonstrating that silicon nanowire field-effect transistors can be readily used as high-throughput biosensors to quantify protein interactions.
326 citations
TL;DR: The type of detection signals read by nanosensors to detect extremely small concentrations of biomarkers are introduced and distinctive examples of high-sensitivity sensors are provided.
Abstract: High sensitivity nanosensors utilize optical, mechanical, electrical, and magnetic relaxation properties to push detection limits of biomarkers below previously possible concentrations. The unique properties of nanomaterials and nanotechnology are exploited to design biomarker diagnostics. High-sensitivity recognition is achieved by signal and target amplification along with thorough pre-processing of samples. In this tutorial review, we introduce the type of detection signals read by nanosensors to detect extremely small concentrations of biomarkers and provide distinctive examples of high-sensitivity sensors. The use of such high-sensitivity nanosensors can offer earlier detection of disease than currently available to patients and create significant improvements in clinical outcomes.
254 citations
References
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TL;DR: A high-capacity system was developed to monitor the expression of many genes in parallel by means of simultaneous, two-color fluorescence hybridization, which enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA.
Abstract: A high-capacity system was developed to monitor the expression of many genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were used for quantitative expression measurements of the corresponding genes. Because of the small format and high density of the arrays, hybridization volumes of 2 microliters could be used that enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA. Differential expression measurements of 45 Arabidopsis genes were made by means of simultaneous, two-color fluorescence hybridization.
10,287 citations
"Quantification of protein interacti..." refers background in this paper
...Equation (1) now has the following analytical solution (for derivation see Supplementary Materials and Methods):...
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...We further simplify equation (1) by assuming that koff is zero, because antibody–antigen dissociation is typically negligible on the 400–1,000 s timescales of our experiments (Supplementary Fig....
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TL;DR: This review describes a new paradigm of electronics based on the spin degree of freedom of the electron, which has the potential advantages of nonvolatility, increased data processing speed, decreased electric power consumption, and increased integration densities compared with conventional semiconductor devices.
Abstract: This review describes a new paradigm of electronics based on the spin degree of freedom of the electron. Either adding the spin degree of freedom to conventional charge-based electronic devices or using the spin alone has the potential advantages of nonvolatility, increased data processing speed, decreased electric power consumption, and increased integration densities compared with conventional semiconductor devices. To successfully incorporate spins into existing semiconductor technology, one has to resolve technical issues such as efficient injection, transport, control and manipulation, and detection of spin polarization as well as spin-polarized currents. Recent advances in new materials engineering hold the promise of realizing spintronic devices in the near future. We review the current state of the spin-based devices, efforts in new materials fabrication, issues in spin transport, and optical spin manipulation.
9,917 citations
TL;DR: This work ascribes this giant magnetoresistance of (001)Fe/(001)Cr superlattices prepared by molecularbeam epitaxy to spin-dependent transmission of the conduction electrons between Fe layers through Cr layers.
Abstract: We have studied the magnetoresistance of (001)Fe/(001)Cr superlattices prepared by molecularbeam epitaxy. A huge magnetoresistance is found in superlattices with thin Cr layers: For example, with ${t}_{\mathrm{Cr}}=9$ \AA{}, at $T=4.2$ K, the resistivity is lowered by almost a factor of 2 in a magnetic field of 2 T. We ascribe this giant magnetoresistance to spin-dependent transmission of the conduction electrons between Fe layers through Cr layers.
7,993 citations
TL;DR: Miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins are developed to facilitate subsequent studies of protein function.
Abstract: Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules
2,940 citations
"Quantification of protein interacti..." refers methods in this paper
...n = nmax 1 − e−kon(C0−nmaxA/V)t 1 − nmaxA C0V e−kon(C0−nmaxA/V)t ⎡ ⎢⎢⎣ ⎤ ⎥⎥⎦ (2)...
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...Dotted lines are predictions using the analytical model in equation (2) and solid lines are experimental data....
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...Dotted lines are predictions using the analytical model in equation (2); solid lines are experimental data obtained for surface loading amounts varying from 5 amol (nmax) to 20 zmol (nmax/256) in serial dilutions of 2×....
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...The GMR sensor used in our experiment has a bottom spin valve structure of the type Si/Ta(5)/seed layer/IrMn(8)/CoFe(2)/Ru/ (0....
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TL;DR: Highly sensitive, label-free, multiplexed electrical detection of cancer markers using silicon-nanowire field-effect devices in which distinct nanowires and surface receptors are incorporated into arrays opens up substantial possibilities for diagnosis and treatment of cancer and other complex diseases.
Abstract: We describe highly sensitive, label-free, multiplexed electrical detection of cancer markers using silicon-nanowire field-effect devices in which distinct nanowires and surface receptors are incorporated into arrays. Protein markers were routinely detected at femtomolar concentrations with high selectivity, and simultaneous incorporation of control nanowires enabled discrimination against false positives. Nanowire arrays allowed highly selective and sensitive multiplexed detection of prostate specific antigen (PSA), PSA-a1-antichymotrypsin, carcinoembryonic antigen and mucin-1, including detection to at least 0.9 pg/ml in undiluted serum samples. In addition, nucleic acid receptors enabled real-time assays of the binding, activity and small-molecule inhibition of telomerase using unamplified extracts from as few as ten tumor cells. The capability for multiplexed real-time monitoring of protein markers and telomerase activity with high sensitivity and selectivity in clinically relevant samples opens up substantial possibilities for diagnosis and treatment of cancer and other complex diseases.
2,396 citations
"Quantification of protein interacti..." refers background in this paper
...5)/Ta(3), where all numbers in parentheses are in nanometres....
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