Theory of “Selectivity” of label-free nanobiosensors: A geometro-physical perspective

Nair, Pradeep R.; Alam, Muhammad Ashraful

doi:10.1063/1.3310531

Cited by 52 publications

(38 citation statements)

References 23 publications

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“…Nair and Alam have modelled physisorption onto unpassivated regions of devices, assuming the rate constants between non-specific and specific binding differ by a factor of 10 9 . Even though this ratio is somewhat arbitrary, their conclusions underscore the importance of dense biofunctionalization surface coverage to achieving high selec-tivity 68 . Their model indicates that target discrimination remains possible with high coverage of specific receptors (∼2 × 10 12 cm −2 ), even when other species that we are not interested in are 10 9 times more abundant in solution.…”

Section: Sensitivity Versus Other Performance Metricsmentioning

confidence: 99%

Comparative advantages of mechanical biosensors

2011

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Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte–sensor interactions on the nanoscale and of stochastic processes in the sensing environment.

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Section: Sensitivity Versus Other Performance Metricsmentioning

confidence: 99%

Comparative advantages of mechanical biosensors

2011

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“…For now, we ignore the details of the spatial distribution of molecules associated with random sequential adsorption (31) and assume a uniform distribution of adsorbed molecules on the sensor surface. Therefore, the conservation of volume suggests ΔH ¼ N s A t H t , where N s is the area density, A t is the effective cross-sectional area, and H t is the effective thickness of the target molecule.…”

mentioning

confidence: 99%

Flexure-FET biosensor to break the fundamental sensitivity limits of nanobiosensors using nonlinear electromechanical coupling

Jain

Nair

Alam

2012

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

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In this article, we propose a Flexure-FET (flexure sensitive field effect transistor) ultrasensitive biosensor that utilizes the nonlinear electromechanical coupling to overcome the fundamental sensitivity limits of classical electrical or mechanical nanoscale biosensors. The stiffness of the suspended gate of Flexure-FET changes with the capture of the target biomolecules, and the corresponding change in the gate shape or deflection is reflected in the drain current of FET. The Flexure-FET is configured to operate such that the gate is biased near pull-in instability, and the FET-channel is biased in the subthreshold regime. In this coupled nonlinear operating mode, the sensitivity (S) of Flexure-FET with respect to the captured molecule density (N s ) is shown to be exponentially higher than that of any other electrical or mechanical biosensor.In other words, while S Flexure ∼ e ðγ 1 ffiffiffiffi N s p −γ 2 N s Þ , classical electrical or mechanical biosensors are limited to S classical ∼ γ 3 N S or γ 4 lnðN S Þ, where γ i are sensor-specific constants. In addition, the proposed sensor can detect both charged and charge-neutral biomolecules, without requiring a reference electrode or any sophisticated instrumentation, making it a potential candidate for various low-cost, point-of-care applications.label-free detection | genome sequencing | cantilever | spring-softening | critical-point sensors N anoscale biosensors are widely regarded as a potential candidate for ultrasensitive, label-free detection of biochemical molecules. Among the various technologies, significant research have focused on developing ultrasensitive nanoscale electrical (1) and mechanical (2) biosensors. Despite remarkable progress over the last decade, these technologies have fundamental challenges that limit opportunities for further improvement in their sensitivity ( Fig. 1A) (3-6). For example, the sensitivity of electrical nanobiosensors such as Si-Nanowire (NW) FET (field effect transistor) (Fig. 1B) is severely suppressed by the electrostatic screening due to the presence of other ions/charged biomolecules in the solution (7), which limits its sensitivity to vary linearly (in subthreshold regime) (3, 7) or logarithmically (in accumulation regime) (4,7,8,9) with respect to the captured molecule density N s . Moreover, the miniaturization and stability of the reference electrode have been a persistent problem, especially for lab-onchip applications (1). Finally, it is difficult to detect charge-neutral biological entities such as viruses or proteins using chargebased electrical nanobiosensor schemes.In contrast, nanomechanical biosensors like nanocantilevers (10, 11) (Fig. 1C) do not require biomolecules to be charged for detection. Here, the capture of target molecules on the cantilever surface modulates its mass, stiffness, and/or surface stress (5,11,12). This change in the mechanical properties of the cantilever can then be observed as a change in its resonance frequency (dynamic mode), mechanical deflection, or change in the resist...

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“…Finally, the problem of selectivity can be understood within the framework of random sequential absorption of capture molecules [69]. Since the theoretical maximum of RSA surface coverage is 54%, one can show that long incubation time and surface passivation by molecules (e.g., PEG) much smaller than the target molecule is the only viable approach to high selectivity.…”

Section: Contact Person: Muhammad Alam Purdue Universitymentioning

confidence: 99%

Investigative Tools: Theory, Modeling, and Simulation

Lundstrom

Cummings

Alam

2011

Nanotechnology Research Directions for Societal Needs in 2020

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As subsequent chapters in this report will describe, theory, modeling, and simulation (TM&S) play a significant role in almost every branch of nanotechnology. TM&S consists of three distinct components. A theory can be defined as a set of scientific principles that explains phenomena-a succinct description of a class of problems. Modeling is the analytical/numerical applications of theory to solve specific problems.Simulation aims to faithfully render the physical problem in the greatest possible detail, so that the critical features emerge organically-not as a consequence of the ingenuity, insights, high level abstractions, and simplifications that characterize modeling. Each of the three TM&S components plays an important role, but the opportunities of the next decade will require a stronger emphasis on the modeling component. Multiscale modeling, in particular, will be essential in addressing the next decade's challenges in technology exploration and nanomanufacturing. Finally, it should be understood that each subdiscipline of nanotechnology has its own TM&S community; these communities share many commonalities in underlying theoretical foundations, numerical and computational methods, and modeling approaches. This chapter focuses on issues, challenges, and opportunities common to TM&S across the broad spectrum of nanotechnology.

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Theory of “Selectivity” of label-free nanobiosensors: A geometro-physical perspective

Cited by 52 publications

References 23 publications

Comparative advantages of mechanical biosensors

Comparative advantages of mechanical biosensors

Flexure-FET biosensor to break the fundamental sensitivity limits of nanobiosensors using nonlinear electromechanical coupling

Investigative Tools: Theory, Modeling, and Simulation

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