Challenges for nanomechanical sensors in biological detection

Calleja, Montserrat; Kosaka, Priscila M.; Paulo, Álvaro San; Tamayo, Javier

doi:10.1039/c2nr31102j

Cited by 97 publications

(78 citation statements)

References 117 publications

(218 reference statements)

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“…However, their application to clinical diagnosis will also demand for a method capable of providing hundreds of measurements in a short time, as well as manageable preparation steps for the microcantilever sensors that can still provide reproducible mechanical patterns. 9,10 All the above reasons highlight the need to pursue in depth understanding of the hybridization process and of the conformations of the DNA layers.…”

Section: Introductionmentioning

confidence: 99%

“…25,26 Alternatively, the gold layer needs to comply with very restrictive conditions regarding surface roughness 13 and surface electrostatics, 16 while long incubation times are also applied, 24 which bans the use of technologies for high multiplexing, such as ink-jet low volume dispensing. 3,10 In this work we study the effect of relative humidity (RH) changes in ssDNA and dsDNA SAMs on gold. Non-ideal DNA SAMs, as those obtained by ink-jet deposition and resulting in a coiled/lying down conformation of the DNA strands are used here.…”

Section: Introductionmentioning

confidence: 99%

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Hydration Induced Stress on DNA Monolayers Grafted on Microcantilevers

et al. 2014

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Surface tethered single-stranded DNA films are relevant biorecognition layers for oligonucleotide sequence identification. Also, hydration induced effects on these films have proven useful for the nanomechanical detection of DNA hybridization. Here, we apply nanomechanical sensors and atomic force microscopy to characterize in air and upon varying relative humidity conditions the swelling and deswelling of grafted single stranded and double stranded DNA films. The combination of these techniques validates a two-step hybridization process, where complementary strands first bind to the surface tethered single stranded DNA probes and then slowly proceed to a fully zipped configuration. Our results also demonstrate that, despite the slow hybridization kinetics observed for grafted DNA onto microcantilever surfaces, ex-situ sequence identification does not require hybridization times typically longer than 1 hour, while quantification is a major challenge.. 2

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hydration Induced Stress on DNA Monolayers Grafted on Microcantilevers

et al. 2014

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“…At the ultimate sensitivity limit of inertial mass sensing facilitating such resonating devices [14], recent experiments using NEMS resonators have successfully achieved the power to resolve single molecules [3], atoms [4], and even individual protons in real time [15]. Yet, in realistic sensing scenarios nanoscale mechanical elements are still fragile in the out-of-lab tests [16], and microscale devices are widely dominant for durably functioning mechanical sensors in applications.…”

Section: Introductionmentioning

confidence: 99%

“…Typically, NEMS and MEMS resonators (operating in dynamic rather than static mode, in the high-frequency acoustic regime [7]) are driven through closed-gap configuration, and sensing in the gas or liquid phase is limited to clean surface preparation procedures, set by limitations related to stiction, viscous drag, and squeezed-film damping [7,[10][11][12]16]. Durable operation under harsh environmental conditions is an important ongoing goal for realistic integrated MEMS/NEMS sensors.…”

Section: Introductionmentioning

confidence: 99%

Liquid Mass Sensing Using Resonating Microplates under Harsh Drop and Spray Conditions

Mahajne

Guetta

Lulinsky

et al. 2014

Physics Research International

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We have performed in situ real time mass sensing of deposited liquid volatile droplets and sprays using plate-like microstructures, with robust and reusable performance attained over harsh conditions and multiple cycles of operation. A home-built electrooptical sensing system in ambient conditions has been used. The bimorph effect on the resonant frequency of altered mass loading, elasticity, and strain had been carefully compared, and the latter were found to be negligible in the presence of nonviscous liquids deposited on top of our microplate devices. In resonant mode, the loaded mass has been estimated from measured resonant frequency shifts and interpreted from a simple, uniformly deposited film model. A minimum submicrogram detectable mass was estimated, suggesting the system's potential for robust, fast, and reusable sensing capabilities, in the presence of volatile liquids under harsh operation conditions.

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“…In this work, we examine the capability of micro-and nanocantilever biosensors in the static mode [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] for end point label-free immunoassays. In these devices, molecular recognition between the analyte and the receptor monolayer anchored on one side of a tiny cantilever induces a nanoscale bending as a consequence of the surface stress variation on the functionalized surface 32 .…”

Section: Introductionmentioning

confidence: 99%

Tackling reproducibility in microcantilever biosensors: a statistical approach for sensitive and specific end-point detection of immunoreactions

Kosaka¹,

Tamayo²,

Ruz³

et al. 2013

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aIn the biomedical field, end-point detection bioassays such as enzyme-linked immunosorbent assays (ELISAs) are essential tools because of their simplicity, high-throughput, and suitability for their use at the point-of-care. End-point bioassays are significantly constrained by the need of sample labeling with fluorescent or colorimetric tags for subsequent detection. A promising strategy to overcome these limitations is to harness recent advances in label-free biological nanosensors. Here we analyse the potential of nanomechanical biosensors based on surface stress for the label-free end-point detection of horseradish peroxidase. We address the variability of the sensor responsethrough the analysis of 1012 cantilevers with different antibody surface densities, two blocking strategies based on polyethylene-glycol (PEG) and bovine serum albumin (BSA) and stringent controls. The study reveals that the performance of the assay critically depends on both antibody surface density and blocking strategies. We find that the optimal conditions involve antibody surface densities near but below saturation and blocking with PEG. We find that the surface stress induced by the antibody-antigen binding is significantly correlated to the surface stress generated during the antibody attachment and blocking steps. The statistical correlation is harnessed to identify immobilization failure or success, and thus enhancing the specificity and sensitivity of the assay. This procedure enables achieving a rate of true positives and true negatives of 90% and 91% respectively. The detection limit is of 10 ng/mL (250 pM) that is similar to detection limit obtained in our ELISA

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Challenges for nanomechanical sensors in biological detection

Cited by 97 publications

References 117 publications

Hydration Induced Stress on DNA Monolayers Grafted on Microcantilevers

Hydration Induced Stress on DNA Monolayers Grafted on Microcantilevers

Liquid Mass Sensing Using Resonating Microplates under Harsh Drop and Spray Conditions

Tackling reproducibility in microcantilever biosensors: a statistical approach for sensitive and specific end-point detection of immunoreactions

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