Nanomechanics of the Formation of DNA Self-Assembled Monolayers and Hybridization on Microcantilevers

Álvarez, Mar; Carrascosa, Laura G.; Moreno, Miguel; Calle, A.; Zaballos, Ángel; Lechuga, Laura M.; Martı́nez-A, Carlos; Tamayo, Javier

doi:10.1021/la0489559

Cited by 102 publications

(92 citation statements)

References 22 publications

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“…Early reports on experiments gave high immobilization densities in the range of 0.13-0.17 chains/nm 2 ; 12,27 the displacement predictions corresponding to these densities are compared to reported experimental measurements 5,6,11,12,23 in Table II. In order to simplify comparison across different experiments, the predicted and measured displacements in the table are multiplied with the square of the aspect ratio h l À Á 2 of the cantilever used in the experiment.…”

Section: Comparison Of Numerical Prediction With Experimental Rementioning

confidence: 87%

“…They predicted possibilities of adsorbate detection of the order of picograms and immediately followed up with another study, in which they detected mercury adsorption on cantilever from mercury vapor in air with picogram resolution. 1,2 Since these initial reports, microcantilever-based sensors have been investigated for sensing of chemicals, 3,4 DNA hybridization, [5][6][7][8][9][10][11][12] explosives, [13][14][15] biomolecules, [16][17][18][19] and markers for cancer. [20][21][22] DNA hybridization is a simple and prominent example of biomolecular recognition and detection, since it is fundamental to most biological processes.…”

Section: Introductionmentioning

confidence: 99%

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Cantilever deflection associated with hybridization of monomolecular DNA film

Zhao

Ganapathysubramanian

Shrotriya

2012

Journal of Applied Physics

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Recent experiments show that specific binding between a ligand and surface immobilized receptor, such as hybridization of single stranded DNA immobilized on a microcantilever surface, leads to cantilever deflection. The binding-induced deflection may be used as a method for detection of biomolecules, such as pathogens and biohazards. Mechanical deformation induced due to hybridization of surface-immobilized DNA strands is a commonly used system to demonstrate the efficacy of microcantilever sensors. To understand the mechanism underlying the cantilever deflections, a theoretical model that incorporates the influence of ligand/receptor complex surface distribution and empirical interchain potential is developed to predict the binding-induced deflections. The cantilever bending induced due to hybridization of DNA strands is predicted for different receptor immobilization densities, hybridization efficiencies, and spatial arrangements. Predicted deflections are compared with experimental reports to validate the modeling assumptions and identify the influence of various components on mechanical deformation. Comparison of numerical predictions and experimental results suggest that, at high immobilization densities, hybridization-induced mechanical deformation is determined, primarily by immobilization density and hybridization efficiency, whereas, at lower immobilization densities, spatial arrangement of hybridized chains need to be considered in determining the cantilever deflection. Recent experiments show that specific binding between a ligand and surface immobilized receptor, such as hybridization of single stranded DNA immobilized on a microcantilever surface, leads to cantilever deflection. The binding-induced deflection may be used as a method for detection of biomolecules, such as pathogens and biohazards. Mechanical deformation induced due to hybridization of surface-immobilized DNA strands is a commonly used system to demonstrate the efficacy of microcantilever sensors. To understand the mechanism underlying the cantilever deflections, a theoretical model that incorporates the influence of ligand/receptor complex surface distribution and empirical interchain potential is developed to predict the binding-induced deflections. The cantilever bending induced due to hybridization of DNA strands is predicted for different receptor immobilization densities, hybridization efficiencies, and spatial arrangements. Predicted deflections are compared with experimental reports to validate the modeling assumptions and identify the influence of various components on mechanical deformation. Comparison of numerical predictions and experimental results suggest that, at high immobilization densities, hybridization-induced mechanical deformation is determined, primarily by immobilization density and hybridization efficiency, whereas, at lower immobilization densities, spatial arrangement of hybridized chains need to be considered in determining the cantilever deflection. V C 2012 American Institute of Physics. [http://dx

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Section: Comparison Of Numerical Prediction With Experimental Rementioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Cantilever deflection associated with hybridization of monomolecular DNA film

Zhao

Ganapathysubramanian

Shrotriya

2012

Journal of Applied Physics

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“…13 The second application is relevant for chemical and biological sensings, in which selective binding of a substance on a previously sensitized cantilever side produces a cantilever bending due to the differential surface stress between opposite cantilever sides. [14][15][16][17][18] In both applications, cantilevers with high lengthto-thickness ratio are used due to the low spring constant. The ultimate sensitivity is determined by the thermomechanical noise that manifests as the Brownian motion of the cantilever.…”

Section: Introductionmentioning

confidence: 99%

Dimension dependence of the thermomechanical noise of microcantilevers

Álvarez¹,

Tamayo²,

Plaza

et al. 2006

Journal of Applied Physics

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Thermomechanical noise determines the lowest detection limits of microcantilever-based devices for measuring forces and surface stress variations. In this work, arrays of 334-nm-thick single-crystalline silicon microcantilevers with dissimilar lengths and widths from 50 to 500 m and 20 to 200 m, respectively, have been fabricated to calculate the minimal detectable force and surface stress on the basis of the measurement of the spring constant, resonance frequency, and quality factor. The calculated minimal detectable force and surface stress are of the orders of 10 −15 N Hz −1/2 and 10 −7 N m −1 Hz −1/2 , respectively, and both follow a nonintuitive dependence on the dimensions. The minimal detectable force decreases as the cantilevers are shorter and narrower, whereas the minimal detectable surface stress decreases by making the cantilevers shorter and wider. Theoretical expressions of the minimal detectable force and surface stress are provided as a function of the material properties, cantilever dimensions, and quality factor, which allow us to interpret the results. Both force and surface stress noises follow the same dependence on the quality factor and material properties, however, exhibit striking differences in the dimension dependences. The force and surface stress noises enhance with the quality factor. If the quality factor is kept constant, the force noise enhances as the cantilever is longer and wider, whereas the surface stress noise enhances by making the cantilever shorter and wider. The observed increase of the force noise with the length is attributed to the strong decrease of the quality factor. The results imply that the design of cantilevers for surface stress measurements in general should be different than for atomic force microscopy probes.

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“…Artifacts complicate protocols 7 and extend processing time. We use an array of nanomechanical microcantilevers for surface stress sensing based on atomic force microscopy 8 to analyze DNA/DNA hybridization [9][10][11][12] . The technique was further adapted to reveal antigen/antibody 13,14 , transcription factor/DNA interactions 15 and effects of antibiotics on bacteria 16 .…”

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confidence: 99%

Fast Diagnostics of BRAF Mutations in Biopsies from Malignant Melanoma

et al. 2016

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According to the American skin cancer foundation, there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate, lung and colon each year and malignant melanoma represents its deadliest form. About 50% of all cases are characterized by a particular mutation BRAF V600E in the BRAF-gene. Recently developed highly specific drugs are able to fight BRAF V600E mutated tumors, but require diagnostic tools for fast and reliable mutation detection to warrant treatment efficiency. We completed a preliminary clinical trial applying cantilever array sensors to demonstrate identification of a BRAF V600E single-point mutation using total RNA obtained from biopsies of metastatic melanoma of diverse 2 sources (surgical material either frozen or fixated with formalin and embedded in paraffin). The method is faster than the standard Sanger or pyrosequencing methods and comparably sensitive as next-generation sequencing. Processing time from biopsy to diagnosis is below one day and does not require PCR-amplification, sequencing and labels.Cancer is the number one cause of death worldwide surpassing cardiovascular disease or all strokes 1 . The most common malignancy in humans is skin cancer 2 . The occurrence of cutaneous malignant melanoma has steadily increased over the past 50 years in fair-skinned populations and still grows in many developed countries as a result of changing sun-seeking behavior. Only up to 5% of all skin cancers are malignant melanomas, but are responsible for almost all fatalities. However, recently novel treatment methods have been developed. They are based on compounds with high specificity that have initiated stratified healthcare therapies by targeting particular driver mutations in various genes, e.g. BRAF inhibitors like vemurafenib for patients with BRAF V600E mutated tumors 3,4 . In combination with new mitogen-activated protein kinase kinase (MAP2K, MEK, MAPKK) inhibitors such as cobimetinib 5 life expectancy can be extended to about one year 6 with fewer side effects than the standard chemotherapeutic drug dacarbazine. The current gold standard for mutation screening in malignant tumors uses realtime polymerase chain reaction (PCR) and sequencing methods for DNA extracted from biopsies. Our method neither needs PCR, nor labelling, nor sequencing. PCR protocols can be error-prone with false positives as a particular hazard. Artifacts complicate protocols 7 and extend processing time. We use an array of nanomechanical microcantilevers for surface stress sensing based on atomic force microscopy 8 to analyze DNA/DNA hybridization 9-12 . The technique was further adapted to reveal antigen/antibody 13,14 , transcription factor/DNA interactions 15 and effects of antibiotics on bacteria 16 . The platform also proved applicability to study transcriptional 3 activity of genes 17,18 and is able to characterize function of transmembrane protein activity 19 .Here, we report on the detection of the BRAF V600E mutation present in a subset of 50-60% malignant me...

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Nanomechanics of the Formation of DNA Self-Assembled Monolayers and Hybridization on Microcantilevers

Cited by 102 publications

References 22 publications

Cantilever deflection associated with hybridization of monomolecular DNA film

Cantilever deflection associated with hybridization of monomolecular DNA film

Dimension dependence of the thermomechanical noise of microcantilevers

Fast Diagnostics of BRAF Mutations in Biopsies from Malignant Melanoma

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