Multiphysics Modeling and Simulation of Nanoscale ...

Vol2 | Issue 1 | Spring Edition | DOI : February 2014 | Pp 15-18 | ISSN 2279 – 0381

Multiphysics Modeling and Simulation of Nanoscale Cantilever Array Sensor for the Detection of HIV Antigens Sowmya Selvaraj *a, Steffie Manoa, PonJanani Sugumaran a, Jaisree Meenaa Pria Jayaraman Meenakshi Sundaram Nachiappan a a

a

Department of Biomedical Engineering, PSG College of Technology, Coimbatore, Tamilnadu, India * e-mail id: [email protected]

receptors to the antigens. When target molecules (antigens) are introduced on the surface of the cantilever, the cantilever bends due to the change in the surface stress which is caused by the change in mass. (Fig 1).

Keywords: Cantilever, Antigen, Antibody, Acquired Immuno Deficiency Syndrome, Human Immunodeficiency Virus, COMSOL Multiphysics. Abstract: Acquired Immuno Deficiency Syndrome (AIDS) is a major immune disease that weakens the ability of the human defense system to protect against infections and certain types of cancer. The causative organism for the disease, Human Immuno Deficiency Virus (HIV) has targeted the global public claiming the lives of about 25 million over the past three decades. This demonstrates the need for an early and accurate detection of HIV. The HIV viral core made of p24 protein, when detected by conventional antigen test could measure only above 10 pg/ml after 10 to 14 days of infection. Eliminating this inefficacy, cantilevers stand out as an alternate platform to detect the virus in a shorter time. The influence of the cantilever dimensions on its sensitivity enables quicker detectability of the virus. Hence, in this paper we propose to design a nanoscale cantilever array sensor for p24 detection using COMSOL Multiphysics 4.3b®. The optimization of the cantilever structure with different materials is also performed. The modeled cantilever will thus be highly sensitive to HIV in comparison to the laboratory p24 antigen test method and detect less than femto gram/ml level of antigen.

Fig 1. Schematic showing the principle of a cantilever sensor The difference in surface stress due to molecular adsorption is given by,

.

(1) [7]

Where Δg = Change in surface stress (N/m) Δh = Cantilever deflection (m) E = Young’s modulus (Pa) v = Poisson’s ratio t = Thickness of the cantilever (m) L = Length of the cantilever (m)

Introduction Micromechanical cantilevers are one of the most promising biosensors. Cantilever-based sensing is basedon a significant deflection of the cantilever beam due to induced surface stress[1], [2], added mass [3, 4] or the transfer of heat [5, 6].

The deflection of the cantilever varies with its length, width, thickness and various other properties of the material used to make the structure. The geometric shape as well as the material used to build the cantilever determines the cantilever's stiffness.Sensitivity of the cantilever is best explained in terms of the spring constant as given by the following equation.

Cantilever array sensors consist of an array of cantilevers of specific shape and dimension. The antibodies specific to the antigen of interest are immobilized over the surface of the cantilever. These probe molecules restricted to only one side of the cantilever act as specific

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Journal of NanoScience and NanoTechnology | Vol 2 | Issue 1 | Spring Edition| ISSN 2279 – 0381

. (2) [8] where, k = Spring constant (N/m) w = Width of the cantilever (m) HIV antibody tests are the most appropriate for identifying infection, but alternate technologies can contribute to an accurate diagnosis and can be used to effectively predict disease outcome. Tests to detect p24 antigen can be used to identify virus or viral components in blood. This method is highly specific and a positive result confirms infection. p24 is a 24 kDa protein that makes up the HIV viral core or capsule. The p24 antigen test measures p24 concentration in blood that is detectable in newly infected individuals in a short period. It occurs early after infection due to the initial burst of viral replication. p24 antigen specifically binds to monoclonal antibody which is 29kDa by mass. This present work demostrates the finite element method to obtain the optimalperformance of the cantilver array sensor for p24 antigen based HIV detection by optimizing the materials and the geometricaldimension of cantilever. COMSOL Multiphysics 4.3b®, a commercial finite element analysis tool for MEMS was used to develop cantilever based array sensors. Experimental design A cantilever array consisting of four beams was constructed with fixed dimensions of length 150 μm, width 10 μm and thickness 1000 nm.The surface of each cantilever is assumed to be functionalized with 10 molecules of p24 antibody. A pressure (3.146167743*10-12 Pa) equivalent to a weight of 10 molecules of p24 antibody was given as input and the deflection was observed. Again, a total pressure(5.749892771*10-12 Pa) equivalent to the weight of 10 molecules of antigen and 10 molecules of antibody was applied. It is assumed that antigens interact with all the antibodies of the cantilever. Therefore the displacement will be equal to the deflection caused by the pressure equivalent of 10 antigens and 10 antibodies. Fig 2 shows the structure of the MEMS cantilever array sensor designed using COMSOL multiphysics 4.3 b®.

Fig 2. Structure of the MEMS cantilever array sensor The performance of the sensor was checked for maximum deflection by varying the structural material of the cantilever array (SiO2, SiC, Si3N4, Si). Properties of the above materials are given in the table 1. Table 1. Properties of structural materials in the cantilever

Name of the material SiC Si3N4 SiO2 Si

Young’s modulus (GPa)

Density (kg/m3)

Poisson’s ratio

748

3216

0.45

250

3100

0.23

70

2200

0.17

150

2330

0.17

Also, the highest displacement obtained for the SiO2 cantilever array is further tested by varying its dimensions. Results and Discussion In order to identify the best material which exhibits maximum sensitivity, four different materials were considered having fixed dimensions of length 150 μm, width 10 μm and thickness 1000 nm. The details of different materials and their corresponding displacement are given in Table 2

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Table 2. Displacement exhibited by the different structural materials in cantilever (L =150 μm) Materi al SiC Si3N4 SiO2 Si

Displacement Antibody Antigen and binding antibody binding (10-14 μm) (10-14 μm) 0.30967 0.56596 0.94911 1.7346 3.3997 6.2133 1.3912 2.5426

On increasing the length of the cantilever beam, an increase in displacement was observed. A highest displacement value of 1.4742 * 10-19 m was obtained for a cantilever length of 200 μm. Fig 5 gives the displacement of SiO2 cantilever of length 200 μm, width 10μm, thickness 1000 nm on binding of antigen to the antibodies.

From the above table it is evident that SiO2 is the most promising structural material as it exhibited maximum displacement. Fig 3 shows the displacement of the SiO2 cantilever array sensor on immoblisation of 10 molecules of antibodies.

Fig 3. Displacement of the SiO2 cantilever array on immobilisation of antibodies. Fig 4 represents the displacement of the SiO2 cantilever array sensor obtained due to binding of 10 molecules of antigen to 10 molecules of antibody.

Fig 5.Displacement of the SiO2 cantilever array of increased length on binding of antigen to antibody. Since SiO2 has the lowest Young’s Modulus of 70GPa among the four materials, the antigenantibody binding led to a maximum displacement. Similarly when the length L of the cantilever beam is increased, the spring constant k decreases and the SiO2 cantilever beam shows increased deflection. The results are in accordance with equations 1 and 2 Conclusion The designed nanocantilever array sensor has high sensitivity of nearly 109 times greater than the conventional laboratory p24 antigen test. Further SiO2 exhibits best displacement among the four materials. It was also found that the sensitivity is directly proportional to the length of the cantilever. References [1] Gimzewski J K, Gerber Ch, Meyer E and Schlittler R R, Observation of the chemical reaction using a nanomechanical sensor, Chem. Phys. Lett. 217 (1994) 589–94. [2] Berger R, Delamarche E, Lang H P, Gerber Ch, Gimzewski J K, Meyer E and Guntherodt H-J, Surface Stress in the Self-Assembly ofAlkanethiols on Gold, Science 276 (1997)2021– 4. [3] Ilic B, Craighead H G, Krylov S, SenaratneW, Ober C and Neuzil P, Attogram detection using nanoelectromechanical oscillators, J. Appl. Phys. 95 (2004) 3694–703. [4] Nugaeva N, Gfeller K Y, Backmann N, Lang H P, Duggelin M and Hegner M, Micromechanical cantilever array sensors for selective fungal immobilization and fast growth detection, Biosens. Bioelectron. 21 (2005)849–56.

Fig 4.Displacement of the SiO2 cantilever array sensor on binding of the antigen to the antibody.

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[5] Barnes J R, Stephenson R J, Welland M E, Gerber Ch and Gimzewski J K, Photothermal spectroscopy with femtojoule sensitivity using a micromechanical device, Nature 372 (1994) 79– 81. [6] Manalis S R, Minne S C, Quate C F, Yaralioglu G G and Atalar A, Two-dimensional micromechanical bimorph arrays for detection of thermal radiation,Appl. Phys. Lett. 70 (1997) 3311–3. [7] Ram Datar, Cantilever Sensors: NanomechanicalTools for Diagnostics, MRS Bulletin, 34, (2009). [8] SuryanshArora, Sumati, ArtiArora, P.J.George, Design Of Mems Based Microcantilever Using ComsolMultiphysics, International Journal of Applied Engineering Research, 17 (2012).

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