Simulation of perforated rectangular cantilever immunosensor for estimation of bacterial pathogens

doi:10.4236/health.2010.211184

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Vol.2, No.11, 1239-1248 (2010)

doi:10.4236/health.2010.211184

Health

Openly accessible at

Simulation of perforated rectangular cantilever

immunosensor for estimation of bacterial pathogens

J. Sakthi Swarrup1, K. Govardhan2, V. Velmurugan1

1Center for Nanotechnology Research, School of Electronics Engineering, VIT University, Vellore-632 014, Tamil Nadu, India

Received 13 February 2010; revised 22 February 2010; accepted 1 March 2010.

ABSTRACT gens are essential for the potential treatment of the dis-

eases. However, it is difficult to treat for gram negative

and positive bacteria due to inherent and acquired resis-

tance to antimicrobial agents. Endospore-forming gram-

positive bacteria produce a unique resting cell called an

endospore. Bacillus Anthrax spore formers cause anthrax

in domestic animals, which may be transmitted to hu-

mans. Pseudomonas aeruginosa pathogen is generated

from gram-negative bacteria. It is the quintessential op-

portunistic pathogen of humans. It is a leading cause of

hospital-acquired infections (nosocomial infections). It is

difficult to eradicate due to its resistance to most antimi-

crobial agents. There is probably no tissue that cannot

become infected by Pseudomonas if the host defenses

are weakened. It is usually involved in soft tissue infec-

tions, urinary tract infections and pneumonia. The best

known and most widely studied species is Coryne Bac-

terium Diptheria, gram-positive bacteria, the causal agent

of Diptheria. The genus corynebacterium consists of a

diverse group of bacteria including animal and plant

pathogens, as well as saprophytes. Some coryne bacteria

are part of the normal flora of humans, finding a suitable

niche in virtually every anatomic site. One of the major

pathogens of humans from spirochetes a phylogenetically

distinct group of bacteria, is Treponema pallidum, the

agent of syphilis, a sexually transmitted disease.

Micro fabricated and multilayered perforated can-

tilever beam immunosensor was modeled using

CoventorWare for the estimation of bacterial an-

tigens of Bacillus Anthrax, Pseudomonas aeru-

ginosa, Coryne Bacterium Diptheria and Tre-

ponema pallidum. A rectangular cantilever beam

with perforations was simulated with dimensions

as length-200 µm, width-10 µm and thickness-0.5

µm. Each perforation is rectangular with length-

10 µm, width-5 µm and thickness-0.5 µm. The

theoretical and FEM simulations were carried out

with five immunoglobulin antibodies, IgA, IgD,

IgE, IgG and IgM for the estimation of bacterial

antigens. The effect of perforation in cantilever

beam and molecular size of antibody and antigen

on the performance of the sensor has been stu-

died. The cantilever beam without perforation

showed a deflection of 1.8 e + 02 µm whereas the

cantilever beam with perforation showed addi-

tional deflection of 1.9 e – 02 µm. With IgG, the

difference between analytical and simulation

values is positive and low especially with low

molecular weight antigens Pseudomonas aeru-

ginosa and Treponema pallidum. The low mo-

lecular weight IgG influences the antigen-anti-

body interaction more favourably. The simulated

perforated rectangular cantilever beam with IgG

antibody is a more promising model for the fab-

rication of a sensor for the estimation of highly

motile Pseudomonas aeruginosa and Treponema

pallidum.

Infectious diseases are generally detected with immu-

nohistochemistry (IHC), flow cytometry, immuno-electron

microscopy, ELISA, western blotting, polymerase chain

reaction (PCR) etc. These systems use an antibody-based

method to detect a specific protein. One of the main

drawbacks with IHC staining is difficulties in over-

coming specific or non-specific background. Optimisation

of fixation methods and times, pretreatment with block-

ing agents, incubating antibodies with high salt, and opti-

mising post-antibody wash buffers and wash times influ-

ence the quality immunostaining. Flow cytometry is less

effective for detecting extremely rare cell populations.

Immuno-electron microscopy can be technically challen-

ging, expensive and require rigorous optimisation. ELISA

test does not identify the amount of antigen present in

Keywords: Modeling; Perforated Rectangular

Cantilever Beam; Immunosensor; Immunoglobulin

Antibodies; Estimation of Bacterial Pathogen Antigen

1. INTRODUCTION

Identification and quantification of bacterial patho-

J. S. Swarrup et al. / Health 2 (2010) 1239-1248

1240

the sample and is expensive and time consuming. West-

ern blot test is technically demanding, expensive, subject

to interpretation, presence or absence of bands, intensity

of those bands. Major disadvantages of the PCR protocol

include length of time needed (2-3 days). PCR tests also

require more sophisticated equipment and greater exper-

tise and hence expensive. Urine and blood tests takes a

long time to analyze. The test should be carried out in

the lab only. Errors may occur due to the carelessness of

the technician.

Openly accessible at

Immunosensors are a type of biosensor, which uses

antibodies or antigen as the biospecific sensing element,

and are based on the ability of an antibody to form com-

plexes with the corresponding antigen. The reaction be-

tween the antibody-antigen reactions is highly selective,

and is analogous to a lock and key fit. The piezoelectric

sensing method is thought to be one of the most sensitive

analytical instruments developed to date, being capable

of detecting antigens in the picogram range. This trans-

duction method is relatively easy to use, cost effective,

and offers direct label-free analysis and overcomes all

the dis-advantages of the existing system. In addition, it

is able to provide the option of several immunoassay

formats for increased sensitivity and specificity.

Development of a simple and multifunctional trans-

ducer to detect two or more species by one cantilever at

one time is a challenge. The cantilever deflection and

output voltage can be influenced by various forces acting

on the probe molecule such as molecular size of the

probe and target molecules, DNA hybridization of probe

molecule [1], nature of grafting of probe molecules on

the surface whether it is ordered or is disordered [2],

grafting density [3] and design and thickness of the can-

tilever beam. Therefore it is relevant to develop simula-

tion methods and design rules that will enable the design

of microcantilever-based biosensing systems. In this pa-

per the effect of molecular size of both antibody and

antigen on the deflection of microcantilever upon ad-

sorption of probe molecules and binding of target mole-

cules has been studied by modeling perforated rectangu-

lar cantilever with immunoglobulin for the detection of

bacterial pathogens of Bacillus Anthrax, Pseudomonas

aeruginosa, Coryne Bacterium Diptheria and Treponema

pallidum.

2. MODELING AND ANALYSIS

2.1. Modeling of Perforated Rectangular

Cantilever Beam

The design of the perforated rectangular cantilever beam

was simulated using commercial CoventorWare-DESIGN-

ER software. The first step involved in the modeling of

the perforated rectangular cantilever beam starts with the

Process Editor, where the properties of the materials for

cantilever beam are applied. The antibodies IgG, IgM,

IgD, IgA and IgE are added to the process editor with

their properties like Young’s modulus, density, weight

etc.

Crystalline silicon (Young modulus 155.8 Gpa, Pois-

son coefficient 0.21 and density 2330 Kg/m3) was used

as the substrate with thickness, 5 µm in the present simu-

lation. Boron phosphor silicate glass (BPSG) material

was deposited for a thickness, 35 µm (selected from the

Materials Database) as a temporary support for the can-

tilever beam using Stack Material option. For construc-

tion of the cantilever beam, certain region in the layer

has been etched in the BPSG using the options Delete

and Straight Cut. Deposition and selective etching of the

silicon material was then carried out using Planar Fill

option and Straight Cut options respectively. A layer of

gold was deposited to give good attachment of the anti-

bodies. Deposition and selective etching of the gold on

the perforated cantilever was then carried out using Pla-

nar Fill option and Straight Cut options respectively. The

sequence of modeling of the cantilever beam using the

Process Editor is given in Figure 1. Once the cantilever

beam was constructed the antibodies were coated in the

beam surface.

To improve the sensitivity of the immunosensor to de-

tect nanogram material, a simple way was to reduce the

size of the beam. The final simulated perforated rec-

tangular cantilever beam sensor has dimensions length-

300 µm, width-100 µm and total thickness-40.5 µm. The

thickness of the cantilever beam is 0.5 µm (Figure 2).

Once the whole structure was built in the 2D the struc-

ture was exported to the MEMMECH analysis, where

the boundaries were fixed and meshing was done. Finite

Element Method was used for the analysis. The model of

the mesh of cantilever beam is given in Figure 2. After

meshing, the pressure was applied at the top surface of

the cantilever equivalent 1 mole (molecular weight in

gram) of antigen for the sensing. The pressure/stress

equivalent 1 mole (molecular weight in gram) of antigen

was calculated using the equation,

-27

-04 2

(Weight ofantigen1.66090210e)

Pressure (kg/cm)



((LB)(e) )

where L is length of the cantilever, and B is width of the

cantilever. The pressure in Kg/cm2 was converted into

pressure in Mpa.

2.2. Detection of Antigens

Four different diseases viz, anthrax, nosocomial infec-

tions, diphtheria and syphilis and the corresponding

bacteria were considered for the present study. In the

present modeling static deflection mode was considered

J. S. Swarrup et al. / Health 2 (2010) 1239-1248

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Figure 1. Sequence of modeling of cantilever using process editor of the coventorware.

3. RESULTS AND DISCUSSION

for the detection. For static deflection, one can apply

Openly accessible at

Stoney’s formula,

6(1)







where R is the can- The antibody and antigen reaction is an important pro-

tective mechanism in human being against invading

foreign substances. The antibody and antigen reaction,

together with phagocytosis, constitute the immune res-

ponse (humoral immune response). Invading foreign

substances are antigens while the antibodies (immuno-

tilever’s radius of curvature, ν is Poisson’s ratio, E is the

substrate’s Young modulus, t is the thickness of the canti-

lever, and Δσ is the differential surface stress. In the pre-

sent modeling, uniaxial and one dimensional approxima-

tion was followed in which Poisson coefficient was not

taken in to account. However, in order to get accurate

results, simulation was carried out with a non zero value

of Poisson coefficient. When analytes bind to only one

side of the cantilever’s surface, the cantilever bends up or

down depending on the side to which the analytes bind.

The deformation of the cantilever, which arises from va-

riations in surface stress (Δσ), is measured from changes

in the resistance of the piezoresistive material. The equi-

valent pressure corresponding to 1 mole of antigen was

applied to the beam and the displacement, voltage and

stress was noted. The deformation induces the current in

the quartz piezo-patch. The output voltage at the upper

surface of the piezo-patch is measured. The deformation

of the beam depends on the applied pressure as well as on

the geometry of the device, molecular size of the anti-

body and antigen-antibody interaction. According to the

deflection of the beam and out put voltage, the intensity

of the disease could be judged.

globulins), are specific proteins generated (or previously

and present in blood, lymph or mucosal secretions) to

react with a specific antigen. Gamma globulins are pro-

duced by B lymphocytes when antigens enter the body.

Immunoglobulins (Ig) have been selected as substrate

antibodies for the construction of cantilever. Immuno-

globulins (Ig) have a basic four-chain monomeric struc-

ture consisting of two identical heavy chains and two

identical light chains with interchain disulfide bonds.

There are five heavy chain classes (M, D, G, E and A),

four G subclasses (G1-4), and two A subclasses (A1,2).

There are two light chain isotypes, K (kappa) and L

(lamda).

The biological characteristics of human immunoglobulins

are given in Table 1. IgA molecules have an average mo-

lecular weight of 250,000 daltons. IgA is found in body

fluids such as tears, saliva, mucosa, and other bodily

secretions. It provides a first line of defense against

invading pathogens and allergens. IgD appears to act in

J. S. Swarrup et al. / Health 2 (2010) 1239-1248

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Openly accessible at

Figure 2. Displacement profile of simulated plain and perforated rectangular cantilever beams under applied pressure.

J. S. Swarrup et al. / Health 2 (2010) 1239-1248

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conjunction with B and T cells to help them in location

of antigens. IgG is the most common type of antibody. It

is the most common immunoglobulin against microbes.

It acts by coating the microbe to hasten its removal by

other immune system cells. It gives lifetime or long-

munoglobulins to recognize an antigen. An antigen has on

its surface a combining site that the immunoglobulin

recognizes from the combining sites on the arms of its

Y-shaped structure. In response to the antigen that has

called it forth, the immunoglobulin wraps its two com-

bining sites like a “lock” around the “key” of the antigen

combining sites. The mode of action of the present im-

munoglobulin varies with different types of antigens. With

its two-armed Y-shaped structure, the immunoglobulin

can interact two antigens at the same time with each arm.

Adsorption of biomolecules on a surface of a microcanti-

lever generates surface stresses that cause the cantilever to

deflect [4-6]. In the present studies, adsorption of various

antigens on the perforated rectangular cantilever influence

displacement, voltage and stress.

standing immunity against infectious diseases. It is highly

mobile, passing out of the blood stream and between

cells, going from organs to the skin where it neutralizes

surface bacteria and other invading microorganisms. IgE

is responsible for allergic reactions. IgE acts by attach-

ing to cells in the skin called mast cells and basophil

cells. In the presence of environmental antigens, IgE

releases histamines from the mast cells. The histamines

cause the nasal inflammation. IgM is the largest among

the immunoglobulins. IgM usually form clusters that are

in the shape of a star. It is effective against larger micro-

organisms. Because of its large size (it combines 5 Y-

shaped units), it remains in the bloodstream where it

provides an early and diffuse protection against invading

antigens. IgG is produced by the plasma cells. IgD and

IgE are susceptible to denaturation by the treatment with

heat and reducing agents under conditions that have little

effect on other immunoglobulins.

To improve the sensor performance and to enhance

the signal transduction to detect nanogram level antigen,

a novel sensor platform with perforated rectangular can-

tilever beam was modeled. By modeling and simulation,

the high surface stress region on the cantilever was iden-

tified. Optimization of cantilever width, thickness and

perforation was carried out with the software packages.

Specific perforated cantilever designs were targeted to

optimize stress localization at the base of the cantilever.

The cantilever beam without perforation showed a de-

flection of 1.8e + 02µm whereas the cantilever beam with

perforation showed additional deflection of 1.9e – 02µm

(Figure 2). Therefore the cantilever beam with perfora-

tion was modeled. The layout of perforated can- tilever

beam is given in Figure 3.

The present selected bacteria, Bacillus Anthrax (1),

Pseudomonas aeruginosa (2), Coryne Bacterium Dipthe-

ria (3), and Treponema pallidum (4), have different mo-

lecular weight and physical characteristics (Table 2). All

immunoglobulins are in a Y-shape with differences in the

upper branch of the Y. These structural differences of in

each of the immunoglobulins enable the individual im-

Openly accessible at

Table 1. Biological characteristic of human immunoglobulins.

Antigen species Shape Gram staining Motility Intra/Extracellular Molecular

Weight (Dalton)

Bacillus Anthrax

Toxin (1) Rods Gram-positive Nonmotile Extracellular 86,000

Pseudomonas

Aeruginosa (2) Rods Gram-negative Motile Extracellular 33,000

Coryne Bacterium

Diptheria (3)

Small, slender,

pleomorphic rods

Gram-positive

(unevenly) Nonmotile Extracellular 60,000

Treponema

Pallidum (4)

Long, slender, flexible,

spiral- or corkscrew-

shaped rods

Gram-negative,

but stains poorly Highly motileExtracellular 34,000

Table 2. Characteristics of antigen species.

Characteristics IgA IgD IgE IgG IgM

Molecular weight (Dalton) 250000

(150000-350000) 180000 190000 150000 900000

Carbohydrate (Approx %) 7 12 12 3 12

Sedimentation coefficient (S20,w) 7 (9-15) 7 8 7 19

Biological survival (plasma T ½ days) 6 3 2 3 5

Serum concentration (mg per 100ml) 250 3 0.01 1100 100

J. S. Swarrup et al. / Health 2 (2010) 1239-1248

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Openly accessible at

Layout of perforated cantilever beam

(Base: Length-300 µm, width-100 µm and thickness-40.5 µm , Beam : Length-200 µm, width-10µm and thickness-0.5 µm,

Antibody-loaded mesh pattern : Length-20 µm, width-100 µm and thickness-0.5 µm)

Base Perforated

Cantilever beam

Antibody-loaded mesh pattern

Quartz peizo patch

Figure 3. Layout of perforated cantilever beam.

The data on the interaction of antigen with IgA, IgD,

IgE, IgG and IgM are given in Table 3. The analytical

and simulation data reveal the variation of displace-

men t, voltage and stress with the interaction of 1 mole

of antigen with the antibody. With all toxins, the dis-

placement, voltage and stress increases with the increase

of molecular weight of the antigen. The variation of can-

tilever response with molecular weight of antigen is

given in Figure 4. The difference between analytical

and simulation values is attributed to the uniaxial and

one dimensional approximation. Moreover the point of

interaction of antigen and antibody in the length of the

cantilever is also an influential factor. Only the part

from the clamping edge to the force applying point pro-

duces a stress. Ramos et al. [7,8] analyzed the effect of

bacterial adsorption onto cantilevers and claimed that

the cantilevers’ response depends on the stiffness of

the sample as well as on its mass. The authors also re-

ported that a stiffer cantilever is relatively insensitive

to the mechanical properties of bioparticles but that its

mass sensitivity is limited. A pliant cantilever usually

has better mass sensitivity, but its response may be

complex [9].

The force applying point is again influenced by the

molecular weight of immobilised-antibody and antigen

and concentration of binding sites. The variation of can-

tilever response with molecular weight of the all immo-

bilised-antibodies is given in Figure 5. With a particular

antigen the output voltage during simulation decreases

with increase of molecular weight of the all immobi-

lised-antibodies except with IgM (Table 4, Figure 5).

However, stress decreases only up to the molecular

weight of 180000. Afterwards the stress increases with

increase of molecular weight of the immobilised-anti-

body (Figure 5). In the case of displacement, the dis-

placement decreases only up to the molecular weight of

190000. Afterwards the displacement increases with

increase of molecular weight of the immobilised-anti-

body (Figure 5). IgM having high molecular weight due

to polymeric nature, the relationship does not hold good.

With all other antibodies, the low molecular size influ-

ences the antigen-antibody interaction more effectively.

Antibody, IgG having low molecular weight yields

higher output voltage with Bacillus Anthrax Toxin which

has higher molecular weight in comparison with all other

antigens. Antibody, IgG yields lower output voltage with

Pseudomonas aeruginosa which has lower molecular

weight. While comparing the output voltage of all the

antibodies, IgG yields higher out put voltage. IgG having

low molecular weight may allow lesser strain on the can-

tilever beam in comparison with the high molecular

weight immunoglobulin. Immunoglobulin having low

molecular weight may favour molecular level changes in

terms of physical and morphological nature of adsorbed

molecules.

It has been reported that the physical and morpho-

logical nature of the probe molecules influence the de-

flection. Hagan and Chakraborty have investigated the

effect of the structure of the adsorbed layer of probe

molecules on the cantilever on the transport of targets on

to the layer and subsequent organization of complement-

tary regions leading to nucleation and completion of

hybridization [1]. The nature of grafting of probe mole-

cules on the surface whether it is ordered or is disordered

influence the deflection [2]. Disordered distributions,

which are most likely in practice, lead to much larger

J. S. Swarrup et al. / Health 2 (2010) 1239-1248

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cantilever deflections. Molecular level self-assembly con-

trols the response of the microdevice. The grafting den-

sity also influences the deflection [3]. At larger grafting

density hybridization of probe molecule does not occur,

but rather, the target chain can bridge across more than

one probe molecule.

Table 3. Response of immunoglobulins to 1 mole of antigen.

Analytical Simulation

Difference between simulation

and analytical

Antigen

Displace-

ment (nm)

Output

voltage

(V)(x1011)

Stress

(Mpa)

(x108)

Displace-

ment (nm)

Output

voltage

(V)(x1011)

Stress

(Mpa)

(x108)

Displacement Output

voltage Stress

IgA immunoglobulin

I 0.318 13.30 5.7 0.063 5.06 5.8 -80.2 -61.5 1.8

II 0.150 5.49 2.3 0.026 2.09 2.5 -82.7 -61..9 8.7

III 0.265 9.97 4.2 0.047 3.80 4.5 -82.3 -61..9 7.1

IV 0.153 5.65 2.4 0.027 2.15 2.7 -82.4 -61..9 12.5

IgD immunoglobulin

I 0.308 12.61 5.7 0.170 15.88 4.6 -44.8 25.9 -19.3

II 0.142 5.20 2.3 0.071 6.55 1.9 -50.0 26.0 -17.4

III 0.234 9.46 4.2 0.130 11.91 3.4 -44.4 25.9 -19.1

IV 0.145 5.36 2.4 0.073 6.75 2.0 -49.7 25.9 -16.7

IgE immunoglobulin

I 0.310 12.94 5.7 0.051 5.83 5.8 -83.5 -55.2 1.8

II 0.146 5.34 2.3 0.021 2.40 2.4 -85.6 -55.1 4.3

III 0.240 9.71 4.2 0.038 4.37 4.4 -84.2 -55.0 4.8

IV 0.149 5.50 2.4 0.022 2.46 2.7 -85.2 -51.3 12.5

IgG immunoglobulin

I 0.295 14.01 5.7 0.220 22.1 6.0 -25.4 57.7 17.1

II 0.092 5.64 2.3 0.093 9.11 2.5 1.1 61.5 8.7

III 0.221 10.25 4.2 0.170 16.56 4.5 -23.1 61.6 7.1

IV 0.093 5.81 2.4 0.096 9.39 2.7 3.2 61.6 12.5

IgM immunoglobulin

I 0.029 12.30 5.7 0.077 6.93 5.8 165.5 -43.7 1.8

II 0.021 5.07 2.3 0.032 2.86 2.5 52.3 -43.6 8.7

III 0.030 9.22 4.2 0.057 5.20 4.7 90.0 -43.6 11.9

IV 0.021 5.23 2.4 0.033 2.95 2.8 57.1 -43.6 16.7

I: Bacillus Anthrax Toxin, II: Pseudomonas Aeruginosa, III: Coryne Bacterium Diptheria, IV: Treponema Pallidum Difference between simulation and ana-

lytical (%) = 100(∆zsim-∆zanal)/-∆zanal

Table 4. Variation of output voltage with molecular weight of antibody.

Output voltage with simulation (V) (x1011)

Antigen

IgA IgD IgE IgG IgM

Bacillus Anthrax Toxin (I) 5.06 15.88 5.83 22.1 6.93

Pseudomonas Aeruginosa (II) 2.09 6.55 2.40 9.11 2.86

Coryne Bacterium Diptheria (III) 3.80 11.91 4.37 16.56 5.20

Treponema Pallidum (IV) 2.15 6.75 2.46 9.39 2.95

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Figure 4. Variation of cantilever response with molecular weight of antigens.

Openly accessible at

J. S. Swarrup et al. / Health 2 (2010) 1239-1248

1247

Figure 5. Variation of cantilever response with molecular weight of immobilized-antibody.

Openly accessible at

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1248

5. ACKNOWLEDGEMENT

With IgG, the difference between analytical and simu-

lation values is positive especially with low molecular

weight and motile antigens Pseudomonas aeruginosa

and Treponema pallidum. The signal transduction is in-

fluenced by the motility of the target molecules. It has

been reported by Schnell and Turner [10] that if signal

transduction occurs on time scales that are slow com-

pared to the motility of the molecules and organelles that

constitute the crowding elements, the effects of crowd-

ing are qualitatively the same as in a homogeneous

3-dimensional medium. In contrast, if signal transduc-

tion occurs on a time scale that is much faster than the

time over which the crowding elements move, the ef-

fects of varying the extent of crowding are very different

when reactions occur both in 2 and 3-dimensional space.

For fast signaling, crowding agents attenuate signaling

and never enhances signaling. In contrast, slow signaling

cascades can be both enhanced and attenuated by

crowding agents [11]. Therefore for the signal transduc-

tion in the case of low molecular weight and motile an-

tigens Pseudomonas aeruginosa and Tr ep on ema pal-

lidum, IgG is an appropriate probe molecule.

The authors acknowledges the support provided by Prof. K. K. Ray,

Prof. Zachriah Alex and Dr. Gargi Raina School of Electrical Sciences,

IT Vellore.

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The theoretical and FEM simulations were carried out

for plain and perforated rectangular cantilever with dif-

ferent immunoglobulin antibodies for the detection of

bacterial antigens. The theoretical and computational ap-

proaches have identified important variables that affect

design of the cantilever beam which are essential for the

design of the prototype device. The cantilever beam with

perforation showed an improved response. With IgG, the

difference between analytical and simulation values is

positive and low especially with low molecular weight

antigens Pseudomonas aeruginosa and Treponema pal-

lidum. The studies reveal that simulated perforated rec-

tangular cantilever beam sensor (length-300 µm, width-

100 µm and thickness-40.5 µm) with IgG antibody is a

more promising system for the fabrication for the detec-

tion of highly motile Pseudomonas aeruginosa and Tre-

ponema pallidum. Monoclonal IgG antibody could be a

more suitable probe for the detection of Pseudomonas

aeruginosa and Treponema pallidum antigens.

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ballos, A. (2006) Origin of the response of nanome-

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