You are on page 1of 18

Journal of the Mechanics and Physics of Solids 68 (2014) 179–196

Contents lists available at ScienceDirect

Journal of the Mechanics and Physics of Solids


journal homepage: www.elsevier.com/locate/jmps

Pipette aspiration of hyperelastic compliant materials:


Theoretical analysis, simulations and experiments
Man-Gong Zhang, Yan-Ping Cao n, Guo-Yang Li, Xi-Qiao Feng
Institute of Biomechanics and Medical Engineering, AML, Department of Engineering Mechanics, Tsinghua University,
Beijing 100084, China

a r t i c l e i n f o abstract

Article history: This paper explores the pipette aspiration test of hyperelastic compliant materials. Explicit
Received 9 July 2013 expressions of the relationship between the imposed pressure and the aspiration length
Received in revised form are developed, which serve as fundamental relations to deduce the material parameters
31 October 2013
from experimental responses. Four commonly used hyperelastic constitutive models, e.g.
Accepted 20 March 2014
Available online 28 March 2014
neo-Hookean, Mooney–Rivlin, Fung, and Arruda–Boyce models, are investigated. Through
dimensional analysis and nonlinear finite element simulations, we establish the relations
Keywords: between the experimental responses and the constitutive parameters of hyperelastic
Pipette aspiration method materials in explicit form, upon which inverse approaches for determining the hyper-
Hyperelastic compliant materials
elastic properties of materials are developed. The reliability of the results given by the
Dimensional analysis
proposed methods has been verified both theoretically and numerically. Experiments
Finite element method
Inverse problem have been carried out on an elastomer (polydimethylsiloxane, 1:50) and porcine liver to
validate the applicability of the inverse approaches in practical measurements.
& 2014 Elsevier Ltd. All rights reserved.

1. Introduction

Determining the mechanical properties of compliant materials such as biological soft tissues, polymeric gels and
elastomers (Li et al., 2012) is of great interest from the viewpoint of biomedical engineering. For instance, many diseases are
accompanied by the variation of the mechanical properties of soft tissues and/or cells. Therefore, measuring the mechanical
properties could help the diagnosis of some diseases (Ophir et al., 1991; O'Rourke, 1995; Cross et al., 2007; Nava et al., 2008;
Kumar and Weaver, 2009). Besides, mechanical characterization of human organs is essential in such cases as surgery
planning and surgical training using virtual reality based simulators, tissue replacement engineering as well as trauma
research (Sun and Lal, 2002; Chabanas et al., 2003; Miller et al., 2010). Tensile and compression tests have been widely used
to test biological soft tissues. However, it remains a challenge to measure the regional properties using these conventional
methods and it is often difficult to isolate the interested portion of the soft tissue without altering the biological conditions.
Several testing methods have been frequently used to probe the local properties of compliant materials, including
indentation tests, the magnetic bead method and the blow bubble method (Smith et al., 1992; Ziemann et al., 1994; Cheng
and Cheng, 2004, 2005; Oommen and Van Vliet, 2006; Tweedie and Van Vliet, 2006; Kranenburg et al., 2009; Hu et al., 2010,
2011; Zimberlin et al., 2010; Fischer–Cripps, 2011; Zhang et al., 2014). The indentation technique can probe various
properties of compliant materials across different length scales. For instance, Briscoe et al. (1998) have demonstrated the

n
Corresponding author. Tel.: þ86 10 6277 2520.
E-mail address: caoyanping@tsinghua.edu.cn (Y.-P. Cao).

http://dx.doi.org/10.1016/j.jmps.2014.03.012
0022-5096/& 2014 Elsevier Ltd. All rights reserved.
180 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

possibility to determine the mechanical properties of polymeric materials using nanoindentation tests. Cheng and Cheng
(2004, 2005) explored the indentation of viscoelastic materials based on dimensional analysis and proposed a number of
analytical solutions correlating the indentation responses with viscoelastic properties of indented solids. Oommen and Van
Vliet (2006) explored the spherical indentation of polymeric films and addressed the effects of film thickness and material
nonlinearity. Tweedie and Van Vliet (2006) investigated the determination of creep functions of polymers using indentation.
Recently, Hu et al. (2010, 2011) and Kalcioglu et al. (2011) used indentation tests to evaluate the poroelastic properties of
polymeric gels. These previous studies have demonstrated that indentation tests are successful in mechanical characteriza-
tion of compliant materials. However, the commercial instruments upon which indentation tests are based are usually
expensive. Besides, it is often hard to interpret the indentation responses in some situation, e.g. when the indenter tip has
defects or surface effects are significant.
This study is concerned with the pipette aspiration method, another promising tool to determine the local mechanical
properties of compliant materials including biological soft tissues, polymeric gels and elastomers, whose elastic moduli are
on the order from tens Pa to MPa. This method has received considerable attention during past years. For example, Evans
(1983) used a micropipette aspiration test to measure the bending rigidity of red blood cell membrane. Aoki et al. (1997)
proposed a pipette aspiration method to evaluate local elastic moduli of soft tissues. Using a similar method, Guilak et al.
(1999) measured the mechanical properties of enzymatically-isolated chondrocytes and their pericellular matrix, and
Hochmuth (2000) studied the deformation behavior of living cells. Kauer (2001) analyzed the pipette aspiration tests based
on finite element analysis, where the viscoelasticity of soft tissues was modeled using a quasi-linear viscoelastic
formulation. Based on finite element simulations, Boudou et al. (2006) derived a new expression of the aspirated length
for linear elastic materials in order to extract the elastic properties from pipette aspiration tests. Recently, Guevorkian et al.
(2010) investigated the aspiration of biological viscoelastic drops and proposed a model to deduce the surface tension,
viscosity, and elastic modulus. Through systematic finite element simulations, Zhao et al. (2011) explored the micropipette
aspiration method to evaluate the mechanical properties of multilayer biological soft materials. Their results help to select
an appropriate pipette size according to the intrinsic length scale of the tested material. The aforementioned studies have
clearly demonstrated that the correlation between the experimental responses and material properties is of central
importance in the use of the pipette aspiration method. In this context, continuum mechanics plays an essential role.
Due to their intrinsic features of low elastic moduli and high sensitivity to external stimuli, compliant materials often
undergo large deformation and exhibit strong nonlinear responses. When both geometric and material nonlinearities are
present in the pipette aspiration test, it is difficult to develop an analytical solution correlating the experimental responses
with material properties. Therefore, the inverse analysis for interpreting the experimental data in the literature (Kauer,
2001; Boudou et al., 2006; Zhao et al., 2011) is usually based on finite element simulations. Based on this premise, we here
explore the pipette aspiration test of hyperelastic soft materials through a combined effort of dimensional analysis, finite
element simulations and experiments, with the following two purposes. Firstly, an effort is made to propose a general
method to establish explicit expressions for the relations between the aspiration pressure, p, and the aspiration length, l, for
four different hyperelastic models. These relations constitute the basis for developing the inverse approaches to extract the
mechanical properties of hyperelastic compliant materials, e.g. the initial shear modulus and locking stretch, from
experimental responses. Secondly, a linear relationship between the pressure and the aspiration length has been assumed
by many authors in the analysis of pipette aspiration tests (Sato et al., 1990; Merryman et al., 2009; Guevorkian et al., 2010)
to deduce either elastic or viscoelastic properties. This assumption may be valid when the deformation of tested material is
smaller than certain critical value (Cao et al, 2014). This study will examine the possibility to determine the initial shear
modulus using this information from the viewpoint of inverse analysis.
The paper is organized as follows. In Appendix A, four widely used hyperelastic models, including neo-Hookean,
Mooney–Rivlin, Fung and Arruda–Boyce model, are described. Dimensional analysis is carried out in Section 2 to
characterize the relations between the experimental responses and material properties, which will be determined in
explicit forms in Section 3 via finite element simulations. Then in Section 4, inverse approaches are established to deduce
the hyperelastic properties of materials from the pipette aspiration experimental data. By introducing the concept of
condition number in the theory of inverse problems, the sensitivity of the solution to data errors is examined. In Section 5,
numerical experiments are performed to verify the effectiveness of the proposed methods. Practical experiments are further
conducted in Section 6 on an elastomer and pig liver to validate the applicability of the proposed methods. Section 7 gives
the concluding remarks.

2. Dimensional analysis on the pipette aspiration test of hyperelastic compliant materials

Dimensional analysis is first utilized to analyze the pipette aspiration tests of hyperelastic compliant materials with the
four constitutive relations described in Appendix A. Dimensional analysis states that a physical law does not depend on the
arbitrariness in the choice of units of physical quantities (Barenblatt, 1996), which has been demonstrated to be useful in
deriving relationships between the physical quantities involved in a problem. We show in this study that dimensional
analysis is valuable to the analysis of pipette aspiration tests. Particularly, only a few geometric and physical parameters are
involved. The combination of dimensional analysis with finite element simulations enables us to establish the relationship
between the experimental responses and material properties though the problem is strongly nonlinear. Fig. 1 illustrates the
pipette aspiration test schematically.
M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 181

Fig. 1. Schematic of the pipette aspiration test.

For a hyperelastic material described with an incompressible neo-Hookean model, the aspiration length l is a function of
the following independent parameters:
l ¼ f ðμ0 ; p; R; tÞ; ð1Þ
where μ0 is the shear modulus at the ground state, p the given pressure, R the internal radius of the aspiration tube, and t the
wall thickness of the tube. Applying Buckingham Pi theorem (Barenblatt, 1996) to Eq. (1) gives
 
p t
l ¼ RΠ ; ; ð2Þ
μ0 R
where Π is a dimensionless function. From Eq. (2), we have
 
p l t
¼ Π nH ; ; ð3Þ
μ0 R R
When ðt=RÞ Z r 1 , Eq. (3) reduces to
 
p l
¼ Π nH ; ð4Þ
μ0 R
where the dimensionless function Π nH can be determined by a single nonlinear finite element simulation, as shown below.
The critical ratio r1 will be determined in Section 3.
Adopting dimensional analysis to the pipette aspiration test of an incompressible Mooney–Rivlin soft substrate gives
 
p l
¼ Π MR ; α ; ð5Þ
μ0 R
where Π MR is a dimensionless function and α ¼ C 10 =ðC 01 þC 10 Þ.
Similarly, the correlations between the experimental responses and geometric and physical parameters of the system for
Fung and Arruda–Boyce models are characterized by
 
p l
¼ ΠF ; b ; ð6Þ
μ0 R
 
p l
¼ Π AB ; λm ; ð7Þ
μ0 R
respectively, where Π F and Π AB are dimensionless functions.
Provided that the dimensionless functions in Eqs. (4)–(7) are known, the relations between the experimental responses
(i.e., p and l) and the material properties will be determined. In next section, we will identify the explicit expressions of the
dimensionless functions Π nH , Π MR , Π F and Π AB using nonlinear finite element simulations.
182 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

3. Determination of the dimensionless functions

Under the guideline of dimensional analysis performed in Section 2, finite element computations are carried out in this
section using ABAQUS (2009) to determine the explicit expressions of Π nH , Π MR , Π F and Π AB . Nonlinear finite element
simulations permit to simultaneously consider the material, geometric and boundary nonlinearities involved in the problem
and, therefore, allow us to determine the dimensionless functions in Section 2 up to large ratios of l=R. Mooney–Rivlin, neo-
Hookean and Arruda–Boyce models introduced in Appendix A have already been included in ABAQUS and can be used
directly. It is pointed out that neo-Hookean model is a particular case of Mooney–Rivlin model when α ¼ 1. We implanted
the Fung model (Fung et al., 1979) into ABAQUS via the user subroutine UHYPER. The parameters used in this study are
taken according to the literature and vary in wide ranges of practical interest, as listed in Table 1. The value of the initial
modulus μ0 can be taken arbitrarily in the determination of the dimensionless functions in Section 2 and is taken as 1 MPa
in our simulations. Varying the imposed pressure leads to the ratio of l=R varying in the range of practical interest. In our
simulations, l=R varies from 0 to 1 by specifying the imposed pressure.
An axisymmetric finite element model is adopted, as shown in Fig. 2. 12,716 eight-node axisymmetric reduced
integration elements are used to discretize the compliant substrate, whose size is much larger than the tube radius and can
be regarded to be semi-infinite. For the boundary conditions, the outer surface nodes are traction-free with fixed lower
surface nodes. The pipette is assumed to be rigid. To examine the effects of friction, we simulate the contact of the pipette
with the substrate by taking two representative values of the coefficient of friction as 0.5 and 0.8. The difference between
the computational results under the two different values is smaller than 1%, indicating that the effects of friction is
insignificant. Therefore, the coefficient of friction will be set as 0.5 in the following calculations. The convergence of

Table 1
Material parameters used in simulations.

Model Parameters Range of parameters

Mooney–Rivlin α ¼ C 10Cþ10C 01 [0, 1]


Fung b [0.05, 10]
Arruda–Boyce λm [1, 10]

Fig. 2. The finite element model.


M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 183

16

14

12 R/a=5
R/a=10
10 R/a=20
R/a=50

p/µ0
8

0
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1
l/R
Fig. 3. p  l curves for different ratios of the pipette inner radius R to pipette fillet radius a. Here, pressure p is normalized by initial shear modulus μ0 , and
aspiration length l is normalized by pipette inner radius R.

computation is guaranteed by comparing the present results with those calculated using a refiner mesh with 18,236 eight-
node axisymmetric reduced integration elements.
We first explore the influence of the parameter t=R in Eq. (3). It is found that when t=R Zr 1 ¼ 0:3, t=R basically has no
effect on the dimensionless functions. We also investigate the influence of the pipette fillet radius a. Our results illustrate
when the pipette fillet radius a is smaller than 5% of the pipette inner radius R, its effect on the dimensionless functions is
also negligible (Fig. 3). In this simulation, we use the Arruda–Boyce model with λm ¼ 1. In the following simulations, the
fillet radius a is taken as 0:02R.
Based on the computational results, the dimensionless function Π nH ðl=RÞ in Eq. (4) is determined as
     2
l l l
Π nH ¼ κ1 þ κ2 ; ð8Þ
R R R

where κ1 ¼2.615 and κ2 ¼2.245. Eqs. (4) and (8) give an explicit expression of the correlation between the experimental
responses and material parameters for neo-Hookean solid
     2
p l l l
¼ Π nH ¼ κ1 þ κ2 ; ð9Þ
μ0 R R R

which is valid up to l=R ¼1.


According to the results shown in Fig. 4, for l=R in the range from 0.1 to 1, the closed-form expressions of the
dimensionless functions Π MR , Π F , and Π AB are obtained as

Π MR ðaÞ ¼ A1 þA2 α þA3 α2 ; ð10aÞ

4
Π F ðbÞ ¼ B0 þ ∑ Bi ½ lnðbÞi ; ð10bÞ
i¼1

4
Π AB ðλm Þ ¼ C 0 þ ∑ C i ½ lnðλm Þi ; ð10cÞ
i¼1

respectively, where the coefficients Ai ði ¼ 1; 2; 3Þ, B0 , C 0 , Bj and C j ðj ¼ 1; 2; 3; 4Þ depend on l=R and are given in Appendix B.
Clearly, Eq. (9) and (10) together with Eqs. (4)–(7) give the explicit expressions of the relationship between the experimental
responses and material parameters for the four hyperelastic models under study.
The explicit results developed here could be very useful. For instance, they may serve as fundamental solutions to extract
the mechanical properties of materials from pipette aspiration tests. Fig. 5 illustrates the p–l curves for different models. It is
clearly seen that when l=R o 0:3, indeed, the relationship between p and l is approximately linear (Cao et al., 2014). However,
when l is comparable with R, the p–l curve is evidently nonlinear. The linear relation between p and l at small ratios of l=R
brings the convenience to the determination of the initial shear modulus; whereas the nonlinear relationship between p and
l at large ratios of l=R reveals the possibility to extract some other hyperelastic properties of soft materials, as shown in
Section 4.
184 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

Fig. 4. Dependence of the dimensionless functions Π MR , Π F and Π AB on the hyperelastic parameters and ratio of l=R.

4. Inverse approaches for determining the hyperelastic parameters of compliant materials

4.1. Determination of initial shear modulus

The explicit results in Section 3 enable us to develop inverse approaches to extract the hyperelastic parameters of
incompressible compliant materials from pipette aspiration tests. Fig. 5 shows a linear relationship between p and l when
l=R is small (e.g. l=R o 0:3), regardless of the constitutive model used. Therefore, the initial shear modulus can be simply
determined by
pR
μ0 ¼ ð11Þ
3:2l
For a neo-Hookean solid and when the deformation is large (e.g. l=R 40:3), Eq. (9) provides a more accurate relation to
evaluate the initial shear modulus, i.e.,
p
μ0 ¼ ð12Þ
κ1 ðl=RÞ þ κ2 ðl=RÞ2

4.2. Determination of some other hyperelastic parameters

The explicit results proposed in Section 3 also permit to determine some other hyperelastic parameters besides the initial
shear modulus, i.e., the parameter α in the Mooney–Rivlin model, b in the Fung model, and the locking stretch λm in the
Arruda–Boyce model.
M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 185

4.2.1. Determining the parameter α in the Mooney–Rivlin model


When the Mooney–Rivlin model is used to describe an incompressible compliant substrate, two material parameters are
involved, i.e., μ0 and α. When μ0 has been determined, e.g. from Eq. (11), it is possible to further evaluate the parameter α
from the experimental data at a large ratio of l=R (e.g. l=R¼1) and the following relation:
p
¼ A1 þ A2 α þA3 α2 ; ð13Þ
μ0
where Ai ði ¼ 1; 2; 3Þ are taken at this large ratio of l=R, and p is the corresponding pressure. In practical measurements, p is
imposed and the specified ratio of l=R can be obtained by interpolating the p  l curve.

4.2.2. Determining the parameter b in the Fung model


Fung model (Fung et al., 1979) has been used by many authors to describe the deformation behavior of biological soft
tissues. With the known μ0 , the hyperelastic parameter b can be evaluated from
p 4
¼ B0 þ ∑ Bi ½ lnðbÞi ; ð14Þ
μ0 i¼1

where p and Bi ði ¼ 1; 2; 3; 4Þ correspond to a large ratio of l=R, e.g. l=R¼0.5 or l=R¼ 1.

4.2.3. Determining the parameter λm in the Arruda–Boyce model


If the Arruda–Boyce model is used to describe the compliant substrate and the initial shear modulus μ0 has been
determined, the locking stretch λm can be extracted from the experimental data at a large ratio of l=R and the following
equation:
p 4
¼ C 0 þ ∑ C i ½ lnðλm Þi ; ð15Þ
μ0 i¼1

where p and the constants C 0 , C i ði ¼ 1; 2; 3; 4Þ are taken at a relatively large value of l=R (e.g. l=R¼1).
It is emphasized that the data at a large ratio of l=R should be used in determining α, b and λm according to Fig. 5. Our
analysis in the sequel shows that the identified results will be sensitive to data errors if the experimental data at relatively
small l=R are used in the inverse analysis.

4.3. Sensitivity of the identified solutions to data errors

Determining the properties of hyperelastic solids using pipette aspiration tests represents an inverse problem. An inverse
problem may be ill-posed provided that the solution to the inverse problem does not exist (existence), the solution is non-
unique (uniqueness) or the solution is unstable (stability) (Hadamard, 1923). In practice, the condition of stability is most
often violated and deserves more attention. Stability of the solution determines the sensitivity of the identified solution to
data errors. The lack of stability can result in the computed solution to an inverse problem to have nothing to do with the
true solution. Here the sensitivity of the parameters determined using the approaches developed above to the input data
errors is evaluated. The data errors in the present problem stem from the measurement of the p l curve. In this case, one
can either assume that the aspiration length l is accurate and an error exists in the pressure p, or equivalently assume that p
is accurate and l has an error. In the following analysis, we adopt the former assumption.
Theoretical analysis is first performed to investigate the stability of the solutions of the inverse problems to data errors.
To this end, we introduce the concept of the condition number in inverse problems. A problem is ill-conditioned if the
condition number is large and ill-posed if the condition number is infinity (Hadamard, 1923). Condition number
quantitatively measures the sensitivity of the identified solution to data errors. For instance, when the condition number
is 3, an error of 3% in the input data will lead to an error of 9% in the identified solution. Eqs. (11) and (12) indicate that the
initial shear modulus scales with the pressure. In this case, 1% error in the pressure will lead to 1% error in the identified μ0 .
Therefore, the condition number for determining μ0 is 1. Here we focus on the determination of other hyperelastic
parameters, i.e., α, b and λm .
Based on Eq. (10), the condition numbers for the determination of the parameters α, b and λm are defined as (Cao and Lu,
2004)
Δα ΔΠ MR Π MR
Ψ MR ¼ = ¼ ; ð16aÞ
α Π MR αΠ 0MR ðαÞ

Δb ΔΠ F ΠF
ΨF ¼ = ¼ ; ð16bÞ
b ΠF bΠ 0F ðbÞ

Δλm ΔΠ AB Π AB
Ψ AB ¼ = ¼ ; ð16cÞ
λm Π AB λm Π 0AB ðλm Þ
where Π 0MR ðαÞ ¼ dΠ MR =dα, Π 0F ðbÞ ¼ dΠ F =db, and Π 0AB ðλm Þ ¼ dΠ AB =dλm . Here ΔðÞ represents a small increment of the
argument. From Eqs. (10a), (13) and (16a), the condition number for the determination of α in the Mooney–Rivlin model is
186 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

Fig. 5. Pressure–aspiration length curves for different hyperelastic models, where pressure p is normalized by initial shear modulus μ0 , and aspiration
length l is normalized by pipette inner radius R.

Π MR A1 þ A2 α þ A3 α2
Ψ MR ¼ 0 ¼ ; ð17Þ
αΠ MR ðαÞ A2 α þ 2A3 α2
From Eqs. (10b), (14) and (16b), the closed-form expression of the condition number for determining b in the Fung model is
given as
B0 þ ∑4i ¼ 1 Bi ½ lnðbÞi
ΨF ¼ : ð18Þ
∑4i ¼ 1 Bi i½ lnðbÞi  1
According to Eqs. (10c), (15) and (16c), the condition number for evaluating λm in the Arruda–Boyce model is
C 0 þ ∑4i ¼ 1 C i ½ lnðλm Þi
Ψ AB ¼ ¼ : ð19Þ
∑4i ¼ 1 C i i½ lnðλm Þi  1
The explicit results derived above permit to quantitatively examine the sensitivity of the identified parameters α, b and λm to
data errors. We plot the reciprocals of condition numbers 1=Ψ in Eqs. (17)–(19) according to Fig. 4 for different material
parameters and l=R in Fig. 6.
It can be seen that the greater the ratio l=R, the smaller the condition number Ψ , indicating that the use of the
experimental data at a large ratio of l=R is necessary and important to obtain a reliable solution. Assuming that the condition
number smaller than 5 is acceptable, the parameters α, b and λm in the three different models could be effectively
determined using the inverse approaches proposed here when they are in the ranges of αZ 0:5, b Z 0:15 and λm o2.5,
respectively. It is noticed that the parameters of most biological soft tissues are within these ranges. Using the experimental
data at an even greater ratio of l=R will lead to wider property ranges in which α, b and λm can be reliably determined; but
M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 187

Fig. 6. Reciprocals of the condition numbers for determining α, b and λm under different ratios of l=R.

large deformation may probably cause permanent deformation or fracture of the tested material, which are beyond the
scope of our study.

5. Numerical validations

To validate the approaches proposed in Section 4, numerical experiments are performed in this section. Forward finite
element analysis for given material parameters is first conducted to evaluate the p l curve. Then the reverse analysis using
the inverse approaches in Section 4.1 is carried out to extract the material properties from the obtained p  l curves. Here we
take the Mooney–Rivlin solid as an example to illustrate the use of the inverse approaches. Eq. (11) is first used to evaluate
the initial shear modulus from the p  l curve, and then with the identified μ0 , Eq. (13) is adopted to determine the
parameter α. The material properties used in the calculations are listed in Table 2, in which the actual solution is the input
parameters of finite element simulations, and the identified hyperelastic parameters are solved via the method described
above. Their comparison indicates that the initial shear modulus can be determined with a good accuracy. For other
hyperelastic properties within the ranges identified by the theoretical analysis in Section 4.3, they have been reliably
determined using the methods proposed in Section 4. However, when they are beyond the applicable range, the errors will
be relatively large. For instance, for the Mooney–Rivlin model with α¼0.115 in Table 2, the identified solution is α ¼0.197,
indicating that the method proposed here is not applicable to a Mooney–Rivlin solid when its parameter C 01 is much greater
than C 10 . In our inverse analysis, the data at l=R¼1 is used. In order to get a more reliable evaluation on a small α, one has to
extend our method to even larger ratios of l=R, which is straightforward.

6. Experiments

Experiments are further carried out to validate the applicability of the proposed method to practical measurements. A
compliant elastomer (PDMS, 1:50) and pig liver are tested by the pipette aspiration method. The material properties are
identified from the measured p  l curves by using the inverse approaches proposed in Section 4. Indentation tests are also
188 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

Table 2
Comparison of the identified hyperelastic properties for three material models with the actual solutions, where large λm and small b represent materials
with large locking stretch.

Mooney–Rivlin model Actual solutions Identified hyperelastic parameters

μ0 (MPa) α μ0 (MPa) α

M1 0.01 0.115 0.0097 0.198


M2 0.01 0.536 0.0101 0.520
M3 0.01 0.875 0.0101 0.834

Fung model μ0 (MPa) b μ0 (MPa) b


M4 0.01 0.813 0.0103 0.785
M5 0.01 2.115 0.0095 2.210
M6 0.01 8.256 0.0098 8.312

Arruda–Boyce model μ0 (MPa) λm μ0 (MPa) λm


M7 0.01 1.156 0.0097 1.141
M8 0.01 1.789 0.0097 1.701
M9 0.01 2.335 0.0097 2.009

performed on the same materials, and the material parameters are extracted from the indentation load–depth curves and
compared with those given by pipette aspiration tests.

6.1. Materials

In our experiments, we use polydimethylsiloxane (PDMS) elastomer (Sylgard 184) purchased from Dow Corning.
By changing the proportion of crosslinker, its elastic properties can be adjusted. Here, polydimethylsiloxane (PDMS) is
prepared by mixing a crosslinker and a degassed elastomer base in a ratio of 1:50 w/w. The pre-polymerized mixture is
filled in a cylindrical mold and cured at 60 1C for 16 h. When the PDMS has become a solid, it is taken out to prepare
experimental specimens.
Pig liver sample was taken from a freshly slaughtered pig and transported to the laboratory within 5 h postmortem. The
experiments were conducted instantly. It should be pointed out that tissue degradation can significantly affect their
properties and the extracted mechanical parameters may have a distinct difference over time (Valtorta and Mazza, 2005).
However, since the indentation tests are carried out immediately after the pipette aspiration tests, the comparison between
the two methods is meaningful.

6.2. Experimental set-up and measurements

Our aspiration pipette test device consists of a glass pipette, a pressure gauge and a vacuum pump (Fig. 7a). The glass
pipette is connected to the vacuum pump and the pressure gauge records the variation of pressure. Both the pressure and
the aspiration length are recorded, which are used in the analysis. In our experiments, the pipette has an internal radius of
3.39 mm and a wall thickness of 1.565 mm. The measurements are conducted at room temperature (23 1C) and a humidity
of about 50%. The cylindrical PDMS specimen has a diameter of 59.3 mm and height of 44.5 mm, which are much greater
than the pipette radius and sufficiently large to neglect the effects of dimensions during pipette aspiration as shown in the
sequel. The pig liver sample has irregular shape and the size is given in Fig. S1 (Supplementary material). Measurements at
six positions of the PDMS sample are conducted, whereas the measurements of the liver sample are performed at four
positions on the center part where the thickness is around 30 mm. The height H and the width W of the samples are
required to be much greater than the radius of the pipette such that they can be regarded as a semi-infinite body. Finite
element simulations are carried out here to identify the critical sample dimension beyond which the dimension effect is
negligible. For an imposed pressure, we examine the variation of l=R with H=R and W=R, and the results for the Arruda–
Boyce model are plotted in Fig. S2 (Supplementary material). It is seen that the sample dimension effect is negligible
provided that the characteristic dimension (W and H) of the sample is 5 times greater than the pipette inner radius.
Indentation tests are carried out using the ElectroForces 3100 test instrument (Bose, Fig. 7b). The machine can reach a
maximum load of 22 N. The displacement resolution is 1 mm and the load resolution is 0.5 mN. Two spherical indenters
made of stainless steel with tip radii of 4 mm and 3 mm are adopted for the PDMS and porcine liver, respectively. The
indenter with the smaller radius is used for the pig liver sample taking the sample thickness and the effects of substrate into
consideration. Displacement controlled loading procedure was applied. The loading rate is 2 mm/s. As in the pipette
aspiration tests, six different positions of the PDMS sample are measured. Indentation tests are performed at different points
of the pig liver surface (Fig. S1, Supplementary material). Considering that the mechanical properties of the pig liver may be
position-dependent, the data at the two points in the central region (Fig. S1) are used for comparison where the pipette
aspiration test is conducted. The maximum indentation depth is taken around 5% of the sample thickness considering the
substrate effect.
M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 189

Fig. 7. (a) Pipette aspiration testing device and (b) depth-sensing indentation instrument based on the Bose ElectroForces 3100.

Fig. 8. Comparison of the experimental p  l curve of PDMS (1:50) with the predicted results using Eqs. (11) and (13).

6.3. Results and analysis

Based on the experimental p  l curve of PDMS (1:50) (Fig. 8) and using Eq. (11), the initial shear modulus is determined
to be around 0.0098 MPa. Using Mooney–Rivlin model and Eq. (13), the parameter α for PDMS (1:50) is further determined
to be about 0.3. The theoretical predicted p l curve with μ0 ¼0.0098 MPa and α¼0.3 is included in Fig. 8. The Fung model is
used to describe the deformation behavior of the pig liver and the hyperelastic parameters are evaluated using the inverse
approach proposed in Section 4. The identified initial shear modulus is around 0.0107 MPa. The parameter b is determined
as 1.6 using Eq. (14) and data at l=R¼0.5. Fig. 9 gives the experimental p  l curve for the tested pig liver, in which the
theoretically predicted p l curve with μ0 ¼0.0107 MPa and b¼1.6 is also included. The error bars in Figs. 8 and 9 give the
standard deviations. The value of the shear modulus is in reasonable range compared with those reported in the literature
(Tay et al., 2006; Samur et al., 2007; Gao et al., 2011). Fitting the tensile curves of the porcine liver reported by Chui et al.
190 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

Fig. 9. Comparison of the experimental p  l curve for porcine liver with the predicted results using Eqs. (11) and (14).

Fig. 10. The indentation load–depth curve given by experiments for PDMS (1:50), and the Hertzian solution is used to fit the experimental curve up to the
ratio of the depth to radius h=R ¼ 0:25 to evaluate the initial shear modulus.

(2004), i.e., Fig. 3 in their paper, using the Fung model gives parameter b in the range of 1.6–3.0. Fitting the compression
curves given by Fig. 9 in the paper of Gao et al. (2010) gives the parameter b in the range of 2–3.0. Comparison with these
previous results, the identified value of b¼1.6 using the present method is reasonable. In this study, we proposed inverse
methods for four commonly used hyperelastic models. When these methods are employed to analyze the indentation
response of a hyperelastic solid, one has to choose a suitable constitutive model based on prior knowledge. For instance, it is
known from previous studies (Chui et al., 2004; Gao et al., 2010) that the Fung model can well describe the tensile and
compressive stress–strain curves of some biological soft tissues including the porcine liver.
Fig. 10 represents the indentation load–depth curve for PDMS. Fitting the experimental curve up to the ratio of the depth
to radius h=R ¼ 0:25 using Hertzian solution gives the initial shear modulus μ0 ¼ 0:0103 MPa. Up to this ratio of the depth to
radius, Hertzian solution is applicable (Zhang et al., 2014) and the effect of surface adhesion is insignificant as shown in
detail below. This value is very close to that given by the pipette aspiration test. From the indentation load–depth curves, we
cannot reliably evaluate the parameter α because the identified solution is very sensitive to data errors. Our recent analysis
(Zhang et al., 2014) shows that the condition number in this case is around 10, i.e. a 5% data error may lead to an error up to
50% in the identified α.
Fig. 11 gives the indentation load–depth curve for the porcine liver. Fitting the load–depth curve up to h=R ¼ 0:25 using
Hertzian solution gives μ0 ¼ 0:0085 MPa, which is significantly smaller than the value given by the pipette aspiration tests. It
is possible to determine the parameter b. However, the indentation method proposed in our recent study (Zhang et al., 2014)
for the Fung model is limited to the case with br 1. Therefore, here we have to rely on the finite element simulations to
conduct the inverse analysis. Finite element analysis is performed to simulate the indentation tests of the porcine liver. The
M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 191

Fig. 11. The indentation load–depth curve given by experiments for porcine liver, and the Hertzian solution is used to fit the experimental curve up to the
ratio of the depth to radius h=R ¼ 0:25 to evaluate the initial shear modulus.

Fig. 12. Strain fields given by finite element simulations for (a) indentation and (b) pipette aspiration of a hyperelastic solid. The Fung model is used for the
indented hyperelastic solid with μ0 ¼ 0.0107 MPa and b¼ 1.6.

spherical indenter is assumed to be rigid and the indenter radius is taken the same as that in the tests. A total of 41121
axisymmetric hybrid elements with reduced integration (CAX4RH) are used to mesh the indented solid. In the simulations,
we take μ0 ¼ 0:0085 MPa and vary the parameter b. Comparing the computed indentation load–depth curves with the
experimental results in Fig. 11, the parameter b is obtained to be around 1.1, which is smaller than that identified from the
pipette aspiration tests. However, this identified parameter using indentation tests may be not reliable because the
indentation loading curves for b ¼ 1:1 and b ¼ 1:6 are close to each other (Fig. 11). When taking the time-dependent
behavior of the pig liver into account in the finite element simulations, indeed, the identified parameter b will be greater, as
discussed in detail in the sequel.
Most biological soft tissues including the porcine liver exhibit complex nonlinear, anisotropic, non-homogeneous, and
rate-dependent behavior (Fung, 1993; Mattice et al., 2006; Constantinides et al., 2008; Kalcioglu et al., 2011, 2013), which
may lead to inconsistent results between indentation and pipette aspiration measurements. For instance, the strain fields in
the tested soft tissues induced by the pipette aspiration and indentation are quite different, which can be seen from the
strain fields beneath the indenter and pipette shown in Fig. 12. Therefore, the anisotropic behavior of soft tissues may cause
that the hyperelastic parameters determined using the two testing methods differ from each other. In our experiment, the
capsule material is not removed and the test is performed at the surface of the pig liver. The mechanical properties of the
capsule material are usually different from those of the interior part (Brunon et al., 2010; Umale et al., 2013). In this sense, it
is more appropriate to model the pig liver as a layered material instead of a homogeneous material assumed in this study.
Besides, the indented surface is not ideally flat for the liver as assumed in our finite element simulations, which may
introduce errors as well. Finally, the effects of surface adhesion and time-dependent deformation behavior of the pig liver
192 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

may come into play. To explore the effects of surface adhesion on the indentation responses, we invoke the Johnson–
Kendall–Roberts (JKR) model (Johnson et al., 1971) which may be used to deal with the adhesive contact between two elastic
solids when the Tabor's parameter defined by the following equation is large (e.g., T μ 4 5:0),
!ð1=3Þ
Rχ 2
Tμ ¼ ð20Þ
E2r z30

R in Eq. (20) is the indenter radius, χ is the work of adhesion, Er is the plane–strain modulus of the substrate and z0 the
equilibrium separation at which the traction between two surfaces disappears. The JKR model gives the correlation between
the penetration depth δ and the contact radius a as (Johnson et al., 1971)
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
δ ¼ a2 =R  2πaχ=Er ð21Þ

The contact radius is related to the indentation load P by


2 sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi3
 
3 3PR4 3πχR 6πχR 3πχR 2 5
a ¼ 1þ þ þ ð22Þ
4Er P P P

In indentation tests, the definition of the initial contact point is important; thus, it should be noted that δ in Eq. (21) usually
is not the indentation depth recorded in practice. There are a number of different ways to locate the first contact point in
indentation tests (Oliver and Pharr, 2004). In a quasi-static measurement, the initial contact point is usually defined as the
point at which the indentation load begins to increase from zero. In this case, the indentation load (P r ) and the depth (hJKR )
recorded by the instrumented may be given by
P r ¼ PðP Z 0Þ
hJKR ¼ δ δ0 ð23Þ

where δ0 is the JKR penetration corresponding to P ¼ 0 and given by


!ð1=3Þ
3π 2 χ 2 R
δ0 ¼ ð24Þ
4E2r

A comparison of the indentation depth hJKR given by Eq. (23) with that corresponding to Hertzian solution (hH ) permits to
evaluate the effects of surface adhesion at different indentation loads. For instance, taking χ ¼ 10 mJ/m2 for van der Waals
interaction (Gao and Yao, 2004), which has not been accurately determined in our problem, when the indentation load is
greater than 30 mN, the difference between hJKR and hH is smaller than 2% for the indentation of both PDMS and the pig
liver. Therefore, the effects of surface adhesion on the determination of the initial shear modulus appear to be insignificant,
because the indentation load is greater than 50 mN when taking the ratio of h=R up to 0.25 in our measurements.
Rate-dependent deformation behavior of the pig liver may affect the results of both indentation tests and pipette
aspiration tests. To examine the influence of the viscosity, indentation tests are performed on a porcine liver to estimate the
viscoelastic kernel function. Particularly, indentation relaxation tests are carried out on the porcine liver and a scaling
relation proposed by Cao et al. (2013) is used to evaluate the viscoelastic kernel function from the indentation relaxation
load. Based on the experimental result, the first-order Prony series is used to describe the viscoelastic kernel function, i.e.,
g ¼ 1  g 1 þ g 1 expð  t=τÞ. The characteristic relaxation time is around 3 s. The relaxation extent at different positions of the
tested sample is contoured in Fig. S1 (Supplementary material), which gives g 1  0:5 at the center part of the sample. Based
on the identified viscoelastic kernel function and a nonlinear viscoelastic model (Simo, 1987), in which the Fung model
(Fung et al., 1979) is used as the initial elastic stored energy function, finite element simulations of the aspiration test are
carried out. The p l curves are plotted in Fig. S3 (Supplementary material) for different loading times t r at which the
pressure reaches the maximum value. Fig. S3 indicates that the effect of viscosity is insignificant when the loading time is
much shorter than τ, e.g. t r ¼0.1τ. The identified hyperelastic parameters from different p l curves using the inverse
approach proposed in Section 4 are given in Table S1 (Supplementary material). The result for the time-independent
hyperelastic model in Table S1 indicates that the present inverse approach to some extent gives an overestimation on the
parameter b. When the pressure rise time t r is not small, the instantaneous initial shear modulus and the parameter b are
somewhat underestimated. The errors could be significant when t r is much greater than τ, e.g. t r /τ ¼33.33. In our porcine
liver test described in Section 6, t r is around 6 s when the ratio of l=R ¼ 0:5. In this case, the results in Table S1 illustrate that
the identified parameter b and the instantaneous initial shear modulus μ0 are reasonable. We further simulate the
indentation tests by taking the nonlinear viscoelastic model with the viscoelastic kernel function given by i.e.,
g ¼ 1  g 1 þ g 1 expð  t=τÞ, where g 1 ¼ 0:5 and τ ¼ 3 s. The indentation curve is included in Fig. 11, which is not far from
the finite element result under the time-independent model. This insignificant difference can be neglected in the
determination of the initial shear modulus. However, it has marked influence on the measurement of the parameter b.
Without the effect of time-dependent deformation behavior, the identified b is around 1.1 as given above, while when this
effect is taken into account, parameter b extracted from indentation tests is around 1.8. This means that parameter b at the
present maximum indentation depth is sensitive to data errors.
M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 193

7. Concluding remarks

Pipette aspiration test is a promising tool to evaluate the hyperelastic properties of soft materials. However, extracting
the material parameters from the experimental responses remains a challenging issue, because material, geometric and
boundary nonlinearities are involved in the test. This paper explored the pipette aspiration method for mechanical
characterization of hyperelastic soft materials through combined theoretical, computational and experimental efforts. In
summary, the following key results have been achieved.
For pipette aspiration tests of hyperelastic soft materials described with the neo-Hookean, Mooney–Rivlin, Fung or
Arruda–Boyce model, we have proposed a general method based on dimensional analysis and finite element simulations to
establish explicit expressions of the relationship between material properties and experimental responses. This method is
applicable when the substrate undergoes finite deformation, e.g., when the aspiration length is comparable with the pipette
radius.
On the basis of the obtained explicit results, we have developed inverse approaches to determine the mechanical
properties of hyperelastic solids. Our results show that the initial shear modulus μ0 could be simply determined using the
experimental data at the ratio of l=R smaller than 0.3. We also demonstrate the possibility to determine some other
hyperelastic properties from pipette aspiration tests. Sensitivity of the identified parameters α, b and λm to data errors have
been explored by deriving the corresponding condition numbers in explicit forms. Our results reveal the property ranges in
which the proposed inverse approaches are applicable.
Numerical experiments have been carried out to further examine the extent to which the hyperelastic parameters can be
determined using the inverse approaches proposed in this study. Practical experiments have been conducted on a soft
elastomer and a porcine liver. The identified initial shear modulus from pipette aspiration tests for PDMS matches that
identified from the indentation experimental curve very well. The identified initial shear modulus μ0 and parameter b in the
Fung model for the porcine liver are reasonable in comparison with those reported in the literature (Chui et al., 2004; Tay et
al., 2006; Samur et al., 2007; Gao et al., 2010, 2011), indicating that the proposed method is applicable to this kind of
materials. It is worth mentioning that the degradation of soft tissues significantly affects their properties (Valtorta and
Mazza, 2005), and the variation of their mechanical parameters with time is an interesting issue which may be explored
using the pipette aspiration method proposed here. Besides, the identified parameters for the porcine liver from pipette
aspiration tests do not match the values given by the indentation tests well, which may be attributed to the complex
nonlinear and anisotropic behavior of the porcine liver and the effects of the capsule layer. In addition, we have discussed
the effects of the time-dependent behavior of the porcine liver and surface adhesion and demonstrated the extent to which
they may affect the parameters identified using pipette and indentation tests.

Acknowledgments

Supports from the National Natural Science Foundation of China (Grant Nos. 11172155 and 31270989), Tsinghua
University (2012Z02103 and 20121087991) and 973 Program of MOST (2010CB631005 and 2012CB934001) are
acknowledged.

Appendix A. Hyperelastic material models used in this study

In this study, we investigate four incompressible hyperelastic models, including neo-Hookean, Mooney–Rivlin, Fung, and
Arruda–Boyce models, which have been widely applied to model the nonlinear deformation behavior of rubber-like
materials and biological soft tissues. These models are briefly introduced as follows.

Mooney–Rivlin and neo-Hookean models

Mooney–Rivlin model was first proposed by Mooney (1940) and then written in the form of invariants by Rivlin (1948).
In this model, the strain energy density function Φ reads
K0
Φ ¼ C 10 ðI 1  3Þ þC 01 ðI 2  3Þ þ ðJ  1Þ2 ðA1Þ
2
where C 10 , C 01 and K 0 are material parameters and J the volume ratio. The initial shear modulus μ0 is given by
μ0 ¼ 2ðC 10 þ C 01 Þ for this model. K 0 is the initial bulk modulus, with K 0 -1 representing the incompressible material. I 1
2 2 2
and I 2 are the first and second deviatoric invariants of the left Cauchy–Green deformation tensor, with I 1 ¼ λ 1 þλ 2 þ λ 3 and
2 2 2  1=3
I 2 ¼ λ 1 þ λ 2 þ λ 3 , where λ i is the deviatoric principal stretch relating to the principal stretch λi by λ i ¼ J λi (i¼1,2,3).
When C 01 ¼ 0, Eq. (A1) reduces to the strain energy density function of the neo-Hookean model
K0
Φ ¼ C 10 ðI 1  3Þ þ ðJ  1Þ2 ðA2Þ
2
and in this case, the initial shear modulus μ0 ¼ 2C 10 . The incompressible neo-Hookean model has only one material
parameter, i.e., μ0 or C 10 .
194 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

Fung model

Fung (1979) proposed a hyperelastic model to describe the nonlinear deformation behavior of some biological soft
tissues. The strain energy density function is given by
!
C bðI1  3Þ K 0 J 2 1
Φ ¼ ðe  1Þ þ  ln J ; ðA3Þ
2b 2 2

where C and b are material parameters. The initial shear modulus μ0 is given by μ0 ¼ C. For incompressible materials, this
model contains only two material parameters, i.e., μ0 and b.

Arruda–Boyce model

Arruda and Boyce (1993) developed a hyperelastic model based on an eight-chain representation of the underlying
macromolecular network structure of the rubber and the non-Gaussian behavior of the chains in the network. The strain
energy density function in this model is given by
( )
1 1 2 11 3 19 4 519 5
Φ ¼ μ ðI 1  3Þ þ ðI 1  9Þ þ ðI 1  27Þ þ ðI 1  81Þ þ ðI 1 243Þ
2 20λ2m 1050λ4m 7000λ6m 673750λ8m
!
2
K0 J  1
þ  ln J ; ðA4Þ
2 2

For an incompressible material, this model captures the cooperative nature of network deformation with only two
material parameters, i.e. the shear modulus μ and locking stretch λm . The two parameters are linked to the physics of
molecular chain orientation involved in the deformation of rubbery materials and elastomers. In this model, the initial shear
modulus μ0 is related to the shear modulus μ by
!
3 99 513 42039
μ0 ¼ μ 1 þ 2 þ þ þ ; ðA5Þ
5λm 175λ4m 875λ6m 67375λ8m

where the locking λm represents the stretch at which the stress starts to increase without limit and can be obtained by the
limit chain λlim as
sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
 ffi
1 2 2
λm ¼ λ þ : ðA6Þ
3 lim λlim

For Arruda–Boyce model, μ is the input parameter in such commercial finite element software as ABAQUS instead of μ0 .

Appendix B. Explicit expressions of the dimensionless functions ΠMR , ΠF and Π AB

Explicit expression of the dimensionless function Π MR based on Fig. 4a is given by


 2
l l l
Π MR ðα; Þ ¼ 0:042875 þ2:653379 þ 0:674110
R R R
"  2 #
l l
þ 0:017343 0:166173 þ 1:785349 α
R R
"  2 #
l l
þ 0:002801 þ 0:029142 0:094008 α2 ðA7Þ
R R

where 0 oðl=RÞ r1. The dimensionless function Π F in explicit form based on Fig. 4b is given by
  h i
l
Π F b; ¼  16:273838 þ 16:210615e0:153497ðl=RÞ þ0:068354e5:904548ðl=RÞ
R
h i
þ 0:103135 þ0:165182e5:998895ðl=RÞ 0:247468e4:698316ðl=RÞ ½ lnðbÞ
h i
þ 0:068740 0:210895e5:090200ðl=RÞ þ0:153131e6:057408ðl=RÞ ½ lnðbÞ2
h i
þ 0:060812 þ0:075863e5:983692ðl=RÞ 0:120863e5:055958ðl=RÞ ½ lnðbÞ3
h i
þ 0:007117 þ 0:006705e  161:871617ðl=RÞ þ 0:000366e8:326869ðl=RÞ ½ lnðbÞ4 ðA8Þ

where 0 oðl=RÞ r1, 0 o br 1. For 1 ob r10 and based on Fig. 4c, Π F is expressed as
  h i
l
Π F b; ¼  2:388971 þ 2:387995e1:246267ðl=RÞ þ 0:001443e12:589383ðl=RÞ
R
M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196 195

h i
þ 0:501577 0:489942e  0:220895ðl=RÞ 0:000042e25:234692ðl=RÞ ½ lnðbÞ
h i
þ 1:013926 1:012529e  0:286049ðl=RÞ þ0:000184e24:557217ðl=RÞ ½ lnðbÞ2
h i
þ 0:390136 þ 0:389345e  0:128033ðl=RÞ  0:000196e24:171280ðl=RÞ ½ lnðbÞ3
h i
þ 0:445555 0:445213e  0:056030ðl=RÞ þ0:000086e23:387736ðl=RÞ ½ lnðbÞ4 ðA9Þ

where 0 o ðl=RÞ r0:5. The dimensionless function Π AB in explicit form based on Fig. 4d is given by
  h i
l
Π AB λm ; ¼ 3:212475 þ 0:178930e4:214117ðl=RÞ  3:393145e  0:705540ðl=RÞ
R
h i
þ  0:899541 þ 2:221280e2:938729ðl=RÞ  1:417685e3:845884ðl=RÞ ½ lnðλm Þ
h i
þ 0:907714  1:932754e2:931440ðl=RÞ þ 1:126595e4:026018ðl=RÞ ½ lnðλm Þ2
h i
þ  0:350130 þ 0:869194e2:997576ðl=RÞ  0:518560e4:063601ðl=RÞ ½ lnðλm Þ3
h i
þ  0:231170 þ 0:223927e  0:406530ðl=RÞ þ 0:009046e5:543763ðl=RÞ ½ lnðλm Þ4 ðA10Þ

with 0 o ðl=RÞ r 1.

Appendix C. Supplementary materials

Supplementary material associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.
jmps.2014.03.012.

References

ABAQUS, 2009. ABAQUS User's Manual, Version 6.9.


Aoki, T., Ohashi, T., Matsumoto, T., Sato, M., 1997. The pipette aspiration applied to the local stiffness measurement of soft tissues. Ann. Biomed. Eng. 25,
581–587.
Arruda, E.M., Boyce, M.C., 1993. A three-dimensional constitutive model for the large stretch behavior of rubber elastic materials. J. Mech. Phys. Solids 41,
389–412.
Barenblatt, G.I., 1996. Scaling, self-similarity, and intermediate asymptotics: dimensional analysis and intermediate asymptotics. Cambridge University
Press, Cambridge.
Boudou, T., Ohayon, J., Arntz, Y., Finet, G., Picart, C., Tracqui, P., 2006. An extended modeling of the micropipette aspiration experiment for the
characterization of the Young modulus and Poisson ratio of adherent thin biological samples: numerical and experimental studies. J. Biomech. 39,
1677–1685.
Briscoe, B.J., Fiori, L., Pelillo, E., 1998. Nano-indentation of polymeric surfaces. J. Phys. D: Appl. Phys. 31, 2395.
Brunon, A., Bruyère-Garnier, K., Coret, M., 2010. Mechanical characterization of liver capsule through uniaxial quasi-static tensile tests until failure. J.
Biomech. 43, 2221–2227.
Cao, Y.P., Lu, J., 2004. Depth-sensing instrumented indentation with dual sharp indenters: stability analysis and corresponding regularization schemes. Acta
Mater. 52, 1143–1153.
Cao, Y.P., Zhang, M.G., Feng, X.Q., 2013. Indentation method for measuring the viscoelastic kernel function of nonlinear viscoelastic soft materials. J. Mater.
Res. 28, 806–816.
Cao, Y.P., Li, G.Y., Zhang, M.G., Feng, X.Q., 2014. Pipette aspiration method for measuring the reduced creep function of viscoelastic soft materials. J. Appl.
Mech. 81, 071006.
Chabanas, M., Luboz, V., Payan, Y., 2003. Patient specific finite element model of the face soft tissues for computer-assisted maxillofacial surgery. Med.
Image Anal. 7, 131–151.
Cheng, Y.-T., Cheng, C.-M., 2004. Scaling, dimensional analysis, and indentation measurements. Mater. Sci. Eng. R 44, 91–149.
Cheng, Y.-T., Cheng, C.-M., 2005. Relationships between initial unloading slope, contact depth, and mechanical properties for conical indentation in linear
viscoelastic solids. J. Mater. Res. 20, 1046–1053.
Constantinides, G., Kalcioglu, Z.I., McFarland, M., Smith, J.F., Van Vliet, K.J., 2008. Probing mechanical properties of fully hydrated gels and biological tissues.
J. Biomech. 41, 3285–3289.
Cross, S.E., Jin, Y.-S., Rao, J., Gimzewski, J.K., 2007. Nanomechanical analysis of cells from cancer patients. Nat. Nanotechnol. 2, 780–783.
Chui, C., Kobayashi, E., Chen, X., Hisada, T., Sakuma, I., 2004. Combined compression and elongation experiments and non-linear modelling of liver tissue for
surgical simulation. Med. Biol. Eng. Comput. 42, 787–798.
Evans, E.A., 1983. Bending elastic modulus of red blood cell membrane derived from buckling instability in micropipet aspiration tests. Biophys. J. 43, 27–30.
Fischer-Cripps, A.C., 2011. Nanoindentation. Springer Verlag, New York.
Fung, Y.C., 1993. Biomechanics: Mechanical Properties of Living Tissues. Springer Verlag, New York.
Fung, Y.C., Fronek, K., Patitucci, P., 1979. Pseudoelasticity of arteries and the choice of its mathematical expression. Am. J. Physiol. Heart Circ. Physiol. 237,
H620–H631.
Gao, H., Yao, H., 2004. Shape insensitive optimal adhesion of nanoscale fibrillar structures. Proc. Natl. Acad. Sci. USA 101, 7851–7856.
Gao, L., Zhang, Q., Liu, M., 2011. Indentation test of soft tissue for investigating needle tissue machining. In: Proceedings of the IEEE 2011 International
Conference on Mechanic Automation and Control Engineering (MACE), pp. 348–351.
Gao, Z., Lister, K., Desai, J., 2010. Constitutive modeling of liver tissue: experiment and theory. Ann. Biomed. Eng. 38, 505–516.
Guevorkian, K., Colbert, M.-J., Durth, M., Dufour, S., Brochard-Wyart, F., 2010. Aspiration of biological viscoelastic drops. Phys. Rev. Lett. 104, 218101.
Guilak, F., Jones, W.R., Ting-Beall, H.P., Lee, G.M., 1999. The deformation behavior and mechanical properties of chondrocytes in articular cartilage.
Osteoarthr. Cartil. 7, 59–70.
Hadamard, J., 1923. Lectures on Cauchy Problem in Linear Partial Differential Equations. Yale University Press, New Haven.
Hochmuth, R.M., 2000. Micropipette aspiration of living cells. J. Biomech. 33, 15–22.
196 M.-G. Zhang et al. / J. Mech. Phys. Solids 68 (2014) 179–196

Hu, Y.H., Zhao, X.H., Vlassak, J., Suo, Z.G., 2010. Using indentation to characterize the poroelasticity of gels. Appl. Phys. Lett. 92, 121904.
Hu, Y., Chen, X., Whitesides, G.M., Vlassak, J.J., Suo, Z., 2011. Indentation of polydimethylsiloxane submerged in organic solvents. J. Mater. Res. 26, 785–795.
Johnson, K.L., Kendall, K., Roberts, A.D., 1971. Surface energy and the contact of elastic solids. Proc. R. Soc. Lond. Ser. A Math. Phys. Sci. 324, 301–313.
Kalcioglu, Z.I., Mrozek, R.A., Mahmoodian, R., VanLandingham, M.R., Lenhart, J.L., Van Vliet, K.J., 2013. Tunable mechanical behavior of synthetic organogels
as biofidelic tissue simulants. J. Biomech. 46, 1583–1591.
Kalcioglu, Z.I., Qu, M., Strawhecker, K.E., Shazly, T., Edelman, E., VanLandingham, M.R., Smith, J.F., Van Vliet, K.J., 2011. Dynamic impact indentation of
hydrated biological tissues and tissue surrogate gels. Philos. Mag. 91, 1339–1355.
Kauer, M., 2001. Inverse Finite Element Characterization of Soft Tissues with Aspiration Experiments (Ph.D. thesis). Swiss Federal Institute of Technology,
Zurich.
Kranenburg, J.M., Tweedie, C.A., Van Vliet, K.J., Schubert, U.S., 2009. Challenges and progress in high-throughput screening of polymer mechanical
properties by indentation. Adv. Mater. 21, 3551–3561.
Kumar, S., Weaver, V., 2009. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metast. Rev. 28, 113–127.
Li, B., Cao, Y.-P., Feng, X.-Q., Gao, H., 2012. Mechanics of morphological instabilities and surface wrinkling in soft materials: a review. Soft Matter 8,
5728–5745.
Mattice, J.M., Lau, A.G., Oyen, M.L., Kent, R.W., 2006. Spherical indentation load-relaxation of soft biological tissues. J. Mater. Res. 21, 2003–2010.
Merryman, W.D., Bieniek, P.D., Guilak, F., Sacks, M.S., 2009. Viscoelastic properties of the aortic valve interstitial cell. J. Biomech. Eng. 131, 041005.
Miller, K., Wittek, A., Joldes, G., 2010. Biomechanics of the brain for computer-integrated surgery. Acta Bioeng. Biomech. 12, 25.
Mooney, M., 1940. A theory of large elastic deformation. J. Appl. Phys. 11, 582–592.
Nava, A., Mazza, E., Furrer, M., Villiger, P., Reinhart, W.H., 2008. in vivo mechanical characterization of human liver. Med. Image Anal. 12, 203–216.
Oliver, W.C., Pharr, G.M., 2004. Measurement of hardness and elastic modulus by instrumented indentation: advances in understanding and refinements to
methodology. J. Mater. Res. 19, 3–20.
Oommen, B., Van Vliet, K., 2006. Effects of nanoscale thickness and elastic nonlinearity on measured mechanical properties of polymeric films. Thin Solid
Films 513, 235–242.
Ophir, J., Cespedes, I., Ponnekanti, H., Yazdi, Y., Li, X., 1991. Elastography: a quantitative method for imaging the elasticity of biological tissues. Ultrason.
Imaging 13, 111–134.
O'Rourke, M., 1995. Mechanical principles in arterial disease. Hypertension 26, 2–9.
Rivlin, R.S., 1948. Large elastic deformations of isotropic materials. IV. Further developments of the general theory. Philos. Trans. R. Soc. A 241, 379–397.
Samur, E., Sedef, M., Basdogan, C., Avtan, L., Duzgun, O., 2007. A robotic indenter for minimally invasive measurement and characterization of soft tissue
response. Med. Image Anal. 11, 361–373.
Sato, M., Theret, D., Wheeler, L., Ohshima, N., Nerem, R., 1990. Application of the micropipette technique to the measurement of cultured porcine aortic
endothelial cell viscoelastic properties. J. Biomech. Eng. 112, 263.
Smith, S., Finzi, L., Bustamante, C., 1992. Direct mechanical measurements of the elasticity of single DNA molecules by using magnetic beads. Science 258,
1122–1126.
Simo, J.C., 1987. On a fully three-dimensional finite-strain viscoelastic damage model: formulation and computational aspects. Comput. Methods Appl.
Mech. Eng. 60, 153–173.
Sun, W., Lal, P., 2002. Recent development on computer aided tissue engineering –a review. Comput. Methods Progr. Biomed. 67, 85–103.
Tay, B.K., Kim, J., Srinivasan, M.A., 2006. in vivo mechanical behavior of intra-abdominal organs. IEEE Trans. Biomed. Eng. 53, 2129–2138.
Tweedie, C.A., Van Vliet, K.J., 2006. Contact creep compliance of viscoelastic materials via nanoindentation. J. Mater. Res. 21, 1576–1589.
Umale, S., Deck, C., Bourdet, N., Dhumane, P., Soler, L., Marescaux, J., Willinger, R., 2013. Experimental mechanical characterization of abdominal organs:
liver, kidney &; spleen. J. Mech. Behav. Biomed. Mater. 17, 22–33.
Valtorta, D., Mazza, E., 2005. Dynamic measurement of soft tissue viscoelastic properties with a torsional resonator device. Med. Image Anal. 9, 481–490.
Zhang, M.-G., Cao, Y.-P., Li, G.-Y., Feng, X.-Q., 2014. Spherical indentation method for determining the constitutive parameters of hyperelastic soft materials.
Biomech. Model. Mechan. 13, 1–11.
Zhao, R., Sider, K.L., Simmons, C.A., 2011. Measurement of layer-specific mechanical properties in multilayered biomaterials by micropipette aspiration. Acta
Biomater. 7, 1220–1227.
Ziemann, F., Rädler, J., Sackmann, E., 1994. Local measurements of viscoelastic moduli of entangled actin networks using an oscillating magnetic bead
micro-rheometer. Biophys. J. 66, 2210–2216.
Zimberlin, J.A., McManus, J.J., Crosby, A.J., 2010. Cavitation rheology of the vitreous: mechanical properties of biological tissue. Soft Matter 6, 3632–3635.

You might also like