PUNCTURE DEPTH AND THE MECHANICAL STABILITY OF

MICRONEEDLES

D. C. C. Lam, Y. H. Lee, K. T. Shek

Department of Mechanical Engineering, The Hong Kong University of Science and Technology

Clear Water Bay, Kowloon, Hong Kong SAR China

G. Pang

Department of Electrical and Electronic Engineering, The University of Hong Kong

Keywords: Drug delivery, microneedles, mechanical behaviour, punctures, silicone rubber.

Abstract: Microneedles penetrating less than 1mm beneath the skin can deliver the drugs directly without piercing

blood vessels or damaging nerves. The mechanical stability and the puncture behaviour were investigated

experimentally by inserting steel needles into silicone rubber and pig skin. Puncture tests revealed that the

length of needle buried in the flesh is less than 50% of the nominal insertion depth when the insertion depth

is less 1mm. The mechanical stability of the buried needle-flesh assembly, characterized by the force needed

to retract the needle, decreased with buried depth and needle diameter. Analysis of the load data suggested

that a 100-micron diameter microneedle buried 100 microns deep in pig skin would have a retraction force

of 0.1mN, which is only 1% of the retraction force of a conventional needle inserted 5mm into the skin.

This suggests that the usage of microneedles in arrays is necessary to increase stability and to enable stable

drug delivery.

1 DRUG INJECTION

Drug delivery in hospitals involves modalities as

diverse as hypodermal injection, intravenous

delivery and oral intake. Drugs taken orally must

pass through the digestive system and deal with the

first-pass effect of the liver. Numerous drugs,

particularly those developed in genetics laboratories,

are chemically incompatible with the oral intake

route (Orive et al., 2004) They must be directly

injected into the body. Hypodermal injection

involves training, some pain and potential blood

loss, making self-injection at home unwelcome for

patients.

Other than direct injection, drugs can be

delivered via absorption through the skin. The skin

is a natural barrier to foreign chemicals and

biological agents. A few drugs such as nicotine and

its substitutes have been customized for absorption

by the skin. Chemical customization of individual

drugs for such absorption is technically challenging,

and in many cases, economically unfeasible. Instead

of traversing the skin via absorption, solid or hollow

microneedles can be used to physically puncture the

skin. Drugs can pass through a capillary-scale

channel in the hollow needle, or can be delivered as

a soluble coating on the needle surface. For such.

0.05

0.1

0.15

0.2

00.511.52

Liver insertion

Retraction force (N/mm)

Needle diameter (mm)

m=0.1N/mm/mm

Figure 1: Retraction load for needles with conical and

beveled tips. Data from (Okamura).

291

C. C. Lam D., H. Lee Y., T. Shek K. and Pang G. (2008).

PUNCTURE DEPTH AND THE MECHANICAL STABILITY OF MICRONEEDLES.

In Proceedings of the First International Conference on Biomedical Electronics and Devices, pages 291-296

DOI: 10.5220/0001054802910296

 SciTePress

applications, the microneedles must be long enough

to bridge the surface skin layer, but short enough to

avoid piercing the blood vessels and nerves that are

typically 0.5 – 1mm under the skin surface

There is now a large body of knowledge,

processes and tools that have been developed for the

design and fabrication of micro- and

nanoelectromechanical systems (MEMS and

NEMS). A number of researchers have developed

silicon microneedles using MEMS processes.

(Stoeber & Liepmann, 2005; Staples et al., 2006; Ji,

et al., 2006). Silicon microneedle arrays have been

fabricated successfully and tested in trials with rats

(Nordquist et al., 2007). These tests were concept

demonstrations showing that drugs can be delivered

using microneedles. However, a variety of issues,

including safety concerns about the use of brittle

silicon microneedles, remains to be solved. Titanium

and polymers are potentially better material choices,

and the fabrications of titanium and polymeric

microneedles (Parker et al., 2007; Park, Allen &

Prausnitz, 2006) has been investigated using

MEMS-based processes.

As another alternative to MEMS-based

technologies, lasers have been used to create arrays

of holes in substrates (Davis et al., 2005).

Microneedle pads have been created by plating a

metal shell onto the holed surface. The microneedles

in arrays fabricated in this fashion are hundreds of

microns long, with walls limited to several microns

thick because of plating limits. Silicon or metal

microneedles fabricated in this way are inherently

small because the processes are inherently micron

and submicron processes. Recognizing the inherent

process limits, microinjection molding suited for

fabricating millimeter-scale parts has been used to

make polymer microneedles (Sammoura et al.,

2007).

Conventional hypodermic needles are typically

more than a few millimetres long with diameters

typically ranging from 220 microns on up. Such

needles are designed to puncture skin and deliver

drugs deep underneath the skin. They are not

designed for drug delivery at insertion depths of

1mm or less. Limited studies had been conducted to

examine systematically the puncture behaviour of

such large needles at deep and shallow depths. Long

needle puncture studies were conducted by Nguyen

& Vu-Khanh on rubber sheets (Nguyen & Vu-

Khanh,, 2004) and by Sherwood’s group (Sherwood

& Fleck, 2004) on solid rubber. They observed

significant indentation deformation occurred before

puncture in these tests.

For microneedles, where penetration is less than

1mm into the skin, indentation is expected to be

significant and to affect drug delivery. The effect of

needle diameter had been examined in a study of

needle insertion into the liver (Okamura, 2004). The

study revealed that the force required to retract the

needle was strongly dependent on the needle

diameter and the insertion depth (Figure 1). Small

microneedles inserted into the surface of the skin

should have retraction forces in the mN range and

each individual puncture may have low mechanical

stability. The effect of depth and needle diameter on

the insertion and retraction behaviour were

examined this study.

2 INVESTIGATIVE APPROACH

The puncture behaviour of single steel needles

pressed to depths of 0.2 to 8mm was examined in

this study. Following the methods pioneered by

(Sherwood & Fleck, 2004), microstructurally

uniform and homogeneous silicone rubber was used

Figure 2: Mechanical testing setup.

Figure 3: 130-micron needle insertion behaviour i

silicone rubber at 0.2mm pressed depth.

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as a reference puncture material to examine the

puncture behaviour. The puncture behaviour of pig

skin was also examined to determine the load and

depth range of puncture behaviour in biological

materials.

The puncture experiments were conducted on a

Tytron 250 press from MTS Systems Corporation

equipped with a linear drive actuator. Silicone

rubber blocks were cast from a Shin-Etsu silicone

premix and cured according to the manufacturer’s

specifications. Medical grade stainless steel needles

130, 220 or 300 microns in diameter were mounted

on a custom designed jig for puncture testing (Figure

2). Once mounted, the loads and positions were

calibrated. The needle was held fixed while the

silicone rubber casting was moved toward the needle

at displacement rates of 0.1 mm/s, 0.13 mm/s, 0.15

mm/s or 0.18 mm/s to a target maximum pressed

depth (MPD), and then reversed at the same rate.

The experiment ended when the displacement

reached zero. The experiment was repeated for a

range of MPDs from 0.2 mm to 8 mm.

3 RESULTS AND ANALYSES

3.1 Shallow Insertion Depths

The load-displacement results at 0.2mm MPD are

shown in Figure 3. The curves indicate that the peak

load was displacement rate dependent. At each

displacement rate, the unload curve collapsed onto

the load curve. This indicates that the deformation

recovered elastically without puncture. The absence

of a hysteresis between the load and unload curves

indicates that no energy was dissipated at 0.2mm

MPD. In addition, the higher peak loads at higher

displacement rates did not result in puncture. This

suggests that needles less than 0.2mm long have

difficulty in puncturing soft silicone rubber.

3.2 Puncture Depth

The results at 6mm MPD are plotted in Figure 4. As

with the tests in Figure 3, the displacement was

reversed from loading to unloading in each trial

upon reaching the 6mm maximum set displacement.

The unloading curves did not retrace the loading

Figure 4: 130-micron needle insertion behaviour in silicone

rubber at 6mm maximum pressed depth.

Figure 5: Ratio of buried to pressed depth for needle

insertion into silicone rubber using 130-micron needles.

0.2

0.4

0.6

0.8

0123456

0.08 mm/s

0.1 mm/s

0.13 mm/s

0.15 mm/s

0.18 mm/s

Buried depth/Pressed depth

Maximum Pressed depth (mm)

Figure 6: Ratio of buried to pressed depth for needle

insertion in pig skin using 130-micron needles.

PUNCTURE DEPTH AND THE MECHANICAL STABILITY OF MICRONEEDLES

293

curves, but rather intersected the zero load line to the

right of the triangle, crossing into the tension region.

Unlike the penetration behaviour at 0.2mm MPD,

where the needle was fully withdrawn at zero load,

the needle retracting from 6mm MPD remained

buried in the rubber. This zero load depth on

retraction was taken to represent the buried depth on

insertion. A plot of the buried needle depth

normalized by the MPD is plotted in Figure 5. At

large MPDs, the ratio approached unity, but at

MPDs less than 1mm, the ratio was significantly less

than one. The low ratios at settings below 1mm

indicate that an increasingly significant proportion

of the needle was left outside the solid during the

loading phase.

The MPD for needle insertion into pig skin is plotted

in Figure 6. Biological materials are less uniform

and the ratio is more scattered. Despite this, the

trend is similar to that observed with the silicone

rubber in that the ratio approaches unity at large

pressed depth, but is 0.5 or less when the pressed

depth was 2mm or less.

3.3 Retraction Force

The maximum retraction load (MRL; bottom right

apex in Figure 3) required to pull a 130-micron

needle out after pressing is shown in Figure 7. The

data show that the retraction forces at different

displacement rates collapsed onto a single line for

the 130 micron-needle. The MRL for the 300-

micron needle is plotted in Figure 8. The MRL for

this larger needle was clearly displacement

Figure 7: Maximum retraction force for 130-micron

needle insertion into silicone rubber.

Figure 8: Maximum retraction force for a 300-micron

needle inserted into silicone rubber.

Figure 9: Rate dependence of retraction force per unit o

uried needle length for needle insertion into silicone

rubber.

Figure 10: Diameter dependence of retraction force

unit of buried depth in silicone rubber.

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-0.25

-0.2

-0.15

-0.1

-0.05

0.05

01234

0.08 mm/s

0.1 mm/s

0.13 mm/s

0.15 mm/s

0.18 mm/s

Retraction force (N)

Maximum Pressed depth (mm)

Figure 11: Comparison of maximum retraction force wit

model (line) at shallow pressed depth.

dependent. The MRL was markedly higher at higher

retraction rates. Thus, while the 130-micron needle’s

rate dependence appeared negligible, this was not

the case with larger diameter needles. The rate of

change of the MRL with buried depth as a function

of the displacement rate is plotted in Figure 9. The

plot shows that the rate dependence was linear for all

the needles tested, and that the MRL decreased with

decreasing needle diameter. The influence of needle

diameter is plotted in Figure 10. The MRL was

greatest at high displacement rates. Fitting a straight

line through the data with the highest displacement

gives a slope of -1.6N/mm/mm, which is the MRL

per unit of buried depth and needle diameter. Using

this as a basis for estimate, in Figure 11 a line is

plotted and compared with the retraction loads

observed with a 130-micron needle at depths less

than 1000 microns. The comparison showed

reasonable agreement between the data and the

prediction.

The MRL for insertion into pig skin is plotted in

Figure 12. As expected, the magnitude of the MRL

increased with the actual buried depth, but the

displacement rate dependence cannot be delineated

given the greater scatter. The rate of change of the

MRL per unit of buried depth and needle diameter

was approximately 0.1N/mm/mm.

4 DISCUSSION

The length of the needle buried in the flesh during

hypodermal insertion is generally assumed to equal

to the pressed depth. This assumption is reasonable

for deep insertions, but breaks down when the

needle is less than 2000 microns long. At pressed

depths under 1000 microns, less than half of the

needle maybe buried; and no penetration was

observed at pressed depths less than 200 microns.

Since the lengths of microneedles fabricated using

MEMS processes are limited by the thickness of the

wafer, which is typically less than 300 microns

thick. Silicon microneedles less than 300 microns

long may have difficulty in puncturing the skin. If

punctured, the maximum buried depth will likely be

less than 100 microns.

Another issue is the mechanical stability of the

microneedles. When punctured, the surrounding

material in the puncture will exert traction onto the

buried needle and prevents it from slipping out of

the puncture hole. The retraction force was found to

decrease at a rate of -1.6N/mm of buried depth/mm

of needle diameter for silicone rubber, and -

0.1N/mm/mm for pig skin (Figure 12). In

comparison, the corresponding value for the case of

needle puncture into liver is -0.1N/mm/mm. Using

this as an estimate for biological materials, a 0.1mm

microneedle buried 0.1mm into the skin would have

a retraction force of 1mN. A conventional 0.22mm

needle inserted into flesh 5mm would have a

retraction force of 110mN, which is 100 times

greater. If an array of 110 microneedles were used,

the retraction force can be increased to 100mN such

that the microneedles can remain stably buried to

allow stable drug delivery. The puncture behavior

and the design guidelines for stably drug delivery

are reported in another paper.

Figure 12: Retraction force for 130-micron insertion in pig

skin.

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295

5 CONCLUSIONS

Examination of the puncture behaviour needles with

a silicone rubber model indicated that indentation

effects are significant at shallow insertion depths for

both silicone rubber and pig skin. Less than 50% of

the needle may be buried because of indentation

when short microneedles are used. The investigation

also revealed that the retraction force providing

mechanical stability to the needle in the skin was

linearly proportional to the buried depth and the

needle diameter. Short microneedles with small

diameters will have low retraction forces and poor

mechanical resistance against being dislodged.

ACKNOWLEDGEMENTS

This work was supported by grants from Hong

Kong’s Research Grants Council. The authors also

acknowledge the use of equipment provided by the

Advanced Engineering Materials facility at the

HKUST.

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