14
Bioinspired, Biomimetic and Nanobiomaterials Volume 1 Issue BBN4 Micro and nano patterning of carbon electrodes for bioMEMS Sharma and Madou 252 ice | science 1. Introduction In recent years, carbon has received much attention as a material for micro and nanofabrication. Rigorous research has been performed on carbon nanotubes (CNTs), carbon microelectromechanical systems (CMEMS), carbon nanomechanical systems (CNEMS), carbon micro/nanofibers, carbon nanospheres, carbon whiskers, and graphene for applications in biomedical engineering, sensor technology, and electronic applications. 1–5 Initially, silicon was employed as the platform of choice for most MEMS fabrication because fabrication methodologies and equipment from the integrated circuit industry, which operates almost exclusively on silicon, could be adapted. 6 In those early days, the mid-80s, MEMS applications were limited to pressure sensors, accelerometers, and gyros, for which Si is an excellent material’s choice. With MEMS being applied more and more to biomedical applications, ‘bioMEMS’ evolved, representing a new class of MEMS that commands its own fabrication tools and involves a much wider range of materials. BioMEMS devices include biosensors such as glucose sensors blood gas blood electrolyte sensors, lab-on-chip systems and diagnostic medical tools such as protein and DNA arrays. 6 Because of the irreversible chemical reactions involved in many medical tests (e.g. nucleic acid and immuno assays) and because of contamination considerations, bioMEMS devices tend to be disposable, and therefore call for an inexpensive material and fabrication technique. Today, biocompatible metals (e.g. silver, gold), 7,8 various biodegradable polymers (e.g. polycaprolactone), 9 soft-biocompatible polymers such as silicone (polydimethylsiloxane (PDMS)) 10 and advanced carbon materials (CMEMS, CNEMS, carbon fibers (CFs) and capsules, CNTs, etc.) 1–5,11 often replace silicon for disposable bioMEMS applications. Carbon, in particular, is a low-cost material that can be derived by the carbonization of certain precursor polymers. Also, CMEMS/ CNEMS fabrication processes are suitable for mass manufacturing and that makes them attractive for a wide-variety of future bioMEMS applications. CMEMS and CNEMS applications employ micro and nanodevices of a wide-variety of shapes, dimensions, and chemical and mechanical properties that are otherwise difficult or very expensive to implement. 12 With advanced photolithographic techniques and the use of appropriate precursor polymer materials such as SU8, fabrication of miniaturized carbon devices has rapidly evolved from the micrometer-sized CMEMS devices to nanometer-sized CNEMS devices. 12 Today, the most common fabrication methodology for CMEMS and CNEMS fabrication is photolithography of a photoresist (mainly SU8), and carbonization of the thus patterned polymer by pyrolysis. 2,11,12 Some of the early attempts of CMEMS fabrication also employed patterning by soft lithography, 13 molding, 14,15 and chemical vapor deposition. 16 Here, the fabrication Micro and nano patterning of carbon electrodes for bioMEMS Swati Sharma* MSc PhD Student, Materials and Manufacturing Technology, University of California, Irvine (UCI), California, USA Marc Madou PhD Chancellor’s Professor, Mechanical & Aerospace Engineering and Biomedical Engineering, University of California, Irvine (UCI), California, USA Carbon based bioMEMS are an emerging class of miniaturized biomedical devices. Due to the numerous advantages such as scalable manufacturing processes, inexpensive and readily available precursor polymer materials, tunable surface properties and biocompatibility, carbon has become a preferred material for a wide variety of future biosensing applications. In this article, we review fabrication methodologies for carbon-MEMS (CMEMS) and carbon-NEMS (CNEMS) devices and strategies for their surface modification for biocompatibility and for biosensing. We also discuss the underlying graphitic and glassy microstructures of carbon since the biocompatibility of carbon and its microstructures are intertwined. We conclude by exploring various CMEMS and CNEMS devices that have been successfully fabricated. 1 2 Pages 252–265 http://dx.doi.org/10.1680/bbn.12.00010 Themed Issue Paper Received 07/05/2012 Accepted 12/06/2012 Published online 27/06/2012 Keywords: carbon MEMS/bioMEMS/biosensor ICE Publishing: All rights reserved 1 2 *Corresponding author email address: [email protected]

Micro and nano patterning of carbon electrodes for bioMEMS · PDF fileBioinspired, Biomimetic and Nanobiomaterials Volume 1 Issue BBN4 Micro and nano patterning of carbon electrodes

  • Upload
    hakien

  • View
    217

  • Download
    1

Embed Size (px)

Citation preview

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

252

ice | science

1. IntroductionIn recent years, carbon has received much attention as a material for

micro and nanofabrication. Rigorous research has been performed on

carbon nanotubes (CNTs), carbon microelectromechanical systems

(CMEMS), carbon nanomechanical systems (CNEMS), carbon

micro/nanofi bers, carbon nanospheres, carbon whiskers, and graphene

for applications in biomedical engineering, sensor technology, and

electronic applications.1–5 Initially, silicon was employed as the

platform of choice for most MEMS fabrication because fabrication

methodologies and equipment from the integrated circuit industry,

which operates almost exclusively on silicon, could be adapted.6

In those early days, the mid-80s, MEMS applications were limited

to pressure sensors, accelerometers, and gyros, for which Si is an

excellent material’s choice. With MEMS being applied more and

more to biomedical applications, ‘bioMEMS’ evolved, representing

a new class of MEMS that commands its own fabrication tools

and involves a much wider range of materials. BioMEMS devices

include biosensors such as glucose sensors blood gas blood

electrolyte sensors, lab-on-chip systems and diagnostic medical

tools such as protein and DNA arrays.6 Because of the irreversible

chemical reactions involved in many medical tests (e.g. nucleic acid

and immuno assays) and because of contamination considerations,

bioMEMS devices tend to be disposable, and therefore call for an

inexpensive material and fabrication technique. Today, biocompatible

metals (e.g. silver, gold),7,8 various biodegradable polymers (e.g.

polycaprolactone),9 soft-biocompatible polymers such as silicone

(polydimethylsiloxane (PDMS))10 and advanced carbon materials

(CMEMS, CNEMS, carbon fi bers (CFs) and capsules, CNTs,

etc.)1–5,11 often replace silicon for disposable bioMEMS applications.

Carbon, in particular, is a low-cost material that can be derived by

the carbonization of certain precursor polymers. Also, CMEMS/

CNEMS fabrication processes are suitable for mass manufacturing

and that makes them attractive for a wide-variety of future bioMEMS

applications. CMEMS and CNEMS applications employ micro and

nanodevices of a wide-variety of shapes, dimensions, and chemical

and mechanical properties that are otherwise diffi cult or very

expensive to implement.12

With advanced photolithographic techniques and the use of

appropriate precursor polymer materials such as SU8, fabrication

of miniaturized carbon devices has rapidly evolved from the

micrometer-sized CMEMS devices to nanometer-sized CNEMS

devices.12 Today, the most common fabrication methodology

for CMEMS and CNEMS fabrication is photolithography of a

photoresist (mainly SU8), and carbonization of the thus patterned

polymer by pyrolysis.2,11,12 Some of the early attempts of CMEMS

fabrication also employed patterning by soft lithography,13

molding,14,15 and chemical vapor deposition.16 Here, the fabrication

Micro and nano patterning of carbon electrodes for bioMEMS

Swati Sharma* MScPhD Student, Materials and Manufacturing Technology, University of California, Irvine (UCI), California, USA

Marc Madou PhDChancellor’s Professor, Mechanical & Aerospace Engineering and Biomedical Engineering, University of California, Irvine (UCI), California, USA

Carbon based bioMEMS are an emerging class of miniaturized biomedical devices. Due to the numerous advantages

such as scalable manufacturing processes, inexpensive and readily available precursor polymer materials, tunable surface

properties and biocompatibility, carbon has become a preferred material for a wide variety of future biosensing applications.

In this article, we review fabrication methodologies for carbon-MEMS (CMEMS) and carbon-NEMS (CNEMS) devices and

strategies for their surface modifi cation for biocompatibility and for biosensing. We also discuss the underlying graphitic

and glassy microstructures of carbon since the biocompatibility of carbon and its microstructures are intertwined. We

conclude by exploring various CMEMS and CNEMS devices that have been successfully fabricated.

1 2

Pages 252–265 http://dx.doi.org/10.1680/bbn.12.00010Themed Issue PaperReceived 07/05/2012 Accepted 12/06/2012Published online 27/06/2012Keywords: carbon MEMS/bioMEMS/biosensor

ICE Publishing: All rights reserved

1 2

*Corresponding author email address: [email protected]

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

253

process for CMEMS/CNEMS with representative examples from

both SU8 and non-SU8 based techniques is described.

The most desirable feature of carbon-based bioMEMS devices is the

amenability to surface modifi cation of carbon. Carbon is easier to

derivatize with organic molecules compared to most other traditional

MEMS materials such as silicon. Carbon surface modifi cation

can entail chemical and electrochemical modifi cation17–19 as well

as topographical changes.20 In this context, it is important to

understand the underlying microstructure of the various allotropes

of carbon, since the carbon surface refl ects its internal molecular

arrangements.21 Carbon microstructures are usually determined

by the fabrication process details and by the choice of polymer

precursor. In this study, glassy carbon (GC) designs are mostly

dealt since GC is the most commonly used material for bioMEMS

applications. However, in order to better understand the surface

modifi cation techniques and the thus resulting biocompatibility,

examples of carbon micro and nanofi bers that often feature a more

graphitic microstructure are also reviewed. CFs, so far, have not

been implemented for bioMEMS purposes; nevertheless, they have

been successfully employed as implant materials.

2. Carbon microstructureThe properties of carbon vary widely as it comes in many different

allotropes based on the fabrication method involved. CNTs,

graphene, carbon whiskers, and carbon nanofi bers (CNFs) are

non-glassy materials, whereas carbon obtained from pyrolysis of

a precursor polymer is usually glassy (GC). The microstructure of

GC is surprisingly dissimilar from the other carbon allotropes of

carbon and its exact nature has been a matter of dispute for many

years.22–24 GC exhibits excellent electrochemical properties and

may substitute more expensive noble metals such as Pt and Au

commonly employed for the fabrication of miniaturized sensing

electrodes.25–27 For electrochemists, GC electrodes are often used as

the gold standard to compare the electrochemical behavior of other

electrodes. Using CMEMS and CNEMS technology, very small GC

electrode designs are possible by lithographic patterning a photoresist

and carbonizing the design, resulting in sensing devices with novel

geometries and unprecedented sensitivities.28 The fabrication cost of

sophisticated carbon electrode designs is small compared with that

of the more involved patterning of noble metal electrodes because

of the simplicity and the wide range of polymer precursors that are

available in CMEMS and CNEMS processing11 (see Section 3).

In most cases, upon pyrolysis of polymer precursors, a GC results that

possesses glass-like properties and shatters upon breaking. Carbon

is one of the few materials that tends to polymerize with itself,

and therefore, when a precursor polymer is heated to temperatures

high enough to remove more volatile elements, new C-C bonds are

formed. This self-polymerization leads to a network of carbon, the

molecular structure of which depends upon several factors including

the nature and chemical structure of the polymer precursor,

fabrication methodology, pyrolysis temperature, mechanical and

electrical forces acting on the precursor polymer chains, etc.12 These

tunable factors may enhance graphitization especially in the case of

polymer derived CNFs as discussed in detail in Sharma et al.12 More

typically, though bulk polymers with high carbon content such as

SU8, polyacrylonitrile (PAN), polyimides, and polyimides yield GC

upon pyrolysis between 800 and 1200°C. CMEMS fabricated using

photolithography of SU8 have attracted much attention in the recent

past because of their compatibility with deep UV photolithography,

high carbon yield of SU8, and a wide variety of high-aspect-ratio

micro/nano designs (see Section 5).

The exact microstructure of GC was a controversial topic among

researchers for a long time because of the uncertainty of the nature

of the prevailing intermolecular cross-links. As far back as 1951,

Rosalind Franklin23 carried out a comparative study employing

X-ray crystallography to investigate the amount of crystallinity in

graphitizing and non-graphitizing carbons. According to Franklin,

a graphitizing carbon is one that gets converted completely to

graphite upon heat treatment whereas a non-graphitizing carbon is

amorphous or glassy in nature and cannot be converted completely

to graphite even at very high pyrolysis temperatures. Jenkins and

Kawamura22 proposed a model for the structure of GC that consists

of a ribbon-like geometry of entangled carbon sheets (Figure

1(a)). Franklin’s and Jenkins et al’s initial observations were made

analyzing X-ray diffraction patterns, using more advanced structural

analysis techniques, such as high-resolution transmission electron

microscopy (HRTEM). It became evident that even non-graphitizing

polymer derived carbons do contain small isolated crystals of

graphite. These graphitic regions, however, may not fully develop

into full graphite sheets because of chain morphology restrictions in

the parent polymer structure and space constrains. Harris24 proposed

a structural model for non-graphitizing carbons based on HRTEM

imaging, and ventured that GC only contains sp2-hybridized carbons

such as those found in fullerenes. These sp2-bonded carbons contain

six-membered rings as well as fi ve and seven membered rings, and

are highly stable. This model is supported by HRTEM images of

commercially available GC (Figure 1(b)). Harris suggested that GC

prepared at different temperatures results in different packing of the

dispersed carbon sheets (Figures 1(c) and 1(d)).

To better understand the microstructure carbon may adopt while it

evolves from its polymer precursor, it is of paramount interest to

discuss the chemical changes that take place during the pyrolysis

process. When a polymer pattern is pyrolyzed, a multi-step

carbonization process takes place.29 Initially, in the 300–500°C

temperature range, called the carbonization regime, there is a rapid

polymer weight loss because of the removal of elements such as

oxygen, nitrogen, chlorine, etc. Above 500°C, hydrogen attached

to carbon atoms is cleaved off and removed. A high purity GC,

that is, one with almost all H atoms removed, is usually obtained

between 800–1200°C. If the temperature is further increased,

graphitic zones start to form. Between 2500 and 3300°C, known

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

254

as the graphitization regime of the pyrolysis process, it is assumed

that the defects (or non-graphitic regions) of the carbon can be

completely annealed out as they become mobile.29 Smaller patterns

or objects, such as CNFs with all surfaces exposed12 tend to become

more graphitic at lower temperatures because defects can reach the

edge of the wire much faster and be annealed out. Other factors

including catalysts, templates, mechanical, and electrical forces

acting on the precursor polymer chains, the polymer precursor

fabrication process itself (e.g. electrospinning, where the polymer

is forced through a small nozzle), etc. may infl uence the degree of

graphitization upon pyrolysis as discussed by Sharma et al.12

3. CMEMS, CNEMS fabrication processIn CMEMS and CNEMS, depending on the desired carbon design, an

organic precursor is patterned by techniques such as photolithography,

electrospinning, electrospinning combined with lithography, CNC

machining, by molding with stamps (soft-lithography or nanoimprint

lithography), or other material patterning means. After patterning,

the polymer is pyrolyzed (also carbonized) and when pyrolysis is

carried out correctly, a shrunk but isometric carbon design results.

In early examples of CMEMS diazo type (e.g. AZ 4330, AZ 1518),

phenol-formaldehyde, and furfuryl alcohol-based resins (poly-furfulyl

alcohol or PFA) were employed as polymer precursor materials.13,30,31

Furfuryl alcohol resin is a furan derivative that is a thermally cross-

linked polymer. As an example of molding a polymer precursor with

a stamp made with soft-lithography, we describe the fabrication of

free-standing carbon microstructures by Schueller et al.13 Using

furfuryl alcohol resins as the polymer precursor, this research team

used a PDMS mold to pattern suspended two-dimensional (2D) GC

patterns that have potential application for actuators as shown in

Figure 2.13 Curing of the furfuryl alcohol resin requires the addition

of a latent (delayed), heat-activated catalyst (such as a 50% aqueous

solution of ZnCl2). The PDMS mold and polymer patterns are pyrolyzed

at 900°C in an argon environment. Upon pyrolysis, the PDMS mold

disintegrates and suspended GC actuators result (Figure 2).

In the CMEMS example in Figure 2, a mold is used to pattern the

precursor polymer. Using photolithography, a photosensitive resist

may also be patterned directly.2,12 Most pyrolysed GC features

derived from traditional positive photoresists are low aspect ratio

(1:1) because most positive photoresists are not very transparent to

the UV exposure light. To meet the challenging demands of higher-

aspect ratio CMEMS and CNEMS applications, a photoresist

with excellent transparency, high contrast and having a range of

viscosities (to enable different resist fi lm thicknesses) is needed.

Figure 1. (a) Jenkins-Kawamura structural model for glassy carbon.22

(b) TEM images of Sigradur G glassy carbon prepared at 2800oC.

(c), (d)) Models for the structure of low-temperature and high-

temperature glassy carbon ((b)–(d)).24

Lc

La

(a)

(c) (d)

(b)

5 nm

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

255

An epoxy novolac-based negative photoresist, SU8, developed by

IBM and marketed by MicroChem Inc., Newton, MA, USA and

Gersteltec SARL, Pully, Switzerland,32,33 meets these requirements

as it has a very high deep UV transparency, good contrast in the

near UV range (350–400 nm) and is available in a wide range of

viscosities.11,33 Unlike some other negative tone photoresists,34

SU8 does not exhibit any oxygen sensitivity, which may lower the

fabrication speed and/or lead to pattern distortions.

The standard procedure for fabrication of high-aspect-ratio

CMEMS (carbon posts in this case) or CNEMS employing SU8 is

illustrated in Figure 3.

SU8 formulation with the optimal viscosity for the intended

application is fi rst spin coated on the desired substrate (Figure

3(a)). Before spin coating, the substrate must be cleaned thoroughly

and depending on the requirement of the process, an adhesive (e.g.

OmniCoat, MicroChem Inc.) may be used before spinning or

casting SU8 on it. In the case of spin coating, the rotation speed

of the spin coater, the resist viscosity, and resist concentration

control the resulting resist thicknesses. The prebake (also soft

bake or preexposure bake) step of the SU8 fi lm thus coated on a

substrate consists of fi rst heating the sample to 65°C and then to

95°C in order to evaporate the solvent slowly. If the fi lm is exposed

to a very high temperature too abruptly (for example, because

of a false reading of the hot plate temperature), the evaporation

of solvent will not be uniform and some solvent may remain

trapped, especially in the case of thicker fi lms. The UV exposure

(Figure 3(b)) is the crucial step in any photoresist patterning

process. During exposure, prebaked SU8 is exposed to UV light

through a mask that is aligned with the substrate in a mask aligner.

The energy supplied by the UV light initiates cross-linking by

activating the photo-initiators present in the SU8 photoresist. The

required exposure dose can be calculated from the commercially

available SU8 data sheets.33 Establishing the correct UV dose for a

given SU8 fi lm is of the utmost importance since both under- and

Figure 2. Scanning electron micrographs of GC structures prepared by

carbonization at 1000°C of furfulyl alcohol resin. (a) and (b) The inner

frame can be electrostatically actuated. This type of structure represents

the sensing unit for an accelerometer. (c) Precursor to an interdigitated

capacitor. The interdigitated comb structures become electrically

isolated once the supporting frame is broken. (d) Optical defl ector. The

initial carbonization step at 1000°C (in a tube furnace) was followed

by heat treatment under Ar up to 1800°C (in an induction furnace).

Electrostatic actuation can induce angular defl ection of the central

plate. The angle of defl ection of a light beam refl ected off the surface

of the central plate can therefore be controlled electrostatically.13

(a)

(c) (d)

(b)

100 μm 100 μm

100 μm 100 μm

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

256

over-exposed fi lms lead to fabrication failure. An under-exposed

design results in incomplete cross-linking at the base of the fi lm

and hence weak adhesion to the substrate. Such patterns are usually

washed away during development. However, an over-exposed

design leads to T-topping, yielding T-shaped features35 having a

hardened top layer that blocks adequate exposure for the bottom of

the SU8 layer. After exposure, the patterns are again baked at 65°C

and 95°C; this step is known as post exposure bake (also PEB or

post bake) to improve fi lm stability and promote adhesion. Next in

the CMEMS/CNEMS fabrication process is the development step

in which a commercially available SU8 developer is employed for

dissolving the uncross-linked SU8 (Figure 3(c)). For very thick

SU8 layers, spray or jet development can be employed.36 Spray

development uses a nozzle that sprays SU8 developer onto the resist

dissolving, thereby, the uncross-linked sections in the design. The

resulting patterns are then washed with isopropyl alcohol and dried

by gently blowing N2 on them. The thus fabricated SU8 patterns

are pyrolyzed (Figure 3(d)) in an inert atmosphere between 800 and

1200°C that yields CMEMS or CNEMS designs.

Depending on the temperature ramp rate during pyrolysis, the

resulting GC may be more or less porous.6 At a typical ramp rate

of 2–5°C/min, the resulting GC is dense and appears to have no

pores even under scanning electron microscope (SEM) inspection

(Figure 4(a)). Figure 4(a) illustrates an intentionally broken carbon

post pyrolyzed under standard pyrolysis conditions (ramp rate 2°C/

min). If the temperature ramp rate of the pyrolysis is increased to

above 15°C/min, the gases being released from the carbonizing

polymer leave micropores behind (Figure 4(b)) as the carbonization

is so fast that micropores cannot be annealed out before solidifi cation

occurs. This microporosity can be further enhanced by using even

faster ramp rates (90°C/min) resulting in pores with a diameter of

10–15 microns (Figure 4(c)).6

Next, some representative work in which the thus fabricated

CMEMS/CNEMS designs are functionalized to modify their

biocompatibility or to make them into biosensors is discussed.

4. Biocompatibility of carbon

4.1 Carbon surface modifi cation for cytocompatibility: chemical and topographical cues

Carbon surfaces resulting from pyrolysis are notoriously unreactive

because of the reducing environment in which carbonization is

Figure 3. Process fl ow of microfabrication of pyrolysed photoresist

patterns (a) Spin- coating SU8 to obtain fi lm of desired thickness, (b)

Exposure to UV light for cross-linking, (c) Development of cross-linked

patterns (d) Pyrolysis for carbonization.75

(a) Spin-coating photoresist

SU8 photoresist

Substrate

(b)

Mask

UV exposureUV light

SU8 post(c) Developing

Carbon post(d) Pyrolysis

Figure 4. SEM images of Microporous C-MEMS obtained using fast

pyrolysis at different ramp rates: (a) 2oC/min (An intentionally broken

carbon post) (b) 90oC/min from room temperature to 900oC.

(c) 15oC/min6.

(a) (b) (c)

5.0kv 16.0mm × 4.00 k 10.0kv 13.3mm × 2.50 k 10.0kv 15.9mm × 50010.0um 20.0um 100um

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

257

carried out.29 Therefore, surface modifi cation of this type of carbon is

particularly important to modify its interaction with biological cells

and tissue for implants or for rendering it into a selective biosensor

surface. Conventional functionalization methodologies such as

microwave and reactive plasma treatment may not yield an optimal

degree of functionalization of the carbon in CMEMS/CNEMS.37–39

Therefore, techniques that may be more gainfully employed to turn

CMEMS and CNEMS devices into implants or biosensors are briefl y

discussed. The objective of carbon surface modifi cation, chemically

or topographically, for implants is quite different than that for in-vitro

carbon-based sensors. In a carbon sensor, we want to facilitate the

reaction rate, sensitivity and selectivity of the device whereas, for

an implant, biocompatibility, durability, absence of cytotoxicty,

and re-absorption upon erosion of the implant material is required.

Despite these different objectives, the surface modifi cation strategies

are often the same for carbon implants and carbon sensors.

Surface modifi cation of carbon can be carried out chemically or

electrochemically.18,19,40–42 Electrochemically-assisted carbon surface

modifi cation methodologies have been extensively studied since they

were fi rst used for the modifi cation of GC electrodes in 1990.41 The two

most commonly used electrochemical modifi cation methodologies for

GC are (i) oxidation of aryl acetates or amines that grafts respective

aryl or amine groups covalently bonded onto carbon surface and (ii)

reduction of aryl diazonium salts leading to aryl terminated carbon.

Allongue et al18 employed the reduction of a variety of diazonium

salts to derivitize GC and highly oriented pyrolytic graphite

and concluded that the attachment of these fi lms is very strong

and persistent. For example, these fi lms require mechanical

abrasion for their removal indicative of the covalent nature of

their attachment. Oxidation of amines however, is preferred over

reduction of diazonium salts for functionalization of GC because

the reduction pathways are limited to aryl compounds because

of the unstable nature of most aliphatic diazonium salts.43 In our

group, a functionalization strategy based on the oxidation of

ethylene diamine and amino benzoic acid have been developed.

An accepted mechanism for the electro-oxidation of amines is

illustrated in Figure 5. In this reaction, an amine radical is formed

by fi rst loosing an electron and subsequently a proton. After a

proton rearrangement, this radical can either proceed to attach to

the electrode surface, or convert back to the amine compound.

Some chemical surface modifi cation techniques for CMEMS and

CNEMS include oxygen plasma treatment,40 nitric acid treatment,44,45

and attachment of biologically important molecules such as ribofl avin.46

In the latter case,46 the authors carried out the surface modifi cation of

GC by oxidizing the electrode anodically in 10% nitric acid and 2.5%

potassium dichromate to yield -COOH functionalities. The electrode

was then activated in a solution of ribofl avin. The authors tested the

thus modifi ed GC electrodes for catalytic properties. Some of the

more harsh chemical treatments such as nitric acid treatment44,45 may

cause damage to carbon because of the harshness of the chemical

reactions and physisorption approaches for most application do not

lead to a suffi ciently strong bond.

Cells take both chemical and topographical cues from the surfaces

they are deposited on. To de-convolute, for a given surface, the

relative contribution of chemical and topographical cues that

a type of cell responds to remains a daunting task as chemistry

and topography is often intertwined.17 Two examples, where

cytocompatibility of carbon on topographically modifi ed surfaces

was investigated, are now reviewed. In both studies,17,20 the authors

concluded that cells display better adhesion and faster growth on

deliberately textured carbon surfaces.

Kulkarni et al20 studied the cytocompatibility of photoresist-

derived patterned carbon fi lm employing intensive SEM studies of

cellular cytoplasmic extension using L929 mouse fi broblast cells.

The authors employed a photoresist (SC-100, a cyclic polyisoprene

photoresist) that was exposed to UV light selectively so as to

obtain a harder (more cross-linked) top layer and a softer bottom

layer. During development, the two layers swell anisotropically.

When drying this composite resist structure, the unequal shrinkage

of the constituent layers results in a buckled polymer fi lm that

is subsequently pyrolyzed to yield a micro-patterned GC fi lm

constituting a platform for faster growth of cells compared to a

smooth carbon surface.

In a similar study on the cytocompatibility of photoresist-derived

carbons, Teixidor et al17 employed various carbon and Si micro-

patterns as substratum for cell growth using two cell lines: murine

dermal fi broblasts and neuroblastoma spinal cord hybrid cells

(NSC-34). The authors treated GC surfaces with oxygen plasma,

and concluded that the thus modifi ed carbon surface promotes cell

adhesion better than non-plasma treated carbon surfaces or silicon-

based substrates. These authors suggest that oxygen-plasma-

treated GC has a higher surface energy and lower hydrophobicity

than untreated GC fi lms because of the introduction of oxygen-

containing surface groups and an increase in surface roughness.

This enhancement in surface roughness again provides a more

favorable platform for cell growth. It is postulated that nano or micro

topographic patterns on GC surfaces promote better adhesion for

Figure 5. Mechanism for electro- oxidation of amines- radical

formation by loss of electron, deprotonation, rearrangement of

proton and attachment of deprotonated radical to electrode (could be

GC or a metal).43

RCH2NH2

R=alkyl, arylE

E=glassy carbon, Au, Pt

NHCH2R

RCH2NH2 RCH2NH2RCH2NH2

+-e– -H+

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

258

cells because patterned carbon surfaces mimic the structural design

of the extracellular matrix more closely than a fl at surface.20

4.2 Erosion behavior of carbon implantsAn implant material must not only be biocompatible, it should also

be free of any toxic effects and be safe for human use. In some

materials, biocompatibility is purely a matter of the wrong surface

chemistry: copper, for example, may cause signifi cant cytotoxicity

by releasing copper ions in the body.47 Carbon on the other hand does

not display any intrinsic toxicity by releasing toxic ions; the surface

of carbon, however, often needs to be modifi ed (topographically

and/or chemically) for its application as a biocompatible material.

The inertness or passive nature of implant material improves its

chances of being utilized as prostheses. In the case of scaffolds,

the erosion (degradation) behavior of the implant is a key factor in

deciding its feasibility for in vivo implementation. More et al,48 for

example, explored the erosion behavior of carbon implants in rats

employing radiotracers. The study describes how carbon implants

dissociate in small pieces, and can be found as eroded carbon

particles or carbon capsules near the implant. Some particles were

also located at a distance from the implant site.48

Interestingly, carbon obtained from pyrolysis of PAN at 1200°C

displays different erosion behaviors than those obtained at

2700°C, which are more graphitic (see section 2).49–53 It appears

that crystalline graphitic carbons are more diffi cult to assimilate

by the body while amorphous (or glassy) carbons readily

undergo partial fragmentation and get gradually resorbed at the

implantation site.50

CFs with modifi ed surfaces offer a great deal of biocompatibility

with osseous tissue, blood and soft tissue, and have a stimulating

infl uence on the growth of connective tissue that is morphologically

identical to the mother tissue.48 Some successful carbon implants

include CF braids for their use in tendons and ligaments prostheses,

carbon plates and screws for osteosynthesis, needled carbon cloth

for fi lling cartilaginous tissue defects, CF support for drug delivery,

etc.50–53 Among these, polymer derived CF braids and scaffolds are

most popular as carbon implants. CF braids have been evaluated

for both in vitro and in vivo response to cells, and for their erosion

behavior as implants over the past two decades.48–53 In a recent

study, Blazewicz group53 compared the biological properties and

bioactivity of hydroxyapatite modifi ed porous CFs with pure CFs.

In this study, in vivo tests were carried out on porous hydroxyapatite

modifi ed CFs which were used as scaffolds for tissue regeneration.

It was shown that the thus modifi ed CFs served as an effective

biologically active agent to stimulate tissue re-growth. The authors

suggest that addition of nanohydroxyapatite to the CFs precursor

can modify the CFs biological properties signifi cantly without the

need for any other surface modifi cations. Figure 6 represents an

optical image of MG-63 cells seeded on porous CFs compared

to those on a control polystyrene plate (Figure 6(a)). As can be

observed in Figures 6(b)–6(d), cells display good adhesion on

carbon surface and can be cultured on them.

Use of CFs as a dental material is yet another fascinating area of

application for carbon micro and nanofi bers.51 Because of their

integration with the surrounding tissues, CFs can be used as

implants for the maintenance of bone volume after tooth avulsion

(complete displacement of a tooth from its socket).

5. CMEMS/CNEMS devicesIn the preceding sections, an attempt have been made to show that,

GC-based MEMS and NEMS devices can be manufactured from

a wide range of precursor materials, they can be patterned with a

wide variety of tools to yield lengths from a few nanometers to a

few hundred microns, CMEMS and CNEMS are often simpler to

make than competing devices and the CMEMS/CNEMS surface

properties can be enhanced to serve as either implants or sensors.

Figure 6. Morphology of MG-63 cells seeded on hydroxyapatite

treated porous CFs after 7 days in culture: (a) cells on control

polystyrene plate and (b)–(d)) cells on porous CFs. Stained with

propidium iodide.53

(a) (b) (c)

(d)

(e)100 μm 100 μm

100 μm

100 μm

100 μm

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

259

To further make this case, CMEMS and CNEMS devices of a wide-

range of sizes made with a variety of manufacturing tools are listed

in Tables 1 and 2. In Table 1, non-SU8 (azide, diazo or furfuryl

alcohol-based polymers) derived devices and SU8 derived designs

compiled in Table 2 are summarized. At the end of the two tables,

two recently developed CMEMS/CNEMS devices are detailed that

is, three-dimensional (3D) CMEMS patterns used in diectrophoresis

(DEP),54,55 and miniaturized carbon nanoelectrode arrays for redox

amplifi cation.

In Tables 1 and 2 CMEMS/CNEMS fabrication techniques that include

photolithography,14,30,31,56,57 laser patterning,58,59 soft-lithography,13,60

electrospinning, electrospinning combined with lithography,12 chemical

methods,16,61 anodic alumina mold fi lling,15 etc. are listed. Today the

use of carbon micro and nano pattern using SU8 as polymer precursor

in photolithography28,55,62–72 has become the dominant approach (Table

2). In some cases, a combination of photolithography with other

microfabrication techniques is used as well (see e.g. electrospinning

combined with lithography. Given the cost of manufacturing, the

authors believe that nano imprint lithography and electrospinning offer

the greatest potential for the ever-expanding CMEMS/CNEMS fi eld.

One of the more recent examples of a successful implementation

of 3D CMEMS electrodes for biological applications is their

use in DEP.54,55 DEP is a non-destructive method for separation,

transportation, trapping, and sorting of small particles such as

biological cells. In positive DEP, the force is towards increasing

fi eld strength and particles collect at the electrode edges where the

highest fi eld strengths are found. In negative DEP, the force is in the

direction of decreasing fi eld strength with particles being repelled

from the electrode edges. The frequency dependence of the DEP

force makes for a powerful method of manipulating particles in

solution. Ma et al54 fabricated CMEMS high-aspect-ratio pillars of

various shapes and implemented these patterns as electrodes for

DEP separation of bioparticles in fl uids. 3D carbon microelectrode

confi gurations offer a much improved particle separation effi ciency

as compared to 2D electrodes as the fi eld in the 3D implementation

penetrates a higher percentage of the liquid volume in which the

electrodes are submerged. In another recent DEP study, Martinez-

Duarte et al55 fabricated 3D carbon microelectrodes and performed

high-throughput fi ltering, particle positioning and cell focusing.

The same group also integrated CMEMS DEP on a centrifugal

platform, simplifying the need for tubing and obviating the need

for a pump.73

Figure 7 is a schematic diagram that illustrates how 3D electrodes

are more effective than 2D electrodes in DEP particle manipulation.

In DEP, the electric fi eld gradient that drives the particles is

confi ned to an area very close to the electrode surface. With

CMEMS technology, electrodes of variable height, diameter, and

spacing contribute to improvement in the fi eld gradient distribution

throughout a larger volume of the solution thus impacting more

particles to be separated.54 In an alternative approach, 3D DEP

was carried out on Au posts,74 a method more expensive and more

laborious than using CMEMS.

A recent CNEMS application is the use of carbon nanoelectrodes

for redox amplifi cation. Redox amplifi cation can be achieved if

two electrodes are placed in close proximity of each other such

that their depletion regions overlap. One of the electrodes, the

generator, is placed at a more positive potential, oxidizing the

reductant of a redox couple. The second electrode, the collector

electrode, is biased at a more negative potential such that the

oxidized ions are now reduced back. The reduced ions can now

fl ow back to the generator electrode to be oxidized again. As

a result, the two electrodes work together creating a feedback

loop used to amplify the measured current with an improved

detection limit.

Heo et al28 fabricated an array of interdigitated carbon electrodes using

SU8 photolithography: the electrode fi ngers in their interdigitated

array were 80 nm in width (height and width, aspect ratio 1:1) and

the electrode separation was 300 nm Figure 8. The authors achieved

a redox amplifi cation factor of 25. The CNEMS process is a one

step-process and does not need the laborious and expensive lift-off

techniques that are required when patterning alternative metals such

as Pt and Au for interdigitated arrays. Moreover, the height of the

interdigitated electrodes also can enhance the redox amplifi cation

and, with CMEMS, a thicker/higher electrode is easy to achieve

without having to resort to electroplating.

6. ConclusionsCMEMS and CNEMS devices are fabricated by the pyrolysis of

designs that are created using a variety of patterning techniques

in a wide choice of precursor polymer materials. The resulting

CMEMS and CNEMS devices typically have a GC microstructure

that features several characteristics that make them an attractive,

inexpensive approach for many bioMEMS applications. Most

importantly, the GC surface thus obtained can be modifi ed by

introducing chemical and topographical changes enabling the

construction of biocompatible implants and sensors. GC electrodes

also feature a wide electrochemical stability window that enables a

variety of electroanalysis experiments that are diffi cult to carry out

on more expensive noble metal electrodes.

Besides innovative CMEMS/CNEMS fabrication methods, carbon-

based implants, biocompatibility studies, and innovative CMEMS

and CNEMS devices are reviewed in this paper. The authors

believe that, from the novel fabrication techniques, the ones based

on nanoimprinting and electrospinning are most promising to

further expand the CMEMS/CNEMS fi eld. It is expected that the

technologies and expertise developed in the fi eld of CMEMS and

CNEMS will play a decisive role in making disposable bioMEMS

technology possible and also impact several emerging electronic

and implant applications.

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

260

S. No Design type Precursor polymerFabrication technique

Minimum resolution

Reference Remarks

1 Grid/ various microstructures

Copolymers of phenol-formaldehydeor furfuryl alcohol-phenol

Soft-lithography 50–100 μm [13]

2 Array of nanopillars

Furfuryl alcohol resin Anodic alumina nanoporous membrane

50 nm [5] Aspect ratio: 10:1

3 Film AZ-4330, OIR-897 Spin coating 2 μm [56]

4 Interdigitated electrodes

AZ-4330, XPSU Photolithography 50 μm [30]

5 Inertdigitated electrodes

OiR897-101

Photo/laser lithography, thermal/ laser pyrolysis

2 μm [58] Carbon fi lm was micro-patterned

6 Inertdigitated electrodes

AZ-4330, XPSU Photolithography 50 μm [31]

7 Electrodes for microchips

AZ 1518, SU8 Photolithography/ molding on PDMS

40 μm [14]

9 Two-dimensional electrodes

AZ 4330 Photolithography 4–5 μm [57]

10 Microbridge Polyimide Treatment with various chemicals, O2 plasma

1.3 μm [61] Pattern was integrated with Cr/Au electrodes

11 Microelectrodes/ microdiscs

- Laser microfabrication ~10 μm [59] Glassy carbon electrodes were patterned using Nd:YAG laser

13 Array of posts Furfuryl alcohol-basedresin

Soft lithography/ molding

100 μm, fl at

[60] Polymer patterned by MIMIC/ micro TM

14 Diamond and diamond-like carbon fi lms

Mixture of gases (CH4, Ar)

CVD, microwave CVD - [16]

15 Carbon fi lm AZ4330 Spin coating Film thickness: 1–2 μm

[76]

16 Microbridge/ girder

Epoxy resin Amine curing/ paraffi n wax mold evaporation

90–230 μm [77] Multi-walled carbon nanotube (MWCNT), silver particles, and carbon black (CB) used as fi llers for spacingSubstrate: Alumina

CVD, chemical vapour deposition.; MIMIC, micro-molding in capillaries; micro TM, micro transfer molding.

Table 1. Carbon MEMS structures: Fabrication techniques that use precursor polymers other than SU8.

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

261

S. No. Structure Precursor TechniqueDimension

RangeReference Remarks

1 Multi-levelsuspended carbon microstructures

SU8 Photolithography 24–200 μm [62]

2 Suspendedbridges and wires, posts

SU8 Photolithography, controlled heating

50 μm [63] Aspect ratio = 10:1

3 Hollow needlearrays

SU8 Photolithography 100 μm [64]

4 Multi-layered pillars/ other structures

SU8 Photolithography 5 μm (top layer)

[65] Aspect ratio = 16:1

5 Pillar: single and multilayered

SU8 Photolithography 10 μm [66] Aspect ratio = 22:1

6 Channels SU8 Photolithography 250 μm [67] Embedded mask was used

7 Pillars of various designs

SU8 Photolithography with megasonic development

43 μm [68] Aspect ratio= 40:1 in open fi eld patterns and 23:1 in cylinders at heights of 1150 and 1500 μm

8 Patterns (trenches/ channels) in thick fi lms

SU8 Photolithography 150 μm [69] Theoretical study of possible pattern height was also incorporated

9 Single- and double-layer electrodes

SU8 10 Photolithography 50 μm [70] Application: Producing fl uid fl ow using carbon electrodes

10 Tapered hollow metallic microneedlearray

SU8 Photolithography/ electrodeposition

33.6–400 μm [71] Aspect ratio: 5: 1

11 3D micropillars of various geometries

SU8 Photolithography [55] Patterns used for DEP

12 Single suspended CNWs on CMEMS

SU8 Photolithography and electrospinning

42 nm [72] Patterns designed for gas sensing

13 Interdigitated nanoelectrode array

SU8 Photolithography 80, 300 nm (height and

width of electrodes)

[28] Patterns used for electrochemical applications

CNWs, carbon nanowires; DEP, diectrophoresis; MEMS, microelectromechanical systems.

Table 2. CMEMS fabricated using SU8 as precursor material.

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

262

REFERENCES

1. Kinoshita, K. Carbon: Electrochemical and Physicochemical Properties. Wiley, New York, 1988.

2. Wang, C.; Zaouk, R. B.; Park B. Y.; Madou, M. J. Carbon as

a MEMS material: micro and nano abrication of pyrolyzed

photoresist carbon. Int. J. Manufacturing Technology and Management. 2008, 13 (2/3/4), 360–375.

3. Baughman, R. H.; Zakhidov, A. A.; de Heer, W. A. Carbon

nanotubes–the route toward applications. Science. 2002,

297(5582), 787–792.

4. Gates, B. D.; Xu, Q.; Stewart, M.; Ryan, D.; Willson, C. G.;

Whitesides, G. M. New approaches to nanofabrication:

molding, printing, and other techniques. Chemical Reviews.

2005, 105(4), 1171–1196.

5. Sharma, C. S.; Patil, S.; Saurabh, S.; Sharma A.;

Venkataraghavan, R. Resorcinol- formaldehyde based carbon

nanospheres by electrospraying. Bulletin of Material Science. 2009, 32, 1–8.

6. Zaouk R. B. PhD dissertation. Carbon MEMS from the nanoscale to the macroscale: novel fabrication techniques and applications in electrochemistry. Department of

Mechanical and Aerospace Engineering, University of

California, Irvine, CA, USA (ISBN/ISSN: 9780549481973).

7. Xu, J. Z.; Zhang, Y.; Li, G. X.; Zhu J. J. An electrochemical

biosensor constructed by nanosized silver particles doped sol-

gel fi lm. Material Science and Engineering C. 2004, 24(6-8),

833–836.

8. Vidotti M.; Carvalhal R. F.; Mendes R. K.; Ferreira D. C. M.;

Kubota L. T. J. Biosensors based on gold nanostructures.

Brazilian Chemical Society. 2011, 22(1), 3–20.

9. Sinha, V. R.; Bansal, K.; Kaushik, R.; Kumria, R.; Trehan, A.

Poly-epsilon-caprolactone microspheres and nanospheres:

Figure 7. Schematic diagram of DEP generation. (a) Schematic of DEP

generation in 2-D planar electrode with K > 0 or K < 0 representing

positive or negative DEP, respectively. (b) Schematic of particles in 3-D

MEMS electrode confi guration.54

E

∇E

K < 0

K > 0

(a) (b)

Figure 8. Scanning electron micrographs of a 1:1 carbon IDA

nanoelectrode pyrolized from a photoresist IDA micropattern.28

(i) Before pyrolysis

Top view Section view

Top view Section view

(ii) After pyrolysis

1 μm

1.65 μm

300 nm

Carbon

1 μm

2.95 μm

100 μm

Carbon

340 nm

300 nm

Photoresist

Photoresist

1 μm

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

263

An overview. International Journal of Pharmaceutics. 2004,

278(1), 1–23.

10. Tambe, N. S.; Bhushan B. Micro/nanotribological

characterization of PDMS and PMMA used for bioMEMS/

NEMS applications. Ultrmicroscopy 2005, 105(1–4), 238–247.

11. Madou M. Fundamentals of Microfabrication, 2nd edn. CRC

Press, Boca Raton, FL, 2002.

12. Sharma, S.; Sharma, A.; Cho, Y. K.; Madou, M. Increased

graphitization in electrospun single suspended carbon

nanowires integrated with carbon-MEMS and carbon-NEMS

platforms. ACS Applied Materials & Interfaces. 2012, 4(1),

34–39.

13. Schueller, O. J. A.; Brittain, S. T.; Marzolin, C.; Whitesides, G. M.

Fabrication and characterization of glassy carbon MEMS.

Chemistry of Materials. 1997, 9, 1399–1406.

14. Fischera, D. J.; Vandaveer, W. R. I. V.; Grigsbyb, R. J.;

Lunte, S. M. Pyrolyzed photoresist carbon electrodes for

microchip electrophoresis with dual-electrode amperometric

detection. Electroanalysis 2005, 17(13), 1153–1159.

15. Rahman S.; Yang, H. Nanopillar arrays of glassy carbon by

anodic aluminum oxide nanoporous templates. Nano Letters,

2003, 3(4), 439– 442.

16. Luo, J. K.; Fu, Y. Q.; Le, H. R.; Williams, J. A.; Spearing

S. M.; Milne, W. I. Journal of Micromechanics and

Microengineering. 2007, 17, S147–S163.

17. Teixidor, G. T.; Gorkin, R. A. 3rd.; Tripathi, P. P.; Bisht, G. S.;

Kulkarni, M.; Maiti, T. K.; Battacharyya, T. K.; Subramaniam,

J. R.; Sharma, A.; Park, B. Y.; Madou, M. Carbon

microelectromechanical systems as a substratum for cell

growth. Biomedical Materials. 2008, 3(3), 034116.

18. Allongue, P.; Delamar, M.; Desbat, B.; Fagebaume, O.;

Hitmi R.; Pinson J.; Saveant J. M. J Journal of the American Chemical Society. 1997, 119, 201–207.

19. Deinhammer, R. S.; Ho, M.; Anderegg, J. W.; Porter, M. D.

Electrochemical oxidation of amine-containing compounds. A

route to the surface modifi cation of glassy carbon electrodes.

Langmuir. 1994, 10, 1306–1313.

20. Kulkarni, M. M.; Sharma, C. S.; Sharma, A.; Kalmodia, S.;

Basu, B. Multiscale micro-patterned polymeric and carbon

substrates derived from buckled photoresist fi lms: fabrication

and cytocompatibility. Journal of Materials Science. 2012, 47,

3867–3875.

21. Brown, N. M. D.; Cui, N.; McKinley, A. A study of the

topography of a glassy carbon surface following low-power

radio-frequency oxygen plasma treatment. Applied Surface Science. 1998, 133(3), 157–165.

22. Jenkins, G. M.; Kawamura, K. Structure of glassy carbon.

Nature. 1971, 231(5299), 175–176.

23. Franklin R. E. Crystallite growth in graphitizing and non-

graphitizing carbons. Proceedings of the Royal Society A.

1951, A209, 196.

24. Harris P. J. F. Fullerene-related structure of commercial glassy

carbons. Philosophical Magazine. 2004, A84, 3159–3167.

25. Shigemitsu, T.; Matsumoto, G.; Tsukahara, S. Electrical

properties of glassy-carbon electrodes. Medical & Biological Engineering & Computing. 1979, 17(4), 465–470.

26. Kotlensky W. V.; Martens H. E. Tensile properties of glassy

carbon to 2900 C. Nature. 1965, 206, 1246–1247.

27. Sawyer, D. T.; Sobkowiak, A.; Roberts, J. L., Jr.

Electrochemistry for Chemists, 2nd edn. New York, John

Wiley, 1995.

28. Heo, J. I.; Shim, D. S.; Teixidor, G. T.; Oh, S.; Madou, M.;

Shin, H. Carbon interdigitated array nanoelectrodes for

electrochemical applications. Journal of Electrochemical Society. 2011, 158(3), J76–J80.

29. Jenkins G. M.; Kawamura, K. Polymeric Carbons- Carbon Fibre Glass and Char. Cambridge, Cambridge University

Press, 1976.

30. Kostecki, R.; Song, X.; Kinoshita, K. Electrochemical analysis

of carbon interdigitated microelectrodes. Electrochemical and

Solid-State Letters. 1999, 2, 461–465.

31. Kinoshita, K.; Song, X.; Kim, J.; Inaba, M. J. Development of

a carbon-based lithium microbattery. Power Sources, 1999,

81–82, 170–175.

32. SU-8: Thick Photo-Resist for MEMS. See http://

memscyclopedia.org/su8.html

33. MicroChem. NaNo SU-8 data sheet. 2008. See http://www.

microchem.com/pdf/SU-82000DataSheet2025thru2075Ver4.

pdf

34. Skarvinko, E. R.; Binghomton, N. Y. Preventing speed loss in oxygen sensing photoresist layers. US Patent 3669667,

1972.

35. Malladi, K.; Wang, C.; Madou, M. Fabrication of suspended

carbon microstructures by e-beam writer and pyrolysis.

Carbon, 2006, 44(13), 2602–2607.

36. Natarajan, S.; Chang-Yen, D. A.; Gale, B. K. J. Large-area,

high- aspect-ratio SU-8 molds for the fabrication of PDMS

microfl uidic devices. Journal of Micromechanics and

Microengineering., 2008, 18, 045021.

37. Chen, C.; Liang, B.; Ogino, A.; Wang, X.; Nagatsu, M.

Oxygen functionalization of multiwall carbon nanotubes by

microwave-excited surface-wave plasma treatment. Journal of Physical Chemistry C, 2009, 113, 7659–7665.

38. Pötschke, P.; Zschoerper, N. P.; Moller, B. P.; Vohrer, U. Plasma

functionalization of multiwalled carbon nanotube bucky papers

and the effect on properties of melt-mixed composites with

polycarbonate. Macromolecular Rapid Communications. 2009,

30, 1828–1833.

39. Pandurangappa, M.; Ramakrishnappa, T. J. Homogeneous

chemical derivatisation of carbon particles: A novel method for

funtionalising carbon surfaces. Solid-State Electronics. 2010,

14, 687–695.

40. Pranevicius L. Tailoring of surface topography of carbon

electrodes for supercapacitors using plasma technologies.

Nanomaterials: Applications and Properties, 2011, 1(2),

448–452.

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

264

41. Barbier, B.; Pinson, J.; Desarmot, G.; Sanchez, M.

Electrochemical bonding of amines to carbon fi ber surfaces

toward improved carbon-epoxy composites. Journal of the Electrochemical Society. 1990, 137, 1757–1764.

42. Downard A. Electrochemically assisted covalent modifi cation of carbon electrodes. Electroanalysis, 2000, 12(14),

1085–1096.

43. Adenier, A.; Chehimi, M. M.; Gallardo, I.; Pinson, J.; Vilà, N.

Electrochemical oxidation of aliphatic amines and their

attachment to carbon and metal surfaces. Langmuir. 2004,

20(19), 8243–8253.

44. Lakshminarayanan, P. V.; Toghiani, H.; Pittman, C. U. Jr.

Nitric acid oxidation of vapor grown carbon nanofi bers.

Carbon. 2004, 42, 2433–2442.

45. Rosca, I. D.; Watari, F.; Uo, M.; Akasaka, T. Oxidation of

multiwalled carbon nanotubes by nitric acid. Carbon, 2005,

43, 3124–3131.

46. Berchmans, S.; Vijayavalli, R. Surface modifi cation of glassy-

carbon by ribofl avin. Langmuir. 1995, 11, 286–290.

47. Cortizo, M. C.; Fernández Lorenzo de Mele, M. Cytotoxicity

of copper ions released from metal: Variation with the

exposure period and concentration gradients. Biological Trace Element Research. 2004, 102(1–3), 129–141.

48. More, N.; Baquey, C.; Barthe, X.; Rouais F.; Rivel J.;

Trinquecoste, M.; Marchand A. Biocompatibility of carbon-

carbon materials: in vivo study using 14carbon labelled

samples. Biomaterials, 1988, 9(4), 328–332, IN1, 333–334.

49. Tran, P. A.; Zhang, L.; Webster, T. J. Carbon nanofi bers and

carbon nanotubes in regenerative medicine. Advanced Drug

Delivery Reviews. 2009, 61(12), 1097–1114.

50. Blazewicz, M. Carbon materials in the treatment of soft and

hard tissue injuries. European Cells & Materials. 2001, 2,

21–29.

51. Louis, J. P.; Dabadie, M. Fibrous carbon implants for the

maintenance of bone volume after tooth avulsion: First clinical

results. Biomaterials. 1990, 11(7), 525–528.

52. Baquey, C.; Bordenave, L.; More, N.; Caix, J.; Basse-

Cathalinat, B. Biocompatibility of carbon-carbon materials:

Blood tolerability. Biomaterials. 1989, 10(7), 435–440.

53. Rajzer, I.; Menaszek, E.; Bacakova, L.; Rom, M.; Blazewicz, M.

In vitro and in vivo studies on biocompatibility of carbon

fi bres. Journal of Materials Science: Materials in Medicine.

2010, 21(9), 2611–2622.

54. Ma, W.; Shi, T.; Tang, Z.; Liu, S.; Malik, R.; Zhang, L. High-

throughput dielectrophoretic manipulation of bioparticles

within fl uids through biocompatible three-dimensional

microelectrode array. Electrophoresis. 2011, 32(5), 494–505.

55. Martinez-Duarte, R.; Renaud, P.; Madou, M. J. A novel

approach to dielectrophoresis using carbon electrodes.

Electrophoresis. 2011, 32, 2385–2392.

56. Kostecki, R.; Schnyder, B.; Alliat, D.; Song, X.; Kinoshita,

K.; Kötz, R. Surface studies of carbon fi lms from pyrolyzed

photoresist. Thin Solid Films. 2001, 396, 36–43.

57. Ranganathan, S.; McCreery, R.; Majji, S. M.; Madou, M.

Photoresist-derived carbon for microelectromechanical

systems and electrochemical applications. Journal of The Electrochemical Society. 2000, 147(1), 277–282.

58. Kostecki, R.; Song, X.; Kinoshita K. Fabrication of

Interdigitated Carbon Structures by Laser Pyrolysis of

Photoresist. Electrochemical and Solid-State Letters. 2002,

5(6), E29–E31.

59. Sternitzke, K. D.; McCreery, R. L. Laser microfabrication and

activation of graphite and glassy carbon electrodes. Analytical Chemistry. 1990, 62, 1339–1344.

60. Schueller, O. J. A.; Brittain, S. T.; Whitesides, G. M.

Fabrication of glassy carbon microstructures by pyrolysis of microfabricated polymeric precursors. Advanced Materials.

1997, 9(6), 477–480.

61. Naka, K.; Nagae, H.; Ichiyanagi, M.; Jeong, O. C.; Konishi, S.

Investigation of pyrolyzed polyimide thin fi lm as MEMS

material. Semiconductor Science and Technology. 2005, 5(1),

38–44.

62. Lee, J. A.; Lee, S. W.; Lee K. C.; Park, S. I.; Lee, S. S.

Fabrication and characterization of freestanding 3D carbon

microstructures using multi-exposures and resist pyrolysis.

Journal of Micromechanics and Microengineering. 2008, 18,

035012.

63. Wang, C.; Jia, G.; Taherabadi L. H.; Madou M. J. A novel.

method for the fabrication of high-aspect ratio C-MEMS.

structures. Microelectromechanical Systems. 2005, 14,

348–358.

64. Huang, H.; Fu, C. Different fabrication methods of out-of-

plane polymer hollow needle arrays and their variations.

Journal of Micromechanics and Microengineering. 2007, 17,

393–402.

65. Mata, A.; Fleischman, A. J.; Roy, S. J. Fabrication of multi-

layer SU-8 microstructures. Journal of Micromechanics and

Microengineering. 2006, 16, 276–284.

66. Peterman, M. C.; Huie, P.; Bloom D. M.; Fishman, H. A.

Building thick photoresist structures from the bottom up.

Journal of Micromechanics and Microengineering. 2003, 13,

380–382.

67. Alderman, B. E. J.; Mann, C. M.; Steenson D. P.;

Chamberlain, J. M. Microfabrication of channels using an

embedded mask in negative resist. Journal of Micromechanics

and Microengineering. 2001, 11, 703–705.

68. Williams, J. D.; Wang, W. Using megasonic development of

SU-8 to yield ultra-high aspect ratio microstructures with UV

lithography. Microsystem Technologies, 2004, 10, 694–698.

69. Dentinger, P. M.; Krafcik, K. L.; Simison, K. L.; Janek, R. P.

Hachman, J. High aspect ratio patterning with a proximity

ultraviolet source. Microelectronic Engineering. 2002,

61–62,1001–1007.

70. Rouabah, H. A.; Park, B. Y.; Zaouk, R. B.; Madou M. J.;

Green, N. G. Producing fl uid fl ow using 3D carbon electrodes.

Journal of Physics: Conference Series. 2008, 142, 012072.

Bioinspired, Biomimetic and NanobiomaterialsVolume 1 Issue BBN4

Micro and nano patterning of carbon electrodes for bioMEMSSharma and Madou

265

71. Kim, K.; Park, D. S.; Lu, H. M.; Che, W. S.; Kim, K. H.; Lee J.

B.; Ahn, C. A tapered hollow metallic microneedle array using

backside expo- sure of SU-8. Journal of Micromechanics and

Microengineering. 2004, 14, 597–603.

72. Sharma, S.; Madou M. A new approach to gas sensing with

nanotechnology. Philosophical Transactions of the Royal Society A. 2012, 370(1967), 2448–2473.

73. Martinez-Duarte, R.; Gorkin, R. A. 3rd; Abi-Samra, K.;

Madou, M. J. The integration of 3D carbon-electrode

dielectrophoresis on a CD-like centrifugal microfl uidic

platform. Lab on a Chip. 2010, 10(8), 1030–1043.

74. Wang, L.; Flanagan, L. A.; Monuki, E.; Jeon, N. L.; Lee, A. P.

Dielectrophoresis switching with vertical sidewall electrodes

for microfl uidic fl ow cytometry. Lab on a Chip. 2007, 7(9),

1114–1120.

75. Wang, C.; Taherabadi L.; Jia G. Y.; Madou, M.; Yeh Y.; Dunn B.

C-MEMS for the manufacture of 3D microbatteries.

Electrochemical and Solid-State Letters, 2004, 7(11), A435–A438.

76. Hebert, N. E.; Snyder, B.; McCreery, R. L.; Kuhr, W. G.;

Brazill, S. A. Performance of pyrolyzed photoresist carbon

fi lms in a microchip capillary electrophoresis device with

sinusoidal voltammetric detection. Analytical Chemistry. 2003,

75(16), 4265–4271.

77. Yamada, Y.; Chung, D. D. L. Three-dimensional

microstructuring of carbon by thermoplastic spacer evaporation

during pyrolysis. Carbon, 2008, 46(13), 1765–1772.

WHAT DO YOU THINK?

To discuss this paper, please email up to 500 words to the managing editor at [email protected]

Your contribution will be forwarded to the author(s) for a reply and, if considered appropriate by the editor-in-chief, will be published as a discussion in a future issue of the journal.

ICE Science journals rely entirely on contributions sent in by professionals, academics and students coming from the fi eld of materials science and engineering. Articles should be within 5000-7000 words long (short communications and opinion articles should be within 2000 words long), with adequate illustrations and references. To access our author guidelines and how to submit your paper, please refer to the journal website at www.icevirtuallibrary.com/bbn