MICROMOLDING AND APPLICATIONS OF

SOFT POLYHEDRA

By

Zhilin Zhang

A thesis submitted to Johns Hopkins University in conformity with the requirements for the

degree of Master of Science in Engineering

Baltimore, Maryland

April 2014

© Zhilin Zhang

All Rights Reserved

II

Abstract

Polymeric particles are important for drug delivery, cell-encapsulation, tissue

engineering, biomedical imaging and self-assembly. In these applications, the

functional behavior and interparticle interactions are strongly correlated to the shape

and size of particles. Although there are several existing methods to create polymeric

particles with sizes ranging from nanometers to millimeters length scale, only

relatively simple geometries such as spheres, cylinders, ellipsoids and cubes can be

formed. In this body of work, a new micromolding approach was developed to create

soft-polyhedra with more complex geometries such as tetrahedra, octahedra,

dodecahedra and truncated octahedra. Compared to conventional methods of

micromolding, this methodology combines the technique of micromolding with

self-folding. Self-folding is an advanced technique for fabrication of metallic,

dielectric and semiconductor polyhedral shapes from planar precursors, where surface

forces or intrinsic stresses fold 2D precursors into corresponding closed 3D objects.

Our micromolding process uses self-folded polyhedra as master objects to make

PDMS molds, which are then used to make copies with different polymeric materials.

Additionally, some applications of these polyhedra were investigated such as

self-assembled functional blocks and drug delivery carriers. Using this method, large

numbers of cell laden polyhedra can be created with biocompatible polymers, which

can be used as bioblocks for tissue engineering to develop artificial organs such as the

III

pancreas. Also, chemical loaded soft polyhedra can be used for controlled chemical

reactions where release of chemicals can be controlled in time and space to achieve

desired chemical patterns. In summary, the micromolding approach described is of

both intellectual significance and wide applicability to a number of engineering

disciplines such as colloidal science, electronics, optics and medicine.

Advisor: Dr. David Gracias

Reader: Dr. Honggang Cui

IV

Acknowledgments

Firstly, I would like to thank my family, my dad, my mom and my younger

sister. It is their support that brings courage to me every time I encountered certain

difficulties, especially when I entered Hopkins in 2012 and had to face the culture

shock, adapt myself to the whole new mind set of learning.

Secondly, I want to thank my girlfriend, Vesper, who always gave suggestions

for me to balance life and intense academic activities. With her guidance and

professionality developed in business school, I solved many tough problems about

data analysis.

I thank my advisor, Dr. David Gracias, who brought me into the region of

advanced technique research and guided me through the past two years. I was

attracted to nano- and micro-fabrication technologies the first time when I attended

the introduction seminar. Dr.Gracias’ impressive work convinced me to step inside

this world.

I would also like to thank my mentor and best friend, Shivendra Pandey, who

guided me to learn almost everything about this lab with intelligence, patience and

encouragement. Of course, his profound background knowledge helped a lot when I

V

was stuck in some problems. Most importantly, he helped to shape my growth in the

academic area, with normative operations and a positive attitude toward lab work.

Additionally, I wish to thank all my fellows in the Gracias lab, who always

regard me as one of them, and are ready to offer help. Changkyu Yoon, who is always

supportive and Hye Rin Kwag, who joined our work with impressive knowledge

about cell culturing. Evin Gultepe, Pedro Anacleto, Qianru Jin, and Tao Deng, all of

them created the attractive academic atmosphere in the lab.

Finally, I want to thank Johns Hopkins University, which offered this

opportunity for me to have the most important 2 years in my life. The creative

atmosphere in the campus will encourage me to look for the unique path in my future.

VI

Table of Contents

MOLDING AND APPLICATION OF SOFT POLYHEDRA.......................................I

Abstract........................................................................................................................II

Acknowledgements.....................................................................................................IV

Table of Contents........................................................................................................VI

List of Figures............................................................................................................VII

Chapter 1: Fabrication of non-spherical micropolyhedra.............................................. 1

Chapter 2: Surface tension driven self-folding of polyhedra...................................... 16

Chapter 3: Molding of microstructures....................................................................... 20

Chapter 4: Combination of micromolding and self-folding......................................... 26

Introduction ..................................................................................................26

Experimental…………...................................................................................27

Self-folding of metallic polyhedra.............................................................27

Preparation of PDMS molds ....................................................................30

Molding of polyhedra................................................................................33

Molding of cell laden polyhedra...............................................................35

Discussion ....................................................................................................36

Yield of master polyhedra.........................................................................36

Molding process........................................................................................37

Porosity of molded structures....................................................................37

Chapter 5: Applications............................................................................................... 39

Adaptive self-assembly..................................................................................39

Functional bioblocks.....................................................................................41

Chapter 6: Conclusions and Future Outlook ............................................................... 44

References .................................................................................................................. 46

Curriculum Vitae......................................................................................................... 55

VII

List of Figures

Figure 1: TEM images of silica spheres at different ethanol to water

(E/W) ratios…………………………………………………………………3

Figure 2: TEM images of gold nano-particles supported by silica spheres…………...4

Figure 3: Surface area-to-volume ratio of different configurations…………………...4

Figure 4: Scanning electron microscope images of particles……………………….…7

Figure 5: Microchannel geometry used to create plugs and disks…………………….8

Figure 6: SEM images of nonspherical colloids……………………………………....8

Figure 7: Optical microscopy images of porous spheres………………………….......9

Figure 8: M-Ink-based color-barcoded magnetic microparticles...……………...…...11

Figure 9: Schematic illustration of micro powder injection molding………………..13

Figure 10: Schematic illustration of the procedure of micromolding……………..…14

Figure 11: Finite element simulation for dependence of fold angle on the

amount of hinge material…………………..……………………………..17

Figure 12: Schematic showing surface tension driven folding and sealing hinges…..18

Figure 13: Self-folding of a polymeric container…………………………………….18

Figure 14: Examples of self-folding three dimensional shapes fabricated via

surface tension driven self-folding……………………………..……...…19

Figure 15: Concept of micro jet molding system…………………………………….22

Figure 16: Cubic structures made by micro-powder injection molding……………...23

Figure 17: Micro molding based on capillaries………………………………………24

Figure 18: Schematic illustration of self-folding and molding processes…………....28

Figure 19: Schematics of particles by self-folding………………………...…………29

Figure 20: Schematic illustration of mold preparation…………………………….…31

Figure 21: Optical images of PDMS mold with dodecahedral shapes……………….32

Figure 22: Optical images of molded particles with different shapes……………….33

Figure 23: Mass producibility of complex shaped microparticles

of different polymers……………………………………………………34

Figure 24: Molding of cell-laden microparticles……………..……………………....35

Figure 25: Master particles with defects after self-folding…………………………..36

Figure 26: Self-assembly behavior of micro polyhedral……………………………..40

Figure 27: Biobolcks made of molded polymeric particles……………………….…42

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Chapter 1: Fabrication of non-spherical micropolyhedra

Microfabrication is the process of miniaturization of structures at micro and

nanometer scales[1][2]. Over the past few decades there have been several techniques

developed for the fabrication of smaller scale structures such as photolithography,

E-beam lithography, laser cutting, and micromachining[3][4][5].

With the development of elaborate manufacturing, structures with small scales

started to attract attention in the scientific area since the 19th

century due to the great

need for sophisticated and convenient instruments in industry, especially for their

applications in the fields of machining and semiconductor engineering[6][7]. But the

world didn’t realize the potential of microstructures until wafer technology became

mature, along with the development of deposition, etching, lithography and thin film

techniques[7][8], which significantly enhanced the ability to construct small

structures for electronics and micro scale devices[4].

On December 29th

, 1959, a classic speech, entitled “There is plenty of Room

at the Bottom: An Invitation to Enter a New Field of Physics” [9] was delivered at the

annual meeting of the American Physical Society at the California Institute of

Technology. During the speech, Richard Phillips Feynman, the famous American

theoretical physicist, conveyed his pioneering idea about diving into the

- 2 -

microscope[10]. He brought up attractive imaginations of the future when

miniaturization is pushed further in the fields of biology, physics, mechanical

engineering and computer engineering[11], where a new world is constructed in the

sub-micro scale, or even at the atomic level. By inspiring students and colleagues to

strive for a path to the field of nano scale miniaturization, the speech introduced

‘Nanotechnology’, as we all know today, to the world and since then, numerous

efforts of scientists and engineers were conducted in this area[10][12]. Nowadays,

micro scale fabrication and manipulation has given rise to various kinds of

interdisciplinary research in the field of miniaturized devices, electronics and sensors,

with which microfabrication technology was born[2].

When objects are made at a smaller scale, one of the most prominent changes

among physical properties is the surface area-to-volume (S/V) ratio[13]. As the

characteristic length scale declines, from large-scale to micro-scale, the influence of

surface area becomes dominant compared to that of volume, and S/V term grows

progressively and eventually reaches an exponential relation at the nan scale[14][15].

When objects are considerably small, they have many more atoms exposed at the

surface than macro scale objects with the same shape[16]. Due to the presence of

these atoms on the surface, nano scale objects present different physical, chemical,

mechanical and electrical properties[17]. With growing needs of research on optical,

magnetic, catalytic, thermodynamic and electrochemical property changes, methods

- 3 -

of fabrication of microparticles have been investigated in the past.

Tao Wang et al. reported a synthesis method of hollow mesoporous silica

spheres (Figure 1), which represents the most recent technique of inorganic

nanoparticle fabrication.

Figure 1: TEM images of silica spheres at different ethanol to water (E/W) ratios

(cetyltrimethy-lammonium bromide (CTAB) 5.4 mM). (a) 0.37; (b) 0.42; (c) 0.47; (d) 0.50; (e) 0.53;

(f) 0.59; (g) 0.62; (h) 0.72. Reprinted from reference [7], © 2014, with permission from Elsevier.

To increase the surface area-to-volume ratio, this group used a

sol-gel/emulsion method to synthesize silica spheres, whose sizes range from 157nm

to 453.08 nm, with shell thickness from 43.5 nm to 73.91 nm[7]. Large surface area

significantly enhances the adherence behavior of gold nano-particles, which is used

for further application (Figure 2).

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Figure 2: TEM images of gold nano-particles supported by silica spheres. (a) HAADF image; and

(b) mapping of gold. Reprinted from reference [7], © 2014, with permission from Elsevier.

Another way to exploit this high Surface area-to volume ratio is to fabricate

particles with different complex shapes. Compared to simple spheres, precisely

shaped objects, like polyhedra, maintain even larger S/V ratios (Figure 3) [18].

Figure 3: Surface area-to-volume ratios of different configurations. Surface area-to-volume rations

are minimal in spherical structures, and increase in polyhedral shapes.

- 5 -

Another important aspect for maintaining complex shape is to obtain different

physical behavior when particles are fabricated into sub-millimeter scale[19][20].

Interparticle interactions strongly depend on the sizes and shapes of particles.

Compared to the single-point and non-directional interaction between spherical

particles, assembly behavior of complex-shaped particles are much more intricate as

desired[21][22]. Polyhedral shaped particles, such as cubes, dodecahedrons and

octahedrons, will locate themselves in precise locations by oriented interactions due

to surface-surface confirmed contact[23][24].

However, the latest outcome of inorganic chemical reactions, shown in Figure

1, suggests that only spherical or other simple shapes can be achieved due to self

-shaping processes where particles are formed, though synthesis processes can be

tuned for particles with different sizes by selecting different conditions for the

reaction.

Trials aiming to obtain higher S/V ratios started to turn to organic materials.

Using various techniques, synthesis processes for polymeric particles are much more

flexible especially when supported by photolithography technology for complex

shaped micro objects[25][26]. Attempts to fabricate non-spherical polymeric particles

can be classified into two distinct groups: ab initio synthesis of non-spherical particles

or modification of fabricated spherical particles into non-spherical geometries[8][27].

- 6 -

Dhananjay Dendukuri et al. reported a one-phase method for high-throughput

microparticle synthesis. By exposing a flowing acrylate oligomer stream (typically

PEG diacrylate), which contains certain concentration of photosensitive initiator, to

controlled pulses of UV light, shapes of particles can be determined by the 2D

transparent area of masks (figure 4). Chain-terminating peroxide radicals are

previously formed to leave a non-polymerizable layer on the bottom of particles,

which are possible to wash out with the flowing streams[28]. This high throughput

process is achieved with rapid polymerization (generally less than 0.1s) for 10-50 µm

particles, whose thicknesses are equal to the height of the micro-channel.

- 7 -

Figure 4: Scanning electron microscope images of particles. Micro particles formed using a ×20

objective (except d, which was formed using a ×40 objective) were washed before being observed

using SEM. Scale bar: 10 μm. a–c, flat polygonal structures, such as triangular, cubic and hexagonal

shapes; d, a colloidal cuboid; e, f, High-aspect-ratio structures of prism and cylinder; g–i, Curved

particles. The inset in the figure is the photomask that was used to make the corresponding particle.

Reprinted from reference [28], © 2014, with permission from Nature Publishing Group.

Kim Tsoi et al. present another path for fabricating non-spherical

microparticles. They formed droplets using a microfluidic device, and modified these

droplets into different shapes in the micro channel (Figure 5). By later polymerization

in ultraviolet light, particles can be formed with permanent ellipsoidal shape (Figure

6). This process also has the potential for different synthesis of monodisperse

non-spherical particles by tuning the flowing rate in the microfluidic device[29].

- 8 -

Figure 5: Microchannel geometry used to create plugs and disks. (a) polymerized plugs in the 200

μm section of the channel, 38 μm height (b) polymerized disks in the 200 μm section of the channel, 16

μm height. Reprinted from reference [29], © 2014, with permission from American Chemical

Society.

Figure 6: SEM images of non-spherical colloids. (a) plug formed at Qd 0.05 μL/min and Ca 1.6 ×

10-3

; (b) disk formed at Qd (0.05 μL/min and Ca) 4.8 × 10-3

; (c) collection of plugs formed at Qd (0.05

μL/min and Ca) 1.6 × 10-3

; and (d) collection of disks formed at Qd (0.05 μL/min and Ca) 9.6 × 10-3

.

Reprinted from reference [29], © 2014, with permission from American Chemical Society.

Researchers kept pursuing better approaches for fabricating, patterning and

modifying microparticles. Many works from other labs are focusing on

post-modification methods of achieving higher S/V ratio of small particles[7][30],

including surface modification like porous structure synthesis, and patterning

techniques.

(a) (b)

- 9 -

Shanqin Liu et al. have introduced a versatile route of preparing porous

polymeric particles; they utilize the combined processes of phase transformation and

emulsion-solvent evaporation to fabricate fine porous structures (Figure 7) on the

surfaces of spherical particles [7].

Figure 7: Optical microscopy images of porous spheres. Images show evolution of the same

emulsion droplet containing 10 mg/mL PS21k and 2 mg/mL HD during chloroform removal at h=0.75

mm. The time elapsed for the images were (a) 5 sec, (b) 12 min, (c) 16 min, (d) 19 min, (e) 20 min, and

(f) 30 min. After dropping the emulsion on the glass slides (~ 5 sec), tiny droplets can be seen within

the emulsion droplet (Fig. 1a). Without the addition of HD, no tiny droplets were observed. Reprinted

from reference [7], © 2014, with permission from Springer.

Firstly, the group dissolved Nile red, n-hexadecane (HD) and polymer, which

contains polystyrene, poly (methyl methacrylate) and poly (methyl methacrylate), in

pre-emulsified trichloromethane containing PVA. Later, in an evaporation device,

chloroform evaporates and leaves the emulsion at room temperature. Porous particles

are formed when the liquid phase completely evaporates, and after centrifugation with

6000 rpm for 15 minutes they are washed and collected in deionized water. The

- 10 -

density of pores can be tuned simply by adjusting the concentration of n-hexadecane

(HD) and the evaporation rate of solvent evaporation[7]. Surface area-to-volume ratio

has been consequently enlarged due to the introduction of roughness onto the surface.

For further modification, patterning is certainly a practical route to fabricate

microparticles with increased surface area[31]. Additionally, surface treatment of

particles enhances the interaction with the external environment, when functional

pieces are introduced onto the surface[6][32]. Different methods are invented for

investigation of possibilities to explore the surface in the micro scale, and attractive

applications are especially welcomed in the biological field.

In 2010, Howon Lee et al. tested a technique to fabricate microparticles with

color-based barcodes on the surface for multiplexed bioassays (Figure 8). The M-Ink,

whose color is varying and controlled by an applied magnetic field, is used to fill the

polydimethylsiloxane(PDMS) micro channel. Periodically changed the magnetic field

triggers the reconstruction of nanostructure, which is fixable by photolithographic

immobilization. Once the desired color on the barcode area is determined by the

magnetic field, the mask with transparent patterns will be illuminated by ultraviolet

light to create a fixed bar code structure on the surface, which is useful for other

application biologically [33].

- 11 -

Figure 8: M-Ink-based color-barcoded magnetic microparticles. a, Coding capacity comparison

between a conventional binary barcode and a color barcode; b, Conceptual description of the process of

generating color-barcoded magnetic microparticles; c, Time-sequential modulation of the magnetic

field; d, Cross-section of the PDMS microfluidic channel; (e) and their transmission micrographs (f); g,

Hexagon-type 2D color-barcoded microparticles; h,i, Bar-type 1D colour-barcoded microparticles (h)

and their transmission micrograph (i). The scale bars indicate 1μm in d, 200μm in e,f, 500μm in g and

250μm in h,i. Reprinted from reference [33], © 2014, with permission from Nature Publishing Group.

Most approaches to microparticle fabrication are based on microfluidic

techniques, for its high throughput and monodispersity in shapes and sizes of

product[34]. However, limitations of microfluidic devices prevent them from

constructing particles with more complex morphologies. Liquid polymeric materials

require fast formation for desired shapes, otherwise particles will be deformed by the

mobility of the liquid itself[34]. Thus ultraviolet light exposure techniques are

normally used for superfast polymerization, whose projective figures only form cross

sections of microparticles in an x-y plane[35][36], and the fabrication of spatial 3D

- 12 -

shapes is not practical for conventional microfluidic devices.

Recently, increasing development of new fabrication methods for shape

controlled particle fabrication has been triggered, and the micro-molding technique is

considered as one of the most important methods for low-cost and rapid polymeric

particles production[37][38]. Conventional micro-molding methods, such as jet

molding, micro-capillary molding, micro-injection molding and micro-fluidic

molding are widely used to make unique shapes for microparticles[27].

S.G.Li et al. introduced a powder injection molding technique in 2007, for 3

dimensional pillars within micro scale. The approach contains four steps: mixing,

microinjection molding, debinding and sintering (Figure 9).

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Figure 9: Schematic illustration of micro powder injection molding. Reprinted from reference [39],

© 2014, with permission from Springer.

Researchers from this group began by preparing a 24×24 array of silicon

micro pillars, standing with uniformed separation with 100 µm diameter and 200 µm

height. Ion etched micro cavities on a 5mm×5mm×0.5mm silicon panel, which are

perfect molds of these micro pillars, are utilized for fabricating replicas, using powder

containing stainless steel feedstock and polymer as binder. After debinding and

sintering, shape of molded micro pillars is fixed with 6%-12% shrinkage in height.

Microstructures made by the process are shown in Figure 10.

- 14 -

Figure 10: Schematic illustration of the procedure of micromolding. (a) Schematic drawing of the

silicon master and a cross-sectional view of the micro cavities; SEM images of section of a pillar array

for (a) molded, (b) debound and (c) sintered parts. Reprinted from reference [39], © 2014, with

permission from Springer.

The path for fabricating microstructures is clear after decades of exploration.

Rigid materials, like silicon, amorphous silicon, glass, quartz, metals and organic

polymers are all tested for possible fabrication process[40][2]. Microfabrication

techniques are growing progressively according to the desired and attractive

utilization in semiconductor fabrication and micro fluidic devices, and it also gives

rise to multi-disciplinary integration involving physics, chemistry, biology and

mechanical engineering[4][41]. Additionally, soft lithography opens a new gate for

mass production of size and shape controlled micro particles, and thus continues as

one of the important methodologies in this field[3][42]. Micromolding represents the

non-photolithographic methods of microfabrication with high possibility of achieving

post modification of micro particles[25][40]. It is believed that utilization of new

(a) (b)

(c) (d)

- 15 -

materials, new techniques and improved processing technology will greatly support

the development in this field.

- 16 -

Chapter 2: Surface tension driven self-folding of polyhedra

Self-folding is a technique where surface tension derived from molten hinges

folds or curves two dimensional precursors into corresponding three dimensional

shapes. In order to fabricate a specific shape, first figure out a planar precursor and

then lithographically pattern panels and hinges on a substrate. It is important to note

that the hinges are low melting point materials. Hinged panels are lifted off from the

substrate and heated above the melting point of the hinge material, molten hinges

ball-up in order to minimize their surface energy and thus generate a torque that

drives the folding of panels. Self-folding is a very unique in that any kind of three

dimensional shapes that can be mapped on 2D can be fabricated using this method. In

this approach, folding angles are controlled by the amount of hinge material. Figure

11 shows a simulation of dependence of folding angles on the amount of tin-lead

solder hinges.

- 17 -

Figure 11: Finite element simulation for dependence of fold angle on the amount of hinge

material. Finite element simulation was done for 200 μm cube. This shows that the fold angle can be

controlled by the amount of hinge material. Reprinted with permission from reference [43], © 2014,

with permission from Springer.

The self-folding technique is highly versatile. It can be used for variety of

materials such as polymers, metals, dielectrics and biological materials to create three

dimensional shapes of different geometries and at a range of length scales. Surface

tension-based hinges also have the added advantages that hinges placed between two

panels work as folding hinges that provide torque to fold these panels and hinges at

the periphery of panels help panels seal together. The folding mechanism of folding

and sealing hinges is schematically shown in figure 12.

- 18 -

Figure 12: Schematic showing surface tension driven folding and sealing hinges. Hinges in blue

color represent folding hinges that generate torque to fold panels and hinges in red represent sealing

hinges that bond two panels together and complete the 3D shapes. Reprinted from reference[44], ©

2014, with permission from Elsevier.

Self-folding has been used to create a variety of shapes with a variety of

materials at sizes ranging from nanometers to millimeter scale. Figure 13 shows

self-folding of a polymeric cube. These polymeric shapes can be used for cell culture,

cargo delivery and for other bio applications. They can be mass-produced and,

importantly, they are tetherless.

Figure 13: Self-folding of a polymeric container. A polymeric cube with SU8 panels and PCL hinges

self-folding in water at 60°C. Reprinted from Reference [45], © 2014, with permission from Springer.

- 19 -

Self-folding is a very viable method for fabricating patterned 3D structures,

one that can leverage the strengths of lithography and self-assembly. Self-folding can

also be used to fabricate truly 3D, smart components that are patterned in all

directions, as shown in Figure 14.

Figure 14: Examples of self-folding three dimensional shapes fabricated via surface tension

driven self-folding. (a) solder based self-folded plates with kickstands (b) surface tension driven

self-folding of interlocked reflectors (c-f) solder based self-folding of truncated pyramid, boat shape

octahedron, dodecahedron and porous cube. Reprinted from reference[18], © 2014, with permission

from John Wiley and Sons.

- 20 -

Chapter 3: Molding of microstructures

Over the past two decades, scientists and engineers have been looking for new

methods for constructing complex structures in the sub-millimeter scale. Micro

machining, inorganic and organic particle synthesis and microfluidic device

techniques have been deeply researched and unfortunately proved to be less capable

for 3D shaping in micro scale[46]. Precision and mass production cannot be achieved

simultaneously, and expense makes conventional techniques unattractive.

To overcome the shortcomings of conventional microfabrication techniques,

micromolding methodology has to be utilized for large scale production of precise 3D

microstructures. Boosting development of micro molding is led by the technology

push and market pull[27][47]. The development of a variety of micro machining

fabrication process, photolithography and electroplating results in the technology

push for micro molding, as they are important constitution of LIGA (Lithography,

Electroplating, and Molding) technology[48][49]. The market pull, on the other side,

results from the great need of miniaturization for technical products. However,

applications with further miniaturization requirement are beyond the abilities of

conventional micro fabrication techniques. Thus, micromolding process, supported by

deep lithography and electroforming, should be designed to realize structures with all

3-dimensional characteristics and micro-scale accuracy.

- 21 -

Generally, micro-molding requires more equipment for precise modification

compared to molding techniques in macro-scale[50][51]. A temperature controlled

unit, external evacuation system and separation unit are necessary for precise

fabrication of mold, and mold inserts. Unlike conventional molding, molds can be

made by LIGA, laser ablation, micro milling , sawing and grinding[52].

Micro-molding methods can be classified into several types like compression

molding, jet molding, micro-capillary molding, micro-injection molding and

micro-fluidic molding[8]. They are widely used to make unique shapes for

microparticles, which maintain sizes in the micro scale.

J. Akedo et al. introduced a jet molding process in 1997, which is applicable

for free-forming, insert molding and mask deposition, as shown in Figure 15.

Microstructure replication begins with heating materials like copper, iron, nickel and

aluminum into liquid, which are guided through chambers to form an extremely fine

stream. Liquid is deposited onto substrates, mostly silicon wafers, with a resolution of

1µm by a substrate holder.

- 22 -

Figure 15: Concept of micro jet molding system. (a) free forming of stream through chamber; (b)

insert-molding process by moving chamber; (c) mask-deposition system with switchable nozzle.

Reprinted from reference [53], © 2014, with permission from Elsevier.

Micro-powder injection molding is considered to be the dominant method for

plastic components fabrication. In this process, high pressure is required to inject the

mixture of polymer and binder into molds, where cavities will be evacuated[54]. After

complete filling, a cooling system starts operating to fix the morphology of liquid

microstructures[38][55].

Z.Y.Liu et al. report a micro-power injection molding method for mass

production of metallic and ceramic microstructures. This group injects mixture

powder, containing PZT, aluminum and stainless steel with binder system that

- 23 -

consists of PVA, water, EVA, PW, PAN250 and HDPE, into the silicon mold inserts.

Figure 16, Cubic structures made by micro-powder injection molding. SEM images of (a) green, (b)

de-bound, and (c) sintered stainless steel micro-components. Reprinted from reference [56], © 2014,

with permission from Elsevier.

After debinding and sintering, 100µm×100 µm×250 µm structures are formed

(Figure 16). Impressively, a water-soluble binder component, containing PVA, proved

to be useful in the micro injection molding. However, molded microstructures do not

perform perfectly due to the physical property of the feedstock, which is not able to

completely fill the cavity.

Another method involving micro molding is micromolding in capillaries

(MIMIC), a combination of microfluidic and micro molding techniques. George M.

Whitesides et al. developed a molding procedure in which capillary channels are used

to pattern the surface of a substrate. They placed the PDMS mold on a platform to

form micro channels, where drops are deposited on one end and in contact with both

PDMS mold and platform. Liquid will fill across the channel driven by capillary force

and evaporate slowly at the opening to cause solidification, leaving freestanding

- 24 -

patterns on the platform when PDMS mold is removed.

Figure 17: Micro molding based on capillaries. SEM images of (a) Poly-urethane on Si/SiO2 using

an elastomeric mold with rectangular recessed pattern; (b) Polyurethane pattern on Si/SiO2 made using

a mold containing a more complex pattern; (c) Polyurethane (NOA73, Norland) structures on Si/SiO2

made using a mold containing a test pattern; it shows MIMIC can be used to pattern films with multiple

thicknesses (0.5, 1.0, and 1.2 μm) in a single step; (d) SEM image of a free-standing film formed using

the structure in (b), by removing the film from its support. The film was removed from the support

(Si/SiO2) by dissolving the support in HF. (e) Schematic of the procedure applied in micro-capillary

molding. Reprinted from reference [51], © 2014, with permission from American Chemical Society.

Figure 17 shows the fabrication procedure and the structures made by

capillary molding, it is very clear that complex and precise patterns are fabricated on

e

- 25 -

the platform. Finalized patterns obtain various configurations with micro accuracy;

angles and separations maximally reproduce the design of PDMS mold. Capillary

effect is successfully introduced in this process and yields desired shapes of different

materials, such as polyurethane and NOA 73[57].

However, micromolding in capillaries (MIMIC) is limited to produce only

convex patterns by its own process feature. Techniques are currently not applicable

for clean separation of microstructures with recessed portions[58]. To produce

complex 3D patterns on flat surface, PDMS molding is expected to create a

multi-layer network of channels, where the filling rate of liquid decreases

significantly due to correspondingly higher drag force[46].

With jet molding, micro-injection molding, micro-capillary molding and other

techniques, the realm of micro molding has been deeply explored and advantages are

discovered. Compared to inorganic materials, polymeric materials have proven more

suitable for microstructure fabrication of micro molding with highly tunable processes.

Though products as small as 10µm[53][34] are created, the concept of making

structures with all 3 dimensional characteristics is still not satisfied.

- 26 -

Chapter 4: Combination of micromolding and self-folding*

Introduction

Micro molding, one of the most promising methodologies of 3D fabrication at

the sub-millimeter scale, has been widely studied as the representative of

non-photolithography processes. Building microstructures by molding should be

considered whenever an industrial design leaves laboratories for markets nowadays.

As mentioned in Chapter 1-3, such an important fabrication process has not only

broadened the ideology, but also provided a variety of applications needed for further

exploration in smaller scales[31][59][60].

Conventional micro-molding methods, such as micro-capillary molding,

micro-injection molding and micro-fluidic molding, are limited to create

microstructures with simply shaped geometries, including spherical, cylindrical[36]

[21], conical and 2D ellipsoidal shapes[61][62][63].

Compared to the single-point and non-directional interactions between two

simple 3D, and 2D particles, assembly behavior of 3-dimensional particles are much

more intricate but desired[60]. Polyhedral shaped particles, such as cubes,

dodecahedrons and octahedrons, will locate themselves in precise location by oriented

interaction due to surface-surface confirmed contact. However, complex 3D structures

* Parts of the chapter are adapted from “Precisely Patterned Polymeric Micropolyehdra of

Complex Shapes By Molding,” by S. Pandey, Z. Zhang, H. R. Kwag, C. Yoon, and D. H.

Gracias; in prepartion (2014).

- 27 -

with nano or micro size are obviously beyond the ability of conventional fabrication

methods. Herein, we report a methodology that combines the self-folding fabrication

process and micro molding process for complex polyhedral structures fabrication on

the micron scale.

Self-folding fabrication process enables us create a large number of metallic or

polymeric particles with any desired size, geometry and patterns in a parallel

process[45][64]. In this process, the patterned 2D templates are heated above the

melting temperature of the hinge materials and the templates self-fold to form

perfectly sealed 3D microparticles of any size, shapes, and patterns with precision[65].

These metallic particles are used as master particles to prepare PDMS molds where

molds have precise patterns on the inner walls. After casting molds, patches patterned

on the surfaces of master polyhedra are transferred to the interior surface of molds

prepared with PDMS. After PDMS has been cured we carefully take out the mold and

fill it with different photo-crosslinkable and chemical crosslinkable polymers and

crosslinked them. After crosslinking we released the molded polymeric polyhedra

from the PDMS molds.

- 28 -

Experimental

Self-folding of metallic polyhedra:

The master microparticles of a variety of shapes-tetrahedra, cubes,

dodecahedra and truncated octahedra-were fabricated on a silicon wafer utilizing

photolithography, thermal deposition, electroplating, wet etching and folding

techniques. The fabrication process and design rules are detailed elsewhere[43]. We

used Autodesk AutoCAD to draw net designs and then printed on transparent sheets to

make photo masks. Each net was fabricated with nickel panels connected by solder

(Pb-Sn) hinges. The preparation procedure is shown in Figure 18.

Figure 18: Schematic illustration of self-folding and molding processes. (a) Layers of silicon-based

support; (b) deposited gold patches; (c) deposited nickel panels; (d) deposited hinges, (e) cross section

of released 2D structure before folding and (f) structure after folding.

- 29 -

The above figure shows the procedure of making polyhedral particles based on

surface-tension-driven self-folding. The side of a panel measured 300 microns, with

two adjacent panels spaced apart by a width equal to 10% of the panel edge length.

Figure 19: Schematics of particles by self-folding. 2D panel and self-folded structures of (a)(b) cube;

(c)(d)dodecahedra; (e)(f) truncated octahedral. (g) mass production of dodecahedra and (h) mass

production of truncated octahedral. Scale bar: 300 micron.

(a) (b)

(c) (d)

(e) (f)

(g) (h)

- 30 -

We used two layers of optical lithography to develop features on a silicon

wafer and electrodeposited nickel panels and Pb-Sn solder hinges respectively. We

released the nets with nickel panels connected with solder hinges from the substrate,

and heated the free standing structures in a high boiling point organic solvent

N-Methylpyrrolidone. At ~183℃ solder hinges melt and 2D nets begin to fold into

3D polyhedra. All different 2D nets for a polyhedron were folded in close proximity

in order to minimize any effect from variation in processing parameters. After etching

off the chromium and copper layers, the particles were stored in an ethanol solution

until further use as master particles to prepare the PDMS molds.

Figure 19 shows the result of self-folding from different 2D shaped panels.

The edge length of each panel is 300 microns and different patterns are designed on

each surface to distinguish the spatial locations of panels when structures are being

folded. SEM and Optical images of folded cubes, dodecahedra and truncated

octahedra show that metallic particles made through self-folding can be perfectly

shaped and sealed with uniform size. Structures remain undeformed while being

transported and sorted by needle, thus proving that they are qualified for use in

molding processes.

Preparation of PDMS molds:

We used PDMS elastomer kit for mold preparation. We mixed the base part

- 31 -

and the curing agent in a 10:1 (w/w) ratio and mixed vigorously using a plastic

spatula. This mixing process resulted into a large number of bubbles. To remove the

bubbles, we placed the mixture in a desiccator for 30 min. After 30 minutes of

desiccation all bubbles were removed and a thick clear liquid was left.

Figure 20: Schematic illustration of mold preparation. (a)Self-folded master particles placed on

petri dish covered by double sided tape; (b) metallic particles immersed in PDMS; (c) PDMS mold; (d)

mold filled with polymeric liquid and (e) molded microparticles.

We attached the metallic polyhedra onto double sided tape that was secured to

the bottom of a petri dish (Figure 20, (a)). This prevented the floating of the structures

(a)

(b)

(c)

(d)

(e)

- 32 -

when PDMS were poured into the petri dish. We poured the elastomer solution gently

into the petri dish until it completely covered the master polyhedra and placed the

petri dish in a desiccator again for 30 min to remove any bubbles present and cured

the elastomer solution at 50℃ for 4 hours (Figure 20, (b)).

The solidified PDMS was gently peeled off the substrate while the metallic

polyhedra remained attached on the tape, thus creating molds with the shape of the

structure (Figure 20, (c)). We used both simple shapes (tetrahedra, cubes) as well as

complex shapes (dodecahedra, truncated octahedra) with and without precise patterns

on the panel surfaces.

Figure 21: Optical images of PDMS mold with dodecahedral shapes. (a) 2D pentagon shape of

PDMS mold and (b) PDMS molds of dodecahedra in one batch. Scale bar: 300 micron.

Figure 21 (a) shows the missing pentagonal parts on the surface of PDMS

mold, which results from the shape of panel on master dodecahedra. Precise and sharp

edges of pentagons suggest that PDMS is suitable for replication of shapes in

micro-scale. Moreover, In the case of metallic polyhedra with gold patches, different

patches on the surface of dodecahedra are well transferred to the inner wall of molds,

(a) (b)

- 33 -

as shown in Figure 21, (b).

Molding of polyhedra:

Figure 22：Optical images of molded particles with different shapes. (a) cube; (b) tetrahedral; (c)

truncated octahedral and (d) dodecahedra. Scale bar: 300 micron.

The solutions used for molding were spread on the molds and since there is a

strong interfacial force that prevents the liquid from filling the small space, we placed

it in a desiccator under vacuum for 2 hours. This step facilitated the liquid filling the

small molds and also removed any bubbles present in the solution (Figure 20, (d)).

Once the molds were completely filled with the photosensitive polymer solution, we

removed the excess and exposed the sample under the UV light for 2 min to crosslink

the polymer. After the polymer crosslinked we separated molded particles from the

molds (Figure 20, (e)).

Molded particles obtain the same shapes of master structures (Figure 22,

(a)-(d)), the great difference in physical properties of PDMS and polymeric materials

(a) (b)

(c) (d)

(b)

- 34 -

guarantees the perfect separation of the two, yielding exact replica of metallic

particles. Patches on the PDMS mold, with only 500nm thickness, are well transferred

to polymeric particles, which shows the great accuracy that PDMS molds can achieve.

We molded microparticles of various shapes made of different materials, e.g.

NOA73, PEGDA, NIPAM etc., as shown in Figure 23, and the combined

micromolding process has proved to be versatile.

Figure 23：Mass producibility of complex shaped microparticles of different polymers. (a) Molded

NOA 73 cubes with smiley patterns; (b) Molded NOA 73 truncated octahedral without surface patterns;

(c) fluorescein stained molded PNIPAM tetrahedra and (d) rhodamine stained PEGDA dodecahedra.

Scale bar: 300 micron.

To remove any flakes on the edges of microparticles, we glued sand paper

onto the bottom of a petri dish, placed molded microparticles, covered it and placed

(a) (b)

(c) (d)

- 35 -

on a vortexer at 500 rpm for 3 hours. We further sonicated it for 10 min to remove any

remnants of flakes.

Molding of cell laden polyhedra:

We used Mouse pancreatic cell β-TC-6 cultured in complete growth medium

containing Dulbecco’s Modified Eagle Medium with 10% fetal bovine serum. In the

photo encapsulation process, we first stained the cells with Calcein AM (0.7 μg/mL)

in PBS solutions for 30 minutes in the incubator (37℃, 5.0% CO2), trypsinized and

centrifuged at 1200rpm to form a pellet.

Figure 24：Molding of cell-laden microparticles. (a) optical image of cell-laden dodecahedra; (b)

fluorescent image of cell laden molded dodecahedra. Scale bar: 300 micron.

We suspended the pellet in 1 mL of PBS and 4 mL of PEGDA (700 MW), and

added Irgacure 2100. The cell-PEGDA solution was spread on a sterilized PDMS

mold and exposed to UV for 2 minutes，cell laden particles are shown in Figure 24.

(b) (a)

- 36 -

Discussion

It has been shown, in this chapter, that it is practical to fabricate complex 3D

polyhedral structures at the micro scale. Moreover, the combined method of

self-folding and micro molding proved to be suitable for shaping, size controlling and

material replacement. Herein, some issues and phenomena, observed in the

experiments, are to be discussed.

Yield of master particles

Figure 25: Master particles with defects after self-folding. (a) (b) half folded structure and (c)(d)

over folded panels on dodecahedra. Scale bar: 300 micron.

The shapes and sizes of polymeric polyhedral are highly controlled by the

master particles, since molded structures are exact replica of metallic ones. However

the self-folding process yields only 10%-20% complete sealed structures for the

(a) (b)

(c) (d)

- 37 -

further process of molding, leaving the rest as defective particles which are either

half-folded or over-folded (Figure 25). This should be considered as one influential

limitation for large scale production.

Molding process

Figure 20 (c) shows the cross section of a mold; molded particles are

immobilized in a semi-enclosed space. When particles are removed from the mold,

the elastic structure of PDMS mold will be damaged due to being bent and expanded.

In order to enhance the sustainability of the mold, a vacuum evacuation unit should be

installed[54].

Porosity of molded structures

Cell laden particles, shown in Figure 24, obtain the rigid and precise shape of

a dodecahedron. However, cells that were encapsulated did not last for long during

further observation, which is contrary to the expectation that cells are able to grow

when particles are placed in nutrient solution.

The characterization of porosity of molded particles is currently not

quantitated, and cell-living environment cannot be evaluated. Network structure that

results from crosslinking polymerization should be further tested, and only

intermediate degrees of polymerization will provide suitable living conditions for cell

- 38 -

growth.

- 39 -

Chapter 5: Applications

Adaptive self-assembly

Self-assembly is the autonomous formation of a disorder system into an

organized structure[66][67][68], the concept is used in various disciplines for studies

of functional structures[69]. It is one of the few applicable methods for building

ensembles at sub-millimeter scales. Self-assembly reflects constructing codes in

elementary units, such as shapes, surface properties[70], mechanical properties,

charge, polarizability, magnetic dipole, mass[71][72], etc. The interparticle behavior

is determined by these characteristics and the design of individual components is

decisive for functionalities and applications of self-assembled structures[73][74][75].

Compared to simple shaped 3D particles, polymeric polyhedrons, produced by

the combined methods of self-folding and micro molding, have a higher tendency to

assemble with spatial accuracy, as shown in Figure 26. The lifetime of interactions

between particles determines the stability of aggregates, and the controlled mobility

of polymeric polyhedrons in the ensemble endows desired ‘bond lifetime’ between

particles, while the interactional lifetime for simply shaped particles, like spheres, is

too short to yield stable entirety.

- 40 -

Figure 26: Self-assembly behavior of micro polyhedra. (a) elementary unit of molded truncated

octahedra and (b) self-assembled structure of molded truncated octahedra. Scale bar: 300 micron.

Self-assembly is a widely utilized strategy in many fabrication methods[76],

and different applications have been investigated, which are listed as following.

Firstly, at all scales crystallization is one of the most desired processes in

engineering[77][78], especially in semiconductor fabrication[79][80], where direct

human intervention is not possible for precise patterning and manipulation. Also,

microelectronic devices may have new fabrication routes using a high density of

repeating units ten to several hundred microns in size[81][82].

Additionally, miniaturization of robotics has been discussed over the last

decade. Self-assembly provides a new route to the assembly robots within micro- or

even nanometer dimensions[83]. Conventional manufacturing processes will fall

when self-assembly become dominant for more sophisticated machines.

(a) (b)

- 41 -

Finally, self-assembled structures could form computing networks. Chips have been

researched for being constructed in all 3 dimensions. Compared to the conventional

circuit on 2D circuit board，self-assembled blocks of micro structures will form

extremely complex networks, similar to neural connections in brains, resulting in an

explosion of computing power.

Functional bioblocks

Bioblocks are created to achieve similar functionality to tissues[84][85], or

even organs like pancreas, thyroid and adrenal gland[62]. Corresponding cells are

encapsulated inside the micro polyhedral, which can construct huge ensembles

through directional self-organization[86][87]. Enlarged surface area-to-volume ratio

(S/V) greatly enhances communications of cells between particles and the outcome

level of products, such as insulin, thyroxin and adrenaline, could be as high as that of

real organs.

- 42 -

Figure 27: Biobolcks made of molded polymeric particles. (a)optical image of aggregate assembled

by cell laded cubes; (b) fluorescent images of aggregate assembled by cell laded cubes ; (c) optical

image of aggregate assembled by cell laded dodecahedra; (d) fluorescent images of aggregate

assembled by cell laded dodecahedra; (e) schematic of pancreas shape (©2007 MediVisuals, Inc.) and

(f) mimic of pancreas shape by assembled cell laded dodecahedra. Scale bar: 300 micron.

Bioblocks that consist of polyhedral particles enjoy certain advantages over

conventional bioblocks that are entireties. Self-healing would be possible when a

small amount of structural particles fail[88][89], and could be replaced with spatial

accuracy by other functioning polyhedral particles. Also, tunable configuration of

assembled bioblocks greatly enhances the compatibility of the structure to the desired

location in the human body. Elementary units, the polyhedral particles, simply

- 43 -

reconstruct new bioblocks by regrouping, guided by the directional interactions

between particles.

Utilization of polymeric polyhedra with micro sizes takes full advantage of

directional self-assembly, material practicability and configuration adaptability. With

further investigation, this combined method of fabricating complex shaped particles

would be involved in more applications in the near future.

- 44 -

Chapter 6: Conclusions and Future Outlook

This thesis has presented many techniques utilized to explore the world of 3D

structures within micro and nano scale. Miniaturization has been widely accepted as

the major tendency of the development in the fields of chemical engineering,

mechanical engineering, biomedical engineering and etc. For more sophisticated

functionalities, attempts have been conducted in various kinds of micromolding

process to pursue microstructures with complex shapes.

The combination of self-folding and PDMS micromolding is a new method for

polymeric polyhedron fabrication with attractive sizes. Although both techniques are

widely investigated, the combined concept that is presented in this thesis is the first

trial in the field. It is shown that the design and manufacturing of 3 dimensional

particles on the micro scale is possible, and the versatility has been proved in

experiments where different sizes, shapes and materials are tested.

Although studies of complex shaped microparticles are growing vigorously,

these structures are still considered as being on macro-scale from a standpoint of

nanotechnology. Further research on micromolding is inevitably pushed by the

scientific trend and future work will focus on achieving smaller characteristic sizes,

and special functionalities by various combinations of current, and newer techniques.

- 45 -

Apart from this thesis, there is still much to be researched and applied after

micromolding process, such as self-assembly and bonding. In the realm of

microfabrication, a wide range of applications has been invented based on micro

molding techniques, and more valuable potentials are expected to be discovered in the

coming future.

- 46 -

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