Spatially controlled chemistry using remotely guided nanoliter scale containers

Article abstract of DOI:10.1021/ja063100z

In this communication we describe a new chemical encapsulation and release platform using 3D microfabricated nanoliter scale containers with controlled porosity. The containers can be fabricated of magnetic materials that allow them to be remotely guided using magnetic fields. The favorable attributes of the containers that include a versatile highly parallel fabrication process, precisely engineered porosity, isotropic/anisotropic chemical release profiles, and remote magnetic guiding provide an attractive platform for engineering spatially controlled chemical reactions in microfluidic systems. Copyright

Full text of DOI:10.1021/ja063100z

Published on Web 08/16/2006
Spatially Controlled Chemistry Using Remotely Guided Nanoliter Scale
Containers
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†
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,†,‡
Timothy Leong, Zhiyong Gu, Travis Koh, and David H. Gracias*
Department of Chemical and Biomolecular Engineering and Department of Chemistry, Johns Hopkins UniVersity,
Baltimore, Maryland 21218
Received May 3, 2006; E-mail: dgracias@jhu.edu
In this communication we describe a new pico-nanoliter scale
chemical encapsulation and delivery system in the form of 3D
metallic containers with controlled surface porosity. The advanta-
geous attributes of the containers are a parallel fabrication process
with versatility in size and shape, precise and monodisperse surface
porosity, and the ability for remote guidance using magnetic fields.
We demonstrate the isotropic and anisotropic release of reagents
from the containers, remotely guided chemical release, and spatially
controlled chemical reactions in microwells. The arbitrary chemical
patterns that can be generated are not limited by flow profiles in
conventional microfluidics that must often be formed downstream
from a channel inlet. These containers suggest a new strategy for
precisely engineering spatially localized chemical reactions with
subnanoliter scale control.
In the past decade, microtechnology has greatly impacted the
chemical and biological sciences with the development of microf-
luidic systems that are capable of manipulating small volumes of
reagents. Microfluidic devices make it possible to execute and
observe chemical reactions with spatial and temporal control. The
applications of microfluidics include the measurement of enzyme
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4
reaction kinetics, capillary electrophoresis, flow cytometry, PCR
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amplification, immunoassays, mass spectrometry, DNA analysis,
cell patterning, 9 and cell separation.10
Along with conventional channel based microfluidic devices,
several nanoliter scale chemical encapsulants have been developed,
including those based on polymers, gels, and liquid drops.11 In
contrast to the above organic systems, micromachined silicon-based
devices can have extreme precision, high reproducibility, excellent
mechanical strength, good chemical stability, as well as the ability
to incorporate sensing, signal conditioning, and actuating functions
in close proximity or on the same substrate. However, 3D
micromachined nanoliter scale reservoir systems with controlled
porosity do not exist at the present time owing to the inherent two-
dimensionality of the photolithographic process that is used in
conventional silicon-based micromachining.
Here, we describe the development of 3D containers with
precisely engineered surface porosity and their utility in chemical
encapsulation, guided delivery, and spatially controlled chemistry.
Briefly, the process involved the photolithographic fabrication of
a 2D metallic template with solder hinges (Figure 1a). The 2D
template self-assembled into the 3D hollow polyhedron when it
was heated above the melting point of the solder hinges, wherein
the surface tension of the molten solder provided the force to drive
self-assembly.12 (see Supporting Information (SI) for details). We
fabricated containers with different shapes and volumes ranging
from 230 picoliters to 8 nanoliters (Figure 1a-d). The fabrication
process was also highly parallel; containers of different shapes and
sizes could be fabricated in a single process run (i.e., from a single
wafer, Figure 1e-g). When the process was optimized, yields
Figure 1. (a) Optical and SEM images showing the different steps (the
photolithographically fabricated 2D template, registry of solder hinges, and
the folded 3D structure) in the fabrication of a cubic container with one
open face. SEM images of a (b) cubic container with all open faces, (c)
pyramidal frustum, (d) square pyramid with an open face on the bottom;
(
e-g) optical image of multiple containers of different shapes demonstrating
the parallel fabrication strategy; (h-k) SEM images of cubic containers
with monodisperse pore sizes of (h, j) 5 microns and (i, k) 3 microns.
ranged from 60 to 90% (yields varied for different shaped containers
depending on the number of folding faces and the symmetry) for
a 3'' wafer. The major yield limiters in the fabrication process were
the photolithographic fidelity in the registry of hinges with respect
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to the faces and the volume of solder in the hinges.
Since
photolithographic microfabrication is highly precise, it was also
possible to pattern one or more faces of the containers with
†
Department of Chemical and Biomolecular Engineering.
‡
Department of Chemistry.
11336
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J. AM. CHEM. SOC. 2006, 128, 11336-11337
10.1021/ja063100z CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Figure 3. Spatially controlled chemical reactions between multiple
containers: (a-c) reaction of copper sulfate and potassium hydroxide in
an aqueous medium resulting in the formation of copper hydroxide along
the central line between the containers; (d-f) the reaction of phenolphthalein
(
(
diffusing out of the two bottom containers) and potassium hydroxide
diffusing out of the top container) in an aqueous medium.
Figure 2. Optical images of chemical release from containers: (a) spatially
isotropic release of a dye from a container with identical porosity on all
faces; (b) anisotropic release of a dye from a container with anisotropic
porosity (five faces with an array of 5 micron pores; the sixth face has a
chemical (Figure 3d-f). These experiments further demonstrate that
the spatial control over chemical reactions can be extended to more
complex reaction fronts involving multiple containers.
1
60 micron sized pore); (c) an example of a remotely guided spatially
controlled chemical reaction. The letter G (for the Gracias lab, see video in
SI) was formed by the direct writing of phenolphthalein in an alkaline
water-glycerol medium.
In conclusion, as opposed to all organic encapsulants, the
containers allow unprecedented spatial control over the release of
chemical reagents by virtue of their versatility in shapes and sizes,
anisotropic faces, monodisperse porosity, and their ability to be
guided in microfluidic channels using magnetic fields. Additionally,
the metallic containers interact with remote electromagnetic fields
that allow them to be easily detected and tracked (using magnetic
monodisperse pores (Figure 1h-k). The size of the pores formed
was limited by the photomasks used (which in our case had a
resolution of 3 microns). By controlling the porosity, it was possible
to engineer the reagent release profiles as shown in Figure 2.
We loaded containers using stereotactic microinjection. We
loaded containers with a solution of a gel (or polymer) and the
chemical to be released. When the solvent evaporated, the gel
remained within the containers. The chemicals were released by
immersing the loaded containers in a solution that softened or
dissolved the gel (or polymer). Since gels (and polymers) are
available with a wide range of solubility and softening temperatures,
it was possible to manipulate the chemical release rates using
different solvents and temperatures. The images shown in the paper
were obtained using containers loaded with a block copolymer
hydrogel (Pluronic). Release experiments were done in a water-
alcohol based medium (details in the SI). By varying the relative
porosity on different faces of the container it was possible to get
both isotropic (Figure 2a) as well as anisotropic (Figure 2b)
chemical release profiles.
1
2c
resonance imaging, MRI) as demonstrated in a previous paper.
Thus, the containers provide an attractive platform for engineering
remotely guided, spatially controlled, chemical reactions in mi-
crofluidic systems.
Acknowledgment. We acknowledge funds from the Beckman
Young Investigator Award and valuable input from Emma Call.
Supporting Information Available: Details of the methods used
in the fabrication, loading, release, chemical reactions, and a video
showing the direct writing of the letter G. This material is available
free of charge via the Internet at http://pubs.acs.org.
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We also visualized spatially localized chemical reactions between
multiple nanoliter scale containers (Figure 3a-c). When two
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