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The unifying theme of our research is the science of miniaturization and the interface between engineered and living systems

Recent highlights: The first ever biopsy with dust sized surgical tools

Bridging the biotic and abiotic worlds: 3D printed bionic ears

Tools for capture, manipulation and analysis of single cells

Self-folding polyhedra and microdevices

We are a highly interdisciplinary group that develops new methods to fabricate very small devices and integrated structures, and characterize these systems using microscopy and spectroscopy. A major thrust of our research is focused on constructing miniaturized 3D devices which are especially challenging to fabricate at small size scales. Here, we have pioneered a variety of self-folding and self-assembly approaches, most notably for self-folding patterned polyhedra, folded metamaterials and actuators. We are also particularly interested in understanding, synthesizing and characterizing self-assembling, intelligent and hybrid biotic-abiotic systems.

We utilize a range of experimental techniques including photo-, e-beam and nano-imprint lithography; 3D printing, thin film deposition, molding, etching, culture of prokaryotic (E coli) and eukaryotic (e.g. fibroblasts, islets, myoblasts, cancer) cells, biological assays (e.g. fluorescent stains, ELISA, cytology), non-linear optical spectroscopy, IR/Raman/UV/Vis spectroscopy, optical / electron microscopy (TEM & SEM with fixation), RF measurements such as GHz spectrum analysis, electrochemical methods such as potentiometry and chronoamperometry and four point electrical testing with femto-amp resolution. We also utilize analytical methods as well finite element methods (HFSS, Surface Evolver, COMSOL) to model data. Students in our lab have multidisciplinary backgrounds in Chemical and Biomolecular Engineering, Electrical Engineering, Physics, Chemistry, Materials Science, Biomedical Engineering and Medicine.


Details of Current Research Themes

We acknowledge research support from the National Institutes of Health (NIH), National Science Foundation (NSF), Defense Threat Reduction Agency (DTRA), Defense Intelligence Agency (DIA), Army Research Office (ARO), Semiconductor Research Corporation (SRC), DuPont, Northrop Grumman, Goldman Philanthropic Foundation, Arnold and Mabel Beckman Foundation, Camille & Henry Dreyfus Foundation, Iacocca Family Foundation and Alexander von Humboldt Foundation

1. Self-folding of thin films / Origami inspired MEMS and NEMS /3D micro-nanofabrication by folding, bending and curving

Problem statement: It is very challenging to manufacture 3D micro and nanostructures in a cost-effective manner. Conventional micro and nanopatterning is inherently 2D or layered 2D to 3D. Even advanced and popular techniques such as 3D printing and 2-photon polymerization are serial processes and cannot be readily used to pattern device grade silicon, metals, inorganics and many polymers / hydrogels.

Potential solution: Bend, curve and fold photo, e-beam and nanoimprint lithographically patterned thin films composed of device grade silicon, metals, inorganics, polymers and hydrogels.

Potential applications: Nanomanufacturing of patterned 3D nanostructures, anatomical models for tissue engineering, metamaterials in a high throughput and cost-effective manner

Prior accomplishments in this research theme

a. High-throughput parallel nanomanufacturing of 3D nanostructures by bending, folding and curving of lithographically patterned thin films.

We were the first laboratory to demonstrate the self-folding of 100 nm sized curved and polyhedral metallic and dielectric structures with 10 nm resolved patterns in all three dimensions. This demonstration opens the door to the creation of precisely lithographically patterned nanoparticles and nanostructures in a highly parallel and possibly cost-effective manner (with nanoimprint lithography).

Representative Publications: Self-assembly of lithographically patterned nanoparticles, Nano Lett. (2009); Three dimensional nanofabrication using surface forces, Langmuir (2010); Curving nanostructures using extrinsic stress, Adv. Mater (2010); Nanoscale origami for 3D optics, Small (2011); Self-folding single cell grippers, Nano Lett. (2014).

b. High throughput folding using surface forces (capillary origami)

We invented a high-throughput methodology to create well sealed and precisely patterned hollow polyhedra with metals, semiconductors and polymers. As compared to unpatterned or weakly patterned 3D microstructures, this approach enables the creation of precisely patterned (with pores or biomolecule patches) containers/capsules/particles. Importantly, the work involves the invention (see patents) of self-aligning hinges that self-align and correct defects during folding. Self-aligning or liquid hinges can be used to seal and self-correct origami structures formed by any method. Consequently, we have been able to fold polyhedra with angles as precise as 116.56 (dodecahedron) or even different angles of 109.47 and 125.26 in the same structure (truncated octahedron). Moreover, on cooling, the polyhedra are well sealed and mechanically rigid.

Representative Publications: Fabrication of micrometer-scale, patterned polyhedra by self-assembly, Adv. Mater (2002); Self-assembled three-dimensional radio frequency (RF) shielded containers for cell encapsulation, Biomed. Microdev. (2005); Surface tension driven self-folding polyhedra, Langmuir (2007); Self-folding micropatterned polymeric containers, Biomed. Microdev. (2011); Self-folding polymeric containers for encapsulation and delivery of drugs, ADDR (2012); Origami inspired self-assembly of patterned and reconfigurable particles, JOVE (2013); US Patents 9,236,259 B2; 8,246,917 B2.

c. High throughput self-folding of containers, sheets and metamaterials using thin film stress

We were the first laboratory to demonstrate geometrically programmable self-folding sheets and metamaterials composed of lithographically patterned metals and polymers. Sheets feature hundreds to thousands of folds, and fold up without any human intervention, wires or circuits. By merely, varying the pattern of hinges on a lattice of rigid segments, we showed in Adv Mater (2008, see Figure 2) that it was possible to program the sheet to self-fold into a variety of different outcomes. Programming a sheet to self-fold into different outcomes is an important feature for programmable matter. Subsequent demonstrations highlighted bidirectional curvature for mechanical metamaterials (APL, 2009), and extension to truly reversible polymer electromagnetic metamaterials based on swelling (Nature Comm 2011).

Representative Publications: Patterning thin film mechanical properties to drive assembly of complex 3D structures, Adv. Mater. (2008); Thin film stress driven self-folding of microstructured containers, Small (2008); Microassembly based on hands free origami with bidirectional curvature, Appl. Phys. Lett. (2009); Three dimensional surface current loops in terahertz responsive microarrays, Appl. Phys. Lett. (2009); Reversible actuation of microstructures by surface chemical modification of thin film bilayers, Adv. Mater. (2010); Differentially photo-crosslinked polymers enable self-assembly microfluidics, Nature Commun. (2011) {See first polymer/metal self-folding EM metamaterials in Fig. 3e-f}; Self-folding thin film materials: From nanopolyhedra to graphene origami, MRS Bull. (2012, Review).

d. High throughput parallel self-folding of biomimetic and anatomically inspired structures

Tissues are highly curved, folded, patterned and vascularized. We were the first laboratory to demonstrate the self-folding of microfluidic networks, synthetic scaffolds and cell-laden hydrogels reminiscent of vascularized leaves and tissues. Importantly, self-folding approaches enable layering, patterning and vascularization which are all important features of native tissues.

Representative Publications: Directed growth of fibroblasts into three dimensional micropatterned geometries via self-assembling scaffolds, Biomater. (2010); Differentially photo-crosslinked polymers enable self-assembling microfluidics, Nature Commun. (2011); Bio-origami hydrogel scaffolds composed of photocrosslinked PEG bilayers, Adv. Healthcare Mater. (2013); Curved and folded micropatterns in 3D cell culture and tissue engineering, (2014).

e. Stimuli responsive self-folding with polymers and hydrogels

We have worked extensively of stimuli responsive self-folding and demonstrated self-folding of metallic and hydrogel devices and actuators in response to a range of stimuli including pH, ionic strength, biochemicals, temperature and light. Importantly we demonstrated Venus fly trap like actuators, the first ever variants of Miura-ori (Nojima-ori) reversible folding stimuli responsive EM metamaterials (Nature Commun 2011 above), porous gel based actuators or theragrippers and other functional devices. To our knowledge we were the first to demonstrate photopatterning of cross-linking to modulate folding vertically, laterally and through gradients.

Representative Publications: Photolithographically patterned smart hydrogel based bilayer actuators, Polymer (2010); Laser triggered sequential folding of microstructures, Appl. Phys. Lett. (2012); Stimuli responsive self-folding using thin polymer films, Curr. Op. Chem. Eng. (2013, Review Paper); Stimuli responsive theragrippers for chemomechanical controlled release, Angew. Chemie (2014). Self-folding thermo-magnetically responsive soft-microgrippers, ACS Appl. Mater. Interfaces (2015); Self-folding graphene polymer bilayers, Appl. Phys. Lett. (2015).

f. Self-folding of functional devices: Sensors, optical, electronic, RF and lab-on-a-chip devices

We have shown how self-folding can be utilized to create a variety of 3D optoelectronic and sensory devices.

Representative Publications: Remote radio frequency controlled nanoliter chemistry and chemical delivery on substrates, Angew.Chem. (2007), Size selective sampling using mobile, three-dimensional nanoporous membranes, Anal. Bioanal. Chem. (2009); Self-assembly of orthogonal 3-axis sensors, Appl. Phys. Lett. (2008); Three-dimensional surface current loops in terahertz responsive microarrays, Appl. Phys. Lett. (2010); Self-loading lithographically structured microcontainers: 3D patterned, mobile microwells, Lab Chip (2008); Three-dimensional microwell arrays for cell culture, Lab Chip (2010); Self-folding immunoprotective cell encapsulation devices, Nanomed. (2011); Tetherless microgrippers with transponder tags, JMEMS (2011); Design for a lithographically patterned bio-artificial endocrine pancreas, Artificial Organs (2013), Self-folding graphene-polymer bilayers, Appl. Phys. Lett. (2015). .....see also papers on self-folding EM metamaterials and nanoscale origami for 3D optics above.

g. Self-folding of rings and helices / Investigating the mechanics of folding of interesting shapes

The shape, edge effects and geometry play an important role in the flat to folded transition. Like the classic saddle shape of a potato chip, self-folding of curved 2D shapes display a rich phase behavior including buckling or helical assembly.

Representative Publications: Plastic deformation drives wrinkling, saddling and wedging of annular bilayer nanostructures, Nano Lett. (2010) {Folding and buckling of a ring}; Bio-origami hydrogel scaffolds composed of photocrosslinked PEG bilayers, Adv. Healthcare Mater. (2013) {See a rectangular strip fold into a helix in Fig. 1 e}.


2. Surgery with untethered tools

Problem statement: Surgery has evolved from very invasive procedures through the advent ot anesthesia and antiseptics to minimally invasive procedures where tube like devices are introduced through natural or incised orifices. However surgical procedures are still invasive.

Potential solution: Perform surgery with untethered tools

Potential applications: Enable less invasive, more effective biopsy, tissue surveillance, targeted surgery

Prior accomplishments in this research theme

a. Physiologically responsive untethered biopsy devices: Towards autonomous surgical tools

We invented the first ever sub-mm scale completely wire-free surgical microgripper and the first enzymatically responsive microgripper. Recently we collaborated with physicians at Johns Hopkins Medicine to perform the first ever biopsy in a live animal using sub-mm scale untethered tools. Elsewhere we have helped create nanoscale tools of relevance to surgery. These research studies have opened the door to the era of surgery with untethered tools towards the goal of making surgery less invasive and more efficient.

Representative Publications: Tetherless thermobiochemically actuated microgrippers, PNAS (2009); Toward a miniaturized mechanical surgeon, Mater. Today (2009); Enzymatically Triggered Actuation of Miniaturized Tools, JACS (2010); Biopsy with thermally-responsive untethered microtools, Adv. Mater. (2013); Rolled-up magnetic microdrillers: Towards remotely controlled minimally invasive surgery, Nanoscale (2013); Biologic tissue sampling with untethered microgrippers, Gastroenterology (2013); Self-folding single cell grippers, Nano Lett. (2014).

b. Self-propelled and magnetically guided devices / drillers

We have helped invent tiny tools that can be guided and self-propelled and mimic macroscale mechanized functions such as *drilling* at the micro and nanoscale.

Representative Publications: Solvent driven motion of lithographically fabricated gels, Langmuir (2008); Pick and place using chemically actuated microgrippers, JACS (2008); Self-propelled nanotools, ACS Nano (2012); Rolled-up magnetic microdrillers: Towards remotely controlled minimally invasive surgery, Nanoscale (2013).


3. 3D Spatio-temporally controlled chemistry in three dimensions

Problem statement: Chemistry in real life and many interesting systems occurs with 3D spatio-temporal control, but most of chemistry is carried out in unpatterned or homogeneous media

Potential solution: Find ways to perform chemistry with reaction diffusion from cellular blocks

Potential applications: Realize intelligent, adaptive, reconfigurable and computational systems via chemistry

Prior accomplishments in this research theme

a. Spatially controlled chemistry in 3D space with extremely precise controlled release blocks

Representative Publications: Spatially controlled chemistry using remotely guided nanoliter scale containers, JACS (2006); Remote radio frequency controlled nanoliter chemistry and chemical delivery on substrates, Angew Chemie (2007); Reconfigurable microfluidics with metallic containers, JMEMS (2008); Chemistry with spatial control using particles and streams, RSC Adv. (2012, review paper).

b. Dynamic chemical patterns through spatio-temporal control

Representative Publication: A chemical display: Generating animations by controlled diffusion from porous voxels, Adv. Funct. Mater. (2015).


4. Self-assembly

Problem statement: Nature fabricates and organizers matter by self-assembly while human engineering does not. We urgently need to learn how to do this to create smart, 3D and intelligent devices

Potential solution: Build model systems to understand the rules of self-organization using synthetic building blocks and biological cells.

Potential applications: Complex 3D aggregates and organized structures that show features of living systems

Prior accomplishments in this research theme.

a. Cellular Self-organization

First demonstration of the self-organization of bacteria into a well-defined 3D space curve; a helix.

Representative Publication: Three dimensional chemical patterns for cellular self-organization, Angew. Chemie (2011).

b. Patchy patterns in aggregative 3D assembly

We have uncovered surface patterning rules for low-defect 3D self-assembly of patchy polyhedra

Representative Publication: The importance of surface patterns for defect mitigation in three dimensional self-assembly, Langmuir (2010).

c. Uncovering design rules of self-assembly by folding

Convincingly demonstrated that compact nets with high vertex connections result in high yielding self-assembly processes

Representative Publications: Compactness determines the success of cube and octahedron self-assembly, PLoS One (2009); Algorithmic design of self-folding polyhedra, PNAS (2011); Building polyhedra by self-assembly; theory and experiment, Artificial Life (2014); Self-assembly of mesoscale isomers: The role of pathways and degrees of freedom, PLoS One (2014)

d. Aggregative self-assembly of functional devices

We have created advanced functional devices by self-assembly including model computational devices.

Representative Publications: Surface tension driven self-assembly of bundles and networks of 200 nm diameter rods using a polymerizable adhesive, Langmuir (2004); Reflow and electrical characteristics of nanoscale solder, Small (2006); Integrating nanowires with substrates using directed assembly and nanoscale soldering, IEEE Trans. Nanotech. (2006); Dielectrophoretic assembly of reversible and irreversible metal nanowire networks and vertically aligned arrays, Appl. Phys. Lett. (2006);Three dimensional electrically interconnected nanowire networks formed by diffusion bonding, Langmuir (2007). A three dimensional self-folding package (SFP) for electronics, MRS proceedings (2010); Quantitative analysis of parallel nanowire array assembly by dielectrophoresis, Nanoscale (2011), A cellular architecture for self-assembled 3D computational devices, (Nanoarch 2013).

e. Pattern formation

Simply on heating, rings appear in these multilayer thin film stacks!

Representative Publication: Concentric ring pattern formation in heated chromium-gold thin films on silicon, Appl. Phys. Lett. (2008).



5. Integration of Bionic devices

Problem statement: Engineered devices enable optical, electronic and magnetic functionalities while biological devices can enable autonomous decision making processes, self-propulsion, swarming and intelligence. It is conceivable that merging functionalities from both worlds could lead to significantly enhanced devices.

Potential solution: Integrate biological (cells, tissues) and engineered devices

Potential applications:Autonomous smart devices, advanced prosthesis, augmented capabilities.

Prior accomplishments in this research theme

a. Bacterial backpacking

Propelling individual nanoscale cargo with a single bacterium.

Representative Publications: Enabling cargo-carrying bacteria via surface attachment and triggered release, Small (2011); Assembling backpacking bacteria for diagnostics and therapeutics, MicroTAS (2011).

b. 3D integration of Bionic organs

3D printing of biotic-abiotic media to create hybrid organs. Importantly, the printing of nanoparticle based materials enables a new strategy to enable electronic integration within tissue bioprinting.

Representative Publication: 3D printed bionic ears, Nano Lett. (2013).


6. Optical spectroscopy at interfaces

Problem statement: It is challenging to measures the structure of molecules at interfaces due to dominant signal from the bulk

Potential solution: Utilize nanoparticle field enhancement and non-linear optical techniques

Potential applications: Gain insight into the behavior of molecules and reaction intermediates at interfaces which is important for a large number of technological and biological problems

Prior accomplishments in this research theme

a. SFG spectroscopy of functional devices

Representative Publications: Probing organic field effect transistors in-situ during operation using SFG, JACS (2006); Correlations between electrical properties and SFG spectra of organic field effect transistors, JPC (2007).

b. SERS spectroscopy

Representative Publication: Nanowire-based surface-enhanced Raman spectroscopy (SERS) for chemical warfare simulants, Proc. SPIE (2012).

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