Browsing by Subject "Engineering, Materials Science"

Antivascular targeting is a promising strategy for tumor therapy. This strategy overcomes many of the transport barriers and has shown efficacy in many preclinical models, but targeting epitopes on tumor vasculature can also promote accumulation in healthy tissues. We used Elastin-like Polypeptide (ELP) to form block copolymers (BCs) consisting of two separate ELP blocks seamlessly fused at the genetic level. ELPBCs self-assemble into spherical micelles at a critical micelle temperature (CMT), allowing external control over monovalent unimer and multivalent micelle forms. We hypothesized that thermal self-assembly could trigger specific binding of ligand-ELPBC to target receptors via the multivalency effect as a method to spatially restrict high-avidity interactions. We termed this approach Dynamic Affinity Modulation (DAM). The objectives of this study were to design, identify, and evaluate protein-based drug carriers that specifically bind to target receptors through static or dynamic multivalent ligand presentation.

ELPBCs were modified to include a low-affinity GRGDS or GNGRG ligand and a unique conjugation site for hydrophobic compounds. This addition did not disrupt micelle self-assembly and facilitated thermally-controlled multivalency. The ability of ligand-ELPBC to specifically interact with isolated AvB3 or CD13 was tested using an in vitro binding assay incorporating an engineered cell line. RGD-ELPBC promoted specific receptor binding in response to multivalent presentation but NGR-ELPBC did not. Enhanced binding with multivalent presentation was also observed only with constructs exhibiting CMT < body temperature. This study establishes proof-of-principle of DAM, but ELPBC requires thermal optimization for use with applied hyperthermia. Static affinity targeting of fluorescent ligand-ELPBC was then analyzed in vivo using intravital microscopy (IM), immunohistochemistry (IHC), and custom image processing algorithms. IM showed increased accumulation of NGR-ELPBC in tumor tissue relative to normal tissue while RGD-ELPBC and non-ligand ELPBC did not, and IHC verified these observations. This study shows (1) multivalent NGR presentation is suitable for static multivalent targeting of tumors and tumor vasculature, (2) multivalent RGD presentation may be suitable for DAM with thermal optimization, and (3) ELPBC micelles may selectively target proteins at the tumor margin.

When developing applications for self-assembling nanostructures, a challenge is to organize the self assembling components within integrated nano-microsystems. One approach is to impart nanostructure recognition properties to patterned surfaces, such that nanostructure placement could be thermodynamically driven. This research focuses upon self assembling nanostructures composed of DNA and their reversible specific assembly upon functionalized planar surfaces. Assembly strategies that have been developed for solution phase assembly are herein demonstrated as potentially appropriate for heterogeneous nanosystem integration.

The assembly of DNA nanostructures relies upon unique base pair interactions between single strands. While DNA hybridization that involves many base pairs results in structures that are strongly bound, an assembly strategy that underlies much DNA nanostructure engineering is formation of nanostructures at temperatures at which the interactions are weak. Here, DNA specific nanostructure immobilization is driven by weak forces. Association is characterized using surface sensitive surface plasmon resonance and quartz crystal microbalance methods. The results suggest that future strategies for nanostructure - system integration that require precise nanostructure placement may be accomplished using specific molecular recognition under thermodynamic control.

Several methods of solution phase nanostructure characterization are explored. The diffusive properties of DNA nanostructures are examined using dynamic light scattering. Effective hydrodynamic radii are found to be large relative to the nanostructure geometric size. The temperature dependence of light scattering from nanostructures is investigated using both resonance light scattering and nonresonant laser light scattering. Additionally, DNA nanostructure building block and superstructure geometry are interrogated in solution using small angle x-ray scattering. Results derived from comparison of small angle data with simulations of scattering from coarse-grained models are compared with structural information derived from imaging immobilized nanostructures with atomic force microscopy.

Finally, plasmon coupling in systems comprised of metal particles of unlike composition is described. Through simulation, three phenomena that contribute to interparticle coupling are explored. Off resonant metal particles positioned in between pairs of particles near resonance are found to promote optical coupling in a manner similar to that provided by bulk dielectric media.

Molecular control of plasmon coupling is investigated in biomolecule-linked nanoparticle assemblies in two-particle, small cluster, and extended network formats. The relationship between structure and optical properties is explored through comparison of measured spectra with simulated spectra calculated using structural models based upon measured structural parameters. A variety of techniques are used to characterize nanoparticle assemblies, including ensemble extinction and elastic scattering spectroscopy, single-assembly scattering spectroscopy, transmission electron microscopy, and dynamic light scattering. Initially, molecular control of plasmon coupling is investigated in ~100 nm assemblies composed of 13 nm gold "satellite" particles tethered by duplex DNA to a 50 nm gold "core" particle. Comparison of core-satellite assemblies formed with duplex DNA tethers of varying length demonstrates that, while core-satellite separation is controlled by the number of base pairs in the DNA tether, structural properties such as core:satellite ratio and yield are independent of DNA tether length. Thus, plasmon coupling within these assemblies is determined by the number of base pairs in the duplex DNA tether; compact assemblies in which tethers are composed of fewer base pairs exhibit plasmon bands that are red-shifted relative to the bands of extended assemblies, indicating increased plasmon coupling in the compact assemblies. Subsequently, core-satellite assemblies are formed with reconfigurable DNA nanostructure tethers that modulate interparticle separation in response to a molecular stimulus. Assembly reconfiguration from a compact to an extended state results in blue-shifting of the assembly plasmon resonance, indicating reduced interparticle coupling and lengthening of the core-satellite tether. Comparison between measured and simulated spectra revealed a close correspondence and provided validation of the structural models that link assembly plasmonic properties with DNA control of interparticle separation.

Plasmon coupling is investigated also in binary metal systems. A new method for forming stable oligonucleotide-silver conjugates is presented, and controlled plasmon coupling is observed in reconfigurable core-satellite assemblies composed of 20 nm silver satellites linked to a 50 nm gold core by DNA tethers. Reconfiguration of the DNA linkers from a compact to an extended state results in decreased plasmon coupling and a blue-shift of the gold core plasmon resonance, similar to the response observed in analogous structures formed with gold satellites. Simulations of structures composed of gold and silver cores and satellites are performed to determine how the optical properties of binary metal assemblies may differ from those composed of a single metal. It appears that gold plasmons are systematically red shifted by silver particles, whereas plasmons supported by silver particles appear differentially sensitive to gold particles according to whether the silver particle is in a core position or a satellite shell. Next, the plasmonic properties of immobilized binary nanoparticle assemblies that incorporate a single strongly scattering component that acts as a template for assembly of weakly scattering plasmonic particles are investigated. Assemblies are composed of a streptavidin-coated gold "core" nanoparticle and BSA-biotin-coated gold or silver "satellite" particles. Through correlation of measured and simulated spectra, the dependence of assembly optical properties upon satellite coverage and satellite orientation about the core is addressed. It appears that plasmon coupling in gold core-gold satellite structures depends upon satellite orientation about the core and can manifest as either peak shifting or peak splitting, while the gold plasmon response to silver satellite assembly appears to be independent of satellite orientation. Finally, binary coupling is studied in one-dimensional particle pairs and three-dimensional extended networks composed of gold and silver particles linked by DNA. Investigation of particle pairs is performed by correlating assembly structure and optical properties. From both measured spectra, and simulated spectra based upon models that incorporate measured structural parameters, it appears that plasmon coupling within gold-silver particle pairs results in damping of the silver band and enhancement of the gold band. The optical response of plasmon coupling in extended networks composed of gold and silver particles is found to be qualitatively similar to coupling observed in unlike particle pairs. However, spectral simulations reveal that interactions between unlike components in binary gold and silver nanoparticle networks lead to modulation of coupling between like particle plasmons as well as pair-wise damping and enhancement.

Regenerative medicine holds the promise of providing relief for people suffering from diseases where treatment has been unattainable. The research is advancing rapidly; however, there are still many hurdles to overcome before the therapeutic potential of regenerative medicine and cell therapy can be realized. Low in frequency in all tissues, stem cell number is often a limiting factor. Approaches that can control the proliferation and direct the differentiation of stem cells would significantly impact the field. Developing an adequate environment that mimics in vivo conditions is an intensively studied topic for this purpose. Collaboratively, researchers have come close to incorporating nearly all biological cues representative of the human body. Arguably the most overlooked aspect is the influence of electrical stimulation. In this dissertation, we examined polyvinylidene fluoride (PVDF) as a new biomaterial and developed a 3D scaffold capable of providing mechanical and electrical stimuli to cells in vitro.

The fabrication of a 3D scaffold was performed using electrospinning. To obtain highly aligned fibers and scaffolds with controlled porosity, the set-up was modified by incorporating an auxiliary electrode to focus the electric field. Highly aligned fibers with diameters ranging from 500 nm to 15 µm were fabricated from colorless polyimide (CP2) and polyglycolic acid (PGA) and used to construct multilayer scaffolds. This experimental set-up was used to electrospin α-phase PVDF into the polar β-phase. We demonstrated the transition to the β-phase by examining the crystalline structure using x-ray diffraction (XRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR) and polarized light optical microscopy (PLOM). We confirmed these results by observing a polarization peak at 80°C using the thermally stimulated current (TSC) method. Our results proved the electrospinning process used in our investigation poled the PVDF polymer in situ.

TThe influence of architecture and topographical cues was examined on 3D scaffolds and films of CP2 polyimide and PVDF. Culture of human mesenchymal stem cells (hMSCs) for 7 and 14 days demonstrated a significant difference in gene expression. The fibers upregulated the neuronal marker microtubule associated protein (MAP2), while downregulation of this protein was observed on films. Gap junction formation was observed by the expression of connexin-43 after 7 days on PVDF films attributed to its inherent pyroelectric properties. Connexin-43 expression on fibers showed cell-cell contact across the fibers indicating good communication in our 3D scaffold.

A scaffold platform was designed using PVDF fibers that allowed us to apply electrical stimulation to the cells through the fibers. The electrically stimulated PVDF fibers resulted in enhanced proliferation compared to TCPS as evidenced by a 10% increase in the uptake of EdU. Protein expression revealed upregulation of neuronal marker MAP2. Our findings indicate this new platform capable of delivering mechanical, electrical, topographical and biochemical stimuli during in vitro culture holds promise for the advancement of stem cell differentiation and tissue engineering.

During the past two decades, soft lithographic techniques that circumvent the limitations of photolithography have emerged as important tools for the transfer of patterns with sub-micron dimensions. Among these techniques, microcontact printing (uCP) has shown special promise. In uCP, an elastomeric stamp is first inked with surface-reactive molecules and placed in contact with an ink-reactive surface, resulting in pattern transfer in the form of self-assembled monolayers in regions of conformal contact. The resolution in uCP is ultimately limited to the diffusion of ink and the elastomechanical properties of the bulk stamping material.

One way to improve resolution is to eliminate diffusion by using inkless methods for pattern transfer. Inkless catalytic-uCP uses a chemical reaction between a stamp-immobilized catalyst and surface bearing cognate substrate to transfer pattern in the areas of conformal contact. By using pre-assembled cognate surfaces, the approach extends the range of surfaces readily amenable to patterning while obviating diffusive resolution limits imposed by traditional uCP.

In this thesis, we report two methods using inkless catalytic uCP: biocatalytic-uCP utilizes an immobilized enzyme as a catalyst whereas catalytic-uCP utilizes an immobilized small molecule as a catalyst, such as an acid or base. Both catalytic techniques demonstrate pattern transfer at the microscale while using unconventional, acrylate-based stamp materials. Previous results produced with catalytic-uCP have shown pattern transfer with sub-50 nm edge resolution. In this demonstration of catalytic-uCP, we use the technique to demonstrate a bi-layered patterning technique for H-terminated silicon, the foremost material in semi-conductor fabrication. This technique simultaneously protects the underlying silicon surface from degradation while a highly-reactive organic overlayer remains patternable by acidic-functionalized PU stamps. Lines bearing widths as small as 150 nm were reproduced on the reactive SAM overlayer, which would not be possible without circumvention of diffusion. Before and after patterning, no oxidation of the underlying silicon was observed, preserving desired electronic properties throughout the whole process. This bi-patterning technique could be extended to other technologically-relevant surfaces for further application in organic-based electronic devices and other related technologies.

This thesis will investigate previously unexplored concepts in magnetic manipulation including controlling the assembly of magnetic and nonmagnetic particles either in bulk fluid or near a substrate. Both uniform glass interfaces and substrates with magnetic microstructures are considered. The main goal of this work is to discuss new strategies for implementing magnetic assembly systems that are capable of exquisitely controlling the positions and orientations of single-component as well as multi-component particle suspensions, including both magnetic and non-magnetic particles. This work primarily focuses on controlling spherical particles; however, there are also several demonstrations of controlling anisotropically shaped particles, such as microrods and Janus colloids.

Throughout this work, both conventional magnetophoresis and inverse magnetophoresis techniques were employed, the latter relying on ferrofluid, i.e. a suspension of magnetic nanoparticles in a nonmagnetic carrier fluid, which provides a strong magnetic permeability in the surrounding fluid in order to manipulate effectively non-magnetic materials. In each system it was found that the dimensionless ratio between magnetic energy and thermal energy could be successfully used to describe the degree of control over the positions and orientations of the particles. One general conclusion drawn from this work is that the ferrofluid can be modeled with a bulk effective permeability for length scales on the order of 100 nm. This greatly reduces modeling requirements since ferrofluid is a complex collection of discrete nanoparticles, and not a homogenous fluid. It was discovered that the effective magnetic permeability was often much larger than expected, and this effect was attributed to particle aggregation which is inherent in these systems. In nearly all cases, these interactions caused the ferrofluid to behave as though the nanoparticles were clustered with an effective diameter about twice the real diameter.

The principle purpose of this thesis is to present novel systems which offer the ability to manipulate and orient multi-component spherical or anisotropic particle suspensions near surfaces or in the bulk fluid. First, a novel chip-based technique for transport and separation of magnetic microparticles is discussed. Then, the manipulation of magnetic nanoparticles, for which Brownian diffusion is a significant factor, is explored and modeled. Parallel systems of nonmagnetic particles suspended in ferrofluid are also considered in the context of forming steady state concentration gradients. Next, systems of particles interacting with planar glass interfaces are analyzed, modeled, and a novel application is developed to study the interactions between antigen-antibody pairs by using the self-repulsion of non-magnetic beads away from a ferrofluid/glass interface. This thesis also focuses on studying the ability to manipulate particles in the bulk fluid. First, simple dipole-dipole aggregation phenomenon is studied in suspensions of both nonmagnetic polystyrene particles and endothelial cells. For the sizes of particles considered in these studies, currently accepted diffusion limited aggregation models could not explain the observed behavior, and a new theory was proposed. Next, this thesis analyzed the interactions that exist in multi-component magnetic and nonmagnetic particle suspensions, which led to a variety of novel and interesting colloidal assemblies. This thesis finally discusses the manipulation of anisotropic particles, namely, the ability to control the orientation of particles including both aligning nonmagnetic rods in ferrofluid as well as achieving near-holonomic control of Janus particles with optomagnetic traps. General conclusions of the viability of these techniques are outlined and future studies are proposed in the final chapter.

Friction is the resistive force that arises when two contacting surfaces move relative to each other. Frictional interactions are important from both engineering and biological perspectives. In this research I focus on the fundamental understanding of friction on polymeric and biological surfaces in aqueous environments. First, I examine the frictional properties of a stimulus-responsive hydrogel, poly-N-isopropylacrylamide (pNIPAAm), to understand how different phase states affect its tribological properties. My measurements indicate that gels in a collapsed conformation at low shear rates, exhibit significantly larger friction than swollen gels. These differences arise from changes in surface roughness, adhesive interactions, and chain entanglements of the gel surfaces associated with the phase transition. Importantly, I show that the changes in friction, triggered by an external stimulus, are reversible.

Second, I examine details of the boundary lubrication mechanism involved in mediating friction and wear in diarthrodial joints. Specifically, I looked at the constituents of the synovial fluid, lubricin and hyaluronic acid (HA) and examined their interactions on model substrates, (1) to determine the effect of surface chemistry on adsorption using surface plasmon resonance (SPR), and (2) to study normal force interactions between these surfaces using colloidal probe microscopy (CPM). I found that lubricin is highly surface-active, adsorbed strongly onto hydrophobic, hydrophilic and also collagen surfaces. Overall, lubricin develops strong repulsive interactions. This behavior is in contrast to that of HA, which does not adsorb appreciably, nor does it develop significant repulsive interactions. I speculate that in mediating interactions at the cartilage surface, an important role of lubricin is one of providing a protective coating on cartilage surfaces that maintains the contacting surfaces in a sterically repulsive state.

Over half a million coronary artery bypass operations are performed annually in the US yielding an annual health care cost of over 16 billion dollars. Only five percent of bypasses are repeat operations in spite of the procedures prevalence. Patients facing repeat coronary artery bypass operations often lack transplantable autologous arteries or veins, necessitating the use of substitutes. Unfortunately, synthetic small diameter vascular grafts have unacceptable patency rates, primarily due to lumenal thrombus formation and intimal thickening. Endothelial cells (EC) mediate the anti-thrombotic activity in healthy blood vessels, and due to the scarcity of suitable autologous vascular replacement, EC-seeded small diameter synthetic vascular grafts represent a clear, immediate, and practical solution. The fundamental goal of this project was to optimize the dual ligand (DL) system on synthetic vascular graft (SVG) surrogates to show enhanced cell adhesion, retention, and native functionality compared to fibronectin alone. Initially, two SVG surrogates were identified through characterization by x-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and 125I radiolabeling. The first modification to the DL system involved direct biotinylation of fibronectin (bFN) as a replacement for co-adsorption of FN with biotinylated bovine serum albumin (bBSA). This was analyzed with a Langmuir model using surface plasmon resonance (SPR) spectroscopy to verify the binding affinity of bFN and ELISA to detect the availability of the RGD binding motif post biotinylation. The second major change in this project examined cell binding and formation of focal adhesion after shifting from direct incubation of HUVECs with RGD-SA to sequentially adsorbing bFN(9) and RGD-SA prior to introducing unmodified HUVECs. These experiments were conducted under static seeding conditions. Next, dynamic cell seeding onto the sequentially adsorbed protein surface was examined as a function of surface immobilized protein and Trypsin/EDTA concentration. SPR results showed statistical differences in α5β1 and αvβ3 integrin binding to RGD cell binding motifs introduced by bFN(9) and RGD-SA. Increase in binding specificity through these integrins lead to rapid cell binding and retention on Teflon-AF surfaces adsorbed with this protein formulation. This system appears to be the nexus at which the DL has proven its value. These results could have broader implications in augmenting EC attachment to SVG prior to implantation.

Quantum chemical computations provide convenient and effective ways for molecular design using computers. In this dissertation, the molecular designs of optimal nonlinear optical (NLO) materials were investigated through three aspects. First, an inverse molecular design method was developed using a linear combination of atomic potential approach based on a Hückel-like tight-binding framework, and the optimizations of NLO properties were shown to be both efficient and effective. Second, for molecules with large first-hyperpolarizabilities, a new donor-carbon-nanotube paradigm was proposed and analyzed. Third, frequency-dependent first-hyperpolarizabilities were predicted and interpreted based on experimental linear absorption spectra and Thomas-Kuhn sum rules. Finally, molecular interferometers were designed to control charge-transfer using vibrational excitation. In particular, an ab initio vibronic pathway analysis was developed to describe inelastic electron tunneling, and the mechanism of vibronic pathway interferences was explored.

Expanding the role of plasmonics in tomorrow's technology requires a broader knowledge base from which to develop such applications today. Several limitations to the current plasmonics field limit progress to incremental advances within a narrow set of materials and techniques rather than developing non-traditional metals and flexible growth and characterization methods. The work described herein will provide an introduction to the burgeoning field of spectroscopic ellipsometry for plasmonic characterization; in particular, the power of its real-time monitoring capabilities and flexibility will be demonstrated. More importantly, a novel plasmonic metal, gallium, is investigated in detail. Critical characteristics of gallium for an array of applications include its tunability over a wide spectral range, phase stability across a wide temperature range, plasmon stability even after air exposure, and an ultra high vacuum evaporation growth process enabling simple, alloyed nanostructure development. Deeper scientific investigation of the underlying ripening mechanisms driving gallium nanoparticle formation and in concert with in situ alloying paves the way for future work contributing to the development of advanced nanostructured alloys. Finally, this work demonstrates the first example of gallium nanoparticle-enhanced Raman spectroscopy - an area craving materials innovation. While the specific application of gallium for SERS detection is interesting, the far-reaching implication lies in the demonstrated potential for plasmonic gallium nanoparticles' ultimate use in a wider variety of applications enhanced by nanoscale materials.

Carbon nanomaterials have a wide range of promising and exciting applications. One of the most heavily investigated carbon nanomaterial in recent history has been the carbon nanotube. The intense interest in carbon nanotubes can be attributed to the many exceptional characteristics which give them great potential to revolutionize modern mechanical, optical and electronic technologies. However, controlling these characteristics in a scalable fashion has been extremely difficult. Although some progress has been made in controlling the quality, diameter distribution and other characteristics of carbon nanotube samples, several issues still remain. The two major challenges which have stood in the way of their mainstream application are controlling their orientation and their electronic characteristics. Developing and understanding a Chemical Vapor Deposition based carbon nanotube synthesis method has been the major focus of the research presented here. Although several methods were investigated, including the so-called "fast-heating, slow-cooling" and large feeding gas flowrate methods, it was ultimately found that high-quality, perfectly aligned carbon nanotubes from a variety of metal catalysts could be grown on quartz substrates. Furthermore, it was found that using MeOH could selectively etch small-diameter metallic carbon nanotubes, which ultimately led to the productions of perfectly aligned single-walled carbon nanotube samples consisting almost entirely of semiconducting carbon nanotubes. Thiophene was utilized to investigate and support the hypothesized role of MeOH in producing these selectively gown semiconducting carbon nanotube samples. Additionally, this sulfur-containing compound was used for the first time to demonstrate a two-fold density enhancement in surface grown carbon nanotube samples. This method for selectively producing perfectly aligned semiconducting carbon nanotubes represents a major step towards the integration of carbon nanotubes into mainstream applications.

Although extremely useful in a variety of technologies, carbon nanotubes have proven impractical for use in H₂ storage applications. As such, microporous carbons have been heavily investigated for such ends. Microporous carbons have distinguished themselves as excellent candidates for H₂ storage media. They are lightweight and have a net-capacity of almost 100%, meaning that nearly all of the H₂ stored in these materials is easily recoverable for use in devices. However, developing a microporous carbon with the appropriately small pore diameters (~1nm), large pore volumes (>1cm3) and large surface areas (≥3000m2/g) has proven exceedingly difficult. Furthermore, maintaining the ideal graphitic pore structure has also been an unresolved issue in many production means. Several microporous carbon synthesis methods were investigated herein, including inorganic and organically templated production schemes. Ultimately, thermally treating poly (etherether ketone) in CO₂ and steam environments was found to produce large surface area porous carbons (≥3000m2/g) with the appropriately small pore diameters (<3nm) and large pore volumes (>1cm3) necessary for optimized storage of H2. Furthermore, the surface chemistry of these pores was found to be graphitic. As a result of these ideal conditions, these porous carbons were found to store ~5.8wt.% H₂ at 77K and 40bar. This represents one of the most promising materials presently under investigation by the United States Department of Energy H₂ Sorption Center of Excellence.

The success of both of these materials demonstrates the diversity and promise of carbon nanomaterials. It is hoped that these materials will be further developed and will continue to revolutionize a variety of vital technologies.

This research presents the development of a phase-based lithographic system for three-dimensional micropatterning and manipulation. The system uses a spatial light modulator (SLM) to display specially designed phase holograms. The use of holograms with the SLM provides a novel approach to photolithography that offers the unique ability to operate in both serial and single-shot modes. In addition to the lithographic applications, the optical system also possesses the capability to optically trap microparticles. New advances include the ability to rapidly modify pattern templates for both serial and single-shot lithography, individually control three-dimensional structural properties, and manipulate Janus particles with five degrees of freedom.

A number of separate research investigations were required to develop the optical system and patterning method. The processes for designing a custom optical system, integrating a computer aided design/computer aided manufacturing (CAD/CAM) platform, and constructing series of phase holograms are presented. The resulting instrument was used primarily for the photonic excitation of both photopolymers and proteins and, in addition, for the manipulation of Janus particles. Defining research focused on the automated fabrication of complex three-dimensional microscale structures based on the virtual designs provided by a custom CAD/CAM interface. Parametric studies were conducted to access the patterning transfer rate and resolution of the system.

The research presented here documents the creation of an optical system that is capable of the accurate reproduction of pre-designed microstructures and optical paths, applicable to many current and future research applications, and useable by anyone interested in researching on the microscale.