Planar arrays of microwells were fabricated in Silicon on borosilicate glass (pyrex) substrates in order to facilitate live cell fluorescence imaging experiments for cells sequestered inside their own individual microenvironments for incubation and quantification of single cell seceretions. Two methods of deep silicon etching were compared: cryogenic deep reactive ion etching (DRIE) and time multiplexed DIRE (Bosch Process). A 200um Si wafer was bonded to a 500um pyrex substrate. Cryogenic DRIE allowed for the reliable fabrication of 75-100um deep microwells with 60x60um openings across a 10x10mm substrate while the Bosh Process allowed for etching entirely through the Si layer, producing 200um deep microwells with transparent bottoms and steep sidewalls while maintaining the target 60x60um opening geometry.

In this paper, we report on a method for fabricating an inexpensive microfluidic platform on parchment paper. Parchment paper was selected for this purpose due to its wide availability for culinary applications and hydrophobic silicone-based surface coating. We were able to selectively modify the surface structure and property (hydrophobic to hydrophilic) using a CO2 laser. The modified surface has highly-porous structure which helps to trap chemical and biological reagents for analysis. The treated surface is stable over time and can be used for aqueous droplet assembly. Finally, we demonstrated the applicability of this platform for performing chemical reaction using luminol-based hemoglobin detection.

Microneedles have applications in drug delivery and biotechnology. We report a novel needle-like hollow cylindrical structure as a base for the growth of carbon nanotubes (CNT) to form a cage-like structure. The formation of hollow microneedle structures is feasible on Si-membranes using proper patterning of the masking layer and combined by a deep reactive ion etching. The formation of highly featured structures at micro and nanometric scale is reported. By controlling the etching parameter one is able to achieve three-dimensional as well as highly vertical structures on silicon substrates. The growth of carbon nanotubes on such structures allows the realization of cage-like carbon-based features which could be suitable for gas and liquid transport.

Monoclonal antibodies are increasingly used in the treatment of cancer due to their enhanced targeting and immune system stimulation properties. Dosage guidelines typically do not account for personal cancer load or metabolism, thereby possibly affecting treatment outcome or causing unwanted side effects. The requirement for an assay that can quickly and precisely measure the concentration of the monoclonal antibody in a serum sample of a patient during therapy is unmet. A bead-based assay with peptide antigen mimetics has been developed to rapidly determine the concentration of antibody drug present in serum specimens with high sensitivity. Alemtuzumab (anti-CD52) and rituximab (anti-CD20) antigen mimetic peptides, as discovered by phage display, were synthesized on 10 um TentaGel resin beads using conventional solid phase peptide synthesis techniques. The beads were modified to allow for multiplexing and microfluidic handling via fluorescent labeling and magnetic functionalization. The antigen-displaying fluoromagnetic particles were incubated with spiked serum samples which allowed free antibody to be captured. Primary antibody detection was performed on alemtuzumab while rituximab detection was used to compensate for non-specific serum binding to the beads. After washing, the beads were incubated with a fluorescently tagged secondary label for detection by flow cytometry. (Results) A fast, low cost, specific assay has been developed with several key techniques which allows detection at low concentration (0.1ug/ml) of spiked samples. Primary to achieving this detection limit was the implementation of a compensation scheme where two antigen mimetic peptides behave linearly (R2=0.996) which enables the calculation of the zero response of the antigen mimetic peptide of interest (alemtuzumab antigen mimetic) while measuring the zero response of the compensatory antigen mimetic peptide (rituximab antigen mimetic) during primary assay measurement. This reduces fluorescence response variation due to variations present due to sample preparation, storage and different patients because of the equivalent interactions these effects have on the compensatory beads. The developed assay is therefore robust against serum variation and enables a lower limit of detection.

Individually propulsive catalytic Janus particle swimmers are observed to self-assemble into aggregate swimmers with a wide variety of translational and rotational velocities. The trajectory for a given doublet is shown to be determined by the frozen in relative orientation of the particles. The new swimmers suggest applications as transport and mixing devices, and will allow study of the interplay between propulsion and Brownian phenomena. Furthermore this random assembly process can be controlled using external magnetic fields to orientate individual ferromagnetic swimming particles so as to favor the production of swimmers with particular desirable configurations resulting in linear trajectories. This approach also produces swimmers that can be orientated, and so “steered” by external fields.

This paper describes the development of nanomonitors, which are electrical immunoassays for detection of multiple protein biomarkers. These devices are hybrid sensors with micro-fabricated electrode arrays on a silicon substrate, and integrated nanoporous alumina membranes to provide protein confinement and signal amplification. The disease biomarkers C-reactive protein and Myeloperoxidase have been detected by the nanomonitors in ultra-low concentrations. Proteins were detected in pure samples, human serum, and patient blood samples. The detection accuracy and sensitivity of the nanomonitors in patient samples was comparable to the Enzyme Linked Immunosorbent Assay (ELISA) method of protein detection. Nanomonitors provide the additional benefits of being rapid, label-free, sensitive, and cost effective, providing improvements over traditional protein detection methods, and having potential applications in disease diagnosis.

The electrowetting equation predicts contact angle modulation to zero degrees as voltage is continually increased. However, in practice contact angle appears to saturate around 60 to 70°. Although several hypotheses have been advanced to explain the physical mechanisms of contact angle saturation, none satisfactorily and unequivocally holds for the large body of electrowetting data. Herein we experimentally demonstrate that under DC voltage electrowetting contact angle saturation is invariant to polymer, fluid, and interfacial materials properties. We furthermore reveal that saturation is also a time-dependant phenomenon.

In this contribution, we present an effective strategy for assembling and integrating functional, in situ formed micro- and nanosized structures. Microfluidic platforms are employed to form anisotropic hybrid structures and coordination polymers at the interface of two precursor streams. Microstamps, embedded in the microfluidic device and actuated by pressure, provide a facile and reliable technology for structure trapping, localization and integration.

Human genomic structural variation (SV) is significant factor in genome complexity, and thus has substantial implications to the cause, development and progression of genetic diseases. These SVs, ranging in size of 1kbp-1Mbp, are challenging to assess with current technologies. As such, we have developed a commercial system (nanoAnalyzer® 1000) for the rapid linear analysis of genomes at single-molecule level.

The core of our system is a nanofluidic chip consisting of an array of channels with a diameter less than 100 nm, nanofabricated on the surface of a silicon substrate. Thousands of unamplified genomic DNA molecules of 100’s kbps to several Mbps can be isolated and linearly streamed into the array for analysis in a parallel fashion. Fluorescently labeled sequence-specific signatures can then be identified and aligned to reference patterns at high resolution with custom software. This automated, multi-color imaging platform will enable a wide range of applications, such as accurate sequencing assembly, discovering genome structural variations, and uncovering epigenomic content. Nanochannel arrays promise to substantially lower the barriers of entry for single-molecule DNA analysis for scientists and clinicians, greatly impacting the advancement of molecular diagnostics, personalized medicine, and biomedical research.

MnO nanoparticles were surface modified using two different multifunctional polymers. By introducing a PEG group, the long term stability, MRI applicability and sterile filtration could be greatly improved. Furthermore, PEGylated MnO NPs were less toxic compared to non-PEGylated NPs. The results suggest that these nanoparticles are suitable for in vivo applications.

Nanofluidic behavior has been an active area of research for the past decade. In addition to modifying nanopore size and surface properties, another important way to adjust system performance is to control the liquid composition. In the current study, we investigate the influence of electrolyte concentration on the infiltration behavior, as well as its dependence on temperature. A hydrophilic zeolite Y can be soaked in pure water, while with the addition of an electrolyte it can’t be soaked spontaneously. It is noticed that the effective solid–liquid interfacial tension in nanopores is highly sensitive to the electrolyte concentration, which may be related to the unique confinement environment in nanoporous material. As a result, with the electrolyte concentration varying, the effective interfacial tension changes rapidly. This phenomenon can be attributed to the amplification effect of nanopore surfaces on the solid–liquid interaction. It provides a scientific basis for developing smart liquids for various temperature and pressure ranges.

DNA possesses inherent recognition and self-assembly capabilities, making it attractive templates for constructing functional material structures as building blocks for nanoelectronics. Here we report the use of DNA towards the assembly and electronic functionality of nanoarchitectures based on conjugates of carbon nanotubes (CNTs), nanowires (NWs) and DNA computing on Si-CMOS platform. First, assembly of CNTs with DNA is demonstrated and electrical measurements of these nanoarchitectures demonstrate negative differential resistance in the presence of CNT/DNA interfaces, which indicates a biomimetic route to fabricating resonant tunneling diodes. End-to-end assembly of NWs is realized with designed DNA sequences and process is carried on silicon CMOS based microarray platform. Second, this microarray platform is adopted to perform DNA computing. To begin with, the information present in an image is encoded through the concentrations of various DNA strands via selective hybridization and decoded on microarray to recreate the original image. Lately, various satisfiability (SAT) problems, which has long served as a benchmark problem in DNA computing, are solved on this platform via DNA. The goal in a SAT Problem is to determine appropriate assignments of a set of Boolean variables with values of either “true” or “false” such that the output of the whole Boolean formula is true. Other than making 1st time silicon compatible DNA computing, our studies make us understand bio molecules, especially DNA has various advantages for future hybrid technologies.

A novel hollow-core photonic crystal fiber platform was used for the first time to observe clear vibrational modes of the CdTe core, CdS0.7Te0.3 interface, and carboxylate-metal complexes in dilute aqueous CdTe quantum dot (QD) solutions. These modes demonstrate the presence of crystalline cores, defects and surface passivation responsible for photoluminescent efficiency and stability. In addition, 3-mercaptopropionic acid (MPA)-capped QDs show higher crystallinity and stability than those capped with thioglycolic acid (TGA) and 1-thioglycerol (TG). This detailed, non-destructive characterization was carried out using Raman spectroscopy for solutions with QD concentration of 2 mg/mL, which is similar to their concentration during synthesis process. This platform can be extended to the in-situ studies of any colloidal nanoparticles and aqueous solutions of relevant biological samples using Raman spectroscopy.

This paper reviews our works about the development of thin composite film based on aligned carbon nanotubes (CNT) forest, embedded in epoxy or PMMA polymer matrix, in order to fabricate membranes dedicated to water purification issue. Indeed, the small internal radius of nanotubes, the smoothness of their inner core and the hydrophobic properties of its interna surface induce remarkable flowing properties for water molecules. In this article, thinnin technology process is investigated to obtain composite film with opened CNT. Different etching techniques as grinding, Chemical Mechanical Polishing (CMP) and isotropic plasma O2ar investigated in term of etching rate and membrane roughness, using AFM and SEM characterizations. Results show CMP process in lapping configuration permits to obtain agreement between high etching rate and membrane roughness. Moreover, to improve water flowing through membrane, O2plasma treatment is used to remove polymer residue spread over CNT. Joint use of lapping and plasma treatment permits to obtain 35μm-thick nanoporous membrane with well-opened protruding nanotubes.

DNA Computing is a rapidly-developing interdisciplinary area which could benefit from more experimental results to solve problems with the current biological tools. In this study, we have integrated microelectronics and molecular biology techniques for showing the feasibility of Hopfield Neural Network using DNA molecules. Adleman’s seminal paper in 1994 showed that DNA strands using specific molecular reactions can be used to solve the Hamiltonian Path Problem. This accomplishment opened the way for possibilities of massively parallel processing power, remarkable energy efficiency and compact data storage ability with DNA. However, in various studies, small departures from the ideal selectivity of DNA hybridization lead to significant undesired pairings of strands and that leads to difficulties in schemes for implementing large Boolean functions using DNA. Therefore, these error prone reactions in the Boolean architecture of the first DNA computers will benefit from fault tolerance or error correction methods and these methods would be essential for large scale applications. In this study, we demonstrate the operation of six dimensional Hopfield associative memory storing various memories as an archetype fault tolerant neural network implemented using DNA molecular reactions. The response of the network suggests that the protocols could be scaled to a network of significantly larger dimensions. In addition the results are read on a Silicon CMOS platform exploiting the semiconductor processing knowledge for fast and accurate hybridization rates.