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Biomedical subjects

Joseph M Jacobson

Publications and source records attributed to Joseph M Jacobson.

8 recordsLinked to original sources

Solid-state bonding technique for template-stripped ultraflat gold substrates.

A simple procedure using gold diffusion bonding for the preparation of template-stripped gold (TSG) surfaces is described. TSG surfaces are useful for surface studies because a very consistent flat gold surface with few defects can be easily prepared. We have developed a method of producing TSG surfaces that relies only on gold diffusion bonding rather than epoxies. The resulting substrates are free from concerns of solvent compatibility, heat stability, and impurities. Bonding of centimeter-sized substrates is performed at 300 degrees C for 2 h using a vise and aluminum foil.

Journal Article↗

Nanoscale patterning on insulating substrates by critical energy electron beam lithography.

This Letter describes a method to generate nanometer scale patterns on insulating substrates and wide band gap materials using critical energy electron beam lithography. By operating at the critical energy (E2) where a charge balance between incoming and outgoing electrons leaves the surface neutral, charge-induced pattern distortions typically seen in e-beam lithography on insulators were practically eliminated. This removes the need for conductive dissipation layers or differentially pumped e-beam columns with sophisticated gas delivery systems to control charging effects. Using a "scan square" method to find the critical energy, sub-100 nm features in 65 nm thick poly(methyl methacrylate) on glass were achieved at area doses as low as 10 microC/cm2 at E2 = 1.3 keV. This method has potential applications in high-density biochips, flexible electronics, and optoelectronics and may improve the fidelity of low voltage e-beam lithography for parallel microcolumn arrays.

Electric Conductivity↗

Robotics: self-replication from random parts.

Autonomously self-replicating machines have long caught the imagination but have yet to acquire the sophistication of biological systems, which assemble structures from disordered building blocks. Here we describe the autonomous self-replication of a reconfigurable string of parts from randomly positioned input components. Such components, if suitably miniaturized and mass-produced, could constitute self-fabricating systems whose assembly is brought about by the parts themselves.

Algorithms↗

Perfecting imperfect "monolayers": removal of siloxane multilayers by CO2 snow treatment.

Self-assembled monolayers (SAMs) of N-(3-triethoxysilylpropyl)-4-hydroxybutyramide were prepared on silicon oxide on silicon (Si/SiO(2)). Initial silane adsorption and high-temperature annealing led to a stable base monolayer with many large over-lying islands of disordered multilayers as a result of the non-self-limited growth process. The disordered multilayers were hydrolyzed and subsequently removed by CO(2) snow treatment. The resulting films were one monolayer thick as measured by ellipsometry. Atomic force microscopy, attenuated total reflection Fourier transform infrared spectroscopy, and contact angle analysis showed that the films were composed of monolayers with full and uniform surface coverage rather than nonuniform coverage by islands or patches of multilayers. Monolayers of octadecyltrichlorosilane were also prepared by multilayer removal via CO(2) treatment, showing the general applicability of the technique toward siloxane SAMs. We believe that CO(2) is an excellent solvent for weakly bound and hydrolyzed molecules that compose multilayers, and this ability to prepare near-perfect monolayer films from imperfect ones allows for less stringent formation conditions.

Journal Article↗

Protein-mediated error correction for de novo DNA synthesis.

The availability of inexpensive, on demand synthetic DNA has enabled numerous powerful applications in biotechnology, in turn driving considerable present interest in the de novo synthesis of increasingly longer DNA constructs. The synthesis of DNA from oligonucleotides into products even as large as small viral genomes has been accomplished. Despite such achievements, the costs and time required to generate such long constructs has, to date, precluded gene-length (and longer) DNA synthesis from being an everyday research tool in the same manner as PCR and DNA sequencing. A critical barrier to low-cost, high-throughput de novo DNA synthesis is the frequency at which errors pervade the final product. Here, we employ a DNA mismatch-binding protein, MutS (from Thermus aquaticus) to remove failure products from synthetic genes. This method reduced errors by >15-fold relative to conventional gene synthesis techniques, yielding DNA with one error per 10 000 base pairs. The approach is general, scalable and can be iterated multiple times for greater fidelity. Reductions in both costs and time required are demonstrated for the synthesis of a 2.5 kb gene.

Bacterial Proteins↗

Synthesis of monofunctionalized gold nanoparticles by fmoc solid-phase reactions.

In this communication, solid-phase reactions for the synthesis of Lys-monofunctionalized gold nanoparticles are described. A controlled and selective fabrication of linear nanoparticle arrays can be achieved through peptide linkage systems, and therefore it is essential to prepare Fmoc amino acid nanoparticle building blocks susceptible to Fmoc solid-phase peptide synthesis. Gold nanoparticles containing carboxylic acids (2) in the organic shell were covalently ligated to Lys on solid supports through amide bond coupling reactions. We employed Fmoc-Lys-substituted polymer resins such as Fmoc-Lys-Wang or Fmoc-Lys-HMPA-PEGA. The low density of Lys on the matrix enabled 2 nm-sized gold nanoparticles to react with Lys in a 1:1 ratio. Subsequent cleavage reactions using 60% TFA reagent resulted in Lys transfer from the solid matrix to gold nanoparticles, and the Fmoc-Lys-monofunctionalized gold nanoparticles (5) were obtained with 3-15% yield. Synthesis using HMPA-PEGA resin increased productivity due to the superior swelling properties of PEGA resin in DMF. Monofunctionalization of nanoparticles was microscopically characterized using TEM for the ethylenediamine-bridged nanoparticle dimers (6). By counting the number of 6, we found that at least 60% of cleaved nanoparticles were monofunctionalized by Lys. This method is highly selective and efficient for the preparation of monofunctionalized nanoparticles.

Acrylamides↗

Polymerization of diacetylenes by hydrogen bond templated adlayer formation.

Adlayers were formed on self-assembled monolayers (SAMs) formed by alkanethiols on gold. Base SAMs exposing amide functional groups at the SAM surface were formed with 12-mercaptododecanamide. Adlayers of diacetylene-containing monomers were then formed via amide hydrogen bonding in decalin and decalin/toluene mixtures. Grazing angle FTIR, contact angle measurements, and ellipsometry suggest that these adlayer films exhibit ordering and packing similar to that of SAMs on gold. Resonance Raman spectroscopy showed that these diacetylene adlayers could be readily polymerized by exposure to UV light.

Acetylene↗

Remote electronic control of DNA hybridization through inductive coupling to an attached metal nanocrystal antenna.

Increasingly detailed structural and dynamic studies are highlighting the precision with which biomolecules execute often complex tasks at the molecular scale. The efficiency and versatility of these processes have inspired many attempts to mimic or harness them. To date, biomolecules have been used to perform computational operations and actuation, to construct artificial transcriptional loops that behave like simple circuit elements and to direct the assembly of nanocrystals. Further development of these approaches requires new tools for the physical and chemical manipulation of biological systems. Biomolecular activity has been triggered optically through the use of chromophores, but direct electronic control over biomolecular 'machinery' in a specific and fully reversible manner has not yet been achieved. Here we demonstrate remote electronic control over the hybridization behaviour of DNA molecules, by inductive coupling of a radio-frequency magnetic field to a metal nanocrystal covalently linked to DNA. Inductive coupling to the nanocrystal increases the local temperature of the bound DNA, thereby inducing denaturation while leaving surrounding molecules relatively unaffected. Moreover, because dissolved biomolecules dissipate heat in less than 50 picoseconds (ref. 16), the switching is fully reversible. Inductive heating of macroscopic samples is widely used, but the present approach should allow extension of this concept to the control of hybridization and thus of a broad range of biological functions on the molecular scale.

Crystallography↗