Louis Brousseau - Academia.edu (original) (raw)
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Papers by Louis Brousseau
TechConnect Briefs, May 3, 2009
Direct observation of single molecular reactions and motions are impossible by optical techniques... more Direct observation of single molecular reactions and motions are impossible by optical techniques due to diffraction limits. However, ensemble measurements of binding dynamics in biological systems offer limited understanding of individual actors in metabolic and reproductive pathways. Questions of protein folding and mis-folding are one area where a more complete view is needed, as over 50% of human cancers and many other diseases are linked to subtle changes in protein conformation that lead to alterations of their function. Here we report the direct observation of molecular reactions and dynamics at sub-millisecond timescales by coupling the reaction state of antibodies and other proteins to the conductivity of a nanscale single electron transistor (SET). By preparing quantum-dot SETs that are the same size (7nm) as the biomolecules under study, the sensitivity of the devices can be utilized to measure the subtle fluctuations in molecular charge associated with single binding events. This "molecular gating" effect is capable of sensing the small electric dipole fluctuations associated with protein folding even in the absence of charge creation/annihilation.
Topochemical dehydration of divalent metal phosphonate salts M(O{sub 3}PR) x H{sub 2}O (M=Zn, Cu;... more Topochemical dehydration of divalent metal phosphonate salts M(O{sub 3}PR) x H{sub 2}O (M=Zn, Cu; R=alkyl, aryl) provides for shape selective intercalation of small molecules onto vacant ligand sites of the metal. The size of the binding pocket can be restricted by choice of R group. Well ordered thin films of these compounds can be grown on surfaces by sequential adsorption of the transition metals and organic spacer molecules. The films exhibit similar selectivity of binding and allow for the design of sensors for ammonia, amines and carbon dioxide when grown on the gold electrodes of a quartz crystal microbalance (QCM). The design of a new sensor for carbon dioxide will be discussed.
Advanced Healthcare Materials, 2013
and a member of the Board of Directors of Arrowhead Research Corporation, and hereby discloses po... more and a member of the Board of Directors of Arrowhead Research Corporation, and hereby discloses potential financial interests in those companies. In addition, Ennio Tasciotti and Xuewu Liu also declare a financial interest in Leonardo Biosystems, while Daniel Fine, Alessandro Grattoni, and Xuewu Liu declare a financial interest in NanoMedical Systems, Inc.
Synthesis, Characterization, and Applications, 2001
Small, 2010
A new generation of nanocarriers, logic-embedded vectors (LEVs), is endowed with the ability to l... more A new generation of nanocarriers, logic-embedded vectors (LEVs), is endowed with the ability to localize components at multiple intracellular sites, creating an opportunity for synergistic control of redundant or dual-hit pathways. LEV encoding elements include size, shape, charge, and surface chemistry. In this study, LEVs consist of porous silicon nanocarriers, programmed for cellular uptake and trafficking along the endosomal pathway, and surface-tailored iron oxide nanoparticles, programmed for endosomal sorting and partitioning of particles into unique cellular locations. In the presence of persistent endosomal localization of silicon nanocarriers, aminefunctionalized nanoparticles are sorted into multiple vesicular bodies that form novel membranebound compartments compatible with cellular secretion, while chitosan-coated nanoparticles escape from endosomes and enter the cytosol. Encapsulation within the porous silicon matrix protects these nanoparticle surface tailored-properties, enhancing endosomal escape of chitosan coated nanoparticles. Thus LEVs provide a mechanism for shielded transport of nanoparticles to the lesion, cellular manipulation at multiple levels, and a means for targeting both within and between cells.
Nanoscale, 2011
Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., ... more Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., gene expression, mitosis, differentiation, proliferation, and apoptosis, as well as tumor initiation, progression and metastasis. However, technical hurdles hinder the use of common fractionation methods to capture phosphopeptides from complex biological fluids such as human sera. Herein, we present the development of a dual strategy material that offers enhanced capture of low molecular weight phosphoproteins: mesoporous silica thin films with precisely engineered pore sizes that sterically select for molecular size combined with chemically selective surface modifications (i.e. Ga 3+ , Ti 4+ and Zr 4+) that target phosphoroproteins. These materials provide high reproducibility (CV = 18%) and increase the stability of the captured proteins by excluding degrading enzymes, such as trypsin. The chemical and physical properties of the composite mesoporous thin films were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy and ellipsometry. Using mass spectroscopy and biostatistics analysis, the enrichment efficiency of different metal ions immobilized on mesoporous silica chips was investigated. The novel technology reported provides a platform capable of efficiently profiling the serum proteome for biomarker discovery, forensic sampling, and routine diagnostic applications. † Electronic supplementary information (ESI) available. See
Crystal engineering, 1998
The current-voltage characteristics of citrate-and octanethiol-capped Au nanocrystals assembled o... more The current-voltage characteristics of citrate-and octanethiol-capped Au nanocrystals assembled on planar Au substrates under ambient conditions in air and in solution are reported. We have found that single electron tunneling (SET) behavior is observed for citrate-capped Au crystals in air. In high dielectric media, however, SET is only seen for nanocrystals protected by the hydrophobic alkane ligands and not for the relatively bare citrate-capped nanocrystals. In addition, we report a new strategy for assembling these nanocrystals into spatially well-organized 1-dimensional (1D) arrays. The method involves trapping the crystals inside 20 nm diameter pores of porous filtration membranes. The 1D linked nanocrystals confined inside the membrane pores were characterized by ultraviolet-visible spectroscopy. "Shrinkwrapping" the nanocrystals with the organic conductive polymer polypyrrole or covalently linking the particles with alkyldithiols and subsequent dissolution of the membrane provided a suspension suitable for characterization by transmission electron microscopy. These studies are important in determining the role of spatial arrangement and chemical environment on the electronic properties of this important class of crystalline material.
Ga(CN) 3 has been prepared for the first time with a new method for preparation of inorganic cyan... more Ga(CN) 3 has been prepared for the first time with a new method for preparation of inorganic cyanides. Pure crystalline material is formed by reaction of Cl 2 GaN 3 with SiMe 3 CN via elimination of SiMe 3 N 3 and SiMe 3 Cl. Reaction of GaCl 3 with SiMe 3 CN also provides Ga(CN) 3. A new convenient route to GeMe 3 CN and SnMe 3 CN is described, but reactions of GaCl 3 with these compounds result in Lewis acid-base adducts. The composition of Ga(CN) 3 was confirmed by spectroscopic and elemental analysis. Quantitative X-ray powder diffraction was used to refine the cubic structure, which has CN groups with orientational disorder in a Prussian-blue-like network structure. The symmetry is Pm3 hm, a) 5.295(2) Å. Ga is octahedrally surrounded by on average three C and three N atoms with a Ga-(C,N) bond length of 2.072(2) Å, and the C-N bond length is 1.148(1) Å. LiGa(CN) 4 was prepared by reaction of Ga(CN) 3 with LiCN and was characterized by quantitative X-ray diffraction. The symmetry is P4 h3m, a) 5.874(2) Å, and the structure consists of LiN 4 and GaC 4 tetrahedra linked by C-N bonds to form two interpenetrating networks of the Zn(CN) 2 type. CuGa(CN) 4 has a similar structure with a) 5.729(5) Å, but Cu,Ga and/or C,N disorder cannot be ruled out.
A method for synthesizing hollow nanoscopic polypyrrole and poly(N-methylpyrrole) capsules is des... more A method for synthesizing hollow nanoscopic polypyrrole and poly(N-methylpyrrole) capsules is described. The method employs gold nanoparticles as templates for polymer nucleation and growth. Etching the gold leaves a structurally intact hollow polymer capsule with a shell thickness governed by polymerization time (ca. 5 to >100 nm) and a hollow core diameter dictated by the diameter of the template particle (ca. 5−200 nm). Transport rates of gold etchant through the polymer shell to the gold core were found to depend on the oxidation state of the polymer, those rates being a factor of 3 greater for the reduced form of the polymer. We show for the first time that not only is the particle a useful template material but also that it can be employed to deliver guest molecules into the capsule core. For example, ligands attached to the gold surface prior to poly(N-methylpyrrole) formation remained trapped inside the hollow capsule following polymer formation and gold etching.
Chem Mater, 1998
Research involving metal and semiconductor nanoparticles is expanding rapidly into the assembly a... more Research involving metal and semiconductor nanoparticles is expanding rapidly into the assembly and characterization of well-ordered 2-and 3-dimensional (2D and 3D) superstructures. Recent advances in nanoparticle organization include the 3D CdSe supercrystals synthesized by Bawendi's group, 1 Mirkin and co-workers' 2D and 3D DNA-linked Au colloid arrays, 2 and the closest-packed surface-confined monolayers of Ag, Au, and CdS colloids studied by Natan, 3 Murray, 4 Cotton, 5 Kubiak, 6 Whetten, 7 and others. 8 These novel structures have revealed electronic and optical properties distinctly different from those of individual nanoparticles (that is, ensemble average measurements on well-spaced particles) or their macroscopic equivalents; practical applications are foreseeable in optical and electronic based chemical sensing, 2,8 nanoscale electronics, 8,9 and catalysis. 5 Despite their potential for fundamental studies on electron and energy transfer in nanoscopic solid-state materials and for applications involving single-electron devices, 8,9 few reports have appeared regarding the synthesis of coupled 1D nanoparticle systems. Notable Scheme 1. Synthetic Protocols for the Synthesis of Coupled 1D Nanoparticle Arrays: Procedures for (A) Ppy-linked Au Colloids and (B) Alkyldithiolate-Linked Au Colloids
TechConnect Briefs, May 3, 2009
Direct observation of single molecular reactions and motions are impossible by optical techniques... more Direct observation of single molecular reactions and motions are impossible by optical techniques due to diffraction limits. However, ensemble measurements of binding dynamics in biological systems offer limited understanding of individual actors in metabolic and reproductive pathways. Questions of protein folding and mis-folding are one area where a more complete view is needed, as over 50% of human cancers and many other diseases are linked to subtle changes in protein conformation that lead to alterations of their function. Here we report the direct observation of molecular reactions and dynamics at sub-millisecond timescales by coupling the reaction state of antibodies and other proteins to the conductivity of a nanscale single electron transistor (SET). By preparing quantum-dot SETs that are the same size (7nm) as the biomolecules under study, the sensitivity of the devices can be utilized to measure the subtle fluctuations in molecular charge associated with single binding events. This "molecular gating" effect is capable of sensing the small electric dipole fluctuations associated with protein folding even in the absence of charge creation/annihilation.
Topochemical dehydration of divalent metal phosphonate salts M(O{sub 3}PR) x H{sub 2}O (M=Zn, Cu;... more Topochemical dehydration of divalent metal phosphonate salts M(O{sub 3}PR) x H{sub 2}O (M=Zn, Cu; R=alkyl, aryl) provides for shape selective intercalation of small molecules onto vacant ligand sites of the metal. The size of the binding pocket can be restricted by choice of R group. Well ordered thin films of these compounds can be grown on surfaces by sequential adsorption of the transition metals and organic spacer molecules. The films exhibit similar selectivity of binding and allow for the design of sensors for ammonia, amines and carbon dioxide when grown on the gold electrodes of a quartz crystal microbalance (QCM). The design of a new sensor for carbon dioxide will be discussed.
Advanced Healthcare Materials, 2013
and a member of the Board of Directors of Arrowhead Research Corporation, and hereby discloses po... more and a member of the Board of Directors of Arrowhead Research Corporation, and hereby discloses potential financial interests in those companies. In addition, Ennio Tasciotti and Xuewu Liu also declare a financial interest in Leonardo Biosystems, while Daniel Fine, Alessandro Grattoni, and Xuewu Liu declare a financial interest in NanoMedical Systems, Inc.
Synthesis, Characterization, and Applications, 2001
Small, 2010
A new generation of nanocarriers, logic-embedded vectors (LEVs), is endowed with the ability to l... more A new generation of nanocarriers, logic-embedded vectors (LEVs), is endowed with the ability to localize components at multiple intracellular sites, creating an opportunity for synergistic control of redundant or dual-hit pathways. LEV encoding elements include size, shape, charge, and surface chemistry. In this study, LEVs consist of porous silicon nanocarriers, programmed for cellular uptake and trafficking along the endosomal pathway, and surface-tailored iron oxide nanoparticles, programmed for endosomal sorting and partitioning of particles into unique cellular locations. In the presence of persistent endosomal localization of silicon nanocarriers, aminefunctionalized nanoparticles are sorted into multiple vesicular bodies that form novel membranebound compartments compatible with cellular secretion, while chitosan-coated nanoparticles escape from endosomes and enter the cytosol. Encapsulation within the porous silicon matrix protects these nanoparticle surface tailored-properties, enhancing endosomal escape of chitosan coated nanoparticles. Thus LEVs provide a mechanism for shielded transport of nanoparticles to the lesion, cellular manipulation at multiple levels, and a means for targeting both within and between cells.
Nanoscale, 2011
Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., ... more Phosphorylated peptides and proteins play an important role in normal cellular activities, e.g., gene expression, mitosis, differentiation, proliferation, and apoptosis, as well as tumor initiation, progression and metastasis. However, technical hurdles hinder the use of common fractionation methods to capture phosphopeptides from complex biological fluids such as human sera. Herein, we present the development of a dual strategy material that offers enhanced capture of low molecular weight phosphoproteins: mesoporous silica thin films with precisely engineered pore sizes that sterically select for molecular size combined with chemically selective surface modifications (i.e. Ga 3+ , Ti 4+ and Zr 4+) that target phosphoroproteins. These materials provide high reproducibility (CV = 18%) and increase the stability of the captured proteins by excluding degrading enzymes, such as trypsin. The chemical and physical properties of the composite mesoporous thin films were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy and ellipsometry. Using mass spectroscopy and biostatistics analysis, the enrichment efficiency of different metal ions immobilized on mesoporous silica chips was investigated. The novel technology reported provides a platform capable of efficiently profiling the serum proteome for biomarker discovery, forensic sampling, and routine diagnostic applications. † Electronic supplementary information (ESI) available. See
Crystal engineering, 1998
The current-voltage characteristics of citrate-and octanethiol-capped Au nanocrystals assembled o... more The current-voltage characteristics of citrate-and octanethiol-capped Au nanocrystals assembled on planar Au substrates under ambient conditions in air and in solution are reported. We have found that single electron tunneling (SET) behavior is observed for citrate-capped Au crystals in air. In high dielectric media, however, SET is only seen for nanocrystals protected by the hydrophobic alkane ligands and not for the relatively bare citrate-capped nanocrystals. In addition, we report a new strategy for assembling these nanocrystals into spatially well-organized 1-dimensional (1D) arrays. The method involves trapping the crystals inside 20 nm diameter pores of porous filtration membranes. The 1D linked nanocrystals confined inside the membrane pores were characterized by ultraviolet-visible spectroscopy. "Shrinkwrapping" the nanocrystals with the organic conductive polymer polypyrrole or covalently linking the particles with alkyldithiols and subsequent dissolution of the membrane provided a suspension suitable for characterization by transmission electron microscopy. These studies are important in determining the role of spatial arrangement and chemical environment on the electronic properties of this important class of crystalline material.
Ga(CN) 3 has been prepared for the first time with a new method for preparation of inorganic cyan... more Ga(CN) 3 has been prepared for the first time with a new method for preparation of inorganic cyanides. Pure crystalline material is formed by reaction of Cl 2 GaN 3 with SiMe 3 CN via elimination of SiMe 3 N 3 and SiMe 3 Cl. Reaction of GaCl 3 with SiMe 3 CN also provides Ga(CN) 3. A new convenient route to GeMe 3 CN and SnMe 3 CN is described, but reactions of GaCl 3 with these compounds result in Lewis acid-base adducts. The composition of Ga(CN) 3 was confirmed by spectroscopic and elemental analysis. Quantitative X-ray powder diffraction was used to refine the cubic structure, which has CN groups with orientational disorder in a Prussian-blue-like network structure. The symmetry is Pm3 hm, a) 5.295(2) Å. Ga is octahedrally surrounded by on average three C and three N atoms with a Ga-(C,N) bond length of 2.072(2) Å, and the C-N bond length is 1.148(1) Å. LiGa(CN) 4 was prepared by reaction of Ga(CN) 3 with LiCN and was characterized by quantitative X-ray diffraction. The symmetry is P4 h3m, a) 5.874(2) Å, and the structure consists of LiN 4 and GaC 4 tetrahedra linked by C-N bonds to form two interpenetrating networks of the Zn(CN) 2 type. CuGa(CN) 4 has a similar structure with a) 5.729(5) Å, but Cu,Ga and/or C,N disorder cannot be ruled out.
A method for synthesizing hollow nanoscopic polypyrrole and poly(N-methylpyrrole) capsules is des... more A method for synthesizing hollow nanoscopic polypyrrole and poly(N-methylpyrrole) capsules is described. The method employs gold nanoparticles as templates for polymer nucleation and growth. Etching the gold leaves a structurally intact hollow polymer capsule with a shell thickness governed by polymerization time (ca. 5 to >100 nm) and a hollow core diameter dictated by the diameter of the template particle (ca. 5−200 nm). Transport rates of gold etchant through the polymer shell to the gold core were found to depend on the oxidation state of the polymer, those rates being a factor of 3 greater for the reduced form of the polymer. We show for the first time that not only is the particle a useful template material but also that it can be employed to deliver guest molecules into the capsule core. For example, ligands attached to the gold surface prior to poly(N-methylpyrrole) formation remained trapped inside the hollow capsule following polymer formation and gold etching.
Chem Mater, 1998
Research involving metal and semiconductor nanoparticles is expanding rapidly into the assembly a... more Research involving metal and semiconductor nanoparticles is expanding rapidly into the assembly and characterization of well-ordered 2-and 3-dimensional (2D and 3D) superstructures. Recent advances in nanoparticle organization include the 3D CdSe supercrystals synthesized by Bawendi's group, 1 Mirkin and co-workers' 2D and 3D DNA-linked Au colloid arrays, 2 and the closest-packed surface-confined monolayers of Ag, Au, and CdS colloids studied by Natan, 3 Murray, 4 Cotton, 5 Kubiak, 6 Whetten, 7 and others. 8 These novel structures have revealed electronic and optical properties distinctly different from those of individual nanoparticles (that is, ensemble average measurements on well-spaced particles) or their macroscopic equivalents; practical applications are foreseeable in optical and electronic based chemical sensing, 2,8 nanoscale electronics, 8,9 and catalysis. 5 Despite their potential for fundamental studies on electron and energy transfer in nanoscopic solid-state materials and for applications involving single-electron devices, 8,9 few reports have appeared regarding the synthesis of coupled 1D nanoparticle systems. Notable Scheme 1. Synthetic Protocols for the Synthesis of Coupled 1D Nanoparticle Arrays: Procedures for (A) Ppy-linked Au Colloids and (B) Alkyldithiolate-Linked Au Colloids