Analytical characterization of microfabricated SU-8 emitters for electrospray ionization mass spectrometry

We present a detailed optimization and characterization of the analytical performance of SU-8-based emitters for electrospray ionization mass spectrometry (ESI/MS). The improved SU-8 fabrication process presented here enhances patterning accuracy and reduces the time and cost of fabrication. All emitters are freestanding and enable sample delivery by both pressure-driven and spontaneous flows. The optimized emitter design incorporates a sharp, double-cantilevered tip implemented to the outlet of an SU-8 microchannel and provides highly sensitive ESI/MS detection. Moreover, the optimized design allows the use of relatively large microchannel dimensions (up to 200 x 50 microm(2), w x h) without sacrificing the detection sensitivity. This is advantageous with a view of preventing emitter clogging and enabling reproducible analysis. The measured limits of detection for the optimized emitter design were 1 nM for verapamil and 4 nM for Glu-fibrinopeptide B with good quantitative linearities between 1 nM and 10 microM (R(2) = 0.9998) for verapamil and between 4 nM and 3 microM (R(2) = 0.9992) for Glu-fibrinopeptide B. The measured tip-to-tip repeatability for signal intensity was 14% relative standard deviation (RSD) (n = 3; 5 microM verapamil) and run-to-run repeatability 4-11% RSD (n = 4; 5 microM verapamil) for all individual emitters tested. In addition, long-term stability of < 2% RSD was maintained for timescales of 30 min even under free flow conditions. SU-8 polymer was also shown to be chemically stable against most of the tested electrospray solvents.     

A [4 + 4] annulation strategy for the synthesis of eight-membered carbocycles based on intramolecular cycloadditions of conjugated enynes

A [4+4] annulation strategy for the synthesis of eight-membered carbocycles is reported that proceeds via a cascade involving two pericyclic processes. In the first step, the [4+2] cycloaddition of a conjugated enyne with an electron-deficient cyclobutene generates a strained six-membered cyclic allene that isomerizes to the corresponding 1,3-cyclohexadiene. In the second step, this bicyclo[4.2.0]octa-2,4-diene intermediate undergoes thermal or acid-promoted 6-electron electrocyclic ring opening to furnish a 2,4,6-cyclooctatrienone. The latter transformation represents the first example of the promotion of 6-electron electrocyclic ring opening reactions by acid.     

Exploring and expanding the structural diversity of self-assembling dendrons through combinations of AB, constitutional isomeric AB2, and AB3 biphenyl-4-methyl ether building blocks

General, efficient and inexpensive methods for the synthesis of dendritic building blocks methyl 3',4'-dihydroxybiphenyl-4-carboxylate, 3',5'-dihydroxybiphenyl-4-carboxylate, and methyl 3',4',5'-trihydroxybiphenyl-4-carboxylate were elaborated. In all syntheses the major step involved an inexpensive Ni(II)-catalyzed Suzuki cross-coupling reaction. These three building blocks were employed together with methyl 4'-hydroxybiphenyl-4-carboxylate in a convergent iterative strategy to synthesize seven libraries containing up to three generations of 3',4'-, 3',5'-, and 3',4',5'-substituted biphenyl-4-methyl ether based amphiphilic dendrons. These dendrons self-assemble into supramolecular dendrimers that self-organize into periodic assemblies. Structural and retrostructural analysis of their assemblies demonstrated that these dendrons self-assemble into hollow and non-hollow supramolecular dendrimers exhibiting dimensions of up to twice those reported for architecturally related dendrons based on benzyl ether repeat units. These new dendrons expand the structural diversity and demonstrate the generality of the concept of self-assembling dendrons based on amphiphilic arylmethyl ethers.     

Silane adsorption onto cellulose fibers: hydrolysis and condensation reactions

The hydrolysis of three alkoxysilane coupling agents, gamma-methacryloxypropyltrimethoxysilane (MPS), gamma-aminopropyltriethoxysilane (APS), and gamma-diethylenetriaminopropyltrimethoxysilane (TAS), was carried out in an ethanol/water (80/20) solution and followed by 1H, 13C, and 29Si NMR spectroscopy, which showed that its rate increased in the order MPS < APS < TAS. The formation of the silanol groups was followed by their self-condensation to generate oligomeric structure. APS and MPS only gave soluble products, whereas colloidal particles precipitated in the medium when TAS was hydrolyzed. Pristine and hydrolyzed MPS were then adsorbed onto a cellulose substrate and thereafter a thermal treatment at 110-120 degrees C under reduced pressure was applied to the modified fibers to create permanent bonding of the coupling agent at their surface.     

Toward an integrated microchip sized 2-D polyacrylamide slab gel electrophoresis device for proteomic analysis

We describe a miniaturized instrument capable of performing 2-DE. Our miniaturized device is able to perform IEF and polyacrylamide slab gel electrophoresis (PASGE) in the same unit. It consists of a compartment for a first-dimensional IEF gel, which is connected to a second-dimensional PASGE gel. The focused samples are automatically transferred from the IEF gel to the PASGE gel by electromigration. Our preliminary experiments show that the device is able to focus and separate a mixture of proteins in approximately 1 h, excluding the time required for the staining procedure. On average, the gel-to-gel retardation factor (Rf) variation was 6.2% (+/-0.9%) and pI variation was 2.5% (+/-0.6%). Separated protein spots were excised from stained gels, digested with trypsin, and further identified by MS, thus enabling direct proteomic analysis of the separated proteins.     

Self-assembly of hybrid dendrons with complex primary structure into functional helical pores

The synthesis of three libraries of self-assembling hybrid dendrons containing a primary structure based on the sequence (4-3,4-3,5)12G2-CO(2)CH(3) generated from benzyl ether, biphenyl-4-methyl ether, and AB(2) repeat units constructed from (AB)(y)--AB(2) combinations of benzyl ethers, is reported. The structural and retrostructural analysis of their supramolecular dendrimers facilitated the discovery of new architectural principles that lead to the assembly of functional helical pores. The self-assembly of an example of hybrid dendron containing -H, -CO(2)CH(3), -CH(2)OH, -COOH, -COOK, -CONH(2), -CONHCH(3), -CO(2)(CH(2))(2)OCH(3), -(R) and -(S)-CONHCH(CH(3))C(2)H(5) as X-groups at the apex demonstrated that these self-assembling dendrons provide the simplest strategy for the design and synthesis of porous columns containing a diversity of hydrophilic and hydrophobic functional groups in the inner part of the pore. The results reported here expand the scope and limitations of dendrons available for the self-assembly of functional pores that previously were generated mostly from dendritic dipeptides, to simpler architectures based on hybrid dendrons.     

Silicon micropillar array electrospray chip for drug and biomolecule analysis

We have developed a lidless micropillar array electrospray ionization chip (microPESI) combined with mass spectrometry (MS) for analysis of drugs and biomolecules. The microPESI chip, made of silicon, contains a sample introduction spot for a liquid sample, an array of micropillars (diameter, height, and distance between pillars in the range of 15-200, 20-40, and 2-80 microm, respectively), and a sharpened tip for direct electrospray formation. The microchips were fabricated using deep reactive ion etching (DRIE) which results in accurate dimensional control. The chip, providing a reliable open-channel filling structure based on capillary forces and a electrospray emitter tip for ionization, allows an easy operation and reliable, non-clogging liquid transfer. The microPESI chip can be used for a fast analysis using single sampling or for continuous infusion measurements using a syringe pump for sample introduction. The microPESI-MS shows high sensitivity, with limit of detection 30 pmol/L (60 amol or 28 fg) for verapamil measured with tandem mass spectrometry (MS/MS) and using a sample volume of 2.5 microL. The system shows also good quantitative linearity (r2 > 0.99) with linear dynamic range of at least six orders of magnitude and good ion current stability (standard deviation <5%) in 1-h continuous flow measurement. The microPESI-MS is shown to be a very potential method for direct analysis of drugs and biomolecules.     

Principe d'incertitude SAK de Fefferman

We give a version of the SAK-Fefferman principle which allows us to compare powers of subelliptic pseudo-differential operators in the setting of Weyl–Hörmander calculus. To cite this article: S. Mustapha, C. R. Acad. Sci. Paris, Ser. I 342 (2006).     

Pulsed laser heating – Fourier and electron kinetic theory approaches

Laser surface pulse heating of engineering metals is in demand in the metal industry and investigation into laser pulse heating becomes fruitful in this regard. Application of Fourier theory to heat conduction due to high power laser irradiation may give closed form solution to the problem. On the other hand, the heat flux through a given plane depends on the electron energy distribution through the material and at the scale of distance required to examine the problem, the material can no longer be considered as being homogeneous continuum, therefore, errors may occur when considering the Fourier theory in laser heating process. The problem requires to be examined in the quantum field. The present study examines the pulse laser heating process when considering both Fourier conduction and electron-kinetic theory approaches. Analytical solution to Fourier conduction equation is obtained for intensity exponential pulses while numerical scheme is introduced to solve the heat transfer equation resulted from kinetic theory approach. It is found that both Fourier and electron kinetic theory approaches result in similar temperature profiles for the pulses having the same energy content. In the case of electron kinetic theory approach the rise time for surface temperature to reach the melting point is shorter than that obtained from the analytical solution. Received on 23 February 1998