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Hybrid Integrated Silicon Microfluidic Platform for Fluorescence Based Biodetection.

The desideratum to develop a fully integrated Lab-on-a-chip device capable ofrapid specimen detection for high throughput in-situ biomedical diagnoses and Point-of-Care testing applications has called for the integration of some of the novel technologiessuch as the microfluidics, microphotonics, immunoproteomics and Micro ElectroMechanical Systems (MEMS). In the present work, a silicon based microfluidic device hasbeen developed for carrying out fluorescence based immunoassay. By hybrid attachment ofthe microfluidic device with a Spectrometer-on-chip, the feasibility of synthesizing anintegrated Lab-on-a-chip type device for fluorescence based biosensing has beendemonstrated. Biodetection using the microfluidic device has been carried out usingantigen sheep IgG and Alexafluor-647 tagged antibody particles and the experimentalresults prove that silicon is a compatible material for the present application given thevarious advantages it offers such as cost-effectiveness, ease of bulk microfabrication,superior surface affinity to biomolecules, ease of disposability of the device etc., and is thussuitable for fabricating Lab-on-a-chip type devices.

N-Heterocyclic Carbene-Catalyzed Ring Opening Polymerization of ε-Caprolactone with and without Alcohol Initiators: Insights from Theory and Experiment.

Computational investigations with density functional theory (DFT) have been performed on the N-heterocyclic carbene (NHC) catalyzed ring-opening polymerization of ε-caprolactone in the presence and in the absence of a methanol initiator. Much like the zwitterionic ring opening (ZROP) of δ-valerolactone which was previously reported, calculations predict that the mechanism of the ZROP of caprolactone that occurs without an alcohol present involves a high-barrier step involving ring opening of the zwitterionic tetrahedral intermediate formed after the initial nucleophilic attack of NHC on caprolactone. However, the operative mechanism by which caprolactone is polymerized in the presence of an alcohol initiator does not involve the analogous mechanism involving initial nucleophilic attack by the organocatalytic NHC. Instead, the NHC activates the alcohol through hydrogen bonding and promotes nucleophilic attack and the subsequent ring-opening steps that occur during polymerization. The largest free energy barrier for the hydrogen-bonding mechanism in alcohol involves nucleophilic attack, while that for both ZROP processes involves ring opening of the initially formed zwitterionic tetrahedral intermediate. The DFT calculations predict that the rate of polymerization in the presence of alcohol is faster than the reaction performed without an alcohol initiator; this prediction has been validated by experimental kinetic studies.

Experimental and computational studies on the mechanism of zwitterionic ring-opening polymerization of δ-valerolactone with N-heterocyclic carbenes.

Experimental and computational investigations of the zwitterionic ring-opening polymerization (ZROP) of δ-valerolactone (VL) catalyzed by the N-heterocyclic carbenes (NHC) 1,3-diisopropyl-4,5-dimethyl-imidazol-2-ylidene (1) and 1,3,4,5-tetramethyl-imidazol-2-ylidene (2) were carried out. The ZROP of δ-valerolactone generates cyclic poly(valerolactone)s whose molecular weights are higher than predicted from [VL]0/[NHC]0. Kinetic studies reveal the rate of polymerization is first order in [VL] and first order in [NHC]. Density functional theory (DFT) calculations were carried out to elucidate the key steps involved in the ring-opening of δ-valerolactone and its subsequent oligomerization. These studies have established that the initial steps of the mechanism involve nucleophilic attack of the NHC on δ-valerolactone to form a zwitterionic tetrahedral intermediate. DFT calculations indicate that the highest activation barrier of the entire mechanism is associated with the ring-opening of the tetrahedral intermediate formed from the NHC and δ-valerolactone, a result consistent with inefficient initiation to generate reactive zwitterions. The large barrier in this step is due to the fact that ring-opening requires a partial positive charge to develop next to the directly attached NHC moiety which already bears a delocalized positive charge.

Bioresistive identification of heat shock protein 90.

90 kDa heat shock protein (HSP90) is a ubiquitous molecular chaperone and is one of the abundant proteins present in a cell under normal and stressed conditions. The adenosine triphosphate (ATP) binding region of HSP90 is currently under a great degree of study because of the interest of its role in cancer and protein maintenance; the binding of ATP to HSP90 induces a large conformational change in the protein as a result of the activity of different types of stressors within the cells. In the present paper, a simple microfluidic biosensor is proposed for the characterization of ATP-HSP90 interactions through the principle of bioresistive variation. The experimental results prove that the present biosensor system is highly suitable for the detection of heat shock proteins present in a real-time biological sample, which is very useful for in-situ biomedical applications and rapid pathogenic detections.