Recombinant antibodies in cancer therapy

The application of recombinant immunotoxin and radioimmunoconjugate in Cancer therapy has revived the "magic bullet" concept predicted a century ago. Many of the recombinant antibodies have received FDA approval for various indication of cancer in recent years and numerous others are in clinical trials.     

Recombinant antibodies for environmental analysis

Initial steps of antibody engineering in the late eighties revolutionized the technology of antibody production, particularly in the area of immunotherapy and diagnostics. Hallmarks that seemed to be out of reach for a long time are now the state of the art, e.g. tailoring of antibodies to match particular needs or by-passing immunization by use of antibody libraries. Despite the apparent benefits of recombinant antibody technologies, this field has been opened up hesitantly for other applications. This review addresses the development of recombinant antibody synthesis in environmental analysis. Examples are given of the molecular evolution of pesticide antibodies and their application for the analysis of real samples.     

Recombinant antibodies and their use in biosensors

Inexpensive, noninvasive immunoassays can be used to quickly detect disease in humans. Immunoassay sensitivity and specificity are decidedly dependent upon high-affinity, antigen-specific antibodies. Antibodies are produced biologically. As such, antibody quality and suitability for use in immunoassays cannot be readily determined or controlled by human intervention. However, the process through which high-quality antibodies can be obtained has been shortened and streamlined by use of genetic engineering and recombinant antibody techniques. Antibodies that traditionally take several months or more to produce when animals are used can now be developed in a few weeks as recombinant antibodies produced in bacteria, yeast, or other cell types. Typically most immunoassays use two or more antibodies or antibody fragments to detect antigens that are indicators of disease. However, a label-free biosensor, for example, a quartz-crystal microbalance (QCM) needs one antibody only. As such, the cost and time needed to design and develop an immunoassay can be substantially reduced if recombinant antibodies and biosensors are used rather than traditional antibody and assay (e.g. enzyme-linked immunosorbant assay, ELISA) methods. Unlike traditional antibodies, recombinant antibodies can be genetically engineered to self-assemble on biosensor surfaces, at high density, and correctly oriented to enhance antigen-binding activity and to increase assay sensitivity, specificity, and stability. Additionally, biosensor surface chemistry and physical and electronic properties can be modified to further increase immunoassay performance above and beyond that obtained by use of traditional methods. This review describes some of the techniques investigators have used to develop highly specific and sensitive, recombinant antibody-based biosensors for detection of antigens in simple or complex biological samples.     

Dynamics of a single copolymer chain

The dynamics of a single copolymer chain in a solution containing identical chains is studied. The intermediate scattering function is calculated, and two different modes are identified and analyzed as a function of wave vector q. The first mode is characteristic of the copolymer system and leads to a peculiar constant relaxation frequency as q goes to zero. The second mode represents the diffusion of the chain in the solution.     

Haptoglobin subtyping with anti-haptoglobin alpha chain antibodies

Specific antibodies against the human haptoglobin (HP) alpha chain were raised and used for immunoblotting after isoelectric focusing to determine Hp alpha subtypes in a reproducible and simplified manner. By eliminating the staining of the HP beta chain, HP alpha subtypes were visualized more precisely and simply than by previously reported methods. Subtypes of a total of 1211 sera, obtained from two different populations in Japan, were examined by the new method. Four HP alpha subtypes (HP 1S-1S,2FS-1S, 2FS-2FS and 2FS-2SS) and five subtypes combined with a new variant (HP 2FS-1V1, 2V1-1S, 2FS-2V1, 2FS-2V2 and 2FS-2V3) were observed. HP 1V1 belonged to HP alpha 1, and HP 2V1, 2V2 and 2V3 belonged to HP alpha 2, and their alleles were designated HP A*1V1, HP A*2V1, HP A*2V2 and HP A*2V3, respectively. The allele frequencies were calculated to be as follows: HP A*1S, 0.2597; HP A*1V1, 0.0004; HP A*2FS, 0.7333; HP A*2SS, 0.0008; HP A*2V1, 0.0045; HP A*2V2, 0.0008; and HP A*2V3, 0.0004. The allele frequency of HP A*2SS, which is common in the European population, is less frequent than HP A*2V1 in the Japanese population.     

Mass sensors with mechanical traps for weighing single cells in different fluids

We present two methods by which single cells can be mechanically trapped and continuously monitored within the suspended microchannel resonator (SMR) mass sensor. Since the fluid surrounding the trapped cell can be quickly and completely replaced on demand, our methods are well suited for measuring changes in cell size and growth in response to drugs or other chemical stimuli. We validate our methods by measuring the density of single polystyrene beads and Saccharomyces cerevisiae yeast cells with a precision of approximately 10(-3) g cm(-3), and by monitoring the growth of single mouse lymphoblast cells before and after drug treatment.     

Thickness dependent sensing mechanism in sorted semi-conducting single walled nanotube based sensors

Single walled carbon nanotube (SWCNT) networks present outstanding potential for the development of SWCNT-based gas sensors. Due to the complexity of the transport properties of this material, the physical mechanisms at stake during exposure to gas are still under debate. Previously suggested mechanisms are charge transfer between gas molecules and SWCNT and Schottky barrier modulation. By comparing electrical measurements with an analytical model based on Schottky barrier modulation, we demonstrate that one mechanism or the other is predominant depending on the percolation of metallic carbon nanotubes. Below the metallic SWCNT percolation threshold, sensing is dominated by the modulation of the Schottky barrier, while above this threshold, it is only attributed to a charge transfer between SWCNT and gas molecules. Both mechanisms are discussed in terms of sensitivity and resolution leading to routes for the optimization of a gas sensor architecture based on highly enriched semiconducting carbon nanotube films.     

Field-effect transistor chemical sensors of single nanoribbon of copper phthalocyanine

Copper phthalocyanine (CuPc) nanoribbon field-effect transistors were implemented as chemical sensors. They showed fast response and high reversibility in the detection of the tetrahydrofuran atmosphere at room temperature. The drain current of the field-effect transistor sensor decreased from 6.7 to 0.2 nA when the transistor was measured under the tetrahydrofuran atmosphere. The sensor was self-refreshable in a few minutes. These results demonstrate that the organic single crystalline nanoribbon transistors could effectively act as chemical sensors. Supported by the National Natural Science Foundation of China (Grant Nos. 20721061, 50725311, 60736004, 60771031), the Ministry of Science and Technology of China (Grant Nos. 2006CB806200, 2006CB932100), and Chinese Academy of Sciences     

Stepwise growth of a single polymer chain

By monitoring the modulation of an ionic current passing through a nanoreactor formed from a protein pore, the step-by-step growth of an individual polymer chain was monitored. The observation of polymer growth at the single-molecule level will be useful for studying the kinetics of chain growth or the movement of polymers under confinement. It might also be used to synthesize "molecular fishing lines" in situ, for applications in stochastic sensing.     

Coils,globules and single chain glasses

The cyclic coil-globule-coil transitions for poly(N-isopropylacrylamide) tethered to an interface exhibit unexpected phenomena. Two, not the predicted single, coil-to-globule transitions can be observed: the one that is predicted occurs in worse than θ-solvents whereas the other is observed in better than θ-solvents. The latter phenomenon appears to be associated with the the formation of n-clusters, first postulated by de Gennes. The chains in their globular form were found to undergo an entropy driven entanglement process that prevents reversible swelling in the globule-to-coil transition and leads to hysteresis in the layer thickness. Single chain glasses of polystyrene prepared by microemulsion polymerisation display physical properties different from those of multichain glasses including a higher conformational temperature, larger free volume and a predominantly exothermic rather than an endothermic DSC scan near T_g. These observations have been attributed to the occurrence of cohesional entanglements.     

Spontaneous vesicle formation of single chain and double chain cationic surfactant mixtures

The concentration vs composition diagram of aggregate formation of the dodecyltrimethylammonium bromide (DTAB) and didodecyldimethylammonium bromide (DDAB) mixture in aqueous solution at rather dilute region was constructed by analyzing the surface tension, turbidity, and electrical conductivity data and inspected by cryo-TEM images and dynamic light scattering data. Although the aqueous solution of DTAB forms only micelles, the transition from monomer to small aggregates and then to vesicle was found at 0.1 < X2 相似文献   

Surface plasmon resonance sensors for real-time detection of cyclic citrullinated peptide antibodies

Surface plasmon resonance (SPR) sensors have been used for detection of various biomolecules because of their simplicity, high specificity and sensitivity, real-time detection, low cost, and no requirement of labeling. Recently, molecularly imprinted polymers that are easy to prepare, less expensive, stable, have talent for molecular recognition and also are used for creation selective binding sites for target molecule on the SPR sensors. Here, we show that preparation of cyclic citrullinated peptide antibody (anti-CCP) imprinted SPR sensor to detect CCP antibodies. For this purpose, anti-CCP/AAm pre-complex was synthesized by interacting acrylamide (AAm) monomer with anti-CCP. Then, anti-CCP imprinted (anti-CCP/PAAm) SPR sensor was obtained by reacting with anti-CCP/AAm pre-complex in the presence of the crosslinker, and initiator/activator pair. Besides this, non-imprinted (PAAm) SPR sensor was also prepared without using anti-CCP template. The SPR sensors were characterized and then adsorption-desorption studies were performed with pH 7.0 phosphate buffer (10 mM) and acetic acid (10%) with Tween 20 (1%) in pH 7.0 phosphate buffer. Selectivitiy of sensors was investigated by using immunoglobulin M (IgM) and bovine serum albumin (BSA). To determine the adsorption model of interactions between anti-CCP solutions and anti-CCP/PAAm SPR sensor, different adsorption models were performed. The calculated maximum reflection, detection limit, association and dissociation constants were 1.079 RU/mL, 0.177 RU/mL, 0.589 RU/mL and 1.697 mL/RU, respectively. Repeatability experiments of anti-CCP/PAAm SPR sensor was performed four times with adsorption-desorption-regeneration cycles without any performance losing. Results showed that anti-CCP/PAAm SPR sensor had high selectivity and sensitivity for detection of CCP antibodies.     

Emergence of multiple tori structures in a single polyelectrolyte chain

We investigated the collapsed structure of a weakly charged wormlike chain under a moderate concentration of 1:1 electrolyte solution. By assuming a torus as a grand state, we found that the size of a torus is determined by the balance between surface energy and electrostatic energy, which leads to a finite torus thickness almost independent of the chain contour length. Owing to this unique characteristic, a long charged wormlike chain forms multiple tori structure as a collapsed product, which is never seen with a neutral wormlike chain. These features were confirmed by a Monte Carlo simulation.     

An atomistic model and key parameters for devising single molecular nanowire sensors

Based on one impurity model Hamiltonian describing a nanowire upon adsorption of a molecule, we obtain an analytical formula of the conductance which is governed clearly by modulating key parameters. The formula shows that the conductance change in nanowire upon adsorption of a molecule is mainly controlled by three factors, electron hopping between adsorbed molecule and nanowire, chemical potential, and the change of atomic configurations of the nanowires near the adsorption site. Conductance is very sensitive to the choice of these key parameters; therefore, a proper nanowire system that renders matched chemical potential as well as hopping strength between the nanowire and the adsorbed molecule should be devised for the sensor applications. Our model calculations give similar conductance features to the conductance obtained by the first principle calculations for a singe-molecule-adsorbed molecular wire. It is worthy of note that the system can be in antiresonance, which is characterized by a quick drop in conductance when a molecule is adsorbed on the nanowires.     

Recent advances in high surface area electrodes for bioelectrochemical applications

The search for high surface area electrodes for bioelectrochemical applications is becoming more intense. In the last few years, new strategies have emerged to develop three-dimensional electrode materials with very well controlled architecture providing at the same time high specific surface, bendability and flexibility. This review will highlight some of the recent work published in the last 2 years and will discuss the issue of mathematical modeling of porous electrodes and what could be the future of high surface area electrodes materials.     

The single chain limit of structural relaxation in a polyolefin blend

The influence of composition on component dynamics and relevant static properties in a miscible polymer blend is investigated using molecular dynamics simulation. Emphasis is placed on dynamics in the single chain dilution limit, as this limit isolates the role of inherent component mobility in the polymer's dynamic behavior when placed in a blend. For our systems, a biased local concentration affecting dynamics must arise primarily from chain connectivity, which is quantified by the self-concentration, because concentration fluctuations are minimized due to restraints on chain lengths arising from simulation considerations. The polyolefins simulated [poly(ethylene-propylene) (PEP) and poly(ethylene-butene) (PEB)] have similar structures and glass transition temperatures, and all interactions are dispersive in nature. We find that the dependence of dynamics upon composition differs between the two materials. Specifically, PEB (slower component) is more influenced by the environment than PEP. This is linked to a smaller self-concentration for PEB than PEP. We examine the accuracy of the Lodge-McLeish model (which is based on chain connectivity acting over the Kuhn segment length) in predicting simulation results for effective concentration. The model predicts the simulation results with high accuracy when the model's single parameter, the self-concentration, is calculated from simulation data. However, when utilizing the theoretical prediction of the self-concentration the model is not quantitatively accurate. The ability of the model to link the simulated self-concentration with biased local compositions at the Kuhn segment length provides strong support for the claim that chain connectivity is the leading cause of distinct mobility in polymer blends. Additionally, the direct link between the willingness of a polymer to be influenced by the environment and the value of the self-concentration emphasizes the importance of the chain connectivity. Furthermore, these findings are evidence that the Kuhn segment length is the relevant length scale controlling segmental dynamics.     

Morphological variation in a toroid generated from a single polymer chain

A single semiflexible polymer chain folds into a toroidal object under poor solvent conditions. In this study, we examined the morphological change in such a toroidal state as a function of the cross-sectional area and stiffness of the chain together with the surface energy, which characterizes the segmental interaction parameter. Changes in the thickness and outer/inner radius on a toroid are interpreted in terms of these parameters. Our theoretical expectation corresponds to the actual morphological changes in a single giant DNA molecule as observed by electron microscopy.