Abstract: The invention involves generating and presenting, typically electronically, a number of design alternatives to persons who are participating in the design, selection, or market research exercise. The participants (referred to as “selectors”) transmit data indicative of their preferences among or between the presented design alternatives, and that data is used to derive a new generation of design alternatives or proposals. The new designs are generated through the use of a computer program exploiting a genetic or evolutionary computational technique. The process is repeated, typically for many iterations or cycles.

Abstract: The invention involves generating and presenting, typically electronically, a number of design alternatives to persons who are participating in the design, selection, or market research exercise. The participants (referred to as “selectors”) transmit data indicative of their preferences among or between the presented design alternatives, and that data is used to derive a new generation of design alternatives or proposals. The new designs are generated through the use of a computer program exploiting a genetic or evolutionary computational technique. The process is repeated, typically for many iterations or cycles.

Abstract: Disclosed is a family of novel protein constructs, useful as drugs and for other purposes, termed “adzymes,” comprising an address moiety and a catalytic domain. In some types of disclosed adzymes, the address binds with a binding site on or in functional proximity to a targeted biomolecule, e.g., an extracellular targeted biomolecule, and is disposed adjacent the catalytic domain so that its affinity serves to confer a new specificity to the catalytic domain by increasing the effective local concentration of the target in the vicinity of the catalytic domain. The present invention also provides pharmaceutical compositions comprising these adzymes, methods of making adzymes, DNA's encoding adzymes or parts thereof, and methods of using adzymes, such as for treating human subjects suffering from a disease, such as a disease associated with a soluble or membrane bound molecule, e.g., an allergic or inflammatory disease.

Abstract: Disclosed is a family of novel protein constructs, useful as drugs and for other purposes, termed “adzymes,” comprising an address moiety and a catalytic domain. In some types of disclosed adzymes, the address binds with a binding site on or in functional proximity to a targeted biomolecule, e.g., an extracellular targeted biomolecule, and is disposed adjacent the catalytic domain so that its affinity serves to confer a new specificity to the catalytic domain by increasing the effective local concentration of the target in the vicinity of the catalytic domain. The present invention also provides pharmaceutical compositions comprising these adzymes, methods of making adzymes, DNA's encoding adzymes or parts thereof, and methods of using adzymes, such as for treating human subjects suffering from a disease, such as a disease associated with a soluble or membrane bound molecule, e.g., an allergic or inflammatory disease.

Abstract: The methods of the invention exploit the mass-to-charge ratio dependent motion of ions in an electrodynamic ion traps in synergy with a charge quenching process. In an electrodynamic ion trap, each mass-to-charge ratio is characterized by a unique set of frequencies of motion. Accordingly, by tailoring the time-varying electrical potential of the ion trap the invention controls which ions are allowed or retained in the ion trap and which ions are subjected to charge quenching reactions. Control of ion retention and charge quenching is used to improve sample throughput, dynamic mass range and signal discrimination in the mass spectrometry of multiply charged ions.

Abstract: Disclosed are chromatography methods and matrix geometries which permit high resolution, high productivity separation of mixtures of solutes, particularly biological materials. The method involves passing fluids through specially designed chromatography matrices at high flow rates. The matrices define first and second interconnected sets of pores and a high surface area for solute interaction in fluid communication with the members of the second set of pores. The first and second sets of pores are embodied, for example, as the interstices among particles and throughpores within the particles. The pores are dimensioned such that, at achievable high fluid flow rates, convective flow occurs in both pore sets, and the convective flow rate exceeds the rate of solute diffusion in the second pore set. This approach couples convective and diffusive mass transport to and from the active surface and permits increases in fluid velocity without the normally expected bandspreading.

Abstract: The invention involves generating and presenting, typically electronically, a number of design alternatives to persons who are participating in the design, selection, or market research exercise. The participants (referred to as “selectors”) transmit data indicative of their preferences among or between the presented design alternatives, and that data is used to derive a new generation of design alternatives or proposals. The new designs are generated through the use of a computer program exploiting a genetic or evolutionary computational technique. The process is repeated, typically for many iterations or cycles.

Abstract: The methods of the invention exploit the mass-to-charge ratio dependent motion of ions in an electrodynamic ion traps in synergy with a charge quenching process. In an electrodynamic ion trap, each mass-to-charge ratio is characterized by a unique set of frequencies of motion. Accordingly, by tailoring the time-varying electrical potential of the ion trap the invention controls which ions are allowed or retained in the ion trap and which ions are subjected to charge quenching reactions. Control of ion retention and charge quenching is used to improve sample throughput, dynamic mass range and signal discrimination in the mass spectrometry of multiply charged ions.

Abstract: A sample holder comprises a substrate microfabricated to define a multiplicity of microscopic islands defining sample support surfaces. At least one sump separates adjacent island surfaces and inhibits transport of samples between adjacent island surfaces.

Abstract: Disclosed are chromatography methods and matrix geometries which permit high resolution, high productivity separation of mixtures of solutes, particularly biological materials. The method involves passing fluids through specially designed chromatography matrices at high flow rates. The matrices define first and second interconnected sets of pores and a high surface area for solute interaction in fluid communication with the members of the second set of pores. The first and second sets of pores are embodied, for example, as the interstices among particles and throughpores within the particles. The pores are dimensioned such that, at achievable high fluid flow rates, convective flow occurs in both pore sets, and the convective flow rate exceeds the rate of solute diffusion in the second pore set. This approach couples convective and diffusive mass transport to and from the active surface and permits increases in fluid velocity without the normally expected bandspreading.

Abstract: Disclosed are chemically-produced specific binding, "molecular imaged" sorbents which reversibly bind a preselected macromolecule by spatially matched multipoint interactions between functional groups synthesized on the surface of the sorbent and functional groups on the surface of the macromolecule. Also disclosed are methods of producing such sorbents. The sorbents typically are high surface area solids comprising surface binding regions which have charged groups, metal coordinating groups, hydrophobic moieties, or various combination thereof anchored thereto and spaced in the mirror image of complementary interactive groups on a surface of the macromolecule.

Abstract: Disclosed are chromatography methods and matrix geometries which permit high resolution, high productivity separation of mixtures of solutes, particularly biological materials. The method involves passing fluids through specially designed chromatography matrices at high flow rates. The matrices define first and second interconnected sets of pores and a high surface area for solute interaction in fluid communication with the members of the second set of pores. The first and second sets of pores are embodied, for example, as the interstices among particles and throughpores within the particles. The pores are dimensioned such that, at achievable high fluid flow rates, convective flow occurs in both pore sets, and the convective flow rate exceeds the rate of solute diffusion in the second pore set. This approach couples convective and diffusive mass transport to and from the active surface and permits increases in fluid velocity without the normally expected bandspreading.

Abstract: Disclosed are chromatography methods and matrix geometries which permit high resolution, high productivity separation of mixtures of solutes, particularly biological materials. The method involves passing fluids through specially designed chromatography matrices at high flow rates. The matrices define first and second interconnected sets of pores and a high surface area for solute interaction in fluid communication with the members of the second set of pores. The first and second sets of pores are embodied, for example, as the interstices among particles and throughpores within the particles. The pores are dimensioned such that, at achievable high fluid flow rates, convective flow occurs in both pore sets, and the convective flow rate exceeds the rate of solute diffusion in the second pore set. This approach couples convective and diffusive mass transport to and from the active surface and permits increases in fluid velocity without the normally expected bandspreading.

Abstract: Disclosed are hydrophilic coatings covalently bound to hydrophobic surfaces as well as methods for their production. To form the coated surfaces, a compound is provided which comprises a hydrophobic domain including an unsaturated group and a hydrophilic domain. Also provided is a hydrophobic surface comprising unsaturated groups. Molecules of the compound are adsorbed onto the hydrophobic surface, and the unsaturated groups in the hydrophobic domains of molecules of the compound then are covalently crosslinked to the unsaturated groups on the hydrophobic surface by a free radical reaction. In one embodiment, hydrophilic coatings may be covalently attached to hydrophobic polymers such as divinylbenzene crosslinked polystyrene. Hydrophilic coatings covalently attached to hydrophobic surfaces are obtained which are stable, which may be readily derivatized, and which are useful in a wide range of chromatography applications.

Abstract: Disclosed are chemically-produced specific binding, "molecular imaged" sorbents which reversibly bind a preselected macromolecule by spacially matched multipoint interactions between functional groups synthesized on the surface of the sorbent and functional groups on the surface of the macromolecule. Also disclosed are methods of producing such sorbents. The sorbents typically are high surface area solids comprising surface binding regions which have charged groups, metal coordinating groups, hydrophobic moities, or various combination thereof anchored thereto and spaced in the mirror image of complementary interactive groups on a surface of the macromolecule.

Abstract: Disclosed is a method for the rapid quantitative determination of low density lipoprotein (LDL) in a biological fluid sample containing LDL, very low density lipoprotein (VLDL) and high density lipoprotein (HDL). The sample is first passed through a matrix to bind LDL to the matrix. The LDL is then eluted from the matrix differentially from VLDL and HDL. A parameter representative of the concentration of a solute exiting the matrix during the interval when LDL is eluted is then determined, wherein the parameter is proportional to the amount of the LDL in the sample. The parameter may be determined, e.g., by electronically integrating under a spectrophotometrically detected peak of eluted LDL.

Abstract: A method of derivatizing a chromatography matrix having a hydrophobic surface involves reacting the hydrophobic surface with a halosulfonating agent to produce a significant amount of halosulfone groups covalently bonded onto the surface. Sulfonamide bonds then are formed between these halosulfone groups and a group of amine functions on a polyaminated polymer to produce a pellicular anion exchange layer covalently bonded to the surface. The resulting layer is stable in the absence of cross-links between the molecules of the polyaminated polymer.

Abstract: Disclosed are chromatography methods and matrix geometries which permit high resolution, high productivity separation of mixtures of solutes, particularly biological materials. The method involves passing fluids through specially designed chromatography matrices at high flow rates. The matrices define first and second interconnected sets of pores and a high surface area for solute interaction in fluid communication with the members of the second set of pores. The first and second sets of pores are embodied, for example, as the interstices among particles and throughpores within the particles. The pores are dimensioned such that, at achievable high fluid flow rates, convective flow occurs in both pore sets, and the convective flow rate exceeds the rate of solute diffusion in the second pore set. This approach couples convective and diffusive mass transport to and from the active surface and permits increases in fluid velocity without the normally expected bandspreading.

Abstract: Disclosed are methods and apparatus for determining the presence of one or more analytes in a sample, wherein the presence of a complex of an analyte and an analyte-specific binding moiety is detected at a location in an elongate pH gradient corresponding to a predetermined isoelectric point of the complex in the gradient. An electric field applied across the elongate pH gradient prior to the detection of the complex transports the complex to the location in the pH gradient corresponding to the predetermined isoelectric point. The analyte-specific binding moiety preferably is provided with a detectable label such as a fluorescent label. A parameter, e.g., fluorescence intensity, indicative of the amount of the complex at the location in the pH gradient corresponding to the predetermined isoelectric point may be determined to quantitate the analyte.

Abstract: Disclosed are chemically-produced specific binding, "molecular imaged" sorbents which reversibly bind a preselected macromolecule by spacially matched multipoint interactions between functional groups synthesized on the surface of the sorbent and functional groups on the surface of the macromolecule. Also disclosed are methods of producing such sorbents. The sorbents typically are high surface area solids comprising surface binding regions which have charged groups, metal coordinating groups, hydrophobic moities, or various combination thereof anchored thereto and spaced in the mirror image of complementary interactive groups on a surface of the macromolecule.