Abstract: This invention provides methods for using liquid junction potentials to control the transport of charged particles in fluid streams that are in laminar flow within microfluidic channels. Applications of the methods of this invention include sample preconditioning (removal of interfering substances), electrophoretic separation (fractionation) of charged particles, enhanced or delayed mixing of charged particles across a fluid interface relative to diffusion only, focusing charged particles in a fluid stream in one or two dimensions, and concentration of charged reactants at a fluid interface.

Abstract: A shaft sealing assembly (10) for providing a seal between a shaft and a housing within which the shaft rotates. The sealing assembly (10) comprises a rotor (40) adapted to be mounted to the shaft and a stator (42) adapted to be mounted to the housing. The rotor (40) and the stator (42) include recesses and/or projections which mate and interlock to form a labyrinth lubricant chamber therebetween. The stator (42) carries at least one electrical-path-establishing element (88) which forms an electrically conductive path between the shaft and an electrical ground to thereby dissipate residual current and/or stray shaft voltage.

Abstract: This invention provides methods for using liquid junction potentials to control the transport of charged particles in fluid streams that are in laminar flow within microfluidic channels. Applications of the methods of this invention include sample preconditioning (removal of interfering substances), electrophoretic separation (fractionation) of charged particles, enhanced or delayed mixing of charged particles across a fluid interface relative to diffusion only, focusing charged particles in a fluid stream in one or two dimensions, and concentration of charged reactants at a fluid interface.

Abstract: A method of forming a biological sensor on a predetermined area of a substrate. The method includes dispensing a plurality of layers on the predetermined area of the substrate. Each of the plurality of layers is formed of a substantially different fluid having a substantially different function. The dispensing of the layers is accomplished by a drop generating member.

Abstract: An improved microscale diffusion immunoassay utilizing multivalent reactants is disclosed. In particular, a method for detecting the presence of analyte particles in an analyte fluid is disclosed, the method comprising: (a) providing the analyte fluid comprising the analyte particles; (b) providing a diffusion fluid comprising binding particles capable of binding with the analyte particles; (c) flowing the analyte fluid and the diffusion fluid in adjacent laminar flow through a microfluidic channel; (d) allowing the analyte particles to diffuse into the diffusion fluid and bind with the binding particles to form analyte/binding particle complexes; and (e) detecting the presence of the analyte particles and the analyte/binding particle complexes, wherein each of the binding particles is capable of binding with more than one analyte particle, and wherein each of the analyte particles is capable of binding with more than one binding particle.

Abstract: A diffusion immunoassay (DIA) for determining the presence and concentration of analyte particles by detecting the diffusion front. A hydrogel containing immobilized binding particles is placed in contact with a carrier fluid containing analyte particles, which analyte particles diffuse into the hydrogel and bind with the immobilized binding particles. A detection device detects the position of the diffusion front formed in the hydrogel to determine the presence and concentration of the analyte particles which have diffused into the hydrogel.

Abstract: This invention provides methods, devices and device components for sensing, imaging and characterizing changes in the composition of a probe region. More particularly, the present invention provides methods and devices for detecting changes in the refractive index of a probe region positioned adjacent to a sensing surface, preferably a sensing surface comprising a thin conducting film supporting surface plasmon formation. In addition, the present invention provides methods and device for generating surface plasmons in a probe region and characterizing the composition of the probe region by generating one or more surface plasmon resonances curves and/or surface plasmon resonance images of the probe region.

Abstract: A channel-cell system is provided for detecting the presence and/or measuring the presence of analyte particles in a sample stream comprising: a) a laminar flow channel; b) two inlet means in fluid connection with said laminar flow channel for respectively conducting into said laminar flow channel (1) an indicator stream which may comprise an indicator substance which indicates the presence of said analyte particles by a detectable change in property when contacted with said analyte particles, and (2) said sample stream; c) wherein said laminar flow channel has a depth sufficiently small to allow laminar flow of said streams and a length sufficient to allow particles of said analyte to diffuse into said indicator stream to the substantial exclusion of said larger particles in said sample stream to form a detection area; and d) outlet means for conducting said streams out of said laminar flow channel to form a single mixed stream.

Abstract: Devices and methods are provided for separation of particles of a first selected electrophoretic mobility or isoelectric point from a fluid comprising particles of at least one other selected electrophoretic mobility or isoelectric point. The devices comprise a microchannel comprising an inlet for introducing the fluid into the microchannel; electrodes to either side of the microchannel for applying a selected voltage to produce an electrical field across the microchannel orthogonal to the length of the microchannel; and outlets in said microchannel placed to receive outlet portions of the fluid containing enhanced concentrations of each type of particle. The devices may be used for particle detection, quantification, separation, mixing, dilution and concentration. Electrophoretic tags may be used to provide particles with altered electrophoretic mobilities and/or isoelectric points. Interior particles of cells or organisms may be released, separated and detected by these devices and methods.

Abstract: The present invention provides microband electrode array sensors for detecting the presence and measuring the concentration of analytes in a sample. The microband electrodes of the invention have both a width and thickness of microscopic dimensions. Preferably the width and thickness of the microbrand electrodes are less than the diffusion length of the analyte(s) of interest. In general, both the thickness and width of the electrodes are less than about 25 micrometers. The electrodes are separated by a gap insulating material that is large enough that the diffusion layers of the electrodes do not overlap such that there is no interference and the currents at the electrodes are additive. Microband electrode arrays of this invention exhibit true steady-state amperometric behavior.

Abstract: This invention provides methods, devices and device components for sensing, imaging and characterizing changes in the composition of a probe region. More particularly, the present invention provides methods and devices for detecting changes in the refractive index of a probe region positioned adjacent to a sensing surface, preferably a sensing surface comprising a thin conducting film supporting surface plasmon formation. In addition, the present invention provides methods and device for generating surface plasmons in a probe region and characterizing the composition of the probe region by generating one or more surface plasmon resonances curves and/or surface plasmon resonance images of the probe region.

Abstract: This invention provides an extraction device and a method for extracting desired particles from a sample stream containing the desired particles. The device has a sample stream inlet, an extraction stream inlet, and an extraction channel in fluid communication with the sample stream inlet and the extraction stream inlet. The extraction channel is for receiving a sample stream from the sample stream inlet in adjacent laminar flow with an extraction stream from the extraction stream inlet. A sequestering material within the extraction channel captures desired particles in the extraction stream. A by-product stream outlet in fluid communication with the extraction channel receives a by-product stream comprising at least a portion of the sample stream form which desired particles have been extracted. A product outlet in fluid communication with the extraction channel receives a product which has the sequestering material and at least a portion of the desired particles.

Abstract: A diffusion immunoassay (DIA) for determining the presence and concentration of analyte particles by detecting the diffusion front. A hydrogel containing immobilized binding particles is placed in contact with a carrier fluid containing analyte particles, which analyte particles diffuse into the hydrogel and bind with the immobilized binding particles. A detection device detects the position of the diffusion front formed in the hydrogel to determine the presence and concentration of the analyte particles which have diffused into the hydrogel.

Abstract: Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be measured in less than a minute.

Abstract: This invention provides a microfluidic device for use in the detection of one or more analytes in a fluid using solid-phase affinity binding assays. The device offers a practical, easy-to-use, portable, inexpensive, robust analytical system for the parallel and quantitative detection of multiple analytes. In addition, this invention provides methods and devices for the formation of concentration gradients of capture molecules immobilized on a solid phase.

Abstract: This invention provides methods for using liquid junction potentials to control the transport of charged particles in fluid streams that are in laminar flow within microfluidic channels. Applications of the methods of this invention include sample preconditioning (removal of interfering substances), electrophoretic separation (fractionation) of charged particles, enhanced or delayed mixing of charged particles across a fluid interface relative to diffusion only, focusing charged particles in a fluid stream in one or two dimensions, and concentration of charged reactants at a fluid interface.

Abstract: Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be measured in less than a minute.

Abstract: An electroösmotic mixing device and a method for mixing one or more fluids for use in meso- or microfluidic device applications. The mixing device provides batch or continuous mixing of one or more fluids in meso- or microfluidic channels. An electric field is generated in the channel in substantial contact with chargeable surfaces therein. No alterations of the geometry of existing flow paths need be made, and the degree of mixing in the device can be controlled by the length of the electrodes, the flow rate past the electrodes, and the voltage applied to those electrodes. The degree of mixing is affected by choice of materials for the chargeable surface (in some cases by the selection of materials or coatings for channel walls) and the ionic strength of the fluids and the type and concentration of ions in the fluids. The ionic strength of fluids to be mixed is sufficiently low to allow electroosmotic flow.

Abstract: This invention provides microfabricated systems for extraction of desired particles from a sample stream containing desired and undesired particles. The sample stream is placed in laminar flow contact with an extraction stream under conditions in which inertial effects are negligible. The contact between the two streams is maintained for a sufficient period of time to allow differential transport of the desired particles from the sample stream into the extraction stream. In a preferred embodiment the differential transport mechanism is diffusion. The extraction system of this invention coupled to a microfabricated diffusion-based mixing device and/or sensing means allows picoliter quantities of fluid to be processed or analyzed on devices no larger than silicon wafers. Such diffusion-based mixing or sensing devices are preferably channel cell systems for detecting the presence and/or measuring the quantity of analyte particles in a sample stream.

Abstract: Methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates. Analyte particles and binding particles are allowed to diffuse toward each other, and slowing of the diffusion front is detected when they meet. From the position of the diffusion front, presence and concentration of analyte particles can be determined. One embodiment provides a competitive immunoassay in a microfluidic format. This diffusion immunoassay (DIA) relies on measuring the concentration of labeled antigen along one dimension of a microchannel after allowing it to diffuse for a short time into a region containing specific antibodies. A simple microfluidic device, the T-Sensor, was used to implement a DIA to measure the concentration of phenytoin, a small drug molecule. Concentrations of analyte over the range of 50 to 1600 nM can be measured in less than a minute.