Caliper Life Sciences, Inc.

Varian Associates, Inc.

Caliper Technologies Corporation

Ring-Ling Chien

Andrea W Chow

J Wallace Parce

Anne R Kopf-Sill

Benjamin N Wang

Michael A Spaid

Dean S Burgi

Jeffrey A Wolk

Samuel D H Chan

Robert S Dubrow

Michael R Knapp

Steven A Sundberg

John C Helmer

Richard J McReynolds

Tammy Burd Mehta

Steven James Gallagher

Josh Molho

Charles B Cooper, Iii

Anubhav Tripathi

Andrew T Zander

Matthew B Kerby

Wallace J Parce

Microfluidic devices and systems having enhanced detection sensitivity, particularly for use in non-fluorogenic detection methods, e.g., absorbance. The systems typically employ planar microfluidic devices that include one or more channel networks that are parallel to the major plane of the device, e.g., the predominant plane of the planar structure, and a detection channel segment that is substantially orthogonal to that plane. The detection system is directed along the length of the detection channel segment using a detection orientation that is consistent with conventional microfluidic systems.

Microfluidic systems with enhanced detection systems

The present invention is directed to a method for determining the molecular weight and diffusivity of a sample solute by providing a plus shaped microchannel network on a microfluidic chip, having at least four microchannels intersecting at a cross point; flowing a sample stream comprising a sample solute of unknown diffusivity and a blank stream from separate microchannels through the cross point and out to separate microchannels; creating a sample curve measuring the concentration of the sample solute that diffuses from the sample stream to the blank stream at the cross point while altering the flowrate of one of the blank stream or the sample stream; and determining a diffusion coefficient of the sample solute by extrapolating data from similar curves of at least two solutes having known molecular weights and/or diffusion coefficients created under similar conditions as those generated by the sample solute.

Method for determining diffusivity and molecular weight in a microfluidic device

Improved microfluidic devices, systems, and methods allow selective transportation of fluids within microfluidic channels of a microfluidic network by applying, controlling, and varying pressures at a plurality of reservoirs. Modeling the microfluidic network as a series of nodes connected together by channel segments and determining the flow resistance characteristics of the channel segments may allow calculation of fluid flows through the channel segments resulting from a given pressure configuration at the reservoirs. To effect a desired flow within a particular channel or series of channels, reservoir pressures may be identified using the network model. Viscometers or other flow sensors may measure flow characteristics within the channels, and the measured flow characteristics can be used to calculate pressures to generate a desired flow. Multi-reservoir pressure modulator and pressure controller systems can optionally be used in conjunction with electrokinetic or other fluid transport mechanisms.

Multi-reservoir pressure control system

Methods and systems that employ hybrid fluid flow profiles for optimized movement of materials through channel networks. These systems employ hybrid pressure-based and electrokinetic based flow systems for moving materials through interconnected channel networks while maintaining interconnection among the various channel segments. In particular, the invention is generally directed to channel networks where flow in a first channel segment is driven by pressure flow with its consequent parabolic flow profile, while flow in an interconnected channel segment is dominated by electrokinetic flow with its consequent plug flow profile. The invention also provides channel networks wherein fluid flow in channel segments is driven by both pressure and electric field and the multiple species contained in a fluid plug are separated by altering the applied pressure and electric fields in the various channel segments of the channel networks.

Mixed mode microfluidic systems

The present invention provides novel methods and devices for testing/verifying the configuration of one or more microfluidic elements in a microfluidic device. In particular the methods and devices of the invention are useful in testing for blockages or the presence of air bubbles in microfluidic elements. For example, a method for verifying the proper function of a microfluidic device is disclosed, which device comprises at least first, second and third fluidic openings, which fluidic openings are fluidly coupled to at least first, second and third microscale channel elements, respectively, the method comprising flowing an electrically conductive buffer through the first, second and third microscale channel elements; setting a known applied voltage potential (or current) between the first and second fluidic openings; setting a current in the third microscale channel element to be approximately zero; detecting a resulting voltage at the third fluidic opening; and, comparing the detected voltage at the third fluidic opening with a calculated target voltage expected at the third fluidic opening to determine whether there is a fault or problem (e.g., air bubble) in at least one of the first and second microscale channel elements. The above method can be repeated one or more times for the other fluidic openings in the microfluidic device to determine whether there is a fault in any one or more microscale elements of the device.

Voltage/current testing equipment for microfluidic devices

Microfluidic devices, systems, and methods measure viscosity, flow times, and/or pressures, other flow characteristics within the channels, and the measured flow characteristics can be used to generate a desired flow. Multi-reservoir pressure modulator and pressure controller systems, electrokinetic systems and/or other fluid transport mechanisms can generate the flow, controllably mix fluids, and the like.

Microfluidic viscometer

The present invention provides novel devices for measuring internal dimensions of microscale structures. Methods in accordance with the invention use the voltage measured at a midpoint between a reference structure and a sample structure to determine the resistance of the sample structure, and to then calculate an internal dimension of the sample structure.

Methods and systems for measuring internal dimensions of microscale structures

Methods for monitoring time dependent reactions that comprise providing a flow channel, typically microscale in dimension, flowing at least two reagents into the flow channel and varying the flow rate of the mixture through the flow channel. By increasing and/or decreasing the flow rate of the reagent mixture from the point of mixing to the point of detection, one alters the amount of reaction time, allowing monitoring reaction kinetics over time.

Continuous flow methods for monitoring time dependent reactions

Microfluidic devices, systems, and methods measure viscosity, flow times, and/or other flow characteristics within the channels, and the measured flow characteristics can be used to generate a desired flow. Multi-reservoir pressure modulator and pressure controller systems, electrokinetic systems and/or other fluid transport mechanisms can generate the flow, controllably mix fluids, and the like.

Methods of concentrating materials within microfluidic channel networks by moving materials into regions in which overall velocities of the material are reduced, resulting in stacking of the material within those reduced velocity regions. These methods, devices and systems employ static fluid interfaces to generate the differential velocities, as well as counter-current flow methods, to concentrate materials within microscale channels.

Microfluidic methods, devices and systems for in situ material concentration

Methods, devices, and systems for monitoring time dependent reactions

Methods, apparatus and systems are provided for introducing large numbers of different materials into a microfluidic analytical device rapidly, efficiently and reproducibly. In particular, improved integrated pipettor chip configurations, e.g. sippers or electropipettors, are described which are capable of sampling extremely small amounts of material for which analysis is desired, transporting material into a microfluidic analytical channel network, and performing the desired analysis on the material.

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San Jose, CA, United States of America

Ring-Ling Chien