Electricity: measuring and testing – Impedance – admittance or other quantities representative of... – Calibration
Reexamination Certificate
1999-08-13
2002-12-24
Le, N. (Department: 2858)
Electricity: measuring and testing
Impedance, admittance or other quantities representative of...
Calibration
C324S607000
Reexamination Certificate
active
06498497
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to a controller and detector system for microfluidic systems, and more particularly, to a microfluidic controller and detector system for use with assay systems for performing chemical and biochemical analyses.
Analysis of chemical and biochemical samples often requires detection and identification of the constituent elements of the sample. Microfluidic devices are often used to separate and control movement of the elements of the sample to detect a property of the elements with a detection system. Microfluidics technology moves small volumes of fluids through channels on a chip to perform a multitude of laboratory tests to obtain biochemical and chemical information. This laboratory-on-a-chip technology enables microfluidics systems to support a range of applications in drug discovery, bioanalytical research and medical diagnostics, including DNA, RNA, and cell analyses.
The microfluidic devices typically include multiple wells that are interconnected with microchannels for transport of the sample. Application of a voltage across the channels permits the electrophoretic migration of macromolecular species in the sample. The samples often include an intercalating dye that becomes more fluorescent upon binding to the species of the sample. The fluorescent dyes are used to identify and locate a variety of cell structures such as specific chromosomes within a DNA sequence.
A variety of devices have been designed to read fluorescent labeled samples. In general the devices include at least one light source emitting light at one or more excitation wavelengths and a detector for detecting one or more fluorescent wavelengths. The light source is often a laser that emits light at one narrow center wavelength (single mode laser).
Despite the improvements achieved using parallel screening methods and other technological advances, such as robotics and high throughput detection systems, current screening methods still have a number of associated problems. For example, screening large numbers of samples using existing parallel screening methods have high space requirements to accommodate the samples and equipment, e.g., robotics etc., high costs associated with that equipment, and high reagent requirements necessary for performing the assays. Additionally, in many cases, reaction volumes must be very small to account for the small amounts of the test compounds that are available. Such small volumes compound errors associated with fluid handling and measurement, e.g., due to evaporation, small dispensing errors, or the like. Additionally, fluid handling equipment and methods have typically been unable to handle these volume ranges within any acceptable level of accuracy due in part to surface tension effects in such small volumes.
What is desirable is an integrated system to increase productivity, increase time- and cost-efficiency, rendering conventional laboratory procedures less cumbersome, less labor-intensive and less expensive and requiring fewer highly trained personnel.
SUMMARY OF THE INVENTION
The present invention provides a microfluidic controller and detector system. The controller and detector system is typically configured to receive a fluidic chip including at least two intersecting channels. The system preferably includes a detection zone and a material direction system comprising an interface configured for contact with the at least two intersecting channels on a different side of an intersection formed by the at least two intersecting channels. The microfluidic controller and detector optionally further includes an optics block comprising an objective lens and is located within the housing adjacent the detection zone. Finally, the microfluidic controller and detector typically includes a control system coupled to the microfluidic controller and detector with a communication channel for controlling operation of the microfluidic controller and detector. The control system is configured for receiving and analyzing data from the optics block.
The microfluidic controller and detector system generally comprises a fluidic chip that includes at least two intersecting channels and a detection zone, a material direction system comprising an interface configured for contact with the at least two intersecting channels, an optics block having an objective lens disposed adjacent the detection zone, and a control system coupled to the optics block and adapted to receive and analyze data from the optics block. The interface may be an electrical interface and/or a vacuum port adapted for interface with a vacuum pump.
In one embodiment, the electrical interface optionally comprises at least three electrodes, each configured for electrical contact with one of the intersecting channels on a different side of an intersection formed by the intersecting channels. In another embodiment, the material direction system includes a lid connected to the electrodes such that when the lid is in a closed position, the electrodes are in electrical contact with the intersecting channels. In yet another embodiment, the electrical interface also includes a reference voltage source for calibrating the channel electrodes. In yet another embodiment, the interface to the fluidic chip includes a vacuum port for moving a material, such as fluids and/or charged chemical species, using vacuum or pressure.
Preferably, the optics block includes a light detector to detect light emitting from the detection zone via the objective lens. The light detector is typically selected from photodiode, avalanche photodiode, photomultiplier tube, diode array, imaging systems, and charged coupled devices. In one embodiment, the light detector is in communication with the control system. The optics block optionally further includes a detector lens assembly positioned adjacent the light detector through which light from the detection zone travels. In addition, the optics block optionally includes a light source operable to direct light toward the detection zone via the objective lens and a mirror that reflects light produced by the light source and transmits light emitted from the detection zone via the objective lens. The light source is typically a laser, a laser diode, or a light emitting diode.
In another embodiment, the microfluidic controller and detector system includes a mounting apparatus for focusing light from the light source onto the detection zone via the objective lens. The mounting apparatus preferably comprises a first and a second adjacent plate, a pivot, and an actuator for displacing the first plate relative to the second plate about the pivot. The mounting apparatus typically includes two actuators each for displacing the first plate relative to the second plate in a different direction about the pivot. The actuator preferably is a stepper motor coupled to a coupler, the coupler being coupled to the first plate and in movable contact with the second plate. In one embodiment, the coupler defines threads therearound and the first plate defines an orifice therethrough, the orifice having internal threads configured to engage the threads of the coupler. Preferably, the second plate includes a hard seat adapted to be in contact with the coupler.
According to another embodiment, a method of calibrating a plurality of electrical source channels generally comprises generating a first electrical reference input at a reference channel and a first electrical source input at each of the electrical source channels, measuring a first electrical value at each of the reference and electrical source channels, generating a second electrical reference input at the reference channel and a second electrical source input at each of the electrical source channels, the second electrical reference input and the second electrical source input being different from the first electrical reference input and the first electrical source input, respectively, measuring a second electrical value at each of the reference and electrical source channels, and determining a readout calibration fac
Chow Calvin Y. H.
Jensen Morten J.
Kennedy Colin B.
Lacy Michael M.
Nagle Robert E.
Caliper Technologies Corp.
Kerveros James
Le N.
Ritter Lang & Kaplan LLP
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