Electricity: measuring and testing – Impedance – admittance or other quantities representative of... – Lumped type parameters
Reexamination Certificate
2002-11-12
2004-06-15
Deb, Anjan K. (Department: 2858)
Electricity: measuring and testing
Impedance, admittance or other quantities representative of...
Lumped type parameters
C324S692000, C324S441000, C374S163000, C204S602000
Reexamination Certificate
active
06750661
ABSTRACT:
FIELD OF THE INVENTION
The present invention generally relates to methods and/or systems for precisely controlling and measuring heating. More particularly, the present invention provides a technique, including methods and devices, for providing and controlling heat to samples in a channel of a micro scale sample handling system. Merely by way of example, the invention is applied to a polymerase chain reaction process, commonly termed PCR, performed in a microfluidic system or device but it will be recognized that the invention has a much wider range of applicability. The invention according to further embodiments also provides techniques for monitoring and controlling a variety of process parameters using impedance and/or conductance measurements.
According to further embodiments, the invention relates to a computer method and/or system for precisely determining temperature and/or controlling heating in specific devices.
BACKGROUND OF THE INVENTION
The discussion of any work, publications, sales, or activity anywhere in this submission, including in any documents submitted with this application, shall not be taken as an admission by the inventors that any such work constitutes prior art. The discussion of any activity, work, or publication herein is not an admission that such activity, work, or publication existed or was known in any particular jurisdiction.
There has been a growing interest in the manufacture and use of microscale systems for the acquisition of chemical and biochemical information. Techniques commonly associated with the semiconductor electronics industry, such as photolithography, wet chemical etching, etc., are being used in the fabrication of microscale systems, such as microfluidic systems. The term “microfluidic” refers generally to a system or device or “chip” having channels and chambers which are generally fabricated at the micron or submicron scale, e.g., having at least one cross-sectional dimension in the range of from about 0.1 &mgr;m to about 500 &mgr;m. Early discussions of the use of planar chip technology for the fabrication of microfluidic systems are provided in Manz et al., Trends in Anal. Chem. (1990) 10(5):144-149 and Manz et al., Adv. in Chromatog. (1993) 33:1-66, which describe the fabrication of such fluidic devices and particularly microcapillary devices, in silicon and glass substrates.
Applications of microscale and/or microfluidic systems are myriad. For example, International Patent Appln. WO 96/04547, published Feb. 15, 1996, describes the use of microfluidic systems for capillary electrophoresis, liquid chromatography, flow injection analysis, and chemical reaction and synthesis. U.S. application Ser. No. 08/671,987, entitled “HIGH THROUGHPUT SCREENING ASSAY SYSTEMS IN MICROSCALE FLUIDIC DEVICES”, filed on Jun. 28, 1996 by J. Wallace Parce et al., and assigned to the present assignee, discloses wide ranging applications microfluidic systems in rapidly assaying large number of compounds for their effects on chemical, and preferably, biochemical systems. The phrase, “biochemical system”, generally refers to a chemical interaction which involves molecules of the type generally found within living organisms. Such interactions include the full range of catabolic and anabolic reactions which occur in living systems including enzymatic, binding, signaling and other reactions. Biochemical systems of particular interest include, e.g., receptor-ligand interactions, enzyme-substrate interactions, cellular signaling pathways, genetic analysis, transport reactions involving model barrier systems (e.g., cells or membrane fractions) for bio-availability screening, and a variety of other general systems.
Many chemical or biological systems also benefit from control over processing parameters such as temperature, concentration of reagents, buffers, salts and other materials, and the like. In particular, some chemical or biological systems require processes to be carried out at controlled and/or controllably varied temperature. In providing such a controlled temperature in miniaturized fluidic systems, external heating elements have generally been used. Such heating elements typically include external resistive heating coils or material, which provide heat to the fluidic system in a conductive manner. This heating unit attaches itself directly to an external portion of the chip to globally heat the chip and to provide a uniform temperature distribution to be present on the chip. This external heating unit, however, is cumbersome. It also complicates chip manufacturing and often affects quality and reliability of the chip. Additionally, the external heating element can fail and generally cannot effectively control heat supplied to the chip, which can cause undesirable temperature gradients and fluctuations in the chip. Accordingly, the external heating element applied to a chip is limited and can be unreliable in controlling process temperature in the chip.
Larger scale temperature controllers have also been used to control reaction temperatures within a reaction vessel, including, e.g., hot-plates, water baths, and the like. Such controllers are not well suited to providing accurate control of temperature within a microfluidic system. In fact, such global heating systems heat the entire material region of the microfluidic device and cannot be used to selectively apply heat to specific regions of the microfluidic device, e.g., specific channels or chambers. Additionally, these large temperature controllers, e.g., hot plates, often require large heating elements, which transfer heat via conduction. These heating elements possess a large characteristic response time, which often relates to a long time to heat or cool material within a reaction vessel in contact therewith in some applications.
SUMMARY OF THE INVENTION
Various strategies have been proposed for providing heating in a microscale (such as microfluidic) device. Among these strategies, three of particular interest to the present invention are (1) Joule (or electrolytic) heating, (2) in-channel resistive heating, and (3) proximal resistive heating. In each of these types of heating, an electric signal is used to provide energy. In Joule heating, the electric signal is passed directly through the sample to be heated (which generally must be an electrolytic material, thus the alternative name electrolytic heating.) Electrical energy is converted to heat as it passes through the sample. In resistive heating, a separate conductor (such as a metal or semiconductor channel) is used to carry the electric signal. The impedance and/or resistance of this separate conductor causes the conductor to heat due to electric signal flow. This heat is then transferred by heat conduction to a sample in a microscale device channel or region. In in-channel resistive heating, one or more heating elements is placed in the channel, possibly in contact with the sample material. In proximal resistive heating, one or more heating elements is placed near the channel.
Various of the above general types of heating strategies has been proposed using either DC electrical signals or AC electrical signals. It has also been proposed to detect effects of heating (such as the temperature) or other effects using conductance or impedance of the applied electrical signal. However, there is a continuing need for refined and improved techniques for effecting and/or detecting heating or other parameters in microscale devices. A number of earlier patents discuss various aspects related to the operation and/or construction of microfluidic systems. An example of these include U.S. Pat. No. 5,965,410 (Electrical current for controlling fluid parameters in microchannels); U.S. Pat. No. 5,779,868; U.S. Pat. No. 5,800,690; U.S. Pat. No. 6,306,590; and U.S. Pat. No. 6,171,850 (Integrated devices and systems for performing temperature controlled reactions and analyses).
According to the present invention, two different signals are used one signal to provide energy for heating (or, in alternative embodiments, effecting other parameters) and
Brooks Carlton F.
Jensen Morten Juel
Stern Seth
Caliper Life Sciences, Inc.
Deb Anjan K.
McKenna Donald R.
Quine Intellectual Property Law Group
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