The present invention relates to devices that add or remove heat from a device or other object, including devices that use treated surfaces and/or miniature compressors.
A variety of heating, cooling and thermocycling devices are routinely used by experimentalists to control the temperature of a particular reagent or reaction mixture. Some such temperature control devices have flat surfaces for heating beakers and the like, while others have surfaces adapted to transfer heat to or from eccentrically shaped objects, e.g., microtubes or round-bottom flasks. In illustrative uses, a heater may be used to boil a liquid in an Erlenmeyer flask, to denature nucleic acid solutions, or maintain a given temperature for stringent nucleic acid hybridization. A cooler may be used, for example, to maintain the stability of a given reactant by holding it near 4° C. prior to use.
Examples of heating and cooling mechanisms that have been incorporated into laboratory temperature control devices include resistive elements, compressors, and thermoelectric devices. Compressor-based cooling systems, found in commercial refrigerators and air conditioners, contain three fundamental parts: an evaporator, a compressor, and a condenser. In the evaporator, pressurized refrigerant is allowed to expand, boil, and evaporate, absorbing heat as it changes from a liquid to a gas. The compressor acts as the refrigerant pump and recompresses the gas to a liquid. The condenser expels the heat absorbed (along with the heat produced during compression) into the ambient environment. Compressor-based systems can cool components far below ambient temperature with tight tolerances.
Temperature control is important in performing at least some forms of electrophoresis. Electrophoresis is a technique that is commonly used in research and clinical laboratory settings for the analytical and preparative separation of macromolecules, such as proteins and nucleic acids. Application of an electric field, typically a DC field of 50 to 200 volts or more, causes migration of charged molecules or molecular complexes through a separation medium. There are two main classes of electrophoretic techniques, capillary and gel electrophoresis. In gel electrophoresis, the separation medium is a hydrogel, usually agarose or polyacrylamide. The gel is typically immersed in electrophoresis buffer, for example Tris-Acetate-EDTA (TAE). In capillary electrophoresis, the separation medium may include a buffer and a linear polymer, such as linear polyacrylamide.
In the practice of gel electrophoresis, application of a greater electric field will effect a more rapid separation, thereby increasing the convenience and reducing the cost of the technique. Application of an electric field during electrophoresis to the electrophoresis buffer causes Joule heating, which increases the temperature of the electrophoretic gel and puts a limit on the level of voltage that can be applied. If too high a voltage is used, the excess heat will distort the electrophoretic separation and may degrade molecules in the sample and gel. It is known in the art to cool an electrophoresis buffer tank by performing the experiment in a refrigerated cold-room or through the use of a plastic cooling core through which a cold heat transfer fluid travels. This cooling allows use of a higher voltage and results in faster separations.
In a first embodiment of the invention there is a temperature regulation system that includes a polished surface that is sufficiently smooth surface to reduce emissivity of the surface less than or equal to 6%. The system has a conduit, in fluid communication with a source of coolant fluid. The conduit is in thermal proximity to the polished surface. Cooled fluid is circulated through the conduit so as to transfer heat from the surface to the coolant fluid therein.
The coolant fluid may be a compressible refrigerant fluid and the apparatus may include a refrigeration assembly adapted to cool the refrigerant fluid and to circulate the fluid through the conduit so as to cool the surface to a given temperature.
The refrigeration assembly may include a miniature rotary compressor having a height of less than 15.5 cm, or 9.4 cm. the refrigeration assembly may be located remotely from the surface and may be connected to the conduit via a tubing assembly.
The refrigeration assembly may be integrally connected to the surface via a connection to a common base. In a specific embodiment, the surface may be disposed above the based on no more than 12 cm. In another specific embodiment the refrigeration assembly extends from the base by no more than 18 cm.
In a related embodiment emissivity of the surface is less than or equal to 4%. In another related embodiment, the surface may be a polished aluminum oxide layer that is disposed on a metallic aluminum substrate.
In a further embodiment the system may have a resistive heating element. The resistive heating element may be sprayed-on resistor.
In yet a further embodiment the system may include a block having at least one recess adapted to hold a laboratory vessel or device. The block has a flat bottom surface so as to establish efficient thermal contact with placed atop the polished surface. The recess may have been emissivity of greater than 50%. The block may be constructed from an aluminum substrate in the recesses may be black anodized. In a related embodiment, the block holds a laboratory device such as, a dialysis cell, a chromatography column, a dry-ice maker and a recirculation conduit.
An embodiment of the invention provides an apparatus for temperature control of an electrophoresis buffer in an electrophoresis tank. The tank is designed for electrophoresis having, for example, electrodes and fixtures for holding electrophoresis gels. At least one of the walls is a heat transfer wall that includes an electrically conductive material and is coated with a durable thermally conductive, but electrically nonconductive coating.
The heat transfer wall may be positioned in fluid communication with the electrophoresis buffer. The heat transfer wall may be a bottom wall. The heat transfer wall is typically coupled to a heat sink. Examples of suitable heat sinks include a recirculating chiller or a thermoelectric device. The heat transfer wall may include a passageway, such as a tortuous passageway, for the flow that the transfer fluid. The transfer fluid may be a liquid or gas, and if a liquid, may be pumped by a peristaltic pump.
The coating may be a spray coating and may cover the entire heat transfer wall. The spray-coating may include aluminum oxide or aluminum nitride. The coating may be applied by chemical or physical vapor deposition, by porcelainzing, or be powder coating with plastic. The interior of the heat transfer wall may advantageously be a metal, such as copper, steel, aluminum, titanium, nickel, or silver. The interior may also be a metal alloy. The interior may also be a semi-metal, or a cermet. The thickness of the coating may be greater than 1 micron.
A buffer stirring mechanism may be included in the apparatus and may be a magnetic mechanism for driving a stir-bar.
The apparatus may have a cooling core. The cooling core sits in, and removes heat from, the electrophoresis buffer tank. The cooling core may have a passageway, which may be tortuous, for the flow of heat transfer fluid such as may be pumped from a recirculating chiller. The recirculating chiller may include a peristaltic pump to urge the transfer fluid through the passageway.
An embodiment of the invention features an apparatus for the temperature control of an electrophoresis buffer that has a buffer holding tank, a cooling core with a passageway for the flow of heat transfer fluid, and a heat transfer block. The device may include a least one electrophoresis electrode and may include a positioning system for the positioning of a separation medium such as a slab gel. The heat transfer block may be a wall of the buffer holding tank and may be, on an interior side, in fluid communication with the electrophoresis buffer.
Another embodiment provides a method for manufacturing an electrophoresis buffer tank by coating an electrically conductive material with a thermally conductive but electrically nonconductive coating to form a heat transfer wall. The wall is incorporated into an electrophoresis assembly.
The foregoing features of the invention will be more readily understood by reference to the following detailed description, taken with reference to the accompanying drawings of embodiments, in which:
a is a schematic diagram of a benchtop heat transfer block with a remote compressor;
c schematically shows a cross sectional view of a heat transfer platen in accordance with
b schematically shows a heat transfer block with tortuous heat transfer fluid conduit;
a-4c show various embodiments of heat transfer blocks;
d schematically shows a cross sectional view of a heat transfer block in accordance with
a to 5d show frames for holding heat transfer blocks in accordance with embodiments of the invention;
a is a schematic top view diagram of the integrated device of
b is a schematic side view diagram of the integrated device of
c is a schematic top view diagram of the integrated device of
d is a schematic side view diagram of the integrated device of
It should be noted that, unless otherwise indicated in the figures or accompanying text, the foregoing figures and the elements depicted therein are not necessarily drawn to a consistent scale or to any scale.
Definitions. As used in this description and the accompanying claims, the following terms shall have the meanings indicated, unless the context otherwise requires:
“Emissivity” shall mean a measure of the flux of thermal radiation of surface in air. Emissivity is expressed herein as a percentage of the theoretical maximum flux at room temperature.’
In accordance with an illustrative embodiment of the invention, a heat transfer surface is polished to create a low emissivity, that is, it radiates heat poorly. Accordingly, the surface may be cooled without undue use of energy and without causing an excess of condensation to collect on it. Adaptations may be included to ensure a uniform degree of cooling across the surface. The surface may be incorporated into a programmably temperature controlled system. By using such a system to control the temperature and placing an object on the surface, the object can be heated, cooled, or held at a given temperature. One or more resistive heaters may also be included and used to elevate the temperature of the surface, and may temporarily work against a cooler, and may elevate the temperature above ambient. Illustrative commercial uses for the surface include commercial food preparation, and pastry making. Illustrative laboratory uses include static or dynamic temperature control of dissection samples, analytical devices (including electrophoresis tanks and chromatography columns), storage containers, laboratory vessels (e.g., beakers, flasks, and reagent troughs), and arrays of vessels (e.g., test-tube racks, and microplates). A further embodiment features a low-profile, integrated heat transfer surface and heat pump.
a diagrammatically shows a heat transfer platen 6 with a highly polished, low emissivity heat transfer surface. The platen 6 is resting on a bench 7 and connected to a refrigeration assembly 2 via a connecting tube assembly 8 that carries refrigerant to and from the plate 6. The refrigerant travels through a conduit (item 16 of
The platen 6 may be constructed of metal. For example, aluminum is a relatively good conductor of heat and is relatively low cost compared to other metals such as copper. The platen 6 is highly polished, e.g. mirror polished in order to impart a low emissivity. As a result, the platen 6 will absorb heat from the air at a reduced rate. However, when a user places a solid object on the platen, heat will be efficiently transferred from the solid object to the platen 6. The solid object may be a laboratory device, examples of which are described below, having a flat, polished, or mirror-polished mating surface to better thermally mate with the platen 6. The smoothness of the polished surfaces, for this and for other embodiments described herein, may be characterized by the center line average roughness Ra (as described, for example, in U.S. Pat. No. 5,744,401). The surface finish may be in the range of Ra=2000 nm to 0.15 nm or less, and more preferably in the range of 10 nm to 2000 nm, however, one of ordinary skill in the art may determine, for a given material, the Ra value needed to reach a thermal emissivity in air at 4° C. of less than or equal to 10%, 6%, 4%, or in a preferred embodiment, 3%.
c shows an embodiment in which the platen 6 has a multilayer structure composed of an internal material 17 and a coating layer 15. The outer coating layer 15 may be composed of an electrically and/or chemically resistant material with a high thermal conductivity (due to its composition, thickness or both). Potential coating layer 15 compositions include metals, metal oxides, and cermets. For example, the coating layer 15, may be aluminum oxide or aluminum nitride. In an embodiment of the present invention, the coating 15 is a sprayed-on ceramic coating, such as may be produced by thermal-spray coating. The thermally sprayed ceramic coating may be formed from of one or more materials derived from a metal such as a metal oxide or metal nitride. The sprayed-on coating should be dense and/or thick enough to provide durability. Suitably dense thermally sprayed coatings of materials such as aluminum oxide and aluminum nitride may be achieved by the use of a high-speed thermal spray device. Examples of high-speed thermal spray devices include those that operate at supersonic velocities, e.g., Mach 2 to Mach 3 or higher. Suitable systems are commercialized by, for example, Praxair of Danbury, Conn. The coating layer 15 may be polished to create a low emissivity in air, in which case the coating should be thick enough to permit polishing. The platen 6 may include a drip catcher to collect condensation; for example, a gutter-like flange around the circumference of the platen 6 and/or a desiccant holder.
The coolant delivery assembly 2 delivers a flow of cooled heat transfer fluid or refrigerant (an expanding and contracting fluid that is part of a heat-pumping cycle). The coolant delivery assembly 2 may be a recirculating chiller that uses a compressor-based system to cool a heat transfer fluid and a separate liquid circuit to pump the cooled heat transfer liquid to the platen 6. Alternately, the conduit may be part of a heat-pump circuit and evaporated refrigerant may travel through the conduit. The refrigerant may be chosen to be stable to elevated temperatures sufficient to allow boiling of aqueous liquids in vessels on the surface. In alternative embodiments described below, the coolant delivery assembly 2 is integrated, as part of a common structure, with the platen 6. The coolant delivery assembly 2 may include a temperature control panel 4, which may allow the input of desired temperature and optionally, timing, control parameters and may have a display for the output of measured temperature, set temperature, set timing parameters, fault conditions, and the like. Alternately, the system may be controlled via a separate computer.
a schematically shows an exploded view of a platen 6, in accordance with a more specific embodiment of the invention. A base 20 supports multiple levels of structures below a temperature controlled plate 12 having a low-emissivity upper surface (e.g., polished to a 3% emissivity). A magnetic mixing mechanism 22 employs electromagnets to create an alternating magnetic field sufficient to rotate a stirbar or the like in a vessel positioned above the platen. A layer of insulation 18, such as a foam, may thermally isolate the electrical components to prevent damage to those component from condensation, and to conserve energy. The conduit 16 may be a may be a tortuous line to give uniform and rapid heat transfer, as in
In another embodiment, a platen is composed or 5 layers (listed in order from bottom to top),
1) A lower chilled metal layer (e.g., an aluminum paten with a cooling conduit),
2) An insulating dielectric layer such as aluminum oxide, which may be sprayed on,
3) An heater, which may be a sprayed-on resistive heater,
4) A second insulating layer (e.g., sprayed on aluminum oxide)
5) An upper plate with an upper polished, low emissivity surface.
a though 4c show several embodiments of receptacle blocks 34 which have cavities 36 suitable for holding laboratory vessels such as test-tubes, microfuge tubes, dialysis cartridges and the like. The cavities may also be large enough to hold a chromatography column, or electrophoresis buffer (described below with reference to
In related embodiments, blocks 34 may include a receptacle for an ice bath, a vortex chiller for making dry-ice, a dialysis chamber holder, a lyophilizer, and a magnet for separating magnetic particles from a liquid.
a through 5c show several frames that may be positioned on the platen 6 to hold blocks 34 of various shapes and sizes. The frames may be constructed of an insulating material.
a is a top view and 7b is a side-view schematic of an integrated device 50 in accordance with an embodiment of the invention. The dimensions are 14 inches (35.6 cm) long, by 12 inches (30.5 cm) wide. The platen height above the base 60 is 2.4 inches (6.1 cm) and the uppermost surface of the refrigeration assembly 2 is 3.7 inches (9.4 cm) above the base 60.
d is a side-view schematic. The device 50 includes a cold plate 6, compressor, condenser, fan(s), power supply, magnetic mixer drive, and control circuitry.
In related embodiments, the device 50 can accept input from a sensor (e.g., a pH or conductivity probe, spectrometer or fluorimeter) and change temperature settings based on that input to effect a chemical process. An imaging system may be used to monitor phase transitions such as melting, freezing or crystallization of a substance positioned in thermal contact with the platen 6. A valve or manifold may also be included to divert heat transfer fluid or refrigerant to another process; e.g., cooling a column, or oven.
The heat transfer block may be any wall of the tank 110. For example, as shown in
To further increase the efficiency of cooling of the electrophoresis unit 120, a stirring mechanism is provided in accordance with an embodiment of the invention. Among other things, this stirring mechanism may be a propeller and shaft with a motor or, as shown in
In an embodiment of the present invention, the durable coating 510 is a sprayed-on ceramic coating, such as may be obtained by thermal-spray coating. The thermally sprayed ceramic coating may be formed from of one or more electrically resistive materials derived from a metal such as a metal oxide or metal nitride. For example, the coating materials may include aluminum oxide or aluminum nitride. The sprayed-on coating should be dense enough to provide electrical insulation and durability, as described above. Suitably dense thermally sprayed coatings of materials such as aluminum oxide and aluminum nitride may be achieved by the use of a high-speed thermal spray device. Examples of high-speed thermal spray devices include those that operate at supersonic velocities such as around Mach 2 to Mach 3 or higher. Suitable systems are commercialized by, for example, Praxair of Danbury, Conn.
A second way of forming the durable coating 510 is by using a porcelainzing process. A ceramic coating 510 may be applied by coating the block interior component 520 with a powdered ceramic and heating to fuse the powder into a durable coating 510. The fused ceramic coating 510 may include glass.
Combinations of plastics and ceramics may also be used to increase thermal transfer rates. The durable coating can also be made of a thermoplastic by a powder coating technique. Thermoplastic particles may be applied to the surface of the interior block 520 in a powder form and thermally or chemically fused to form a durable electrically insulating coating 510. Electrically insulating particles may be included in the coating to enhance thermal conductivity. The electrically insulating particles should have a higher thermal conductivity than the plastic used and could include ceramic materials such as aluminum oxide.
A durable coating 510 may also be produced by other techniques. For example, chemical vapor deposition (CVD), plasma enhanced chemical vapor deposition, physical vapor deposition (PVD), or plating techniques such as electroplating may be used. Note that any of the processes for making the durable coating 510 may also be used to create the coating layer 15 of
The heat transfer block 100 also may have an interior passageway for the flow of a heat transfer fluid (liquid or gas). The fluid will remove heat in a manner similar to that described with reference to cooling core shown in
The on-board electrophoresis power supply of the integrated device 700 may provide DC current. The electrical parameters are typically in the range of 50-3000 volts of potential, 0.1-2 amperes of current, and 75-400 watts of power. Electrical connection to one or more sets of electrophoresis electrodes may be provided by electrical output jacks 730, into which electrode leads are plugged-in during use.
Various controls and read-outs (e.g. LED or LCD displays) are included, typically on a faceplate 720 of the device 700. A switch 740 turns the device 700 on and off. A mode button 785 toggles between constant current, constant potential, and constant power modes. A constant current, potential (voltage), or power setting may be entered using buttons electrical control buttons and an electrical setting display 765. The actual current or potential is shown by an electrical reading display 785. Temperature control buttons 750 and a temperature display 755 are used to adjust and/or monitor the temperature settings. A stirring mechanism (e.g., actuation of a stir-bar 410) may be toggled on and off with a stir-bar power button 795, the speed of the stir-bar may be adjusted with stir-bar power buttons 798 and a stir-bar setting display 797.
Although the above discussion discloses various exemplary embodiments of the invention, it should be apparent that those skilled in the art can make various modifications that will achieve some of the advantages of the invention without departing from the true scope of the invention.
This application claims priority from the following U.S. Provisional Patent Applications: Ser. No. 60/781,892 for “Electrophoresis Buffer Cooling” filed Mar. 13, 2006 (Attorney Docket No. 3094/103); Ser. No. 60/786,047 for “Remote Bench Top Compressed Air Refrigeration System for Laboratory Use” received by the U.S.P.T.O. on Mar. 27, 2006 (filed pro se); and Ser. No. 60/796,493 for “Electrophoresis Buffer Cooling” filed May 1, 2006 (Attorney Docket No. 3094/106).
Number | Date | Country | |
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60781892 | Mar 2006 | US | |
60786047 | Mar 2006 | US | |
60796493 | May 2006 | US |