EP1377379B1 - Incubator system provided with a temperature control system - Google Patents

Incubator system provided with a temperature control system Download PDF

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Publication number
EP1377379B1
EP1377379B1 EP02750535A EP02750535A EP1377379B1 EP 1377379 B1 EP1377379 B1 EP 1377379B1 EP 02750535 A EP02750535 A EP 02750535A EP 02750535 A EP02750535 A EP 02750535A EP 1377379 B1 EP1377379 B1 EP 1377379B1
Authority
EP
European Patent Office
Prior art keywords
incubator
thermal
array
thermal resistance
resistance barrier
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP02750535A
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German (de)
French (fr)
Other versions
EP1377379A1 (en
Inventor
Wilhelmus Marinus Carpaij
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PamGene BV
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PamGene BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by PamGene BV filed Critical PamGene BV
Priority to EP02750535A priority Critical patent/EP1377379B1/en
Publication of EP1377379A1 publication Critical patent/EP1377379A1/en
Application granted granted Critical
Publication of EP1377379B1 publication Critical patent/EP1377379B1/en
Anticipated expiration legal-status Critical
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices

Definitions

  • the invention pertains to an incubator system provided with a temperature control system.
  • Incubation systems are known in the art.
  • a substrate such as a metal oxide membrane having through-going oriented channels that can be manufactured cheaply through electrochemical etching of a metal sheet.
  • Such membranes have oriented channels with well controlled diameter and advantageous chemical surface properties.
  • the channels in at least one area of the surface of the electrochemically manufactured metal oxide membrane are provided with a first binding substance capable of binding to an analyte.
  • the metal oxide membrane may comprise aluminum oxide. Reagents used in these assays are immobilized in the channels of the substrate and the sample fluid will be forced through the channels to be contacted with the reagents.
  • the device comprises one or more round wells with a certain diameter, said wells exposing a substrate of a specific thickness, said substrate having oriented through-going channels, and the area of the substrate exposed in the well being provided with at least one binding substance specific for at least one of said analytes.
  • An amount of sample fluid is added to one or more of the wells of the device, the amount of added sample fluid being calculated on the basis of the dimensions of the wells and the substrate.
  • An alternating flow is generated through the substrate in the wells whereby the liquid volume of sample fluid is forced to pass through the channels in the substrate from the upper side of the substrate to the lower side of the substrate and back at least one time, under conditions that are favorable to a reaction between an analyte present in the sample and the binding substances.
  • any signal generated in any of the wells is read and from said signals the presence, amount, and/or identity of said one or more analytes are determined.
  • a transparent material such as a glass cover
  • the wells can be analyzed and the reading signal can be determined through the glass.
  • WO01/08800 discloses an incubator according to the preamble of claim 1: In this incubator, condensation on the transparent cover is prevented by the use of a resistance heater coated on the cover.
  • the present invention therefore provides an incubator system provided with a temperature control system as defined in claim 1.
  • the incubator system comprises a casing 1 made of a metal or another heat-conducting material and a wall 2 that is partially or wholly transparent. These transparent parts are made of glass or transparent plastics, such as Plexiglass®, and the like. The transparent parts are at least situated above the wells, so that the sample signal can be determined.
  • the system comprises a chamber 14, which contains as a substrate an array-membrane holder system with an array-membrane 3 and a holder 4 comprising wells 5, having for instance a cylindrical structure wherein the sample can be introduced.
  • the array-membranes are known as such, for instance from EP 0 975 427.
  • the array-membrane holder comprising the wells can be made of any material, for instance, metals or plastics.
  • the incubator system may further comprise one or more switching means 10, in order to select the array cuvettes in which the sample flow is to be driven by a pressure control system (not further shown).
  • At least one heater 6 is required to keep the temperature within well defined narrow ranges. The temperature is measured by one or more temperature sensors 11.
  • the heater 6 can be any sort of heater, but usually it is electrically driven, such as by means of a spiral filament.
  • the heater 6 and the temperature sensor(s) 11 are connected to a controller (not shown), so that a temperature control system with feedback loop is obtained.
  • the incubator system further comprises a thermal resistance barrier.8 that is provided between the transparent wall 2 and the array-membrane holder 4.
  • This thermal resistance barrier separates the array-membrane holder from the transparent wall.
  • a thermal flow is generated for keeping the temperature constant within the array-membrane holder system.
  • a circulating thermal flow is generated.
  • This thermal flow results in a heat flow in the direction from the thermal resistance barrier 8 to the array-membrane holder 4.
  • a thermal flow system 7 which may comprise a heat pump, a heat exchanger, or preferably, a Peltier element.
  • the space between the thermal resistance barrier and the array-membrane holder is filled by a metal or another heat-conducting material 13, which may be different or the same as the metal or the heat-conducting material 1.
  • the thermal resistance barrier can have a single-layered structure or a multi-layered structure, each layer being made of any well chosen heat-resistant material that has suitable heat capacitance characteristics such that the instrument can be controlled in two ways, i.e., the temperature height at sample level, and the temperature gradient in and between the different sections of the incubator system.
  • the thermal resistance barrier can be made of any heat-resistant material.
  • one or more organic polymeric materials are used, such as polyvinylchloride, polycarbonate, and the like. When multi-layered structures are used, a combination of such materials can be applied.
  • the heating system 9 in the embodiment of the Figure 1 and 2 consists of a heating element in series with, for instance, a Peltier element.
  • the latter will generate a circulating heat flow through the incubator system such that the temperature of the transparent wall (i.e., the cover) will always be higher than the temperature of the sample volume, notwithstanding major cooling effects across the transparent cover towards ambient temperature.
  • the temperature sensor 11 is preferably located on the casing 1 near the array-membrane holder. Because of the relatively high heat conductance characteristics of the aluminum surrounding (if an aluminum casing is used) the array-membrane temperature accuracy of the array-membrane and the sample fluid will be high throughout the chamber.
  • the heater and the system for providing the thermal flow are positioned together in the heating system.
  • the heater and the system for providing the circular thermal flow, together as the heating system, are thermally isolated from the array-membrane holder and the thermal resistance barrier by using thermal isolation material 12. According to the invention the heating system is held in such isolation material to provide a sufficient heat stream from the thermal resistance barrier to the array-membrane holder.
  • the usual thermal isolation material that is known to the skilled man can be used therefor.

Abstract

The invention pertains to an incubator system provided with a temperature control system comprising a chamber (13) that is suitable for housing a substrate (3,4), and at least one wall that is partially or wholly transparent (2), characterized in that the incubator system comprises a heater (6), a system for providing a thermal flow (7), and a thermal resistance barrier (8) that thermally separates the chamber and the partially or wholly transparent wall.

Description

  • The invention pertains to an incubator system provided with a temperature control system.
  • Incubation systems are known in the art. For instance, in WO 01/19517 an incubator system was disclosed suitable for comprising a substrate such as a metal oxide membrane having through-going oriented channels that can be manufactured cheaply through electrochemical etching of a metal sheet. Such membranes have oriented channels with well controlled diameter and advantageous chemical surface properties. When used in an assay the channels in at least one area of the surface of the electrochemically manufactured metal oxide membrane are provided with a first binding substance capable of binding to an analyte.
  • The metal oxide membrane may comprise aluminum oxide. Reagents used in these assays are immobilized in the channels of the substrate and the sample fluid will be forced through the channels to be contacted with the reagents.
  • The device comprises one or more round wells with a certain diameter, said wells exposing a substrate of a specific thickness, said substrate having oriented through-going channels, and the area of the substrate exposed in the well being provided with at least one binding substance specific for at least one of said analytes. An amount of sample fluid is added to one or more of the wells of the device, the amount of added sample fluid being calculated on the basis of the dimensions of the wells and the substrate. An alternating flow is generated through the substrate in the wells whereby the liquid volume of sample fluid is forced to pass through the channels in the substrate from the upper side of the substrate to the lower side of the substrate and back at least one time, under conditions that are favorable to a reaction between an analyte present in the sample and the binding substances. Any signal generated in any of the wells is read and from said signals the presence, amount, and/or identity of said one or more analytes are determined. When the upper wall of said incubator is covered by a transparent material, such as a glass cover, the wells can be analyzed and the reading signal can be determined through the glass. It goes without saying that it is advantageous to close the incubator at the side of the wells to prevent contamination and an uncontrolled process. When closed, the well must remain visible to enable measurement of the generated signals. A problem is then that water that is present in the incubator system condenses onto the walls that are relatively cold. The condensation of the water onto a glass cover seriously decreases the transparency thereof, thereby hampering the determination of the signals.
  • WO01/08800 discloses an incubator according to the preamble of claim 1: In this incubator, condensation on the transparent cover is prevented by the use of a resistance heater coated on the cover.
  • It is an object of the present invention to provide a solution and to prevent condensation of water onto the transparent wall.
  • The present invention therefore provides an incubator system provided with a temperature control system as defined in claim 1.
  • The invention is further explained by reference to the drawings. Of course, it is clear that the invention is not restricted to these embodiments which can be varied in a number of ways within the scope of the claims.
    • Fig. 1 shows a cross-section of an embodiment of the invention.
    • Fig. 2 shows in more detail the incubator system of the embodiment of Fig. 1.
  • Referring to the figures there is shown an embodiment of the incubator system of the invention. Generally, the incubator system comprises a casing 1 made of a metal or another heat-conducting material and a wall 2 that is partially or wholly transparent. These transparent parts are made of glass or transparent plastics, such as Plexiglass®, and the like. The transparent parts are at least situated above the wells, so that the sample signal can be determined. The system comprises a chamber 14, which contains as a substrate an array-membrane holder system with an array-membrane 3 and a holder 4 comprising wells 5, having for instance a cylindrical structure wherein the sample can be introduced. The array-membranes are known as such, for instance from EP 0 975 427. The array-membrane holder comprising the wells can be made of any material, for instance, metals or plastics. The incubator system may further comprise one or more switching means 10, in order to select the array cuvettes in which the sample flow is to be driven by a pressure control system (not further shown). At least one heater 6 is required to keep the temperature within well defined narrow ranges. The temperature is measured by one or more temperature sensors 11. The heater 6 can be any sort of heater, but usually it is electrically driven, such as by means of a spiral filament. Preferably, the heater 6 and the temperature sensor(s) 11 are connected to a controller (not shown), so that a temperature control system with feedback loop is obtained.
  • The incubator system further comprises a thermal resistance barrier.8 that is provided between the transparent wall 2 and the array-membrane holder 4. This thermal resistance barrier separates the array-membrane holder from the transparent wall. In the system shown a thermal flow is generated for keeping the temperature constant within the array-membrane holder system. A circulating thermal flow is generated. This thermal flow results in a heat flow in the direction from the thermal resistance barrier 8 to the array-membrane holder 4. Such a thermal flow is provided by a thermal flow system 7, which may comprise a heat pump, a heat exchanger, or preferably, a Peltier element.
  • The space between the thermal resistance barrier and the array-membrane holder is filled by a metal or another heat-conducting material 13, which may be different or the same as the metal or the heat-conducting material 1.
  • The thermal resistance barrier can have a single-layered structure or a multi-layered structure, each layer being made of any well chosen heat-resistant material that has suitable heat capacitance characteristics such that the instrument can be controlled in two ways, i.e., the temperature height at sample level, and the temperature gradient in and between the different sections of the incubator system. The thermal resistance barrier can be made of any heat-resistant material. Preferably, one or more organic polymeric materials are used, such as polyvinylchloride, polycarbonate, and the like. When multi-layered structures are used, a combination of such materials can be applied.
  • The heating system 9 in the embodiment of the Figure 1 and 2 consists of a heating element in series with, for instance, a Peltier element. The latter will generate a circulating heat flow through the incubator system such that the temperature of the transparent wall (i.e., the cover) will always be higher than the temperature of the sample volume, notwithstanding major cooling effects across the transparent cover towards ambient temperature.
  • The temperature sensor 11 is preferably located on the casing 1 near the array-membrane holder. Because of the relatively high heat conductance characteristics of the aluminum surrounding (if an aluminum casing is used) the array-membrane temperature accuracy of the array-membrane and the sample fluid will be high throughout the chamber. The heater and the system for providing the thermal flow are positioned together in the heating system. The heater and the system for providing the circular thermal flow, together as the heating system, are thermally isolated from the array-membrane holder and the thermal resistance barrier by using thermal isolation material 12. According to the invention the heating system is held in such isolation material to provide a sufficient heat stream from the thermal resistance barrier to the array-membrane holder. The usual thermal isolation material that is known to the skilled man can be used therefor.

Claims (6)

  1. An incubator system provided with a temperature control system, the incubator system comprising:
    (i) a casing (1) including an upper part and a lower part both made of heat-conducting material, and at least one wall (2) that is partially or wholly transparent covering said upper part ;
    (ii) a heater (6) in contact with said upper part of the casing (1);
    the incubator system being characterised in that it further comprises:
    (iii) an array-membrane holder (4) with wells (5), the holder (4) being housed in a chamber (14) defined between upper and lower parts of the casing (1), wherein the transparent parts of the said wall (2) are at least situated above the wells (5);
    (iv) a thermal resistance barrier (8) provided between the upper part of the casing and the array-membrane holder (4);
    (v) a heat-conducting material (13) filling the space between said thermal resistance barrier (8) and said array-membrane holder (4);
    (vi) a heating system (9) consisting of the heater (6) and a thermal flow system (7) wherein said thermal flow system (7) comprises a heat pump, or a heat exchanger, or a Peltier element, with said thermal flow system (7) being in series with said heater (6) and being in contact with the said lower part of the casing;
    (vii) thermal isolation material (12) thermally isolating said heating system (9) from said array-membrane holder (4) and said thermal resistance barrier (8); so that a thermal circulating flow is generated through the incubator system resulting in a heat flow in the direction from the said thermal resistance barrier (8) to the said array-membrane holder (4), said thermal flow system ensuring that the temperature of said transparent wall (2) is always higher than the temperature of the sample volume defined by said wells of said holder (4).
  2. The incubator system of claim 1, wherein the thermal resistance barrier (8) has a single- or multi-layered structure.
  3. The incubator system of any of claims 1 or 2, wherein the thermal resistance barrier (8) is made of polyvinylchloride, polycarbonate, or a combination thereof.
  4. The incubator system of claim 2, wherein the layers of the thermal resistance barrier (8) are chosen such as to control the temperature at sample level or the temperature gradient in and between the different sections of the incubator system.
  5. The incubator system of any of claims 1-4, wherein the transparent wall is made of glass.
  6. The incubator system of any of claims 1-5, wherein the system further comprises a heat sink provided at the lower side of said casing (1).
EP02750535A 2001-03-13 2002-03-05 Incubator system provided with a temperature control system Expired - Lifetime EP1377379B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02750535A EP1377379B1 (en) 2001-03-13 2002-03-05 Incubator system provided with a temperature control system

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP01200948 2001-03-13
EP01200948 2001-03-13
PCT/EP2002/002448 WO2002072266A1 (en) 2001-03-13 2002-03-05 Incubator system provided with a temperature control system
EP02750535A EP1377379B1 (en) 2001-03-13 2002-03-05 Incubator system provided with a temperature control system

Publications (2)

Publication Number Publication Date
EP1377379A1 EP1377379A1 (en) 2004-01-07
EP1377379B1 true EP1377379B1 (en) 2006-10-18

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ID=8180011

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02750535A Expired - Lifetime EP1377379B1 (en) 2001-03-13 2002-03-05 Incubator system provided with a temperature control system

Country Status (5)

Country Link
EP (1) EP1377379B1 (en)
JP (1) JP2005509128A (en)
AT (1) ATE342771T1 (en)
DE (1) DE60215477T2 (en)
WO (1) WO2002072266A1 (en)

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2835477A (en) * 1955-05-02 1958-05-20 Tovrog Theodore Temperature control apparatus and method
US4427415A (en) * 1979-01-05 1984-01-24 Cleveland Patrick H Manifold vacuum biochemical test method and device
FI833076A0 (en) * 1983-08-30 1983-08-30 Labsystems Oy ANORDNING FOER MAETNING AV UPPVAERMBARA VAETSKEPROV
DE3815528C1 (en) * 1988-05-06 1989-08-10 W.C. Heraeus Gmbh, 6450 Hanau, De
EP0615783A1 (en) * 1993-03-16 1994-09-21 Resona Innovation Ag Protector for rotary evaporator
US6337435B1 (en) * 1999-07-30 2002-01-08 Bio-Rad Laboratories, Inc. Temperature control for multi-vessel reaction apparatus
US6657169B2 (en) * 1999-07-30 2003-12-02 Stratagene Apparatus for thermally cycling samples of biological material with substantial temperature uniformity
US6383748B1 (en) * 1999-09-14 2002-05-07 Pamgene B.V. Analytical test device with substrate having oriented through going channels and improved methods and apparatus for using same

Also Published As

Publication number Publication date
EP1377379A1 (en) 2004-01-07
WO2002072266A1 (en) 2002-09-19
JP2005509128A (en) 2005-04-07
ATE342771T1 (en) 2006-11-15
DE60215477D1 (en) 2006-11-30
DE60215477T2 (en) 2007-08-30

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