Device for carrying out chemical reactions

• US 6,989,133 B1
• Filed: 12/16/1999
• Issued: 01/24/2006
• Est. Priority Date: 12/30/1998
• Status: Expired due to Fees

• Current Assignee: MWG-Biotech AG (Eurofins Scientific SE)
• Original Assignee: MWG-Biotech AG (Eurofins Scientific SE)
• Inventors: Heimberg, Wolfgang, Weichselgartner, Michael
• Primary Examiner(s): JOHNSON, JONATHAN J
• Application Number:
  US09/869,230
• Time in Patent Office: 2,231 Days
• Field of Search: 422/62, 422/63, 422/64, 422/131, 422/188
• US Class Current: 422/131
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00319 the blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00326 Movement by rotation
• CPC Class Codes: B01J 2219/00337 Valves
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00394 in multiple arrangements
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries

Abstract

The invention relates to an apparatus for the conduct of chemical reactions, comprising:

• • a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,
  • a selector slider located on the upper surface of the reaction slider and having at least one continuous control orifice, wherein the selector slider is movable relative to the reaction slider in such a way that its control orifice may be brought into alignment with one of the reaction chambers of the reaction slider, so that a through connection to supply the reaction chamber with a predetermined reagent may be made, and
  • a chemical slider, located beneath the reaction slider and provided with passages to supply chemicals to the individual reaction chambers of the reaction slider.

The invention is distinguished on the one hand by a device to apply a predetermined force to the sliders and on the other hand by a valve assembly by means of which chemicals may be supplied to the chemical slider in premixed form.

Claims

1. An apparatus for conducting chemical reactions comprising:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved relative to the chemical slider by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made, and

a device is provided for applying a force to the sliders in order to seal their contact faces, this device is acting on a connecting rod, which extends through central openings in the sliders, so that a force, which is applied by the device for applying a force to the sliders, acts in the area of the axis of rotation.

2. Apparatus according to claim 1, wherein the reaction slider and the selector slider are plate-shaped, in particular in the form of an annular disc.

3. Apparatus according to claim 1, wherein the selector slider and the reaction slider are driveable independently of one another.

4. Apparatus according to claim 1, wherein the device for applying pressure to the sliders may be driven electrically.

25. The apparatus according to claim 4, wherein the device for applying pressure to the sliders is a combined spring and magnet mechanism which presses a pressure piston against a pressure plate, with the sliders being arranged between the pressure plate and a stationary drive housing.

26. The apparatus according to claim 1, wherein a drive unit with a stationary cylindrical drive housing and two concentric hollow shafts arranged one inside the other, on which the reaction slider and the selector slider may be non-rotatably fitted.

27. The apparatus according to claim 26, wherein the connecting rod extends through the hollow shafts and is pivotally connected, at the end furthest from the pressure piston, to a rocker arm which is pivotally connected at its other end to the device for applying pressure to the sliders.

5. An apparatus for conducting chemical reactions comprising:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made,

a device, provided for applying a force to the sliders in order to seal their contact faces, the device acting on a connecting rod, which extends through central openings in the sliders, so that a force, which is applied by the device for applying a force to the sliders, acts in the area of the axis of rotation,

wherein the device for applying pressure to the sliders is an electrically driven combined spring and magnet mechanism which presses a pressure piston against a pressure plate, with the sliders being arranged between the pressure plate and a stationary drive housing.

6. An apparatus for conducting chemical reactions comprising:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made; and

,

a device, provided for applying a force to the sliders in order to seal their contact faces, the device acting on a connecting rod, which extends through central openings in the sliders, so that a force, which is applied by the device for applying a force to the sliders, acts in the area of the axis of rotation,

wherein a drive unit with a stationary cylindrical drive housing and two concentric hollow shafts arranged one inside the other, on which the reaction slider and the selector slider may be non-rotatably fitted.

7. An apparatus for conducting chemical reactions comprising:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made; and

,

a device, provided for applying a force to the sliders in order to seal their contact faces, the device acting on a connecting rod, which extends through central openings in the sliders, so that a force, which is applied by the device for applying a force to the sliders, acts in the area of the axis of rotation,

wherein a drive unit with a stationary cylindrical drive housing and two concentric hollow shafts arranged one inside the other, on which the reaction slider and the selector slider may be non-rotatably fitted, and

wherein the connecting rod extends through the hollow shafts and is pivotally connected, at the end furthest from the pressure piston, to a rocker arm which is pivotally connected at its other end to the device for applying pressure to the sliders.

8. Apparatus for conducting chemical reactions, comprising:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made, and

one or more of the feed holes connected to a chemical feed line, which is connected to a valve assembly, via which at least two different chemicals may be supplied to the feed hole.

9. Apparatus according to claim 8, wherein the valve assemblies have at least two valves, each controlling the supply of a reagent.

10. Apparatus according to claim 8, wherein the valve assembly has a multiway valve which is switched alternately between the feed hole and at least two branch lines in such a way that the feed hole can be brought into communication with one of the two branch lines.

11. Apparatus according to claim 10, wherein the multiway valve is located directly on the chemical slider.

12. Apparatus for the conduct of an oligonucleotide synthesis, with several reaction chambers into which reagents may be metered, wherein there is provided a display unit with a window for each reaction chamber, wherein a significant value for the quality of the reaction proceeding in a particular reaction chamber is displayed in each of the individual windows.

13. Apparatus according to claim 12, wherein an optical sensor is provided to detect the light transmittance of the intermediate and end products produced in the reaction chambers.

14. Apparatus according to claim 13, wherein the optical sensor is mounted directly adjacent to the selector slider.

15. Apparatus according to claim 12, wherein the significant value for the reactions is the correlation coefficient R of measured values of a light transmittance measurement of the intermediate and end products.

16. Apparatus according to claim 15, wherein the significant value for the reactions is the absolute value of the correlation coefficient R of measured values of light transmittance measurement of the intermediate and end products.

17. Apparatus according to claim 15, wherein in each case the most recent value in the calculation of the correlation value is weighted more heavily than the other measured values.

18. Apparatus according to claim 12, wherein the apparatus for the conduct of an oligonucleotide synthesis comprises:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made, and

a device is provided for applying a force to the sliders in order to seal their contact faces, this device is acting on a connecting rod, which extends through central openings in the sliders, so that a force, which is applied by the device for applying a force to the sliders, acts in the area of the axis of rotation.

19. Apparatus according to claim 12, wherein the apparatus for the conduct of an oligonucleotide synthesis comprises:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made, and

one or more of the feed holes is or are connected to a chemical feed line, which is connected to a valve assembly, via which at least two different chemicals may be supplied to the feed hole.

20. An assembly having several apparatuses for conducting chemical reactions comprising:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made, and

a device is provided for applying a force to the sliders in order to seal their contact faces, this device is acting on a connecting rod, which extends through central openings in the sliders, so that a force, which is applied by the device for applying a force to the sliders, acts in the area of the axis of rotation,

wherein there is provided a common supply unit for reagents, with several storage vessels, wherein the storage vessels are provided with a level indicator, and a level monitoring device automatically monitors the levels of the individual storage vessels.

21. Assembly according to claim 20, wherein the common supply unit is also designed to supply gas and electrical power.

24. The assembly according to claim 20 wherein the reaction slider and the selector slider may be moved relative to the chemical slider.

22. Assembly with several apparatuses for the conduct of chemical reactions comprising:

a reaction slider in which are formed a multiplicity of through holes serving as reaction chambers,

a selector slider located on a side of the reaction slider at which the reaction chambers emerge, and having a continuous control orifice, wherein the selector slider is movable relative to the reaction slider,

a chemical slider, located on the opposite side of the reaction slider to the selector slider, wherein feed holes for the supply of chemicals emerge on the surface of the chemical slider facing the selector slider, and the reaction chambers of the reaction slider and the feed holes of the chemical slider are arranged along an orbit, and the reaction slider and the selector slider may be so moved by rotation around a common axis of rotation which passes through the centre point of the orbit that one of the feed holes, one of the reaction chambers and the control orifice may be brought into alignment, so that a through connection to supply the reaction chamber with a predetermined reagent may be made, and

one or more of the feed holes is or are connected to a chemical feed line, which is connected to a valve assembly, via which at least two different chemicals may be supplied to the feed hole,

wherein there is provided a common supply unit for reagents, with several storage vessels, wherein the storage vessels are provided with a level indicator, and a level monitoring device automatically monitors the levels of the individual storage vessels.

23. Assembly according to claim 22, wherein the common supply unit is also designed to supply gas and electrical power.