Relative Humidity Control Apparatus

Abstract

A relative humidity control apparatus for control of the relative humidity in a gas space has a nebulizer source with an outlet for nebulized liquid, a frame surrounding an open area and comprising an opening arrangement to the open area and in operational flow connection with the outlet, and a flow drive arrangement generating a gas flow from the outlet to and out of the opening arrangement. A liquid handling robot comprising this apparatus, a method of operating the apparatus, an immunoassay method and methods of controlling the time course of the relative humidity in a gaseous space and of producing a predetermined volume of a liquid are also disclosed.

Claims

1. A relative humidity control apparatus (100) for control of the relative humidity in a gas space comprising a nebulizer source having an outlet (12) for nebulized liquid, a frame (30), preferably a frame forming a closed loop, surrounding an open area and comprising an opening arrangement (33) to said open area and in operational flow connection with said outlet, a flow drive arrangement (50) generating a gas flow from said outlet to said and out of said opening arrangement, characterized in that the frame (30) comprises at least one groove (34), said at least one groove being open towards said open area and wherein at least a part of said opening arrangement (33) is provided opposite a wall of said groove (34).

2. The control apparatus of claim 1, said nebulizer source comprising a container (10) and an ultrasonic nebulizer arrangement (20) operationally connected to said container.

3. The control apparatus of one of claims 1, said flow drive arrangement (50) comprising a pressure source generating a pressure gradient from said outlet (12) to said open space via said opening arrangement (33), preferably a blower, preferably with a blower output operationally connected to an input opening (11) to said container (10).

4. The control apparatus (100) according to claim 1, wherein said groove (34) extends all along said frame.

5. The control apparatus (100) according to claim 1 further comprising a second container (14) flow-interconnected between said outlet (12) and said opening arrangement (33).

6. The control apparatus (100) according to claim 1, wherein the frame defines a plane and is preferably substantially circular or substantially rectangular.

7. The control apparatus (100) according to claim 1, wherein said open space is one-side limited by a wall one of adjacent to and of on said frame, said wall comprising preferably a titer plate with wells exposed to said open space.

8. The control apparatus (100) according to claim 1, comprising a holder for an exchangeable plate said plate on said holder one-side limiting said open space surrounded by said frame.

9. The control apparatus (100) according to claim 1, wherein the apparatus comprises at least one of at least one humidity sensor (60) and of at least one temperature sensor operationally connected to said open space, at least one of said sensors being preferably provided on or adjacent said frame.

10. The control apparatus (100) according to claim 1, wherein said flow drive arrangement (50) comprises at least one of a fan, a piston pump, a rotary vane pump.

11. The control apparatus (100) according to claim 1, comprising a source of a dry gas, preferably at least one of a hygroscopic substance and of a pressurized gas tank with dry gas, preferably with at least one of dry air and of nitrogen, and in controllable operational flow connection with said open space, controllable by means of an adjustable flow controller arrangement.

12. The control apparatus (100) according to claim 1, further comprising a control unit (70), wherein an input to the control unit (70) is operationally connected to at least one humidity sensor (60) and a control output of said control unit is operationally connected to a control input of at least one of the nebulizer source, of the flow drive arrangement (50) and of a dry gas source to said open space.

13. Method of operating the control apparatus (100) according to claim 1, wherein pulse width modulation is applied to control the time average power delivered to at least one of the nebulizer source and of the flow drive arrangement (50).

14. A liquid handling robot comprising a control apparatus (100) for control of relative humidity according to claim 1.

15. A liquid handling robot according to claim 14 comprising at least one pipetting unit and wherein the at least one pipetting unit is operative through said open space.

16. A liquid handling robot according to claim 14 comprising at least one washing unit having a pair of pipette tips configured to simultaneously dispense into and aspirate from the same well.

17. Method of establishing a predetermined relative humidity in a gaseous space to which an object is exposed and through which the object is treated including a mechanical manipulation in said gaseous space, the method involving the steps of placing a frame around said object and in proximity or on said object, said frame comprising at least one groove open towards said gaseous space, feeding nebulized water into said groove, distributing said nebulized water in said groove by performing said feeding towards and onto a wall of said groove, feeding said distributed nebulized water into the gaseous space surrounded by said, controlling at least one of the amount of nebulized water and of a dry gas fed per time unit to said gaseous space.

18. The method of claim 17 wherein said controlling is performed by a negative feedback control loop, wherein the prevailing relative humidity in said gaseous space is monitored as a controlled variable.

19. The method according to claim 17, wherein the object is a titer plate (80) carrying liquid samples (81), in particular a microtiter plate or a nanotiter plate, wherein preferably form and dimension of the frame (30) match the form and dimension of the outer contour of the titer plate (80).

20. An immunoassay method, particular a radioimmunoassay (RIA) method or an immunofluorescence assay (IFA) method, or a magnetic immunoassay (MIA) method, or an enzyme immunoassay (EIA) method or an enzyme linked immunosorbent assay (ELISA) method, or of a genome expression profile analysis method, comprising an incubation step including the method according to claim 17.

21. An immunoassay apparatus, particular a radioimmunoassay (RIA) apparatus or an immunofluorescence assay (IFA) apparatus, or a magnetic immunoassay (MIA) apparatus, or an enzyme immunoassay (EIA) apparatus or an enzyme linked immunosorbent assay (ELISA) apparatus, or of a genome expression profile analysis apparatus, comprising an incubation unit including the control apparatus of claim

1.

22. A method of producing a predetermined volume of a liquid comprising at least one liquid component, comprising the steps of: I. providing a predetermined volume of the liquid comprising the at least one liquid component and with a surface exposed to a gaseous atmosphere unsaturated at least with respect to said one liquid component II. manipulating said liquid of said volume during a predetermined manipulation time exposed to said atmosphere and III. maintaining said volume of liquid constant during said time span by providing a buffer-atmosphere between said volume of liquid and said unsaturated atmosphere, said buffer atmosphere being kept saturated at least with respect to said liquid component by nebulizing a liquid which is equal to said liquid component and feeding said nebulized liquid in a distributed manner upon the surface of said volume, wherein said distributed manner is realized by feeding the nebulized liquid into a groove provided in a frame surrounding said volume and towards and onto a wall of said groove.

Description

[0059] The invention shall now be further exemplified with the help of figures. The figures show:

[0060] FIG. 1 a schematic view of the apparatus according to the invention;

[0061] FIG. 2 a schematic view of an embodiment of the apparatus according to the invention;

[0062] FIG. 3 a schematic view of an embodiment of the apparatus according to the invention;

[0063] FIGS. 4.a) and 4.b) are cross-sectional views through an embodiment of the frame of the apparatus

[0064] FIG. 4.a) a cross-section along a horizontal plane

[0065] FIG. 4.b) a cross-section perpendicular to the plane in 4.a).

[0066] FIG. 5 shows a perspective view of a frame of the apparatus together with a titer plate and a pipette.

[0067] FIG. 1 shows in a partially cross-sectional, partially perspective view, schematically and simplified, a relative humidity control apparatus according to the invention. A first container 10 contains water 13. Small water droplets are formed above the water surface when an ultrasonic nebulizer 20 is switched on and transmits ultrasonic waves into the water. The ultrasonic nebulizer is arranged in the first container. A flow drive arrangement 50 in form of a pump is placed in front of an air inlet 11 of the first container 10. Air is taken in from the outside of the container and flows into an air duct 40 carrying with it the small water droplets. These small water droplets quickly evaporate, thereby increasing the relative humidity of the air. The air having increased relative humidity flows through an air inlet 33 in the frame 30. The air inlet 33 leads through the outer wall 31 of the frame. In the region enclosed by the frame 30 an equilibrium forms between the humidity of the air flowing through the air inlet of the frame and the humidity of the air surrounding the frame.

[0068] FIG. 2 shows in a partially cross-sectional, partially perspective view, schematically and simplified, a relative humidity control apparatus of an embodiment of the invention. A first container 10 contains water 13. Small water droplets are formed above the water surface when an ultrasonic nebulizer 20 is switched on and transmits ultrasonic waves into the water. The ultrasonic nebulizer is arranged in the first container. A flow drive arrangement 50 in form of a pump is placed in front of an air inlet 11 of the first container 10. Air is taken in from the outside of the container and flows into an air duct 40 carrying with it the small water droplets. These small water droplets quickly evaporate, thereby increasing the relative humidity of the air. The air having increased relative humidity flows through an air inlet 33 in the frame 30. This air inlet is not directly visible in the current view. Dashed lines in this figure mark the air inlet 33. The air inlet 33 leads into a groove separating an outer wall 31 and an inner wall 32 of the frame. In order to help distinguishing inner wall 31 and outer wall 32, they are marked by oblique and vertical hatching, respectively. The air inlet 33 lies behind the inner wall in this view. The air flows inside the groove along the perimeter of the opening surrounded by the frame 30 and enters into the opening by flowing below the lower edge of the inner wall. In the region enclosed by the frame 30 an equilibrium forms between the humidity of the air flowing through the air inlet of the frame and the humidity of the air surrounding the frame.

[0069] FIG. 3 shows in a partially cross-sectional, partially perspective view, schematically and simplified, an embodiment of the relative humidity control apparatus according to the invention. In addition to the elements already present in FIG. 2, this embodiment further comprises a second container 14, a humidity sensor 60, a control unit 70, a first power supply 71 and second power supply 72. In this embodiment, the frame 30 has the form of ring such that an opening in the form of a circle results.

[0070] In order to help distinguishing inner wall 31 and outer wall 32, they are marked by oblique and vertical hatching, respectively. The air inlet 33 lies behind the inner wall in this view and is marked by dashed lines. The humidity-enriched air leaving the first container through the air outlet 12 is guided into the second container 14 by means of a first section 40 of the air duct. In this second container 14, the residual water droplets have time to evaporate completely. This second container has no other openings than the air inlet 15 and the air outlet 16, such that the same amount of air entering at the air inlet 15 leaves through the air outlet 16 and flows through the second section 40 of the air duct and through the air inlet 33 of the frame 30. A humidity sensor 60 is arranged at the inner wall 31 of the frame 30. The resulting relative humidity can be monitored by means of this humidity sensor. The control unit 70 is operatively connected to the humidity sensor 60, the first power supply 71 and the second power supply 72. This connection is indicated by dash-dotted lines. The operative connection may be implemented as electrical wire connection, but it may as well be a connection established by transmitting optical or radio signals. The control units receives signals from the humidity sensor transmitting the current humidity at the sensor position. Based on this value, the power supplies may be switched on and off or the power of the ultrasonic nebulizer or the volume flow of the pump may be adjusted. This way a negative feedback control loop is possible. With the help of such a negative feedback control loop the relative humidity inside the frame 30 can be kept constant on a predetermined value.

[0071] FIGS. 4.a) and 4.b) show cross-sectional views through an embodiment of the frame of the apparatus. In this embodiment, the frame encloses an opening of rectangular form. FIG. 4.a) and FIG. 4.b) show cross sections through two mutually perpendicular planes.

[0072] FIG. 4.a) shows a cross-section along a horizontal plane. This horizontal plane lies above the lower edge of the inner wall, such that the plane cuts through both walls, the inner wall 31 and the outer wall 32. The plane also cuts through the air inlet 33 of the frame, which at this level enters into the groove 34 separating the inner and the outer wall. The frame 30 encloses a clear opening in the form of a rectangle. The position marked with a dash-dotted line and the reference sign B is the position of the cross-section shown in FIG. 4.b).

[0073] FIG. 4.b) shows the arrangement of the inner wall 31 and the outer wall 32 separated by the groove 34. In dotted lines the possible position of a titer plate 80 carrying liquid samples 81 is shown. In this case, the titer plate is a planar titer plate having hydrophobic coating separating the individual wells. The liquid samples have the form of droplets sitting on the titer plate. The space above the titer plate is supplied by humidity-enriched airflow entering through the air inlet 33 of the frame and being distributed through the groove 34. A humidity sensor 60 is arranged close to the surface of the titer plate and in proximity of the air inlet 33. Positioning means near the lower edge of the outer wall define the position of the titer plate 80. The position marked with a dash-dotted line and the reference sign A is the position of the cross-section shown in FIG. 4.a).

[0074] FIG. 5 shows a perspective view on a frame 30 of the apparatus together with a titer plate 80 carrying liquid sample 81 droplets and a pipette 82. FIG. 4 illustrates the use of the inventive apparatus to prevent evaporation of samples while allowing free access to the individual sample positions on a titer plate by a pipette. The pipette visible here may be a part of a pipetting unit of a liquid handling robot as well as of a manually operated pipette. Humidity controlled air enters through the air inlet 33 and homogenously distributes in the circular opening of the frame accommodating the titer plate 80. In this embodiment, the titer plate 80 has the form of a disc. A hydrophobic coating (not displayed in the figure) separates the individual wells on the disc from each other and prevents the sample droplets from flowing together. A humidity sensor 60 is arranged on the inside of the frame 30 in a position close to the surface of the titer plate 80. With the humidity sensor placed in this position, it is possible to monitor the relative humidity in the atmosphere surrounding the samples.

[0075] Some further technical details not specific to a certain figure are addressed in the following. The ultrasonic nebulizer 20 can e.g. be built as a piezo-electric actuator. A heater and/or a cooler may be comprised in the apparatus to control the temperature of the water in the first container. The flow drive arrangement 50 for creating an airflow through the air duct may be arranged in an other position than shown in FIGS. 1, 2 and 3. It can be positioned anywhere along the path of airflow between the air inlet of the first container to the air inlet of the frame in order to perform its function. The air duct 40 may be a tube made of flexible material. The frame can for example consist of a metallic material and be coated in order to protect it from corrosion. It may be made of stainless steel, or a plastic material.

LIST OF REFERENCE SIGNS

[0076] 10 First container [0077] 11 inlet [0078] 12 outlet for nebulized liquid [0079] 13 water [0080] 14 second container [0081] 15 inlet of second container [0082] 16 outlet of second container [0083] 20 ultrasonic nebulizer arrangement [0084] 30 frame [0085] 31 outer wall [0086] 32 inner wall [0087] 33 opening arrangement (of the frame) [0088] 34 groove [0089] 40 air duct [0090] 40 first section of the air duct [0091] 40 second section of the air duct [0092] 50 flow drive arrangement [0093] 60 humidity sensor [0094] 70 control unit [0095] 71 first power supply [0096] 72 second power supply [0097] 80 titer plate [0098] 81 liquid sample [0099] 82 pipette [0100] 100 relative humidity control apparatus