Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
  • G01N35/1079—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices with means for piercing stoppers or septums
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
  • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
• • G—PHYSICS
  • G05—CONTROLLING; REGULATING
  • G05D—SYSTEMS FOR CONTROLLING OR REGULATING NON-ELECTRIC VARIABLES
  • G05D7/00—Control of flow
  • G05D7/06—Control of flow characterised by the use of electric means
  • G05D7/0617—Control of flow characterised by the use of electric means specially adapted for fluid materials
  • G05D7/0629—Control of flow characterised by the use of electric means specially adapted for fluid materials characterised by the type of regulator means
  • G05D7/0676—Control of flow characterised by the use of electric means specially adapted for fluid materials characterised by the type of regulator means by action on flow sources
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L13/00—Cleaning or rinsing apparatus
  • B01L13/02—Cleaning or rinsing apparatus for receptacle or instruments
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2300/00—Additional constructional details
  • B01L2300/08—Geometry, shape and general structure
  • B01L2300/0809—Geometry, shape and general structure rectangular shaped
  • B01L2300/0825—Test strips
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
  • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
  • B01L2400/0478—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure pistons
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2400/00—Moving or stopping fluids
  • B01L2400/04—Moving fluids with specific forces or mechanical means
  • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
  • B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
  • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
  • B01L3/50255—Multi-well filtration
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L9/00—Supporting devices; Holding devices
  • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips

Definitions

• the present invention relates to a system for controlling the flow of a fluid, in particular a sample fluid, through a substrate having first and second surfaces and at least one area with a plurality of through-going capillary channels.
• a system of this type is described in PCT/US00/24885.
• a controlled pressure difference In this system means are provided for applying and/or maintaining a sufficient amount of time a controlled pressure difference.
• the pressure difference can be regulated by a programmable unit.
• the invention aims to provide an improved system of this type.
• the system comprises a housing having a chamber for receiving the substrate, means for generating a pressure difference over the substrate to trans- port the fluid from the first to the second surface or vice versa through the channels of said at least one area, and means for maintaining the pressure difference at a controlled level during the transport of the fluid through the channels.
• the means for generating a pressure difference comprises means to change the volume of the chamber, wherein the maintaining means comprises a pressure measuring device and a control device to operate the volume changing means .
• Fig. 1 schematically shows an embodiment of the system of the invention.
• Fig. 2 shows a cross-section of the housing of the system of fig. 1, wherein a substrate is accommodated in the housing.
• Fig. 3 shows a perspective view of an example of the substrate shown in cross-section in fig. 2.
• Fig. 4 shows a cross-section of the housing of fig. 2, wherein a washing device is placed on the housing.
• a system for controlling the flow of a sample fluid through a substrate 1 which is shown in a perspective view by way of example in fig. 3.
• the substrate 1 is made as a laminated array- membrane comprising upper and lower outer layers 2 and an intermediate strip of aluminium oxide .
• the outer layers 2 are provided with four openings 3 , the openings 3 of the upper and lower layers 2 being aligned.
• the strip of aluminium oxide is exposed at four areas or wells 4.
• the strip of aluminium oxide comprises a large number of through-going capillary channels oriented mainly perpendicular to the upper and lower surfaces of the strip. The capillary pressure of the channels is very high.
• the channels in the strip of aluminium oxide may have a spacing of approximately 150-200 nm, wherein a binding substance is bound to the substrate in groups of channels at a spacing of 200 ⁇ m.
• a group of channels can be indicated as a dot or dot area.
• Each area 4 of the substrate 1 may have approximately 400 dots.
• the system shown in figs. 1 en 2 comprises a housing 5 having an upper housing part 6 and a lower housing part 7.
• the upper and lower housing parts 6,7 determine a chamber 8 for re- ceiving the substrate 1.
• the substrate 1 is received in the chamber 8 together with a holding device 9 which includes an upper and lower structure 10 and 11, respectively.
• Both upper and lower structures 10, 11 are provided with four cylindrical extensions 12 mainly aligned with the ar- eas 4 of the substrate 1.
• the holding device 9 is made of a plastic material.
• the device 9 is further described in a co- pending patent application "Device for holding a substrate" of the same applicant.
• the chamber 8 comprises cylindrical chamber sections 13 in the upper and lower housing parts 6, 7, in which the cy- lindrical extensions 12 are received.
• these cylindrical chamber sections 13 are interconnected by a channel 14 providing a connection between the cylindrical chamber sections 13 and the environment of the housing 5, so that an ambient pressure reference is available in these upper cylindrical chamber sections 13.
• the cylindrical chamber sections 13 are also interconnected by a channel 15.
• the channel 15 is connected to a means for generating a pressure difference over the substrate 1.
• the means for generating a pressure difference over the substrate 1 is made as means to change the volume of the chamber 8, in this case the part of the chamber 8 under the substrate 1.
• the means for generating a pressure difference are implemented as a cylinder piston assembly 16 schematically shown in fig. 1.
• a sample fluid 17 is schematically shown in two cylindrical extensions 12 of the device 9, so that only at the corresponding areas 4 of the substrate 1 the sample fluid can be passed through the capillary channels of the substrate 1.
• two cylindrical chamber sections 13 are sealed with respect to the channel 15 so that a pressure difference over the substrate 1 is only generated at the areas 4 where a sample fluid 17 is present .
• the system shown in fig. 1 is provided with means 19 for maintaining the pressure difference over the substrate at a controlled level during the transport of the sample fluid 17 through the capillary channels.
• said means 19 will be implemented in a programmable processing unit.
• the pressure difference is maintained at a constant level dur- ing the transport of the sample fluid.
• the processing unit 19 comprises means for setting a desired pressure difference.
• the means for generating a pressure difference over the substrate to transport the sample fluid 17 from the upper surface of the substrate 1 to the lower surface is implemented as a cylinder piston assembly 16 having a piston 20 which is moveable by means of a schematically indicated ac- tuator 21.
• This actuator 21 or control device is controlled by the processing unit 19 in dependence on the pressure in the chamber 8 as measured by means of a schematically indicated pressure measuring device 22.
• the processing unit 19 starts to generate a pressure difference over the substrate 1 by generating in the chamber 8 under the substrate 1 a pressure lower than the ambient pressure. This pressure difference transports the sample fluid 17 through the capillary channels of the substrate 1 so that the sample fluid 17 will gradually be transported towards the lower cylindrical extensions 12 of the lower structure 11. This would result in an increase of the pressure in the chamber 8 under the substrate 1 and this pressure increase is measured by the measuring device 22. In view of this pressure increase as measured by the processing unit 19, the processing unit 19 operates the actuator 21 to displace the piston 20 to maintain the pressure difference at a constant level .
• the sample fluid 17 is transported through the capillary channels of the substrate 1 in an accurately determined time period.
• the sample fluid 17 should be transported through the capillary channels of the substrate 1 a number of times in order to allow for a sufficient binding action of the binding substance in the capillary channels of the substrate 1.
• the time for reversing the transport is reduced by monitoring the operation of the processing unit 19 for maintaining the pressure difference at a constant level.
• the processing unit stops to operate the actuator 21 for maintaining the pressure difference at a constant level, the pres- sure difference over the substrate is changed immediately in such a manner that the sample fluid 17 is transported in the reverse direction from the lower surface of the substrate 1 towards the upper surface through the capillary channels.
• the piston 20 is displaced in the opposite direction by the actuator 21.
• the sample fluid 17 is transported towards the upper surface of the substrate 1.
• the pressure in the chamber 8 under the substrate 1 would decrease and this is measured by the measuring device 22.
• the processing unit 19 operates the actuator 21 to displace the piston 20 to maintain the pressure difference at a constant level. In this manner the sample fluid 17 can be transported in opposite directions through the capillary channels of the substrate 1 in a minimum time period.
• the processing unit 19 is adapted to measure the change of volume required to transport the sample fluid 17 completely through the capillary channels from the upper to the lower surface and vice versa.
• the change of volume can be measured for example by measuring the displacement of the piston 20.
• This change of volume should be constant for each transport step of the system, i.e. each time the sample fluid 17 is transported from the upper to the lower surface or vice versa. If the change of volume required to completely transport the sample fluid varies, this is an indication that a leak is present somewhere in the system so that the system should be checked by an operator.
• the processing unit 19 can provide a warning indication to signal an operator a variation in the change of volume.
• the processing unit 19 can measure the change of volume required to transport the sample fluid completely through the capillary channels of the substrate 1 in order to compare this change of volume with the initial volume of the sample fluid 17 provided in the cylindrical extensions 12.
• This initial volume can be provided as an input to the processing unit 19.
• the processing unit 19 could also be used to automatically provide a predetermined initial volume in the cylindrical extensions 12 for performing an assay. If a difference between the initial volume and the required change of volume is measured, this is also an indication of a leak in the system. This difference can be indicated by the processing unit 19 to warn an operator.
• the processing unit 19 can measure the time to transport the sample fluid through the capillary channels of the substrate 1, i.e. the flow rate.
• this time or flow rate varies this is an indication that an air bubble or a contamination is blocking at least a part of the capillary channels.
• the processing unit 19 can determine the flow rate and/or the time required to transport an amount of the sample fluid through the substrate. Any deviation from the expected time or flow rate can be used as an indication of an error situation.
• the system described shows the advantage that a washing operation to clean the capillary channels of the substrate 1 can be carried out in an easy manner. According to fig. 4 a washing device 23 is placed on top of the housing 5 after re- moval of an upper glass cover 24 normally located on top of the housing 5.
• the glass cover allows a direct vision on to the upper surface of substrate areas 4 during transport of the sample fluid 7 through the channels.
• the washing device 23 is provided with washing fluid feed and discharge tubes 25 and 26. Washing is performed in a programmable manner.' For example, a washing fluid can be can be fed on top of the substrate 1, the washing fluid can be transported through the capillary channels of the substrate 1 a number of times and the washing fluid can be discharged. Discharging of the washing fluid may occur for example in a continuos flow at a slightly higher rate than feeding. If the processing unit 19 generates a positive pressure under the substrate 1 the washing fluid will stay on top of the substrate 1.
• the washing fluid By generating a negative pressure under the substrate 1, the washing fluid is transported through the capillary channels of the substrate 1 to the lower side in the same manner as described for a sample fluid. By reversing the pressure difference the washing fluid is transported back to the upper side of the substrate 1 again. In this manner the capillary channels of the substrate can be cleaned in an efficient manner. Contamina- tion of the channel 15 is prevented as the washing fluid will not be pushed off of the lower side of the substrate 1.
• the washing device is connected to a source of washing fluid not shown by means of schematically indicated tubes 27. The washing operation is controlled by the processing unit 19.
• the invention is not restricted to the above-described embodiment which can be varied in a number of ways within the scope of the claims .

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• 2002
  • 2002-03-05 EP EP02704734A patent/EP1368122A1/de not_active Withdrawn
  • 2002-03-05 WO PCT/EP2002/002447 patent/WO2002072263A1/en active Application Filing
  • 2002-03-05 JP JP2002571215A patent/JP2004525758A/ja active Pending

Non-Patent Citations (1)

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