WO2005033714A1 - Compact dispenser - Google Patents
Compact dispenser Download PDFInfo
- Publication number
- WO2005033714A1 WO2005033714A1 PCT/SE2004/001423 SE2004001423W WO2005033714A1 WO 2005033714 A1 WO2005033714 A1 WO 2005033714A1 SE 2004001423 W SE2004001423 W SE 2004001423W WO 2005033714 A1 WO2005033714 A1 WO 2005033714A1
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- WIPO (PCT)
- Prior art keywords
- inlet
- liquid
- dispenser
- flow
- arrangement
- Prior art date
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Classifications
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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
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0241—Drop counters; Drop formers
- B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
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- 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
-
- 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
- B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
- B01L2300/0867—Multiple inlets and one sample wells, e.g. mixing, dilution
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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
- 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
- B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
- B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
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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
- 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
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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
- 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
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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
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/02—Burettes; Pipettes
- B01L3/0203—Burettes, i.e. for withdrawing and redistributing liquids through different conduits
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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
- B01L9/00—Supporting devices; Holding devices
- B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
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- 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
- G01N2035/1027—General features of the devices
- G01N2035/1034—Transferring microquantities of liquid
- G01N2035/1041—Ink-jet like dispensers
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- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N35/00069—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides whereby the sample substrate is of the bio-disk type, i.e. having the format of an optical disk
Definitions
- the present invention relates to novel methods and dispenser arrangements, dispenser systems and dispenser set ups that provide an improved interface between macro-world storage of liquids and microdevices.
- the invention enables reliable and reproducible dispensation of defined liquid aliquots to predetermined target areas (TAs) of a microdevice.
- TAs target areas
- the microdevic is typically in the form of a disc with a number of target areas in the same side of the disc.
- Microdevices typically permit parallel and/or serial processing of different or identical liquid aliquots in order to accomplish predetermined synthetic, preparative, analytical etc protocols within natural sciences, primarily biological and/or chemical sciences such as life science.
- the preferred microdevices are called microfluidic devices and provide enclosed microchannels for the transportation of the liquid aliquots.
- the devices and the process protocols are in the microformat by which is meant that the processed liquids are in the ⁇ l-range ( ⁇ 5,000 ⁇ l, such as ⁇ 1 ,000 ⁇ l or ⁇ 100 ⁇ l or ⁇ 10 ⁇ l), typically in the nl-range ( ⁇ 5,000 nl, nl-format) including also the picolitre-range ( ⁇ 5,000 pi, pl-format).
- the nl-format includes that at least one of the processed liquid aliquots has a volume ⁇ 5,000 nl, such as ⁇ 1 ,000 nl or ⁇ 500 nl or ⁇ 100 nl.
- Dispensation is drop-wise with drops that typically have volumes in the nl-range, preferably within the pl-range.
- miniaturization has been obvious and include possibilities to a) design devices in which the protocol can be carried out with a high degree of parallelism, b) provide compact arrangements and instrument set-ups, c) reduce the amount of reagents and samples needed, d) speed up the times needed per run of a protocol, e) increase the productivity with respect to number of runs per time unit, f) etc.
- Miniaturization has encountered problems with interfacing individual microdevices with macro-world storages of liquid e.g. liquids containing analytes, reagents, washing liquids, buffers etc.
- microdispenser arrangement for microdevices which comprised a housing with one or more flow through microconduits that via tubes are connected to liquid reservoirs and waste reservoirs to permit transportation of liquid through the arrangement.
- Each flow through microconduit has a dispenser orifice through which the liquid aliquots are drop-wisely dispensed to target areas that may be present on a microdevice.
- Pressure pulse actuating means is/are acting on the walls of the flow through microconduits in order to force droplets through the orifices.
- Reference (i) suggests various orientations of dispenser orifices and target areas relative to each other.
- the objects of the invention are to provide dispenser arrangements, dispenser instrument set-up, dispensing methods etc that provide improvements regarding the problems and/or advantages discussed herein.
- Figure 1 illustrates the instrument set-up and the dispenser arrangement of the invention used in the experimental part.
- Figure 2 illustrates a variant of the instrument set-up of figure 1.
- the priming arrangement and waste arrangements differ between the variants.
- Figure 3 illustrates another variant of the set-up of figure 1 , which presents a third variant of priming and waste arrangements.
- Figure 4 illustrates still another variant, which presents a fourth variant of priming and waste arrangements.
- Figure 5 illustrates the microchannel structures of the microdevice that has been used in the experimental part.
- the device is circular and has a size comparable to the CD-format.
- the first digit in a reference number refers to the number of the drawing.
- the last two digits refer to a particular feature and are typically the same for corresponding features in different drawings.
- the present inventors have recognized a number of different principles that when applied, either alone or in combination, to flow through dispensation systems will assist in reducing the problems and enhancing the advantages discussed above. These principles relate to: a) Making the internal volume between a dispenser orifice and a storage for liquid as small as possible. b) Dispensing against gravity, i.e. upwards. c) Collecting the liquids to be dispensed from an essentially planar array of reservoirs containing different or identical liquids, for instance parallel collecting from selected reservoirs. d) Parallel dispensing from an array of dispenser orifices arranged for transfer of liquid to an array of target areas on a microdevice.
- the volumes (aliquots) of the liquids to be collected and dispensed may differ between reservoirs and between target areas, respectively. Volumes are in the ⁇ l- range as defined elsewhere in this text, with preference for the nl-range.
- tubes, conduits, channels, reservoirs, wells, orifices etc are connected to or communicate with each other shall mean that liquid is intended to be transported between them if not otherwise is apparent from the context (fluidly connected, in fluid communication etc).
- the primary goal is to reduce the internal volume of a dispenser arrangement and/or to facilitate transformation of the geometric arrangement of a number of liquid samples to the geometric arrangement of the target areas (100) of a microdevice (101).
- the aspect is a flow through dispenser arrangement (102) for drop-wise dispensation (103) of liquid and comprises: a) a housing (104) that comprises (i) a flow through microconduit (105) with an upstream end (106) and a downstream end (outlet) (107), and (ii) a dispenser orifice (108) between these two ends (106 and 107), b) pressure actuating means (109) associated with said housing (104) for dispensing drops (103) of liquid through the dispenser orifice (108), and c) an inlet tube (110) which is attached to the upstream end (106) and provides an inlet (inlet end) (111) that can be connected to a storage (112) for liquid (113) that is to be transported in the inlet tube (110) and flow through microconduit (105),
- the total inner volume (V to t) between the inlet (111) and the downstream end (107) and/or the total inner volume (V'tot) between the inlet (111) and dispenser orifice (108) are ⁇ 10 ⁇ l, such as ⁇ 5 ⁇ l or ⁇ 2 ⁇ l or ⁇ 1 ⁇ l.
- V to t and/or V't o t typically have a cross-sectional area (perpendicular to the flow direction) ⁇ 0.5 mm 2 , such as ⁇ 0.1 mm 2 or ⁇ 0.05 mm 2 or ⁇ 0.01 mm 2 .
- the length of a flow through microconduit (105) plus the inlet tube (110) (along the flow direction) is typically > 5 mm, such as > 10 mm, and/or ⁇ 200 mm, such as ⁇ 100 mm or ⁇ 50 mm or ⁇ 25 mm.
- Each flow through microconduit (105) may comprise one, two or more dispenser orifices (108). If there are two or more dispenser orifices (108) in a flow through microconduit (105), the inner volume V' to t is calculated from the most upstream of them.
- the inner volume (V cond ) of the flow through microconduit (105) is typically ⁇ 5 ⁇ l, such as ⁇ 2.5 ⁇ l or ⁇ 1 ⁇ l or ⁇ 0.6 ⁇ l or ⁇ 0.25 ⁇ l.
- the housing (104) may comprise one, two or more flow through microconduits (105).
- Each flow through microconduit (105) typically has a separate inlet tube (110) with an inlet opening (111). If there are two or more flow through microconduits (105), the inlet tube (110) for at least two of them may merge in the upstream direction to a common inlet (not shown).
- a flow through microconduit (105) may divide into microconduit branches within the housing (104) of the dispenser arrangement.
- Each daughter microconduit may have one, two or more dispenser orifices and/or a downstream end (outlet) that is separate from the downstream ends of other branches, and/or may rejoin with other branches within the housing and end in a common outlet end (not shown).
- the inner volume of the inlet tube (110) (V in ⁇ e t) is typically larger than the inner volume of the flow through microconduit to which it is connected.
- volume values (Vj n i et ) are found in the intervals ⁇ 10 ⁇ l, such as ⁇ 5 ⁇ l or ⁇ 2 ⁇ l or ⁇ 1 ⁇ l.
- the length of the inlet tube is typically larger than the length of the flow through microconduit. Suitable lengths are typically found in the interval > 5 mm, such as > 10 mm, and/or ⁇ 200 mm, such as ⁇ 100 mm or ⁇ 50 mm or ⁇ 25 mm.
- Ltot is the length in the flow direction between the outlet (106) and the inlet (111)
- L't ot is the length between the dispenser orifice (108) and the inlet (111)
- L cond is the length of the flow through microconduit (105).
- the inlet tube (110) comprises only one inlet (111) that is intended to be in fluid communication with a liquid storage (112) containing one, two or more reservoirs (114) for liquid (113), i.e the inlet tube has no branches with inlets for the introduction of liquids into the dispenser arrangement.
- An inlet thus typically is intended to be in direct fluid communication with a liquid reservoir (114).
- the inlet (111) may be connected to a tubing that in the upstream direction comprises a junction at which two or more flow tubes coming from separate liquid reservoirs merge. These latter liquid reservoirs may or may not be part of the liquid storage (112) (not shown).
- the downstream end (107) of the flow through microconduit (105) is for fluid connection to a waste arrangement (115), possibly via tubes that provide fluid communication with arrangements that have other functions.
- Other arrangements are one or more other flow through dispenser arrangements, a priming arrangement (116) (see below), a generator for liquid transport (generator I) (117) etc.
- the dispensation function is based on the presence of a dispensing actuator (109) that is associated with a dispensing orifice (108), for instance with the wall in close proximity of the orifice such as opposite to the orifice.
- the actuator typically creates pressure pulses in the liquid meaning that each pulse of sufficient amplitude and/or frequency will actuate pressure on the liquid and eject a droplet (103) through the dispenser orifice (108).
- the actuator (109) comprises a piezoelectric element, magnetorestrictive element, an element sensitive to externally applied pressure pulses etc enabling well-defined dispensing pulses.
- the desired size of droplets (103) is typically found in the range of 10 "6 - 10° ⁇ l, for instance ⁇ 5 x 10 "3 ⁇ l such as ⁇ 5 x 10 "4 ⁇ l with the lower limits being 1 x 10 "5 or 1 x 10 "4 ⁇ l.
- the dispenser orifice (108) may have different geometric forms, for instance circular, ellipsoid, oval and have otherwise rounded forms.
- the orifice may comprise a collection of minor holes or pores that in turn may be rounded and/or be delineated by straight sides. In this latter case the holes or pores are typically symmetrically arranged relative to the centre of the orifice.
- the diameter of the orifice is typically within 10-200 ⁇ m.
- the orifice may be in the form of a tip.
- the outer rim and typically also the surface surrounding the orifice are preferably hydrophobic (non-wettable).
- Pressure actuating means may be common for two or more dispensing orifices in the same flow through microconduit, in different microconduits or in different branches of the same microconduit .
- Suitable flow through drop dispenser arrangements are known from the publications given above (Laurell et al., Thomell et al, Tormod, Stjernstrom et al., Jesson et al, Andersson et al, and Ekstrand et al).
- the housing (108) has two or more flow through microconduits (105) each of which is connected to an inlet tube (110) with an inlet (111), i.e. two or more inlet tubes/inlets in one housing (104).
- the geometric configuration of the inlets relative to each other may be fixed or adjustable and adapted/adaptable to fit to the geometric configuration of an array of liquid reservoirs or to fit into one single common reservoir. Compare the array of reservoirs in the storage plate discussed elsewhere in this specification.
- the dispenser orifices typically have a geometric configuration relative to each other that fit the configuration of target areas on a microfluidic device.
- Each of the flow through microconduits may contain one, two or more dispenser orifices.
- This kind of dispenser head is extremely potent for parallel dispensation to an array of target areas from an array of liquid reservoirs having another or the same geometric configuration as the target areas, and will henceforth be called "transformation dispenser”. As indicated this kind of dispenser head can also be used for collecting liquid from a common reservoir into which two or more of the inlets can be dipped.
- the second aspect will be described based on figure 2 except for the microdevice, which will be described based on figure 5.
- the second aspect aims at designing compact systems for dispensation of liquids (203) to microdevices (201) of the kind described in this specification.
- the second aspect of the invention is an instrument set-up or a system (218) for the drop-wise dispensation (203) of liquid to target areas (200) that are present in the same side of a microdevice (201).
- the characteristic feature comprises: a) a flow through drop dispenser arrangement (202) comprising: one or more flow through paths (220) which each has (i) an outlet (221), (ii) an inlet (222), and (iii) a dispenser orifice (208) between the outlet (221) and the inlet (222), and b) a generator for liquid transport (transport generator I) (217) that is capable of causing transport of liquid through said flow through paths (220) in the direction from an inlet (211) to an outlet (221) by aspirating or pushing liquid.
- transport generator I generator for liquid transport
- the second aspect typically also comprises: a) a support (224), to which the microdevice (201) is retained, b) a waste arrangement (215), and c) a liquid storage (212) comprising one, two or more reservoirs (214) for storing liquid (213) to be dispensed to the microdevice (201).
- transport generator I is acting via the outlet end (221) by applying suction and/or subpressure to suck/pull liquid from a liquid reservoir (214) through the flow through path (220) via the inlet (222).
- the transport generator I is acting via the inlet (222) by applying overpressure gas to the liquid to be passed through the flow through path (220), e.g. in the reservoirs (214) of the liquid storage (212).
- A) the outlet (221) of the dispenser arrangement (202) is capable of being fluidly connected to the waste arrangement (215)
- the inlet (222) of the dispenser arrangement (220) is capable of being fluidly connected to one or more of the reservoirs (214) of the liquid storage (212)
- C) the dispenser orifice(s) (208) and the side comprising the target areas (200) of a microdevice (201) are turned against each other
- D) either one or both of the microdevice (201) and the dispenser orifice(s) (208) are movable relative to each other thereby enabling dispensation of liquid droplets (203) from a dispenser orifice (208) to one, two or more target areas (200).
- the orthogonal distance between a dispenser orifice (208) and the side of the microdevice (201) comprising the target areas (200) is typically within the interval 1-30 mm. This distance may be fixed, or adjustable. Adjustment is preferably by moving the support (224) towards or away from the dispenser orifice (208). See for instance WO 03035538 (Gyros AB). If there are two or more dispenser orifices (208) they are preferably at the same orthogonal distance from the microdevice (201). The dispensation direction from the orifice (208) is typically orthogonal to the microdevice side that contains the target areas (200).
- the openings of one or more of the reservoirs (214) of the liquid storage (212) are located on a planar side of a plate (storage plate, e.g. microtitre plate) (223).
- a plate storage plate, e.g. microtitre plate
- the side containing the openings of the reservoirs (214) is turned in a direction that is opposite to the direction of the microdevice side containing the target areas (200).
- the dispenser housing (204) is placed between the storage plate (223) and the microdevice (201) with the dispenser orifice (208) turned against the microdevice to provide an orthogonal dispensation direction towards the microdevice (201). See figures 1-4.
- the target areas (200) and the microdevice (201) are horizontally oriented while the dispensation direction is vertical, typically with the target areas (200) turned downwards combined with an upward dispensation direction (203).
- the liquid storage (212) in these latter variants is in the form of a plate (223) containing the reservoirs (214) in one of its sides, the opening of the reservoirs are typically turned upwards. If the openings of the reservoirs (214) are turned in other directions, e.g. up and down, they should be sealed unless they contain volumes that are sufficiently minute to be self-adhering to surfaces (i.e. inner surfaces of the reservoirs).
- Such volumes may be found in the interval, ⁇ 30 ⁇ l, such as ⁇ 15 ⁇ l or ⁇ 5 ⁇ l.
- a leakage-proof membrane that can be penetrated by the inlet (222) of the flow through path (220) can be used for sealing the reservoirs in order to prevent evaporation and/or other losses.
- the required movement of the target areas (200) and a dispenser orifice (208) relative to each other depends on the configuration of the target areas (200).
- Typical variants includes that the support (224) is linked to a rotor axis (219) or to an XN-robot (not shown) for circular or linear/lateral movements, respectively, of the target areas in front of the dispenser orifices.
- the circular movement caused by a rotor axis (219) can be combined with lateral movement of either the support/microdevice (224/201 ) and/or the dispenser orifices/dispenser (208/202) if the target areas (200) are located at different radial positions from the rotor axis (219).
- An alternative for an XN-robot to move the support would be a robot that separately could move the support/microdevice (224/201) and the dispenser/dispenser orifice (202/208).
- the drop dispenser arrangement (202) is according to the various embodiments that are outlined for the first aspect of the invention. This means that the inlet (222) and the outlet (221) of each flow through path (220) are equal to an inlet (211) and an outlet (207), respectively, of the dispenser arrangement of the first aspect (as shown in figures 1-4).
- the support (224) is capable of retaining a microdevice (201) during dispensation.
- the support also assists in individually aligning target areas (200) with dispenser orifices (208) of the dispenser arrangement (202).
- the term "align” in this context means that a target area (200) is in a position for receiving a droplet (203) ejected from a dispenser orifice (208), e.g. includes ejection while the target areas (200) are moving in front of a dispenser orifice (208), ejection while the target areas (200) are not moving, ejection when the dispenser orifices (208) are displaced relative to each other etc.
- WO 03035538 Gyros AB
- the support (224) may be in the form of a plate, holder and the like.
- the support (224) is linked to the appropriate arrangements (robotics) for moving the microdevice/target areas (201/200) as described above.
- Microdevice The microdevices that are used in the system of the invention are of the type indicated in the introductory part.
- Figure 5 shows a group (553) of microchannel structures (552) in a sector of a circular microfluidic device. The structures are linked together by a common distribution manifold. See below and WO 02074438 (Gyros AB), WO 02075312 (Gyros AB) and WO 0275775 (Gyros AB). See also PCT/SE2004/000440 (Gyros AB).
- a "target area” (TA) (500a,b) contemplates a discrete predetermined area for which the position co-ordinates relative to a reference point are known before dispensation.
- Chemical and/or physical barriers (550 and 551, respectively)) typically wholly or partly surround a target area in order to prevent undesired wetting around the target area.
- a chemical barrier may be in the form of hydrophobic patch (550).
- a physical barrier may be in the form of the inner walls (551) of a target area (500).
- a target area (500a,b) is linked to a microchannel structure (552) in which one or more liquid aliquots are transported and processed.
- the individual TAs (500a,b) typically have sizes ⁇ 2.5 x 10 1 mm 2 , such as ⁇ 10° mm 2 or ⁇ 10 "1 mm 2 or ⁇ 10 "2 mm 2 or ⁇ 10 "3 mm 2 .
- the lower limit is typically > 10 "5 mm 2 , such as ⁇ 10 "4 mm 2 or > 10 "3 mm 2 or > 10 "2 mm 2 .
- the microdevice (501) is typically in the shape of a disc.
- the microdevice (501) typically comprises one, two or more target areas (500) and/or microchannel structures (552), such as > 10, or > 50 or > 100 target areas and/or microchannel structures.
- the TAs and microchannel structures may be arranged in subgroups (553) such that all TAs in a subgroup are at the same X- or Y-co-ordinate or radial coordinate (shown).
- the TAs of a subgroup may be at the same radial co-ordinate (radial distance) but at different angular co-ordinates.
- the TAs may also be arranged in other configurations, e.g. in spiral-like manner around a C n -axis.
- microchannel structure contemplates that the structure comprises one or more cavities/chambers and/or channels that have a cross-sectional dimension that is ⁇ 10 3 ⁇ m, preferably ⁇ 10 2 ⁇ m.
- the volumes of cavities/chambers are typically ⁇ 1000 nl, such as ⁇ 500 nl or ⁇ 100 nl or ⁇ 50 nl or ⁇ 25 nl.
- the nl-range in particular applies to microcavities that are used for detection and/or for performing various reactions, such as enzymatic and/or affinity reactions including also cell reactions and separations and enzymatic reactions with a solid phase exhibiting an affinity reactant or an enzyme reactant placed in the microcavity.
- the transport of liquid within the microchannel structures (552) may be driven by various forces, for instance inertia force such as centrifugal force, electrokinetic forces, capillary forces, hydrostatic forces etc.
- Pumping mechanisms of various kinds may be used, for instance pumps.
- centrifugal force and/or capillary force are utilized for transporting liquids from an inlet port/target area (500a,b) into different individual fluidic functions of a microchannel structure (552).
- the disc (501) may be made from different materials, such as plastic material, glass, silicone etc. Polysilicone is included in plastic material. From the manufacturing point of view plastic material is many times preferred because this kind of material are normally cheap and mass production can easily be done, for instance by replication. Typical examples of replication techniques are embossing, moulding etc. See for instance WO 9116966 (Pharmacia Biotech AB, Ohman & Ekstrom). Replication processes typically result in open microchannel structures that are exposed in a substrate which subsequently is covered by a lid or top substrate, for instance according to the procedures presented in WO 0154810 (Gyros AB, Derand et al) or by methods described in publications cited therein.
- interior surfaces of the microchannel structures are typically hydrophilic by which is meant that the water contact angle of the surfaces deriving from the replicated part and/or a cover is at least ⁇ 90°.
- hydrophilic surfaces have water contact angles that are ⁇ 50°, such as ⁇ 40° or ⁇ 30° or ⁇ 20°.
- the basic criterion is that hydrophilicity should be sufficient to allow for self-suction of aqueous liquids into the microchannel structures, in particular from the inlet port. These ranges also apply to the hydrophilicity of target areas.
- the microchannel structures may also have inner surfaces that are hydrophobic, for instance at valve functions, anti-wicking functions and pure venting functions. See below. Surfaces that are not hydrophilic are hydrophobic, i.e. have a water contact angle > 90°.
- a target area/inlet port (500a,b) is fluidly connected to a microcavity (554,555), which is capable of retaining and/or metering a liquid volume in the nl-range.
- nl-range means ⁇ 5,000 nl including the pl-range ( ⁇ 5,000 pi) and typically is 5-1 ,000 nl, such as > 50 nl and/or ⁇ 750 nl.
- This kind of microcavity may be a metering microcavity (554,555) and is typically located in direct fluid communication and/or close to an inlet port (500a,b) and used for metering a liquid volume that is to be transported further downstream (556a,b) into the microchannel structure(s) that is(are) fluidly connected to the microcavity (554,555) and inlet port (500).
- a typical metering microcavity is in its downstream end delineated by a valve function (557,558) and in its upstream end has some kind of overflow system or overflow microconduit (559,560).
- the microcavity may thus be A) a single volume-metering microcavity (554) in the case the inlet port (500a) and the metering microcavity (554) are only connected to one microchannel structure (552) or B) a distribution manifold in the case the inlet port (500b) and the metering microcavity (555) are fluidly connected to two or more microchannel structures (552). If the microcavity (555) corresponds to a distribution manifold it will comprise one metering submicrocavity (555a, b,c.) per microchannel structure (552) associated with the inlet port target area (500b).
- the distribution manifold/microcavity (555) typically comprises a fluidic function between two neighbouring submicrovacities (555a,b,c.) that will assist in a reliable and reproducible partition of the metered volume into the different microchannel structures, e.g. hydrophobic patches (shown), vents to ambient atmosphere (561), upward bents (562) etc.
- the wettability of this kind of inlet arrangement should be sufficient to fill a metering microcavity (554,555) with liquid by capillarity or self-suction once liquid has been dispensed to the corresponding inlet port (500a,b).
- Preferred valves to be used at one or more of the positions within a microfluidic device as discussed herein are non-closing and are illustrated with passive valves or capillary valves in which the valving function often is based on a change in
- the change is local meaning that the interior surface upstream and downstream the valve function is wettable.
- the difference in wettability across a boundary of a passive valve used in the invention is typically > 30°, such as > 30° or > 40°.
- Suitable metering microcavities and non-closing valves are well-known in the literature. See for instance WO 0274438 (Gyros AB), WO 0308198 (Gyros AB) etc. See also the microfluidic device used in the experimental part.
- Waste arrangement generator for liquid transport (transport generator I), and priming arrangement.
- vacuum system includes appropriate "sub-pressure systems”.
- the generator for liquid transport (117) in this variant is a vacuum system (130) connected to the outlet (107) of the dispenser arrangement (102).
- the vacuum system is used for aspirating liquid through the dispenser arrangement (via the inlet (211 ) and for emptying the dispenser arrangement after dispensation.
- the vacuum system(130) may be part of the waste arrangement (115).
- the priming arrangement (116) is represented by a reservoir (131) for priming liquid and a syringe pump (132) used for introducing priming liquid via the outlet (107) of the dispenser arrangement (102).
- This variant illustrates that separate liquid moving systems can be used for moving priming liquid and liquids that are to be aspirated through the inlet (211).
- the generator for liquid transport (217) comprises in this variant a syringe pump (233) for aspirating liquid via the inlet (211,222) and a vacuum system (234) for subsequent emptying of the dispenser arrangement.
- the priming arrangement (216) comprises a separate reservoir (235) for priming liquid and a syringe pump (233) for introducing priming liquid via the outlet (207,221) of the dispenser arrangement.
- the waste arrangement (215) comprises a separate reservoir for waste (236) and possibly also reservoirs for waste within the vacuum system (234).
- the generator for liquid transport (317) comprises in this variant a syringe pump (337) for aspirating liquid via the inlet (311,322) and for subsequent emptying of the dispenser arrangement (302).
- the priming arrangement (316) comprises the same syringe pump (337) as the generator for liquid transport and a separate reservoir (338) for priming liquid.
- the waste arrangement (315) comprises a separate waste reservoir (339) linked to the syringe pump (337).
- the generator for liquid transport (417) comprises in this variant a separate syringe pump (440) for aspirating liquid through the dispenser arrangement (402) via the inlet (411 ,422).
- Emptying of the dispenser arrangement may be accomplished by the same syringe pump (440) or by a separate vacuum system (not shown) (part of generator for liquid transport).
- the syringe pump (440) is emptied into a separate waste reservoir (441) that is part of the waste arrangement (415).
- the priming arrangement (416) comprises a separate syringe pump (441) and a separate reservoir (442) for priming liquid.
- Appropriate valves are present at junctions in the tubings used for linking various parts of the waste arrangement, generator for liquid transport and priming arrangement to each other. See 143a,b and 244a,b and 345, and 446a,b,c.
- Waste arrangement is fluidly connected to the outlet (107,221,321,421) of the dispenser arrangement and typically comprises one or more reservoirs for waste liquids. These reservoirs may be common for two or more, preferably all of the outlets in the case the dispenser arrangements comprises a plurality of outlets.
- Waste liquid typically comprises liquids that have been allowed to enter the flow through path(s) but haven't been dispensed through the dispenser orifice(s) (reagents, sample possibly containing analyte, diluents, washing liquids, etc).
- the waste liquid may also comprise used priming liquids. Washing liquids in this context means liquids used to clean the flow through path(s) (105+110,220,320,420) and/or liquids used to wash the microchannel structures (552) of the microdevice (201).
- the waste arrangement comprises also suitable valves and tubings that are necessary to connect the waste reservoirs and/or the outlet(s) with each other. See above 143a,b and 244a,b and 345, and 446a,b,c.
- Valves and tubings may permit that waste liquid is collected in predetermined waste reservoirs.
- Liquid transport generator I is primarily for transporting samples, reagents, washing liquids and other liquids used in an intended process protocol.
- the generator causes transport from a reservoir (114,214,314,414) of the liquid storage (112,212,312,412) to the waste arrangement and is based on aspirating or pushing liquid from a reservoir (114,214,314,414) of the liquid storage through the inlet and further downstream to a waste reservoir of the waste arrangement.
- Aspirating in this context means that the liquid flow is driven by a pressure differential through the flow through paths.
- the differential provides reduced pressure at the outlet (107,221,321,421) of a flow through path (105+110,220,320,420) and/or in other appropriate positions downstream the outlet (107,221,321,421), e.g. in the waste reservoir(s).
- Aspirating is typically accomplished by a pumping mechanism that makes use of a pump selected amongst piston-driven pumps (e.g. syringe pumps), peristaltic pumps, electroosmotically driven pumps, membrane pumps, hydrostatic pumps, vacuum pumps (as part of a vacuum system linked to the waste arrangement) etc.
- the pumps may be with or without mechanical parts.
- the reduced pressure may in principle be created at any position downstream the outlet (107,221,321,421) as long as there is no disturbing leakage upstream the application of sub-pressure.
- Sub-pressure is typically initated within a waste arrangement.
- Pushing contemplates that the liquid transport is driven by a pressure differential that provides over-pressure at the inlet (111 ,222,322,422) of a flow through path (105+110,220,320,420).
- Pushing may be accomplished by having gas of elevated pressure acting on the surface of the liquid in the reservoirs (114,214,314,414) of the liquid storage (over pressure, typical relative to atmospheric pressure).
- gas of elevated pressure acting on the surface of the liquid in the reservoirs (114,214,314,414) of the liquid storage (over pressure, typical relative to atmospheric pressure).
- the liquid storage is in the form of a plate with open reservoirs the whole plate is placed in a space permitting elevated gas pressure in contact with the liquid surface in each reservoir, e.g. in a pressurized box. .
- the set up may also comprise a second liquid transport generator II for priming liquid and/or a third transport generator III for washing liquid.
- a second liquid transport generator II for priming liquid and/or a third transport generator III for washing liquid.
- Each of these transport generators may fully or partly be used also as one or more of the other transport generators even if they are named differently.
- Priming typically means that an empty part (priming section) of the flow through part is filled with a liquid (priming liquid, sacrificing liquid) before the liquid to be dispensed to a target area is introduced.
- the priming section preferably extends from the inlet (111,222,322,422) and downstream to the dispenser orifice (108,208,308,408) which also is part of the section. In the case the flow through path comprises several dispenser orifices the priming section extends to cover all of them.
- priming of the flow through path (105+110,220,320,420) with liquid is highly recommendable, if aspiration is to be used for filling up the flow through path with liquid from a liquid storage (112,212,312,314) fluidly connected to the inlet (111,222,322,422). Without priming, air will be sucked into the flow through path via the dispenser orifice (108,208,308,408) instead of liquid via the inlet (111,222,322,422).
- the incorporation of a priming arrangement facilitates the design of efficient dispensing set-ups and systems, and also leads to reduction of the liquid volumes required for dispensation.
- the priming liquid typically should contain no reagents/reactants that participate in the reactions used in the protocol to be performed within the microdevice (201).
- the priming liquid may be the same or similar to a washing or cleaning liquid. This does not exclude that in some variants the priming liquid may contain reagents/reactants, sample possibly containing an analyte etc, in particular if liquids containing these substances are cheap and/or easily accessible.
- the priming arrangement typically comprises two parts: a) a reservoir for priming liquid, and b) a generator for transport of priming liquid (transport generator II) for driving a n prriimmiinn ⁇ g l liinqnuiirdl t tno n prriimmiinnrgt
- the same priming arrangement preferably is used for all of them.
- the reservoir for priming liquid may be fluidly linked to (i) the outlet(s) (107,221,321,421) of the flow through path(s), e.g. via suitable tubings, or (ii) the inlet (111 ,222,322,422) of a flow through path, e.g. being part of the liquid storage.
- Alternative i) is preferred.
- the generator for transport of priming liquid (generator II) is typically pressure driven and comprises a pumping mechanism that creates a suitable pressure differential along the flow through path (105+110,220,320,420) for driving the priming liquid to the priming section.
- the reservoir (131,235,338,442) for priming liquid in alternative (i) is positioned downstream the outlet (107,221,321,421) and the pumping mechanism creates an elevated pressure on the priming liquid that is pushed through the outlet (backwards)
- priming liquid stored downstream the outlet (107,221,321,421) is aspirated into the priming section.
- a closable venting function (not shown) associated with the dispenser orifice (108,208,308,408) for precluding air from entering the priming section during priming.
- Alternative ii) may utilize a pumping mechanism associated with either a position downstream the outlet or a position upstream the inlet (aspirating and pushing, respectively).
- the pumping mechanism used in the priming arrangement may the same as outlined for transport generator I.
- the liquid storage (112,212,312,412) may contain one, two or more reservoirs (114,214,314,414) for storing liquids (113,213,313,413) such as wash liquids for cleaning a flow through path, liquids to be dispensed through a dispenser orifice (108,208,308,408) of the set-up, etc.
- the liquid storage may also comprise a reservoir for priming liquid. See above.
- Each of the reservoirs is capable of being fluidly connected to an inlet (111,222,322,422) of the dispenser arrangement (102,202,302,402).
- the inlet(s) and the liquid storage are adjustable relative to each other such that liquid from one, two or more, preferably any, of the reservoirs (114,214,314,414) of the storage arrangement is able to enter a flow through path via an inlet.
- the alternative illustrated in figures 1-4 is preferred (first alternative) and will now be detailed with reference to figure 2.
- the reservoirs (214), e.g. wells, are present in one side of a plate (storage plate) (223), e.g. a microtitre plate (in fact have openings in one side of the storage plate).
- the inlet(s)/inlet tube(s) (222/210) of the dispenser is(are) directed against this side. This means that fluid communication can be established between an inlet (222) and individual liquid storage reservoirs (214), if the storage plate (223) and/or the inlet (211 ) can be moved relative to each other in an XN-plane and in the Z-direction (XN-plane parallel to the storage plate (223).
- This movement may e.g. be accomplished by keeping the inlet(s) (211 ) of the dispenser arrangement (202) at a fixed position and a) manoeuvring the storage plate (223) in the X-, Y-, and Z-directions, or b) rotating the plate (223) around an axis that is orthogonal to XN-plane combined with lateral and orthogonal movement (Z-movement) of the storage plate (223).
- the side of the storage plate (223) containing the openings of the reservoirs (214) is preferably oriented horizontally with the Z-direction vertical, preferably upwards.
- Movement of the dispenser head (204) and the inlet(s) (222) of the dispenser arrangement (202) is less preferred because this would interfere with and complicate the targeting with the microdevice (the TAs) during dispensation.
- a storage plate (223) is combined with the transformation dispenser discussed in the context of the first aspect and selected such that an array of inlets (arrayiniet) (222) defined by the inlets of the dispenser (102) matches an array of reservoirs (array re servoir) defined by at least some of the reservoirs (214) of the storage plate (223) such that the inlets of arrayini e t can be fluidly connected in parallel the opening(s) of to one, two or more reservoirs of array reSe rv o ir-
- Each of the inlets of array in iet may for instance be connected to a reservoir that no other inlet of arrayiniet is connected to, or all of the inlets of arrayini e t may be connected to one common reservoir.
- the storage plate/dispenser configuration discussed in the preceding paragraph is preferably combined with a microdevice that has an array of target areas (arrayrA) that matches an array of dispenser orifices (array or ifi C es) defined by the dispenser arrangement used, such that dispensation can take place in parallel from each of the dispenser orifices of array or i f ices to each of the target areas of the arrayrA on the microdevice.
- arrayTM comprises only a part (subarray) of the target areas of the microdevice
- the complete dispensation process will encompass repetitive arrayr A or subarray dispensation, in particular if the configuration of target areas within arrayr A is occurring repetitively on the microdevice.
- the volume of liquid (213) retained in each reservoir (214) in the liquid storage (212) is typically in the ⁇ l-range as defined in the introductory part, e.g. ⁇ 5,000 ⁇ l, such as ⁇ 1 ,000 ⁇ l or ⁇ 500 ⁇ l or ⁇ 100 ⁇ l.
- the volume may be small enough for surface forces between the liquid and the inner surface of a reservoir to override gravity.
- the storage plate (223) can be kept at any direction relative to gravity.
- a sealing membrane to keep the liquid in place is not required.
- the reservoirs may be in the form of holes passing through the storage plate.
- a second alternative for liquid storage comprises tubings comprising branchings and/or valves to connect an inlet (222) of a flow through path (220) of a dispenser arrangement (202) with anyone of the different reservoirs (214) of the liquid storage (212).
- tubings comprising branchings and/or valves to connect an inlet (222) of a flow through path (220) of a dispenser arrangement (202) with anyone of the different reservoirs (214) of the liquid storage (212).
- the washing arrangement is for cleaning the inlet(s) (222) and/or the interior of the flow through path(s) (220) including the dispenser orifice(s) (208).
- the washing arrangement comprises one or more reservoirs for washing liquid. These reservoirs may be part of the liquid storage (212) or may be separate.
- the reservoir for washing liquid intended to pass through flow through path(s) is typically connected to a flow through path (220) either upstream the inlet(s) (222) or downstream the outlet(s) (222).
- Washing may include cleaning the outside of the inlet(s) by dipping an inlet into a washing liquid or by flushing the tip with the washing liquid.
- the reservoir for washing liquid may according to both alternatives be part of the liquid storage or be separate, in particular with respect to flushing liquids.
- the transport generator for washing liquid may be separate from or be the same as transport generators I and/or II.
- the mechanisms for liquid transport may be as discussed for these other two generators for liquid transport.
- instrument set-up also includes suitable software and computers that can be programmed for dispensation according to predetermined protocols and microdevices.
- the instrument set-up of this aspect utilizes drop-wise dispensation of liquid to the same kind of microdevices (201) as in the second aspect, with preference for microfluidic devices.
- This set-up is characterized in comprising: a) a drop dispenser arrangement (202) that has (i) one or more inlets (222) connected to a liquid storage plate (223), (ii) one or more dispenser orifice(s) (208) for dispensing drops (203) of liquid to the target areas (200), and (iii) a microconduit (part of 220) fluidly connecting an inlet (222) with the dispenser orifice (208), b) the microdevice (201), and c) the storage plate (223) that comprises liquid reservoirs (214) in one of its sides,
- the microconduit in (iii) goes from an inlet (222) an at least down to the dispenser orifice (208).
- the side of the microdevice (201) containing the target areas (200) is turned against the dispenser orifice (208).
- the dispenser arrangement is in a preferred variant the transformation dispenser arrangement discussed in the context of the first aspect.
- the inlet(s) (222) and the storage plate (223) are movable relative to each other such that fluid communication can be established between one, two or more of the inlets (222) and at least one of the liquid reservoirs (214) per inlet at a time. Typically contact is established in parallel for two, three or more inlets. See the other aspects.
- the dispensation direction from the orifice is typically orthogonal to the side of the microdevice comprising the target areas.
- the side of the microdevice (201) comprising the target areas (200) and the side of the storage plate (223) comprising the openings of the liquid reservoirs (214) are turned in opposite directions.
- the dispenser orifice (208) is between these sides and turned against the microdevice (against the side comprising the target areas).
- the dispenser orifice is directed upwards, preferably vertically.
- Dispenser arrangements based on the flow through principle with a dispenser orifice (208) between the ends (222,221) of a liquid through flow path (220) are preferred. See the publications discussed as back-ground technology above and the variants given in the context of the first and second aspect of the invention.
- drop dispensers can be used in this aspect, for instance drop dispensers in which the microconduit going from the inlet (211 ) to the dispenser orifice (208) is not part of flow through path (220) having an outlet (222) for excess of liquid that is separate from the dispenser orifice (208).
- drop dispensers comprise a liquid transport channel which a) starts with an inlet to be fluidly connected to a liquid reservoir, b) ends in a dispenser orifice, and c) has a dispensing actuator associated with the channel in an upstream position relative to the orifice.
- the actuator may be ring-formed and fully or partially embracing the liquid flow passing through the channel.
- the ring may comprise a piezoelectric material.
- This kind of drop dispensers is available from Cartesian (England) and can be used in the third aspect of the present invention if properly modified.
- Other candidate dispensers are based on the bubble-jet principle developed for example by Olivetti (Italy), or based on other pieozoelectric transducers or speakers available from MicroFab (USA) and/or based on continuous mode ink-jet working according to Rayleigh break up principle and/or where droplets are directed under a deflection field.
- the dispenser variants described in the preceding three paragraphs are likely to require more complex design and/or complicated procedures for replacing the dispensing liquid or deflecting droplets under an electric field (necessitating the droplets to be charged) in order to secure safe targeting.
- the aspirating principle is not applicable to liquid transport within this kind of dispensers.
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Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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JP2006532236A JP4837564B2 (en) | 2003-10-04 | 2004-10-04 | Small distribution device |
EP04775513A EP1668374A1 (en) | 2003-10-04 | 2004-10-04 | Compact dispenser |
US10/570,491 US20070086922A1 (en) | 2003-10-04 | 2004-10-04 | Compact dispenser |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0302649A SE0302649D0 (en) | 2003-10-04 | 2003-10-04 | Compact dispenser system |
SE0302649-9 | 2003-10-04 | ||
US50827803P | 2003-10-06 | 2003-10-06 | |
US60/508,278 | 2003-10-06 |
Publications (1)
Publication Number | Publication Date |
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WO2005033714A1 true WO2005033714A1 (en) | 2005-04-14 |
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ID=34425472
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/SE2004/001423 WO2005033714A1 (en) | 2003-10-04 | 2004-10-04 | Compact dispenser |
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EP (1) | EP1668374A1 (en) |
WO (1) | WO2005033714A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008079598A1 (en) | 2006-12-22 | 2008-07-03 | Abbott Laboratories | Liquid waste management system |
US8292990B2 (en) | 2008-09-05 | 2012-10-23 | Tsi, Incorporated | Nebulizer waste pressure reducer for HPLC systems |
CN110449196A (en) * | 2019-09-18 | 2019-11-15 | 中国人民解放军军事科学院军事医学研究院 | A kind of multidirectional isocon |
Citations (6)
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WO1997001085A1 (en) * | 1995-06-21 | 1997-01-09 | Pharmacia Biotech Ab | Flow-through sampling cell and use thereof |
WO2001030500A1 (en) * | 1999-10-29 | 2001-05-03 | Gyros Ab | Device for dispensing droplets |
US20030007898A1 (en) * | 2001-06-20 | 2003-01-09 | Coventor, Inc. | Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system |
US20030094502A1 (en) * | 2001-10-21 | 2003-05-22 | Per Andersson | Method and instrumentation for micro dispensation of droplets |
WO2003053581A2 (en) * | 2001-12-11 | 2003-07-03 | Astrazeneca Ab | Biomolecule handling method and machine using an array dispenser |
US6623613B1 (en) * | 1999-10-01 | 2003-09-23 | The Regents Of The University Of California | Microfabricated liquid sample loading system |
-
2004
- 2004-10-04 WO PCT/SE2004/001423 patent/WO2005033714A1/en active Application Filing
- 2004-10-04 EP EP04775513A patent/EP1668374A1/en not_active Withdrawn
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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WO1997001085A1 (en) * | 1995-06-21 | 1997-01-09 | Pharmacia Biotech Ab | Flow-through sampling cell and use thereof |
US6623613B1 (en) * | 1999-10-01 | 2003-09-23 | The Regents Of The University Of California | Microfabricated liquid sample loading system |
WO2001030500A1 (en) * | 1999-10-29 | 2001-05-03 | Gyros Ab | Device for dispensing droplets |
US20030007898A1 (en) * | 2001-06-20 | 2003-01-09 | Coventor, Inc. | Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system |
US20030094502A1 (en) * | 2001-10-21 | 2003-05-22 | Per Andersson | Method and instrumentation for micro dispensation of droplets |
WO2003053581A2 (en) * | 2001-12-11 | 2003-07-03 | Astrazeneca Ab | Biomolecule handling method and machine using an array dispenser |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008079598A1 (en) | 2006-12-22 | 2008-07-03 | Abbott Laboratories | Liquid waste management system |
US8449839B2 (en) | 2006-12-22 | 2013-05-28 | Abbott Laboratories | Liquid waste management system |
US8292990B2 (en) | 2008-09-05 | 2012-10-23 | Tsi, Incorporated | Nebulizer waste pressure reducer for HPLC systems |
CN110449196A (en) * | 2019-09-18 | 2019-11-15 | 中国人民解放军军事科学院军事医学研究院 | A kind of multidirectional isocon |
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