LU103207B1 - Method and device for dispensing fluids - Google Patents

Abstract

The invention relates to a method and device for dispensing fluids. The disclosure provides a manifold for distributing fluids, wherein the manifold has a cuboid shape with smaller upper, lower, and two lateral surfaces and larger front and back surfaces, comprising: an interface for connecting the manifold to a fluid flow: a dispensing comb comprising a plurality of injectors projecting from a smaller side of the manifold: a branching distribution channel for connecting the interface with the dispensing comb. A method using the device is also disclosed.

Description

w

STRATEC SE rorimann Tegethoff 30001.20478LU Sa he IL AM

LU103207

METHOD AND DEVICE FOR DISPENSING FLUIDS

DESCRIPTION Field of the Invention

[0001] The invention relates to a method and device for dispensing fluids.

Brief description of the related art

[0002] Automated analyser systems for use in clinical diagnostics and life sciences are produced by a number of companies. l'or example, STRATEC® SE, Birkenfeld. Germany. produces a number of devices for specimen handling and detection for use in automated analyser systems and other laboratory instrumentation.

[0003] Many different reagents are used in human diagnostics analysis systems. They are usually used depending on the desired chemical/biological reaction. for example to prepare or purify a sample in reaction containers (c.g. cuvettes) or to determine a result (eg. via chemiluminescence).

[0004] In many analysis systems. cuvettes are used as reaction containers in which a volume of a fluid is dispensed into the reaction container via an injector by means of a fluid jet. In addition to the pure delivery of the fluid volume, the kinetic energy of the jet can be used to mix the dispensed fluid volume as quickly and effectively as possible when the fluid hits the cuvettes walls. Likewise. components of the overall reaction can be washed and rinsed from the container wall.

[0005] In order to achieve the highest possible efficiency in this application, several injectors. including so-called dispensing combs, can be used. They comprise two or more small-cross- section dispensing nozzles and form a so called fluid curtain across the entire width of the reaction container when the reagents are dispensed. However, due to the large number of dispensing needles in a dispensing comb. uniform dispensing cannot be guaranteed when using 1

STRATEC SE rorrmann Tegethoff 30001.20478LU A eA

LU103207 only one precision pump. This risk arises especially when only one channel is used for distribution to the individual injectors/dispensing needles. Thus. duc to minor deviations, eg. clogging of individual nozzles, it may not be possible to dispense an inappropriate volume.

[0006] The prior art provides devices with single injectors up to devices comprising dispensing combs, One example is a system comprising an injector with two nozzles. The aim of this arrangement is to flow over the largest possible area in a reaction container like a farge-volume cuvette. With only one injector. the washing efficiency would not be given. In order to achieve uniform distribution over an even larger area, additional injectors would have to be used.

[0007] Another device from the prior art relates to an oscillating nozzle comprising a special internal geometry which creates an instable flow during operation. causing the injection jet to move back and forth. With a corresponding oscillation frequency. à quasi-l'an with an adjustable injection angle is created. This allows larger areas to be covered. Due to a minimum volume flow as well as the impulse generated by the oscillating jet, splashes can cause contamination ol the surrounding geometries. This can have negative effects in corresponding processes.

[0008] The prior art further provides devices with dispensing combs. wherein a comb is used to dispense volumes as equal as possible into the different cavities of a reaction container. like multi well plates. An equal distribution over a surface 1s not intended here. Nevertheless, there is a requirement to distribute the wash buffer evenly over the individual dispensing needles or injectors. However, the dispensing combs consist of only one large cross-sectional bore from which all dispensing needles extend. This supply bore must be unequally larger than the outgoing bores for the dispensing needles. otherwise there will be Mow-related distribution effects. This can lead to unevenly delivered volumes at the injectors. so that no uniform dispensing can be guaranteed due to the large number of dispensing needles. This risk arises especially when only one channel is used for the distribution to the individual injectors or dispensing needles. In addition, the size of this hole results in an increased space requirement in terms of the thickness of a potential chip design, which in turn would have an influence on the stacking size of several dispensing units.

[6009] To avoid these disadvantages, the use of a single nozzle would in principle be preferable.

However, the following problems may arise - Using a single injector can be related to 2

STRATEC SE rorfmann Tegethoii 30001.20478LU ede bt Brn At

LU103207 - a high kinetic energy of the single beam which may damage sensitive samples and thus influence reactions. The impact point of the beam is local and thus problematic for a desired uniform distribution in larger reaction arcas. Due to the local impact point. very narrow tolerances are required for ensuring its position. - an increased high space is required tor multi-injector arrangements or injector combs. - the same geometry is provided for different fluids with different physical properties. - the risk of potential distribution effects with multi-injector arrangements is given. - Using a double injector can be related to - low distribution effects, and - an increased space requirement for multiple injector arrangements. - Using an oscillating nozzle can be related to - A strong dependence between geometry and fluid. and - A potential contamination due to the moving jet. - Using a dispensing comb can be related to - an increased space requirement with multiple arrangement. - higher manufacturing costs for a device. - lower flexibility when using different fluids. because no adaptation to the individual properties ol a [luid is possible. - If a change between different liquids is permitted in a dispensing chamber. the dispensing chamber must first be rinsed before another liquid can be dispensed which is time consuming.

[0002] Thus. there is a need for a device and method avoiding the above mentioned disadvantages from devices and methods provided by the prior art.

Summary of the Disclosure

[0010] The present disclosure provides a manifold for distributing fluids, wherein the manifold has a cuboid shape with smaller upper. lower. and two lateral surfaces and larger front and back 3

LU

STRATEC SE rorimann Tegethoif 30001.20478LU jdn CE SE

LU103207 surfaces. comprising: an interface for connecting the manifold to a fluid flow: a dispensing comb comprising a plurality of injectors projecting from a smaller side of the manifold: a branching distribution channel arranged inside the manifold tor connecting the interface with the dispensing comb.

[0011] An embodiment of the manifold 1 comprises an distribution channel which is symmetrically branched with respect to a fictional central axis and the volume of the branching distribution channels.

[0012] It is further envisaged that the diameter or volume of the distribution channel changes between interface and injectors of the dispensing comb.

[0013] It is further intended that a cross-sectional diameter of the channel of the injectors can be smaller than a cross-sectional diameter of the distribution channel.

[0014] Another embodiment of a manifold according to the disclosure comprises at least one positioning member for connecting two manifolds with another, wherein the at least one positioning member is selected from the group comprising protrusions and recesses, snap-fits. a bolt and hole, magnets. and tongue and groove.

[0015] One part of the positioning member can be located on a first larger side of the manifold and the other part of a connecting member is located on the opposite larger side of the manitold.

[0016] The manifold according to the present disclosure may also comprise at least one fastening clement for the fixation of the manifold to a supporting structure. wherein the at least one fastening element is selected from the group comprising boreholes. screws. magnets. and hook.

[0017] The manifold according to the present disclosure may further comprise a hose that is connected to the interface.

[0018] It is also envisaged that the manifold according to the present disclosure comprises injectors with injector tips tapering off towards their outflow opening, having a rectangular shape or comprising chamiers. 4

LU Fortmann Tegethoff

STRATEC SE ) oem A ke bir ail 30001.20478LU heb RÉ E

LU103207

[0019] Another object of the present disclosure is a system comprising a manifold as described above and a precision pump which is connected by a hose to the interface for providing the fluid.

[0020] The system may further comprise a pump which is parameterizable. wherein the adjustable parameters are selected from the group comprising the volume of the fluid to be dispensed. acceleration of the fluid flow and a back draw of the fluid.

[0021] The system may also comprise a supporting structure for the fixation of the manifold.

[0022] The system may also comprise one manifold for each fluid.

[0023] Another object of the present disclosure is an automated analyser system, comprising a system as described above.

[0024] A further object of the present disclosure is a method for dispensing of a fluid. comprising the steps of: - pumping of a fluid through a hose from a fluid reservoir to an interface of a manifold: - distributing the fluid in the manifold through a branching distribution channel connected to the interface to a plurality of injectors of a dispensing comb. wherein the branching distribution channel reduces the volume of the distribution channel 10 which a single injector is connected: and - dispensing the fluid through the injectors of the distribution comb.

[0025] Another object of the present disclosure is a method for manufacturing a manifold for dispensing a fluid, the method comprising: - preparing a mold tor a manifold which has a cuboid shape with smaller upper. lower. and two lateral surfaces and larger front and back surfaces, comprising: i. an interlace for connecling the manifold to a Nuid flow: ii. a dispensing comb comprising a plurality of injectors projecting from a smaller side of the manitold: - a branching distribution channel for connecting the interface with the dispensing comb: - applying a polymer Lo the mold:

LU Fortmann Tegethofi

STRATEC SE | Zoom i vet bp ei 30001.20478LU Patrie MOT AT

LU103207 - hardening the polymer in the mold.

[0026] The method may comprise in an embodiment a manifold comprises a hose that is connected to the interface.

[0027] Still other aspects. features, and advantages of the present invention are readily apparent from the following detailed description, simply by illustrating preferable embodiments and implementations. The present invention is also capable of other and different embodiments and its several details can be modified in various obvious respects. all without departing [rom the spirit and scope of the present invention. Accordingly. the drawings and descriptions are to be regarded as illustrative in nature, and not as restrictive. Additional objects and advantages ol the invention will be set forth in part in the description which follows and in part will be obvious trom the description. or may be learned by practice of the invention.

Summary of the Figures

[0028] The disclosure will be described based on figures. [It will be understood that the embodiments and aspects of the disclosure described in the figures are only examples and do not limit the protective scope of the claims in any way. The disclosure is defined by the claims and their equivalents. It will be understood that features of one aspect or embodiment of the disclosure can be combined with a feature of a different aspect or aspects of other embodiments of the disclosure. in which:

[0029] FIG. 1 shows a manifold from the state of the art.

[0030] FIG. 2 shows a manifold according to the present disclosure with eight injectors: in A: a view onto a front surface. in B: à view onto a back side, in C: a sectional view through the manifold. and in D: à view onto the injectors on the lower lateral side.

[0031] FIG. 3 shows a manifold according to the present disclosure with four injectors; in A: a view onto a front surface, in B: a view onto a back side. in C: a sectional view through the manifold. and in D: a view onto the injectors on the lower lateral side. 6

LU Fortmann Tegethoff

STRATEC SE |“ sm 30001.20478LU cube We ELITE ..

LU103207

[0032] FIG, 4 shows a stack of a plurality of dispensing combs.

[0033] FIG. 5 shows different tip geometries of the injectors. the lower section shows sectional views through the tips shown above.

Detailed Description of the Disclosure and the Figures

[0034] The technical problem is solved by the independent claims. The dependent claims cover further specific embodiments of the invention.

[0035] The term container relates to a consumable which relates within the present disclosure a device which provides cavities. receptacles, or recesses for receiving a fluid which can be a liquid like a patient sample for instance. A container can be a tube.

[0036] The term fluid refers to a liquid or gas which both may comprise solids. The term patient sample relates to any body liquid like whole blood, urine, lymph or saliva. A sample may already have undergone prior treatments like centrifugation so that the sample is provided in a specific state.

[0037] The centre of the dispensing comb relates to a position between the two outer injectors of the dispensing comb. A change of the distribution channel's diameter relates to a diameter becoming wider or smaller inn the course of the distribution channel and its branches.

[0038] The present invention relates to a manifold comprising a dispensing comb with a symmetrical channel structure, wherein the disadvantageous distribution effects are mitigated and homogeneous dispensing can be ensured. In an embodiment, the dispensing comb of the present invention can also be operated by a precision pump without loss of performance.

[0039] The manifold comprises a dispensing comb with a symmetrical distribution channel structure instead of a common chamber above the injectors. The distribution channel structure mitigates the disadvantageous distribution effects and ensures homogeneous dispensing. In contrast to known solutions from the prior art as shown in FIG. 1, the injectors are not connected to a volume of a common channel above the injectors, The branching distribution channel 7 ic Forfmann Tegethoff 30001.20478LU rites Tena

LU103207 structure of the manifold according to the present disclosure has the technical effect to reduce the volume to which a single injector is connected. Depending on the branching structure of the distribution channel, one or two neighbouring injectors for instance can be connected to a common branch of the distribution channel structure. The effect of the branching structure of the distribution channel is a uniformly distributed fluid delivery in a multi-injector arrangement by the symmetrical distribution channel structure in combination with a fluidic control via a parameterizable precision pump. The pump can be parametrized with respect to the volume of the fluid to be dispensed. acceleration of the Muid flow and to a back draw of the fluid which is reliably possible due to the reduced distribution volume to which an injector is connected.

Another technical effect of the branching distribution channel structure is an improved equal fluid Now behaviour in comparison to a single chamber which is connected to the plurality of injectors (comp. FIG, 1).

[0040] The geometry of the injector tip can be adapted to the respective application or properties of the fluid within the meaning that a fluid with a higher viscosity requires another geometry of the injector tip than a fluid with a low viscosity. The surrounding wall of the injector channel may taper towards its end, be rectangular, or chamfered. The geometry of the injector tip shall provide a smooth droplet break which contributes to a controlled dispense of a fluid.

[0041] A very compact design is possible due to a stackable injection molding design. which reduces costs in manufacturing. The manifold according to the present disclosure provides a single injector comb per liquid, eliminating the need for changing the dispensing comb when using different fluids or for intermediate rinsing when changing fluids. Finally, the injector comb becomes part of the connected hose assembly.

[0042] FIG. 1 shows a manifold 1 which is known from the state of the art. The injectors 5 are all connected to the same chamber 4 above them providing a fluid (not shown).

[0043] FIG. 2 shows a manifold according to the present disclosure with eight injectors. FIG. 2 shows in A: a view onto a front surface. in B: a view onto a back side, in C: a sectional view through the manifold and in D: a view onto the injectors on the lower lateral side. 8

STRATEC SE Fortman n Teg ethoif 30001.20478LU PE EC RS

LU103207

[0044] FIG. 2A shows that a manifold ! according to the present disclosure provides positioning members for a correct positioning of two manifolds | which shall be connected to another (comp. FIG. 4). The positioning members comprise snap-fits. a bolt and hole, magnets, and tongue and groove. In the embodiment of the manifold sown in FIG. 2, the larger front side of the manifold 1 comprises protrusions 13a which are configured to accommodate in recesses 13b on the larger backside of manifold 1 so that the protrusions 13a and recesses 13b form positioning members of the manifold 1 (comp. FIG. 1).

[0045] The manifold 1 also provides fastening clements 15 for the fixation of a manifold 1 to a supporting structure of an automated analyser system for instance. Fastening elements 15 are shown in FIG. ZA and can be selected from the group comprising boreholes, screws, magnets, and hook.

[0046] The manifold 1 according to the present disclosure comprises a dispensing comb 2 (comp FIG. 2A and FIG. 2C). The manifold 1 comprises an interface 3 to the fluid transfer line which will commonly be a hose which is connected to the interface 3 as shown in FIG. 2C.

[6047] The manifold 1 further comprises several injectors 5 with a cross-sectional diameter for transport of the fluid that is smaller than the diameter of the internal distribution channels 10 as can be taken from the embodiment in FIG. 2C. The design of the distribution channel 10 connecting interface 3 with injectors 5 1s optimized with respect to the fluid’s properties and thus ensures a uniform distribution of the fluid from the hose to the injectors, thereby enabling a homogeneous dispensing. The optimization of the distribution channels comprises their diameter, including a change of or a different diameter of the fluid channel of interface, distribution channel and injectors. The respective diameters or angles of the distribution channels 10 when their direction changes can be adapted to the properties of the fluid which is provided to the manifold 1.

[0048] FIG. 3 shows a manifold according to the present disclosure with four injectors; in À: a view onto a front surface, in B: a view onto a back side, in C: a sectional view through the manifold, and in D: a view onto the injectors on the lower lateral side. A can be taken from The embodiment of FIG. 3 comprises only four injectors so that the provided fluid will be equally distributed to the four injectors. 9

STRATEC SE rortmann Tegethoff 30001.20478LU in ee A

LU103207

[0049] FIG. 4 shows that depending on the application. several manifolds 1 can be connected to another, For the connection of the manifolds 1 to each other, protrusion 13a of the positioning members is accommodated in recesses 13b of the positioning members and a fastening feature 15 is used for fixation of manifolds 1 to another. The fastening can be reversible (e.g. screws, plug-in connection. clip connection) or irreversible (e.g. plug-in connection with adhesive). 10050] The embodiment in FIG. 4 shows a stack of manifolds 1 with different numbers of injectors 5. One dispensing comb provides eight injectors 5 while other dispensing combs | in the stack provide four injectors 5. It is thus possible to combine dispensing combs with different numbers of injectors. Protrusions 13a are visible on the manifold in the front position. Fastening feature 15 is also visible. It is also possible to combine dispensing combs which arc configured for different fluid properties. Thus. a stack ol dispensing combs according to the present disclosure can be adapted to the respective required set-up of an automated analyser.

[0051] FIG. 5 shows different tip geometries of the injectors, the lower section shows sectional views through the tips shown above.

[0052] The advantages of a device and method according to the present disclosure can be summarized as - Fluid delivery via a multi-injector arrangement: This allows the liquid to be dispensed to be evenly distributed over a larger area, This allows generous compensation for manufacturing, assembly and positioning tolerances. Larger specimens can be flowed faster and more evenly, Distribution over several injectors increases the total cross- section and reduces the purging pressure. This is particularly advantageous for sensitive specimens. - I'luidic control via a parameterizable precision pump: In addition to being influenced by the geometry of the manifold. the fluid to be dispensed can also be influenced by the operating parameters of the pump. For example. itis possible to set the dispensing speed or the acceleration and deceleration ramps. or whether the liquid column should be retracted a little at the end of a dispense to provoke a drip break. Optionally. the kinetic energy of the jet can be used by means of the dispensing speed in order to achieve the fastest and most effective mixing possible upon impact into the volume located in the reaction vessel.

LU Fortmann Tegethoff

STRATEC SE |r se va 30001.20478LU

LU103207 - Individual adaptation to the physics of the respective medium through specific injectors:

In addition to the geometry of the manifold, the injectors can also be individually adapted to the fluid to be used. For example. depending on the polarity of the fluid, the injector material can be selected to achieve the largest possible contact angle. As a result. the fluid can creep along the injector less (spreading) and thus contaminate it less. The individual chemical resistance can also be influenced by a suitable material. - Very compact design due lo stackable injection molding design: Due to the fluid chip- like design. a single manifold can achieve very small sizes. With an edge length of e.g. mm x 25 mm and a total height of 3 - 5 mm it is possible to stack several units. For example, up to 8 manilolds can be stacked in à total space of 25 mm x 25 mm x 24 mm, with each manifold conveying only one liquid. - One injector comb per liquid, thus no time-consuming change of liquids necessary:

Different properties ol the liquids (e.g. viscosity, contact angle. surface tension) require different materials and geometries. If one tries to solve this with one design. compromises are made. which lead to different negative effects (spreading, poor droplet break-off, ctc.). In addition, the use of several liquids in one manifold requires time- consuming rinsing between the individual reagents. In addition to the risk of cross- reactions, this results above all in increased consumption of these liquids. With the individual design, the present invention can address the respective fluid properties.

Intermediate rinsing 1s not necessary. This also reduces the use of reagents. - Injector comb is part of the connected hose assembly: The compact design allows the manifold to be connected directly to the transfer line. Compared to a detachable connection. a material-locking connection can save further installation space. - This results in a cost-efficient component which can be produced as a unit (distributor, transfer line. connection coupling) ready for testing. This increases process stability in production and reduces the risk of leakage at possible separation points, In addition. the manifold does not have to be cleaned at great expense. Instead. the complete compound can be replaced regularly as a cost-effective unit if required.

[0053] Alternatively. the entire manifold could be designed and manulactured as a multilayer manifold. This would save further installation space and there would be only one component. which would simplify assembly. Multilayer manifolds exist in this form. but their manufacture is complex and cost intensive. 11

STRATEC SE lortmann Tegethoil 30001.20478LU PRE TL Ae

LU103207

[0054] The entire manifold could also be manufactured by milling. However, this would result in complex bore geometries which must be coordinated with cach other. Particularly with the small cross-sections. there is a high risk of clogging duc to residues. e.g. chips.

[0055] The design could also be injection molded. However, for further simplification, the injectors and/or a hose to the interface can be directly molded on. This would climinate the need for time-consuming and potentially error-prone assembly of a hose to the interface.

[0056] Optical monitoring: In the design of the mantfold. it is possible to provide individual channels with optical monitoring. On the one hand, this makes it possible to check whether the specified dispensing volume has actually been dispensed. On the other hand. air bubbles in the channel can be detected, which allows conclusions to be drawn about the dispensed volume.

[0057] The foregoing description of the preferred embodiment ol the invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or 10 limit the invention to the precise form disclosed. and modifications and variations are possible in light of the above teachings or may be acquired [rom practice of the invention. The embodiment was chosen and described in order to explain the principles of the invention and its practical application to enable one skilled in the art to utilize the invention in various embodiments as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto, and their equivalents. The entirety of cach of the aforementioned documents 1s incorporated by reference herein. 12

LU

STRATEC SE Fort mann Teg ethoff 30001.20478LU che ee LPT, At A

LU103207

Reference Numeral ] manifold 2 dispensing comb 3 interface 4 chamber injector distribution channel 13a protrusion 13b recess fastening element 13

Claims (17)

v Fortmann T STRATEC SE Loi mann egethoff 30001.20478LU CE EL RES LU103207 CLAIMS

1. A manifold for distributing fluids. wherein the manifold has a cuboid shape with smaller upper. lower, and two lateral surfaces and larger front and back surfaces. comprising: - an interface for connecting the manifold to a fluid Now: - a dispensing comb comprising a plurality of injectors projecting from a smaller side of the manifold: - a branching distribution channel arranged inside the manitold for connecting the interface with the dispensing comb.

2. The manifold of claim |. wherein the distribution channel is symmetrically branched with respect to a fictional central axis and the volume of the branching distribution channels.

3. The manifold of claim 1, wherein the diameter or volume of the distribution channel changes between interface and injectors of the dispensing comb.

4 The manifold of any one of claims 1 to 3. wherein a cross-sectional diameter of the channel of the injectors is smaller than a cross-sectional diameter of the distribution channel.

5. The manifold of any one of claims | to 4, comprising at feast one positioning member for connecting two manifolds with another, wherein the at least one positioning member is selected from the group comprising protrusions and recesses. snap-fits. a bolt and hole. magnets, and tongue and groove.

6. The manifold of claim 5, wherein one part of the positioning member is located on a first larger side of the manifold and the other part of a connecting member is located on the opposite larger side of the manifold.

7. The manifold of any one of claims 1 to 7. comprising at least one fastening element for the fixation of the manifold to a supporting structure. wherein the at least one fastening element is clected from the group comprising boreholes. screws. magnets. and hook. 14

LU STRATEC SE Forman Tegethoff 30001.20478LU hte nun Ae LU103207

8. The manifold of any one of claims 1 to 7. comprising a hose that is connected to the interface.

9. The manifold of any one of claims 1 to 8. comprising injectors with injector tips tapering off towards their outflow opening. having a rectangular shape or comprising chamlers,

10. A system comprising a manifold of any one of claims 1 10 9 and a precision pump which is connected by a hose to the interface for providing the fluid.

11. The system of claim 9, wherein the pump is parameterizable. wherein the adjustable parameter are selected from the group comprising the volume of the fluid to be dispensed. acceleration of the fluid flow and a back draw of the fluid.

12. The system of any onc of claims 9 or 10, comprising a supporting structure for the fixation of the manifold.

13. The system of any onc of claim 9 to 12. comprising one manifold for each fluid.

14. An automated analvser system. comprising a system according to any one of claims 9 to

13.

15. A method for dispensing of a fluid, comprising the steps of: - pumping of a fluid through a hose from a fluid reservoir to an interface of a manifold: - distributing the fluid in the manilold through a branching distribution channel connected to the interface to a plurality of injectors of a dispensing comb, wherein the branching distribution channel reduces the volume of the distribution channel to which a single injector is connected: - dispensing the fluid through the injectors of the distribution comb.

16. A method for manufacturing a manifold for dispensing a fluid. the method comprising: - preparing a mold for a manifold which has a cuboid shape with smaller upper. lower. and two lateral surfaces and larger front and back surfaces. comprising:

i. an interface for connecting the manifold to a fluid flow:

TE Onn, A LU103207 il. a dispensing comb comprising a plurality of injectors projecting from a smaller side of the manifold:

iil. a branching distribution channel for connecting the interface with the dispensing comb: - applying a polymer to the mold, - hardening the polymer in the mold.

17. The method of claim 16, wherein the manifold comprises a hose that is connected to the interface. 16