WO2010091685A1

WO2010091685A1 - Degassing unit for micro fluid system

Info

Publication number: WO2010091685A1
Application number: PCT/DK2009/000038
Authority: WO
Inventors: René Bogelund NYBERG
Original assignee: Danfoss Ventures AS
Current assignee: Danfoss Development AS
Priority date: 2009-02-10
Filing date: 2009-02-10
Publication date: 2010-08-19
Anticipated expiration: 2011-08-10

Abstract

The present invention relates to a flow construction adapted to degas a fluid, preferable flowing with micro-flow rates or less, where gas in the form of micro bubbles, possibly due to pressure reductions in the system, may block micro channels and hence destroy the flow in the specific applications. The idea is to introduce bubble generating and pressure reducing units in fluid connection with a chamber, wherein at least part a of the walls enclosing the chamber is made of a gas permeable membrane. A filter is positioned at the fluid outlet of the chamber inhibiting the bubbles from leaving the chamber with the rest of the fluid.

Description

DEGASSING UNIT FOR MICRO FLUID SYSTEM

BACKGROUND

It is a well known phenomenon and problem especially within the field of micro fluid devices, that bubbles may arise and block the fluid conduits of the micro fluid device. A number of ways have been introduced to inhibit the formation of bubbles, or to trap them before entering the critical parts of the devices, and possibly removing the gas from the bubbles when trapped.

One such device is for example seen in US2005266582A describing a microfluidic system for performing chemical reactions or biochemical, biological, or chemical assays utilizing a microfabricated device or "chip." The system may include, among others, an integrated membrane fabricated from a chemically inert material whose permeability for gases, liquids, cells, and specific molecules, etc. can be selected for optimum results in a desired application. The document shows in FIG. 6 a cross sectional view of a microfluidic chip assembly 100a according to aspects of the present teachings. Substrate assembly 118a, i.e. a fabricated substrate is fabricated from substrate material 101a. Fabricated substrate 118a comprises an inlet access port 104a and an outlet access port 112a extending between a channel surface 103a and an access port surface 103b. A fluid channel 106a is located on channel surface 103a of substrate 101a, extending between inlet access port 104a and outlet access port 112a defining a channel floor surface 108a. A gas permeable membrane 110a is sealably attached to channel surface 103a of fabricated substrate 118a defining a membrane surface 108a within fluid channel 106a. Fluid 102a flows into inlet 104a, through fluid channel 106a where it passes between the channel floor 108a and membrane surface 109a and then exits through outlet 112a. Due to the relatively high gas permeability of the membrane and thin channel depth, exchange of gas 114 occurs between the fluid and the exterior environment of the chip. Bubbles formed in the channel during priming with fluid or in operation can escape through the membrane.

Another document US2008118790 uses bubbles actively and removes them again in a gas venting region, describing a bubble generator 14 generating multiple bubbles 16 or a "bubble train" within the channel 8. The bubble train produces pulsatile movement of the fluid within the channel 8.

In relation to the bubble generator, it is disclosed that the bubble generator 14 is disposed at or adjacent to the channel 8 and is used to generate a plurality of individual gaseous vesicles or bubbles 16 within the channel 8. The bubble generator 14 may be formed, for example, from one or more electrodes that generate bubbles form the electrolytic decomposition of the fluid contained within the channel 8. Alternatively, the bubble generator 14 may be formed from a heating element that creates vapor bubbles 16 from the fluid within the channel 8. In still another embodiment, the bubble generator 14 may be formed from a cavitation element. Bubbles 16 are generated by cavitation within the fluid. For example, the application of high frequency sound waves (e.g., ultrasonic energy) may be used as the cavitation source. In still another aspect, the bubble generator 14 may be formed from a gas injector. To remove the bubbles again from the system and optional one-way valve 18 may be introduced ensuring that the bubbles 16 are retained in the gas venting region of the device 2 which is covered by the venting membrane 20. The one-way valve 18 may be constructed as a partial obstruction of the channel 8 as is explained in detail above. The one-way valve may be formed, for example, from a smaller-sized or partially obstructed microchannel. In addition, a venting membrane is disposed over a portion of the passageway in or downstream of the bubble generating region. The bubbles are able to exit the liquid by passing through the porous venting membrane."

None of these documents, however, describes to remove gas in a fluid, when the gas has not yet formed into bubbles.

SUMMARY

It is an object of the present invention to overcome problems with bubbles in microfluidic structures, or microfluid systems, preferably being a part of an analysis apparatus, which is solved by introducing a degassing unit comprising a fluid inlet and a first fluid conduit having a first fluid inlet and a first fluid outlet, the first fluid outlet having fluid connection with to a first chamber, wherein a first bubble generating device is situated between the first fluid inlet and the first chamber.

In order to remove trapped bubbles of gas, at least a part of the walls enclosing the first chamber is permeable to gas.

To prevent bubbles from entering the microfluid system , the degassing unit further comprises a second fluid conduit having a second fluid inlet fluidic connected to the first chamber, and a second fluid outlet, a filter is being situated between the first chamber and the second fluid outlet. To enhance degassing even further, a second bubble generating device is situated between the second fluid inlet and the second fluid outlet, and the second fluid outlet of the second fluid conduit is in fluid connection with a second chamber, at least a part of the walls enclosing the second chamber being permeable to gas. The device then further comprises a third fluid conduit having a third fluid inlet and a third fluid outlet, a filter being positioned between the third fluid inlet and the third fluid outlet.

Depending on the task, the first and optionally the second bubble generating device may be used separately, combined in series or parallel to remove any unwanted micro bubbles, whether these are formed due to pressure reduction, chemical reaction or other bubble generating devices or phenomena or simply present in the fluid.

FIGURES

Fig. 1 Illustration of a simple bubble trap.

Fig. 2 Illustration of the basic degassing unit of the present invention.

Fig. 3 Illustration of a more advanced degassing unit of the present invention.

Figs. 4 and 5 Illustration of degassing units of the present invention in a micro fluid chip.

DETAILED DESCRIPTION

Fig. 1 is a simple illustration of the basics of the present invention. The figure shows a first fluid conduit (3) extending between a first fluid inlet and a first fluid outlet the first fluid outlet being in fluid connection with a first chamber (4), at least a part of the wall enclosing the first chamber (4) being permeable to air or gas but impermeable to fluid, being the gas permeable wall or gas permeable membrane (5).

The gas permeable membrane (5) should consist of a non-wetting material which retains fluid but permits gas to diffuse through. It may be fixed either mechanically (lock ring, holding plate, etc..) or chemically (adhesive, plasma, etc..) to the substrate wherein the first chamber (4) is formed and on top of the first chamber (4). The pressure P₂ in the first chamber (4) should not exceed the water penetration limit for the gas permeable membrane (5).

A second fluid conduit (6) extending between a second fluid inlet and a second fluid outlet has the second fluid inlet in fluid connection with the first chamber (4). A filter (9) is positioned preferably between the second fluid inlet and the second fluid outlet, or inside the first chamber (4) in such a manner, that it covers the second fluid inlet. The filter (9) may be any filter known in the art, such as a membrane being perforated with milli- or nano- sized pores, only, it has to be passable to the fluid to flow in the system, but impassable to larger sized particles and the like, such as bubbles of gas (10).

A fluid flowing through the fluid device of the present invention is entering the first fluid inlet and flowing through the first fluid conduit (3), the first chamber (4), the second fluid conduit (6) and is leaving through the second fluid outlet (8), as it is illustrated with the arrows.

The filter (9) should have pore sizes of maximum but not limited to 10 μm, preferably less than 2 μm pore sizes. The relation between the pressure P and the maximum diameter of the pores of the filter, Dpore, ensuring that no bubbles are able to pass through the filter, is given by:

Dpore < (4γ * cos θ) / P = K1 / P, where Y = Surface tension of the liquid, θ = Liquid-solid contact angle, P = bubble point pressure (P2 in the first chamber (4)), K1 = Empirical factor.

The figure also illustrates a bubble (10) that has entered the first chamber (4). The bubble is too large sized to follow the fluid flow through the filter (8) and is thus constrained within the first chamber (4). In time the gas of the bubble (10) then diffuses (11) through the air permeable membrane (5) leaving the system altogether.

The problem, however, is that gas dissolved in the fluid, but not yet having been formed into bubbles will continue to flow with the fluid through the filter (9).

The solution introduced in the present invention is to introduce or insert a first bubble generating and pressure reduction unit (12) at least partly positioned somewhere in the first fluid conduit (3) between the first fluid inlet and the fluid outlet, or alternatively at the inlet face of the first fluid inlet or at the outlet face of the first fluid outlet. Fig. 2 illustrates such a first bubble generating and pressure reducing unit (12) positioned partly in the first fluid conduit (3) having the first outlet section (13) reaching into the first chamber (4). This ensures a minimum dead volume in the system, but also, which is more important, it is ensured that all bubbles are formed inside the first chamber (4).

Water enters the system with an external pressure P1 and undergoes a pressure drop to P2 as it passes the pressure reduction unit (12). The pressure reduction from P1 to P2 causes dissolved gas in the water to degas and form bubbles by Henry's law which states: "the amount of air dissolved in a fluid is proportional with the pressure of the system".

The flow restriction of the combined flow system from inlet to and including the first chamber (4) in the direction of the fluid, shall preferably be less than the water penetration pressure for the gas permeable membrane (5) divided by the System flOW, FR < Ppenetration, membrane / F_system-

The first chamber (4) should be large enough to contain an incremental water volume with the bubble(s) trapped inside, without the bubble(s) having an impact on the continuous flow. If the degassing chamber (4) is too small, the formed bubble(s) can clog the entire flow system. The volume of the degassing chamber should follow but is not limited to the statement:

Vchamber > Vbubble,

where V_bUbbi_e is the volume of the bubble and is directly proportional to the inner diameter of the pressure reduction unit where the fluid flows and the outer diameter of the pressure reduction unit.

The second fluid conduit (6) preferably comprises a first small cavity (14) at the second inlet section, the first cavity (14) being a small section of the second fluid conduit (6) having a larger cross sectional area than the average cross-sectional area of the whole second fluid conduit (6). The second pressure reduction unit (16) is positioned between the second fluid inlet and the second fluid outlet. The purpose of the second pressure reduction unit (16) is to create a pressure P2 in the degassing chamber (4) that is high enough to force the generated micro bubbles out through degassing membrane (5), even at micro or nano flows (ul or nl / min) and also to diminish any diffusion of gas back through the gas permeable membrane (5), which will eventually form micro bubbles. If only a very small or no pressure P2 exists, the flow (micro or nano- flow) will not fill up the degassing chamber (4) and any dissolved gas in the water will be carried through filter (9) and further into the system where it can form micro bubbles. The first cavity (14) ensures that the pressure drop across filter (9) is kept to a minimum and the area cross section of cavity (14) should follow, but is not limited to, the relation

(P2 - P3) → < Dpressure reduction unit (8)

The statement says: The diameter of the bubble formed from the pressure reduction ΔP2-3 across the filter in volume formed by first cavity (14) and the second fluid conduit (6) due to Henry's law must not be bigger than the diameter of the inlet of the second pressure reduction unit (8). Otherwise the bubble will be big enough to influence, partially or completely block the pressure reduction unit (16).

The filter (9) may be positioned and fixed either mechanically (lock ring, holding plate, etc..) or chemically (Adhesive, plasma, etc..) on top of a small cavity (14).

Such a flow system comprising a first fluid conduit (3), a first bubble generating and pressure reducing unit (12), a first chamber (4) with a gas permeable membrane (5), a filter (9) positioned somewhere before a second fluid outlet containing a second pressure reduction unit (16) and a small cavity (14) , shall in the following be referred to as the basic degassing unit

(1).

In a more advanced version of the present invention, the second fluid conduit (6) has the second fluid outlet in fluid connection with a second chamber (15), at least a part of the wall enclosing the second chamber (15) being permeable to air or gas but impermeable to fluid, another gas permeable wall or membrane (23). This is an embodiment where at least two basic degassing flow systems are connected in series. A second bubble generating and pressure reduction unit (17) is at least partly positioned somewhere in the second fluid conduit (6) between the second fluid inlet and the second outlet, or alternatively at the inlet face of the second fluid inlet positioned after the first filter (9), or at the outlet face of the second fluid outlet (18). Fig. 3 illustrates such a second bubble generating and pressure reducing unit (17) positioned partly in the second fluid conduit (6) having the first outlet section (18) reaching into the second chamber (15).

A third fluid conduit (20) extending between a third fluid inlet and a third fluid outlet has the third fluid inlet fluidic connected to the second chamber (15).

A second small cavity is optionally positioned at the third fluid inlet section (not shown), the second cavity formed as the first cavity (14) being a small section of the third fluid conduit (20) having a larger cross sectional area than the average cross-sectional area of the whole third fluid conduit (20).

The present embodiment illustrated in Fig. 3 shows a design with two chambers (4, 15) and with the corresponding fluid conduits (1 , 6, 20), gas permeable membranes (5, 23), filters (9, 19), small cavities (14) and bubble generating and pressure reduction unit (12, 17). However, any additional numbers of such basic degassing systems (1) may be introduced into the system of the present invention, either in series or in parallel, to form a degassing unit (2).

The second outlet in Fig. 2 and the third outlet in Fig. 3 are the outlets is where the fluid leaves the fluid device of the present invention, and would typically either be directly succeeded by the rest of the fluid system wherein the degassed fluid is to be used, or is connected thereto in any known manner in the art.

Figs. 4-6 illustrate the fluid device of the present invention in an embodiment where it is a built-in design in a flow system formed as channels in substrates, a fluid chip, or micro fluid chip when the flows in the system are in the range of microlitres per minute or less, the dimensions of the channels typically being in the range of micro meters or less.

It is important to inhibit bubbles from entering the channels of especially micro fluid chips, since, given the small dimensions of the channels, they may clog the channels on the chip and hence destroy the operation of the chip, such as for example analyses based on the measuring of the fluid mixed with reagents to form some reaction corresponding to the measured quantity or parameter. This might for example be an optic reaction corresponding to the concentration of some substances in the fluid.

Fig. 4is a schematic a top view of a micro fluid chip (30) having two fluid inlets (31 , 32) for example being bores through the cover on a substrate, and making fluid communication from the externals to the two first fluid channels (33, 34) respectively, each of the two first fluid channels corresponding to a first conduit (4), and being connected to the two chambers (35, 36) corresponding to two first chambers (4), thus each having a gas permeable membrane (37, 38) covering the chambers (35, 36).

In each of the two first fluid channels (33, 34) is positioned a bubble generating pressure reduction unit (39, 40) that may in preferred embodiments optionally either be flow channels having substantially narrowed cross sectional areas compared to the rest of the flow channels in the micro fluidic chip, partial obstructions, a filter, small tubes, such as glass capillary tubes inserted into the channels (33, 34), etc. As seen, the micro fluid chip (30) shows an example of a degassing unit (2) comprising two parallel basic degassing units or systems (1).

Filters are positioned at the inlet faces of two second fluid channels corresponding to two second fluid conduits (20), as seen in Fig. 5 being a side view of the micro fluid chip (30). Fig. 5 shows one non-limiting example of a micro chip design of a plural of bodies, in the figure being three (50, 51 , 52), being stacked on top of each other. In the figure is seen one first fluid channel (33), the fluid inlet (31), the bubble generating pressure reduction unit (39) and the first chamber (35).

The figure shows the first of the two basic degassing systems comprising a first channel (34) formed in the surface of the middle body (50), but it could also be made in the first cover body (51) or in both. The first chamber (35) is formed in the first cover body (51), but could alternatively be formed in the middle body (50) or both. The fluid inlet (31) is seen as a bore through the first cover body (51). The gas permeable membrane (37) is attached to the first cover body (51) forming one side wall of the first chamber (35). The filter (41) is squeezed between the two bodies (50, 51) and could optionally be positioned in a small cavity formed in one of the bodies or both. The bore (43) operates as the second fluid channel corresponding to a second fluid conduit (6), optionally having the small cavity (42). The bore (43) is in fluid connection with flow channels (45) optionally formed at the opposing surface of the middle body (50). The outlet of the flow channels (45) is seen as a bore (47). The second basic degassing system comprising the first fluid channel (34), fluid inlet (32), the bubble generating pressure reduction unit (40), the first chamber (36) etc., is preferably designed as a flow system comprising the first channel (34) as described above.

Returning to Fig. 4, the channel (45) is seen as a broken line indicating they are running along the surface of the body (50) opposite to the surface. The first channels (33, 34) are running along. The channels (45) comprise a meandering section and a meeting point (44) of branches, where fluids are mixed.

During operation fluids flowing into the system from the two fluid inlets (31 , 32) are flowing through the system to the meandering section (46) where some detector may be connected to measure effects of reactions occurring in the mixed fluids. One of the fluids may be a sample fluid being a fluid comprising substances of interest, the other fluid (or other fluids if more than two such basic degassing systems are present in the system) being a reagent to be mixed to the first fluid. The fluids are mixed according to Fick's laws about diffusion and a chemical reaction occurs depending on the properties of the fluid and the external conditions such as adding of energy to the system in the form of light (electromagnetic waves), heat, sound, etc.

The reaction(s) may form a chemical reaction giving, for example, an optic effect corresponding to some property or parameter like the concentration of a substance in one of (or all) the fluids. A detection of this may then occur somewhere between the mixer meander inlet and the mixer meander outlet, without any interference from bubbles. A pressure reduction unit (46) may be positioned between the outlet of the meandering section and the outlet (47) of the micro chip.

Claims

1. Degassing unit comprising a fluid inlet and a first fluid conduit having a first fluid inlet and a first fluid outlet, the first fluid outlet being in fluid connectection to a first chamber, wherein a first bubble generating device is situated between the frist fluid inlet and the first chamber.

2. Degassing unit according to claim 1 , wherein at least a part of the walls enclosing the first chamber is permeable to gas.

3. Degassing unit according to claim 2, wherein the device further comprise a second fluid conduit having a second fluid inlet being in fluid connection to the first chamber, and a second fluid outlet, wherein a filter is situated between the first chamber and the second fluid outlet.

4. Degassing unit according to claim 3, wherein a second bubble generating device is situated between the second fluid inlet and the second fluid outlet.

5. Degassing unit according to claim 4, wherein the second fluid outlet of the second fluid conduit is being in fluid connecttion to a second chamber, at least a part of the walls enclosing the second chamber being permeable to gas.

6. Degassing unit according to claim 5, wherein the device further comprises a third fluid conduit having a third fluid inlet and a third fluid outlet, and where a filter is positioned between the third fluid inlet and the third fluid outlet.

7. Degassing unit according to any of the preceding claims, wherein the first and optionally the second bubble generating and pressure reduction devices are used separately, combined in series or parallel to remove any unwanted micro bubbles, whether these are formed due to pressure reduction, chemical reaction or other bubble generating devices or phenomena or simply present in the fluid.

8. Degassing unit according to any of the preceding claims, wherein the device is formed in a first surface of a body covered by a first cover body forming channels and chambers of the structures.

9. Degassing unit according to claim 8, wherein a micro fluid system is formed in a second surface of the substrate covered by a second cover body, the degassing unit and the micro fluid system being in fluid connectection by bores through the substrate.

10. Degassing unit according to claim 9, wherein the first chamber is formed in the first cover body.