Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
  • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
  • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
  • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
  • B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00788—Three-dimensional assemblies, i.e. the reactor comprising a form other than a stack of plates
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00891—Feeding or evacuation
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
  • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
  • B01J2219/00781—Aspects relating to microreactors
  • B01J2219/00905—Separation
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
  • B01L2200/02—Adapting objects or devices to another
  • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
  • B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
  • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
  • B01L2200/14—Process control and prevention of errors
  • B01L2200/141—Preventing contamination, tampering

Definitions

• the invention enables gas or liquid separation from microfluidic flow systems which can be operated regardless of the position.
• microfluidic flow systems The area of application of microfluidic flow systems is diverse and includes analysis technology for medical diagnostics. In some areas of medicine, in particular in the area of diabetes monitoring, it is of great advantage to carry out continuous or at least quasi-continuous monitoring of the glucose level. In this way, on the one hand, impending hypoglycemic conditions, which can lead to the death of the patient, can be recognized in good time, and on the other hand, a warning of hyperglycemic conditions, which are usually associated with long-term damage (blindness, gangrene, etc.). Therefore, considerable efforts have recently been made to enable continuous monitoring of the blood glucose concentration. Conventional ways of monitoring the glucose content of blood are often implemented using portable devices, so-called blood glucose meters. A disadvantage of this analysis method is, however, that a body fluid must first be removed, which generally limits the area of application to individual measurements.
• microdialysis technology is nowadays a reliable method for monitoring analyte concentration in vivo.
• the patient can carry it inconspicuously and without major disabilities in everyday life and use it for regular checks.
• a small microdialysis probe is inserted into the body easily and not very traumatically for the patient.
• a perfusion liquid is passed through a catheter and an analyte determination is carried out in the dialysate exiting the catheter, which has taken analyte (glucose) out of the body in the catheter.
• microdialysis probes are in the prior art known, for which reference is made here only to the arrangement described in German patent application file number 10010587.4.
• microdialysis there are numerous requirements in the field of fluid handling.
• the liquid within the microdialysis must be free of bubbles, since this is the only way to guarantee reproducible liquid transport that enables exact analyte determination.
• the channels are connected to a hydrophobic membrane so that the gas can escape through the hydrophobic membrane into the atmosphere of the environment.
• this presupposes that the pressure of the liquid is higher than the external pressure.
• Another disadvantage which arises in particular in the case of miniaturization, is the use of a membrane which makes the construction of a microdevice complex and expensive in terms of a disposable microdevice.
• the object of the invention is to free any fluid from any bubbles and to pass it through a microfluidic system.
• the invention relates to a device for gas or liquid separation, which is operated in a microfluidic flow system regardless of the position.
• the invention includes a device with a hollow body that can be connected to a microfluidic system so that a liquid to be transported is passed through the body.
• the hollow body has an inlet and outlet opening for an inflow or outflow of liquids.
• the exit opening is connected to a supply line that extends into the interior of the body.
• the inlet opening has no feed line or has a feed line which projects into the interior of the body in such a way that an essentially direct flow from the inlet opening to the outlet opening is prevented.
• the hollow body can have a plurality of inlet and outlet openings, the properties of which correspond to the features described.
• the invention further includes a device for liquid separation from microfluidic flow systems, which can be operated regardless of the position.
• the device contains a hollow body which can be connected to a microfluidic system, so that a gas to be transported is passed through the hollow body.
• the hollow body has an inlet and outlet opening for an inflow or outflow of gases, the outlet opening being connected to a feed line which projects into the interior of the body, and the inlet opening has no feed line or has a feed line which in the Protrudes into the interior of the body in such a way that an essentially direct flow from the inlet opening to the outlet opening is prevented.
• the hollow bodies consequently have an essentially analog structure and only differ in their function.
• the cross section of the hollow body for gas or liquid separation in relation to the inlet opening or its feed line is so large that the flow rate is reduced when the fluid is introduced into the cavity.
• the pressure within the liquid rises relative to the environment due to the reduction of the flow rate, whereby gas separation from the liquid is promoted.
• gas bubbles can rise from the liquid, so that gas bubbles and gas dissolved in the liquid are consequently separated out.
• liquid separation is preferably carried out analogously. In the device for gas or liquid separation, the separated phase remains in the cavity of the body, the phase in the flow being displaced.
• a device for gas separation can be connected to a microdialysis system for bubble separation.
• a microdialysis system for bubble separation is used to determine the concentration of at least one analyte in a body fluid.
• analyte includes all possible analytes, such as B. glucose, lactate, proteins, minerals and neurotransmitters.
• liquid can encompass all possible body fluids, such as in particular interstitial fluid, blood and brain fluid.
• the system is primarily designed for in-vivo diagnostics in humans, but other possible applications such as B. be included on the animal.
• the term microdialysis system is used for an embodiment in which there is a membrane exchange between the exterior and a perfusion fluid.
• Microdialysis systems which are known in the prior art are described, for example, in documents EP 0 649 628 and US 5,174,291.
• the device is suitable for. B. also for processes that are generally referred to as ultrafiltration. Filtration of the body fluid surrounding the system is achieved through the membrane.
• the membrane primarily serves to exclude higher molecular substances that interfere with the analysis or cause aging of the sensor.
• the documents US 4,777,953 and US 4,832,034 describe the process of ultrafiltration by way of example.
• the exchange area in which the membrane is present preferably has an elongated shape, so that it has the shape of a rod. The end of the rod can be made pointed, for example, so that an introduction into the human body is facilitated.
• perfusion fluid If perfusion fluid is passed through a microdialysis probe while the exchange area is in contact with a body fluid, the perfusion fluid absorbs substances from the body fluid. This enriched perfusion liquid, the dialysate, is then passed on to an analysis unit which, for. B. the glucose concentration in the dialysate is missing.
• At least one sensor for detecting an analyte is arranged in the measuring area of the analysis unit.
• a metal electrode can be used which is coated on its surface with glucose oxidase or a reagent mixture containing glucose oxide.
• glucose oxidase a reagent mixture containing glucose oxide.
• dissolved glucose oxidase can also be added to the measuring cell.
• This measurement method is e.g. B. described in document EP B 0 393 054.
• This measurement method is e.g. B. described in document EP B 0 393 054.
• Here is an essential aspect for one exact detection of the analyte concentration a bubble-free transport of the liquid so that there is no gas at the electrodes, which would lead to undefined conditions.
• a reservoir for perfusion liquid and / or a reservoir for holding dialysate after the analysis which reservoir is connected directly or via a channel to the exchange area.
• a pump is provided to transport perfusion fluid through the exchange area and to the sensor area.
• Such a pump can, for example, work in pressure mode and thus push liquid out of the reservoir for perfusion liquid, or it can also work in suction mode and draw liquid through the system.
• a pump can, for example, be arranged such that it draws liquid out of the fluid reservoir and supplies it to the exchange area.
• the latter variant can be carried out analogously to a conventional peristaltic pump, in which liquid is displaced by a roller element acting from the outside by squeezing together a compressible region of the fluid channel.
• Corresponding systems are used, for example, in the area of "implanted delivery devices".
• channels with a diameter in the range of 10-1000 ⁇ m can be used in microdialysis. With channel lengths in the range of a few centimeters, it is found that pressures in the range of a few millibars are sufficient to achieve linear flow rates of approximately 1 cm / min.
• such systems have an evaluation unit connected to the sensor, which are used to convert sensor signals into concentration values of the analyte.
• a device for liquid separation proves to be necessary, for example, in CO 2 analysis systems which are used for the analysis of breathing air.
• CO 2 analysis systems which are used for the analysis of breathing air.
• measurement errors frequently occur which are caused by liquid drops in the gas analyzer. These arise in which the z. B. gas exhaled by humans is cooled in the analysis system from body temperature.
• the water contained in the breathing air condenses out.
• a device according to the invention enables, for example, water to be separated from the breathing air before it is passed into the CO 2 analyzer.
• the invention consequently includes devices for a bubble-free fluid transport, which prove to be necessary, for example, in the fields of application mentioned.
• An essential aspect of the present invention is the structure of the hollow body, which is used for both gas and liquid separation.
• the hollow body has a high degree of symmetry and is spherical in an optimized embodiment. This simplifies the structure of the body and reduces the manufacturing costs, which are particularly important when using the device as a disposable device.
• the feed line of the outlet opening of the hollow body preferably protrudes into the center of the body of the body, and in a preferred embodiment the inlet opening has no feed line into the interior of the room but ends in the wall of the cavity. With this arrangement, the formation of the bubble of the separated phase in maximum size can be ensured before the bubble can escape from the hollow body through the feed line of the outlet opening.
• the maximum volume of the bubble in relation to the volume of the entire cavity can be greater than 0.3 without the separated phase getting out of it regardless of the position of the hollow body.
• the maximum volumes of the amount of gas and the liquid in the cavity of the body are so small that when the body is shaken due to capillary and adhesive forces, the phases do not mix, so that there is no impairment of the gas or liquid separation.
• the outlet opening in relation to the inlet opening.
• the outlet opening is arranged in relation to the inlet opening in such a way that an imaginary connection between the inlet opening, the outlet opening and the center of space of the body forms a right-angled triangle and its supply line or supply lines are arranged on the legs of the imaginary triangle.
• the outlet opening can lie next to the inlet opening, or be surrounded by it, or can be arranged opposite the inlet opening and have a shield which prevents a direct flow from the inlet opening to the outlet opening.
• the body is composed of several layers, which have different designs, so that cavities are created when the layers are joined together.
• the layers are designed in such a way that they have depressions or recesses which form channels when they are assembled. In this way, both manufacturing and miniaturization can be simplified.
• the layers can be designed and joined together, for example, with foils of different thicknesses.
• the films can e.g. B. can be brought into the desired shape by cutting plotting or punching. Inlet and outlet openings and their supply lines are taken into account.
• the foils are connected to one another in such a way that a cavity of the desired shape is created in the body with the properties of the hollow body according to the invention for gas or liquid separation.
• silicon can also be used to manufacture the device.
• the layers are structured using the known methods of micromachining silicon.
• the layers are z. B. brought into the appropriate shape with photolithography and subsequent etching.
• the body or bodies can be produced in a simple and inexpensive manner from polymers in the injection molding process, z. B. wells can be introduced directly by injection molding.
• plastics that can be used for this purpose are, for example, polymethyl methacrylate and polycarbonate.
• the device is used in the field of microdialysis, care should be taken when selecting a material that is used to manufacture the system that the material is compatible with the dialysate or microperfat and that there are no changes that the Concentration of the analyte to be determined or influence the analysis as such unpredictably.
• the invention Before starting up the device for gas separation, it proves to be advantageous to fill it with liquid in order to avoid the inclusion of ambient air in the device when starting up. When filling the body with liquid before commissioning, inclusion of the ambient air should also be avoided. Gas bubbles that are present in the hollow body before commissioning reduce the body's capacity to absorb gas from the liquid. Accordingly, in a preferred embodiment, before the device for liquid separation is put into operation, it is previously filled with gas.
• the invention before the device for liquid separation is put into operation, it is previously filled with gas.
• the invention includes a microfluidic flow system that ensures position-independent gas or liquid separation.
• the microfluidic flow system includes a device according to the invention for gas or liquid separation according to claim 1 or 2 and a material control system which introduces a fluid into the hollow body through the inlet opening by means of a connection at the inlet opening of the device according to the invention.
• the fluid is conducted through the feed line of the outlet opening, which projects into the interior of the hollow body and through the outlet opening of the device according to the invention from the hollow body.
• the fluid is passed on by means of a connection to the outlet opening of the device.
• the device should be removed from a microfluidic flow system in good time before the separated phase reaches the feed line of the outlet opening and can escape from the hollow body. This can be ensured that, for. B. the volume of the separated phase is calculated or estimated at a given flow rate or at a given fluid volume and thus an exchange of the device is recommended after a certain flow or a defined time.
• a sensor in the microfluidic flow system is also conceivable, for example, which sends a signal as soon as the fluid has bubbles after flowing through the device according to the invention. Such a sensor is conceivable both within the fluid line downstream with respect to the device according to the invention or z. B. in the microdialysis probe.
• the senor monitors the function of the device according to the invention and consequently enables the user to exchange it from the flow system as soon as the function of a gas or liquid separation is no longer guaranteed.
• Preferred embodiments of the device of the microfluidic flow system result, as already described.
• the microfluidic flow system for gas separation further includes a pump by means of which the flow rate of the liquid is controlled so that the amount of liquid to be analyzed can be determined.
• the system is preferably operated at normal pressure and is preferably independent of the pressure of the environment.
• a flow system for gas separation in the sense of the invention includes in a preferred embodiment in addition to the Device with a hollow body, a microdialysis probe and a liquid reservoir, such as. B. has already been described.
• the device is positioned upstream of the microdialysis probe in the flow system.
• the device according to the invention for gas or liquid separation is preferably a disposable unit in the flow system, which, as already described, is exchanged in the system before the separated phase comes into contact with the supply line of the outlet opening in the interior of the room.
• FIG. 1 Device for gas or liquid separation
• Figure 2 Device for gas or liquid separation, in which the inlet opening is arranged next to the outlet opening.
• Figure 3 Device for gas or liquid separation, in which the inlet opening is arranged opposite the outlet opening.
• Figure 4 Manufacturing process of a device for gas or liquid separation by embossing suitable structures.
• FIG. 5 Microfluidic flow system of a microdialysis
• FIG. 1 illustrates a preferred embodiment of a device for gas or liquid separation.
• the hollow body (10) shown is spherical and has an inlet opening (11) through which the fluid is passed and an outlet opening (12) which extend through the wall (16) of the hollow body (10).
• the inlet and outlet openings are each connected to the inside of the room with a feed line, the feed line (13) of the outlet opening reaching to the center point (17) of the hollow body.
• the feed line (14) of the inlet opening protrudes only slightly into the cavity (15) of the hollow body (10).
• the cavity (15) is delimited by the wall (16) of the hollow body.
• Inlet (11) and outlet opening (12) form, with the center (17) of the cavity, an imaginary right-angled triangle (18), which is drawn in for clarification.
• the supply lines (13) and (14) are arranged on the legs of the right-angled triangle.
• the fluid flows through the inlet opening into the cavity (15) of the body.
• the flow velocity of the fluid is reduced in the cavity of the body.
• the fluid that has entered initially remains in the hollow body.
• a gas separation gas bubbles rise from the liquid or gas dissolved in the liquid are released.
• the separated gas rises into the upper area of the hollow body, where it collects in a gas bubble (separated phase (20)).
• the phase separation is illustrated in the figure by marking the phase limit (19).
• the fluid reaches the inlet (21) of the feed line (13) after a certain dwell time, through which the fluid exits the hollow body.
• the separated phase (20) remains in the hollow body while the fluid is passed on through the outlet opening (12). This presupposes that the volume of the separated phase (20) is so small that, regardless of the position of the hollow body (10), it does not come into contact with the inlet (21) of the feed line (13), which is located in the middle ( 17) of the cavity.
• FIG. 2 shows a hollow body (10), in which the inlet opening (111) is arranged concentrically to the outlet opening (12).
• the outlet opening (12) is connected to a feed line (13) which, as already shown in FIG. 1, extends into the center of the hollow body.
• the embodiments of the device in FIGS. 1 and 2 differ only in the arrangement of the inlet openings 11 and 111 in the wall (16) of the hollow body (10).
• the inlet opening (111) has no feed line.
• the feed line (13) projects analogously to FIG 1 also up to the center (17) of the cavity (15).
• FIG. 3 Another embodiment is shown in FIG. 3.
• the inlet opening (11) of the hollow body (10) is positioned opposite the outlet opening (12) and its feed line (13).
• a shield (200) is arranged above the inlet (21) of the inlet (13). The space between
• the inlet (21) of the feed line (13) and the shield (200) is sufficiently large that the fluid can flow in unhindered through the inlet (21) or the fluid located in the cavity (15) can flow out of the outlet opening (12) ,
• the shield (200) is fastened within the hollow body by means of webs (201).
• Figure 4 shows an example of some process steps for the manufacture of a device according to the invention.
• the method by embossing two molded plastic parts, which are then connected, proves to be particularly suitable, since it enables inexpensive and simple manufacture of a microdevice.
• the molds (401, 402) required for embossing can be produced for a large number of microsystem technology methods, so that in principle a large number of embodiments of the plastic molded parts are conceivable.
• the molded plastic parts have, for example, rectangular shapes.
• a plastic block (400) is embossed by means of the mold (401), so that the plastic block (400) is designed in accordance with the mold (401).
• the molded part (403) is obtained by the first stamping step.
• the molded part (403) has a rectangular cavity (415) and a web (413) extending from the edge (416).
• the molded part (403) is then shaped in a second stamping step by means of the mold (402).
• the second embossing step forms recesses for an inlet opening (411) and an outlet opening (412), which extend through the wall (416), and a recess in the web (413) through which the feed line (413) of the outlet opening (412 ) the completed device is made possible.
• the molded part (404) can be combined both with a molded part (404) that is identical to it, as well as, for example, with a molded part (403) that is obtained after the first embossing step.
• Figure 5 shows a microfluidic flow system that uses a hollow body (10) for gas separation.
• the cave body (10) is connected to a fabric guidance system.
• the material control system has a connection (300) which is connected to the inlet opening (11) of the hollow body (10).
• the system also includes a pump (301).
• the pump (301) conducts liquid from the liquid reservoir (302) by means of a suitable one Hoses (303) to the connection (300) of the inlet opening (11).
• the liquid flows through the inlet opening (11) of the hollow body (10) into the cavity (15) in which gas separation takes place.
• the gas separation is illustrated in FIG. 5 by the representation of a phase boundary (19).
• the separated gas collects in the gas bubble (20).
• the essentially gas-free liquid is passed through the feed line (13) to the outlet opening (12), while the gas (20) remains in the hollow body (15).
• the essentially gas-free liquid passes through the connection (304) of the material control system from the outlet opening to the microdialysis probe (305).
• the connections (300 or 304) of the inlet or outlet opening are connected directly to the liquid reservoir (302) or to the milk dialysis (305), so that no additional hoses (303) are necessary are.
• the hollow body (15) is positioned upstream of the microdialysis (305) so that the liquid reaches the microdialysis essentially gas-free. With a defined amount of liquid, an exact measurement of an analyte to be examined is now possible.
• the volume of the gas bubble (20) is decisive. It is important to ensure that the volume of the gas bubble does not increase to the extent that the gas bubble comes into contact with the inlet (21) of the feed line (13). Before the gas bubble comes into contact with the inlet (21), the hollow body (10) is removed from the flow system as a disposable unit.

Landscapes

• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Clinical Laboratory Science (AREA)
• Analytical Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Hematology (AREA)
• Dispersion Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Sampling And Sample Adjustment (AREA)
• Separation Using Semi-Permeable Membranes (AREA)
• Degasification And Air Bubble Elimination (AREA)
• Physical Or Chemical Processes And Apparatus (AREA)
• Jet Pumps And Other Pumps (AREA)

Applications Claiming Priority (3)

Publications (1)

Family

ID=7695875

Family Applications (1)

Country Status (7)

Families Citing this family (13)

Family Cites Families (16)

• 2001
  • 2001-08-18 DE DE10140565A patent/DE10140565B4/de not_active Expired - Fee Related
• 2002
  • 2002-08-13 US US10/487,101 patent/US7682430B2/en not_active Expired - Fee Related
  • 2002-08-13 JP JP2003520467A patent/JP4113841B2/ja not_active Expired - Fee Related
  • 2002-08-13 CA CA002457629A patent/CA2457629C/en not_active Expired - Fee Related
  • 2002-08-13 WO PCT/EP2002/009040 patent/WO2003015919A2/de not_active Ceased
  • 2002-08-13 AU AU2002327829A patent/AU2002327829A1/en not_active Abandoned
  • 2002-08-13 EP EP02762441A patent/EP1425100A2/de not_active Withdrawn

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events