CN101657150B - Sensor for an analysis system - Google Patents
Sensor for an analysis system Download PDFInfo
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- CN101657150B CN101657150B CN2008800030654A CN200880003065A CN101657150B CN 101657150 B CN101657150 B CN 101657150B CN 2008800030654 A CN2008800030654 A CN 2008800030654A CN 200880003065 A CN200880003065 A CN 200880003065A CN 101657150 B CN101657150 B CN 101657150B
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- A61B5/14525—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis
- A61B5/14528—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis invasively
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- A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
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- A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
- A61B5/1459—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters invasive, e.g. introduced into the body by a catheter
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Abstract
An analysing unit for a system for analysing a fluid, the analysing unit comprising a first fluid communication link for communicating fluid with a base station, a second fluid communication link for communicating fluid with a substance collecting device, and sensing means adapted to provide data representing a content of a substance in the fluid.
Description
Technical field
The present invention relates to a kind of system for analysing fluid, particularly, measure the content of material in the fluid.This system comprises analytic unit and material gathering-device.
Background technology
The system of the above-mentioned type can be used for measurement of species in the concentration of fluid, for example measures the material in the body fluid, for example measures glucose.
In medical skill or scientific domain, such as the supervision of chemical process, can be accurately and measure continuously in such as the material of tissue or in such as some fluids of body fluid the importance of concentration of material well known.A kind of important medical application is the concentration of chemical substance in the monitoring bio environment, as the glucose level in the monitoring of blood.
For diabetics, monitoring glucose level is vital, because the raising of glucose in blood level represents such as produce or utilize the inadequate hyperglycemia that causes or the situation of glycosuria owing to insulin.Perhaps, abnormal low glucose concentrations can be the signal of insulin surplus.Therefore, the measurement of blood sugar concentration is the important tool of diagnosing, treat or control various imbalances, and wherein in described imbalance, known glucose concentrations is the indication of situation existence or the order of severity.Thereby have following emergency, namely existing amount of insulin is to surpass or be less than to process at any time the needed amount of particular glucose level.When diabetic individual this stress situation under, such as operation or farrowing interval, this situation is especially serious.
Be not only diabetics, also can need to monitor their blood sugar level for the ND, such as the acute patient of the corticosteroid treatment of using pharmacology dosage.
In biotechnology, other interested application be keep and control nutrient in the cell culture reactor, such as the specific concentration level of glucose, wherein need long-term stability to control computerization for the required feedback information of medicine system to provide, thereby specific chemical drugs can be maintained in the pre-set limit.
Measure particular chemicals in the solution, illustrate in many files such as the example of the concentration of glucose, such as WO9939629A1 and US4452887.The latter has described a kind of assay method, wherein uses oxydasis test material or its product, and determines by the whole bag of tricks with the hydrogen peroxide that oxidation forms simultaneously.This becomes very important recently.Reason is that the mensuration of hydrogen peroxide can at the color producing reaction (dye-forming reaction) that uses peroxidase afterwards by the colorimetry Accurate Measurement, perhaps be passed through electrode reaction.According to US4452887, the known colorimetry of using Trinder reagent based on aforementioned principles.Adopt the method, hydrogen peroxide and peroxidase reaction that the oxide enzyme reaction forms, with the oxidation coupling reaction of catalytic amino peace body than woods and phenol, colorimetric method for determining is passed through in the dyeing that forms thus.The value of response system is that the same detection system can be used for oxidase not of the same race, and system to the application of various analyses just under study for action.In these oxidase, especially the important enzyme in the clinical chemistry has glucose oxidase, cholesterol oxidase, uricase, glycerol oxidase, phosphoglucose oxidase etc.
For improved system, can introduce enhancer, such as what in WO9105872A1, describe, it has described a kind of chemiluminescence assay method of enhancing, wherein such as the DPD (dihydrophthalazinedione) of luminol (luminol) reagent, such as the peroxidase of HRP and such as the oxidant of H2O2 in the situation that exist and jointly react such as (p)-iodophenol.Enhancer produces by the enzymic catalytic reaction of positive enhancer (pro-enhancer), and for example (p)-iodophenol is decomposed by alkali phosphatase (alkalinephosphatase), and this endonuclease capable is chemically examined but not peroxidase.Selectively, add enhancer, such as the anti-enhancer (anti-enhancer) of (p)-nitrophenols by such as pNPP (p-NitrophenolPhosphate) just-enzymatic reaction of anti--enhancer produces, and the minimizing of luminescence emissions is measured.
This chemiluminescence chemical examination is described to " enhancings " in the sense: the total light yield of reaction and/or signal/background compares total light yield and the signal/background ratio that obtains greater than the same reaction of carrying out in without the reinforcing agent situation.
Known general patient monitoring system, a kind of surveillance as having described among the US3972320, when situation about monitoring when monitoring station surpassed predetermined threshold, it produced alarm at central station.This surveillance is particularly suited for monitoring the important function of a plurality of patients in the hospital, and therefore a person on duty can be warned whether any client need emergent management is arranged.Monitor unit can be carried by patient, and with the form of wrist accessory, the communication line of suitable wireless radio transmission is provided for the one-way transmission from the monitoring station to the central station suitably.Each monitoring station development and deal with data are to determine whether situation about monitoring has value to surpass and limit boundary; If have, confirmation signal is transferred to central station, has the signal of emergency to send monitoring station.Each monitoring station all comprises the data processor that is composed of program, thereby does not need variable data is transferred to central station.In order to confirm the purpose of monitoring station, only data fixing or storage are transmitted.The processor electronic component is properly mounted in the large-scale integrated circuit.
Multiple systems has been developed for this continuous material and has measured, and has described a kind of implantable sensing arrangement with long-time stability such as WO99/39629.This sensing arrangement utilizes the microdialysis Sampling techniques, and comprises the miniflow reservoir, and it makes reagent and target chemical qualitative response, and is connected to the sensor of miniflow reservoir, and it is used for surveying the reaction of reagent and target chemical matter.Sensor can comprise thermopile or optics battery (optical cell).
In a sensor construction, invention comprises: (i) optics battery and (ii) microdialysis tube for transfusion.This sensing arrangement combines the microdialysis Sampling techniques with the micro-fluidic system that utilizes the optics battery, to produce the system that can accurately measure with the concentration of glucose in the complex solution of protein and other chemical substance.In the described embodiment of this document, the biochemical sensitive system comprises the pressurizing vessel that has for the contraction bag that keeps reagent, calibration solution and scanning solution (sweep solution).Flowing of they regulated by resistance tube, and as previously mentioned, the diameter of this resistance tube and length can be selected, to realize the typically flow rate of per minute time microlitre mode.
Scanning solution is by connection tube, typically microporous pipe is directed to the microdialysis fiber, and this microdialysis fiber spreads and contacts (diffusive contact) with experimental enviroment, biological example reactor perfusion loop.With the speed of 300nl/min roughly and about 2 minutes dead time by about 10 to 2000mm microdialysis fiber, the target chemical matter concentration in the scanned fluid can reach and the experimental enviroment diffusive equilibrium.The dialysis solution that returns (that is the scanned fluid that, comprises target chemical matter) then mixes with particular agent.Mixed solution moves along single tube or capillary tube, and wherein the chemical reaction of reagent and glucose carries out, and optical change generation, i.e. reagent-dialysis solution mixing volume.The stream that flows is measured by the optics battery with light emitting diode and microdiode photodetector (optical cell) the absorption of the chemical-sensitive dyestuff of stable color.The photo detector signal that produces is calibrated about concentration of glucose by microcontroller.
The microdialysis that contacts with testing liquid, be also referred to as the film doughnut and made by the material of permeable glucose, but do not comprise the macromolecule material.Typically, the microdialysis tube for transfusion is made by following material, and such as cellulose acetate, polysulfones and polyacrylonitrile, form is diameter 200 micron-sized hollow pipes usually.Select the reagent that mixes mutually with scanned fluid, thereby their color or fluorescence has the special response for the biochemical substances that requires, as known in the art.
Optics battery measurement color or change in fluorescence at the receiving terminal place of mix reagent stream, and be associated with chemical substance concentration by microcontroller from the signal of its acquisition.
Miniflow reagent reservoir can be connected to sensor away from sensor and by the conduit that comprises microporous pipe (microbore tubing).Typical embodiment is, contains the reservoir of enzyme or chemical system away from sensor, and the conduit of the appropriate length by having microporous pipe and electric lead is connected to sensor.The form of this system also can be the reservoir of little storage, may be the size and shape of pacemaker, and it comprises the device that recharges be used to the syringe needle that passes the container septation.This system can be by recharging with the similar mode of implantable drug-supplying system, and barrier film is pierced through by percutaneous syringe needle thus.
Yet be mixed into scanned fluid when a plurality of reagent fluids, perhaps during sample fluid, this system is not very suitable.If before adding the second reaction liquid, first fluid needs fully mix especially this situation with scanned fluid.Reason is, needs connection tube for scanned fluid reagent fluids different from each, and needs other pipe after each mixes, with before interpolation novel agent fluid so that the response time complete.This will need the connection of a plurality of different pipes, increase thus a plurality of manufacturing steps, and damage one probability in the little and relatively frangible pipe.Further, consider the microsize of pipe, may be difficult to they correct also evenly alignment, therefore fluid to be mixed also mixes with predetermined layer and design layering.
Other method that stream is communicated with per minute microliter amount level comprises the microchannel that forms with silicon or glass, is used for chemical analysis.An example is to be used for US5,644, the system of the injection flow analysis described in 395, wherein a small amount of chemical reagent and sample mutually mixed being incorporated in this running system react, wherein size is guaranteed Capillary Flow, and product by optically, electrically or alternate manner detect.Mobile for regulating, little valve is mounted from the teeth outwards.Capillary channel comprises be used to the part that fluid is mixed, and is used for the part that generation need to be reacted, and probe portion.
Also known to the technology of utilizing chemical reaction to analyze in the microdialysis field, monitor constantly material, such as the concentration of glucose in tissue.At US5,640,954, in the microdialysis probe implanting tissue, and to be given by perfusion of fluid and to be sent, this perfusion of fluid is removed as sample after being rich in the material of self-organizing.Fluid is guided through guard system, and wherein enzyme is added and electrochemical sensor records measurable chemical reaction.Flow rate in the system is quite little, and its scope is that 0.1 microlitre per minute is to 15 microlitre per minutes.Mobile for producing, introduce the first and second transmitting devices, preferably with rotation or piston pump, wherein compactness arranges and will use single pump (single pump) also by using the management and control flow rate processed of different-diameter.
At another US6, in 572,566 the patent, the idea that is flowing in the groove is combined with the direct analysis of body fluid.System comprises the integrated reservoir that is connected to groove, and exchange area, from entering groove around the material of body fluid by exchange area, for example passes through dialyzer.In order to transmit fluid, pumping system is recommended based on pressure vessel, is filled with the pressure vessel of gas-pressurized and contacts with the second container that is divided into two parts by compliant member.First comprises liquid, and second portion holds gas-pressurized, makes the compliant member displacement, and liquid is clamp-oned tank systems.Current limiter with the amount of liquid of restriction from the reservoir appearance, and makes constant flow in the pumping system downstream.
File WO2005111629 has described a kind of be used to utilizing fluid media (medium) to analyze the micro-analysis system of species, described system comprises for the sensing device from the medium collection species, described sensing device has entrance and exit, the analytical equipment that comprises groove, described groove is defined at least a portion of mixing, the at least a portion that is used for reaction, measure detecting structure to be determined at least a portion of described measurement section office species concentration with being used for, the first fluid reservoir that keeps carrier fluid, with at least one the second fluid reservoir that keeps reagent fluid, connecting device, it comprises the first connecting device that connects for the fluid between first fluid reservoir and the analytical equipment, and be used for the second connecting device that the fluid between the entrance of second fluid storage part and sensing device connects, and be used for the outlet of sensing device and the 3rd connecting device that the fluid between the analytical equipment connects, described the first connecting device comprises that at least one first current-limiting apparatus and described the second connecting device comprise at least one second current-limiting apparatus, it is characterized in that described micro-analysis system further comprises the storage device with described first fluid reservoir and described second fluid storage part, described storage device is connected with the device fluid that is used for the pressurization of described fluid storage section in the downstream, and described storage device separates with described analytical equipment with described pressue device.
Yet in this document, analytical equipment (50) is the integration section of analytical system (200), also comprises reservoir (12-15) and pressue device (1).Therefore, consider: for example system moves to monitor patient's physiological conditions, this system can not be in conjunction with following: patient needn't put on whole analytical system (200) convenience, sample device (60) is connected to the short response time of analytical system (200) by adopting short tube, and the mobility of this short tube reduction that will bring to patient.
Summary of the invention
The objective of the invention is to improve said system, and realize such system, wherein the material in the fluid is measured continuously, and this system has the independent use part cheap and that easily exchange that is easy to make.
Therefore the present invention relates to a kind of system for analysing fluid, this system comprises preferred reusable base station, preferably away from the analytic unit of the disposable use (single-use) of the cheapness of base station, and away from the base station and away from the disposable use material gathering-device of the preferred cheapness of analytic unit, the first fluid communication line that is used for communication of fluid between base station and analytic unit, and be used for the second fluid communication line of communication of fluid between analytic unit and material gathering-device, wherein analytic unit comprises sensing device, described sensing device is suitable for providing the data of content of material in the expression fluid, and wherein the base station comprises data processing equipment, and this data processing equipment is suitable for processing the data that provide about the information of content of material in the fluid.
The first fluid communication line has the flow resistance less than second fluid communication line, and in order to ensure the response time that shortens material gathering-device collection of material sample, the second fluid communication line is shorter than first fluid communication line, and this also is the reason of introducing remote analysis unit.
The base station comprises accountant, and cheap disposable stocking system, and this stocking system is connected to analytic unit by the first fluid communication line, and wherein stocking system can be dismantled from accountant.The base station further comprises pumping installations, and this pumping installations can and be dismantled from analytic unit thus from the stocking system dismounting.Separate so that easily replace the wet end of using with the new wet end the sterilization wrap from disposable stocking system, analytic unit and material gathering-device (being referred to as wet end) this reusable base station.
For the transmission of data and/or energy, analytic unit and accountant electrical communication.
In order to ensure the fluid that does not have in the exterior materials pollution stocking system, stocking system comprises the flexible reservoir of at least one and pressure chamber pressure communication, this pumping installations, thus with the liquid extruding stocking system and does not directly contact with fluid all the time with air or fluid filled pressure chamber.
This measurement investigate the optical change of material concentration to produce expression, so analytic unit comprises the optical pickocff that is arranged to the micro-fluid chip optical communication based on adding fluid to sample fluid.
Preferably, analytic unit and material gathering-device are made by the material monolithic that allows nuclear magnetic resonance scanning at least.
Analytic unit is used for the content of material of analysing fluid, and therefore comprises sensing device, and it is suitable for providing the data of content of material in the expression fluid, and wherein sensing device comprises:
-have an analysis micro-fluid chip of at least one analysis vat; With
-optical pickocff.
The reaction that obtains optical change is carried out in analyzing micro-fluid chip, and in order to ensure the abundant mixing of fluid, at least one analysis vat of analyzing micro-fluid chip comprises circuity part.
Can observe optical change in order to ensure optical pickocff, at least part of of this at least one analysis vat covered by transparent top.
In order to distribute a fluid to the analysis micro-fluid chip, it is communicated with at least one afflux chip concentrated flow body of afflux micro-fluid chip.
In order to ensure not having undesirable element or particulate matter to enter the analysis micro-fluid chip, then filter is disposed in the afflux micro-fluid chip and analyzes micro-fluid chip.
For regulated fluid flowing in system, at least one that analyze in micro-fluid chip and the afflux micro-fluid chip comprises at least one groove, and slot part of the flow resistance of the increase of providing is provided for it.
Preferably, the flow resistance of increase is provided by a capillary tube that is arranged in the groove.
Owing to measuring based on optical detection, therefore importantly guarantee do not have external light source to enter analytic unit, therefore supporting construction is arranged in optical pickocff and analyzes between the micro-fluid chip, supporting construction comprises the first window, and described the first window is arranged to help optical pickocff and analyzes optical communication between the micro-fluid chip.
For guaranteeing stability, optical sensor arrangement is in depression, and this depression is arranged on the first side of supporting construction, and optical pickocff is fixed in the shell that comprises the second window, and this shell and sensor localization are in depression, thereby the first window aligns with the second window.
For guaranteeing to analyze the free optical communication between micro-fluid chip and the optical pickocff, and guarantee that the reaction that obtains the detectable effect of optics has enough time, analyzing micro-fluid chip and comprise the transparent top that covers at least one circuity part, aligns with the first window in the top.
For reservoir is easily constructed, it comprises:
-element on the pressure side, it has the inner surface that forms the opening that leads to first group of chamber;
-fluid side element, it has the inner surface that forms the opening that leads to second group of chamber; With
-flexibility or deformable film,
On the pressure side element becomes opposite inner surface on the opposition side of film with the fluid side arrangements of elements, the register in the chamber on the opening that therefore leads to the chamber on the side of film and the opposition side that leads to film, and film makes the chamber on film one side separate with chamber on the film opposition side, on the pressure side the inner surface of element comprises the first pattern recess, with film, chamber and the fluid between the outside that this first pattern recess forms first group of chamber are communicated with.
For guaranteeing the fluid issuing of fluid in the reservoir, the inner surface of fluid side element comprises the second pattern recess, and this second pattern recess is communicated with chamber and the fluid between the outside that film forms second group of chamber.For guaranteeing that further film never blocks fluid issuing, at least one in the first and second pattern recesses extends in the chamber.
For forming groove from the first and second pattern recesses, at least one in the element is connected to film, preferably by welding, such as laser weld or ultrasonic bonding.
Barometric gradient in order to ensure the film both sides can be with the liquid extruding reservoir, in the first embodiment, film comprises flexible portion, its other parts than film have more elasticity, flexible portion is between the chamber of alignment, and wherein flexible portion is suitable for being badly deformed at least one shape in two chambeies on each side of flexible portion.
In a second embodiment, membrane portions is shaped as the interior shape that at least roughly cooperates at least one in the chambeies of two alignment.
Be the chamber of sealant flow side element, film also is connected to the fluid side element around the recess of the second pattern recess around the marginal portion in second group of chamber.
Equally, for the chamber of sealing load side element, film also is connected on the pressure side element around the recess of the first pattern recess around the marginal portion in first group of chamber.
For preventing from using flowing of front fluid, the fluid side element comprises the valve through hole, wherein film centers on the valve through hole to being connected to the fluid side element, therefore at least one another valve through hole on the inner surface of each valve through hole and fluid side element is centered on by engaging zones, along described engaging zones, film is connected with the fluid side element.Then, removable valve portion be positioned to first end on the flexible membrane flexible membrane is pressed on the fluid side element, block thus any fluid intake that passes the valve through hole.
For the fluid between two valve through holes realizing every a pair of valve through hole is communicated with, the fluid side element is connected to the afflux element with afflux recess, and this afflux recess forms the interior geometry in the afflux component inner surface.The afflux element is connected to the fluid side element, and wherein inner surface is towards the outer surface of fluid side element, and outer surface is opposite with the inner surface of fluid side element.
The second pattern recess is communicated with afflux recess fluid by storing through hole, and the fluid that the afflux recess produces between the second pattern recess and the valve through hole thus is communicated with.
In order to store safely the waste liquid that returns from analytic unit, in reservoir, introduce waste chamber, it is communicated with first's fluid of recess in being formed on the fluid side component inner surface, the first of recess is communicated with the first check-valves vented liquid, and the second portion of recess is communicated with the second check-valves vented liquid, wherein the internal fluid communication of each in the check-valves through hole and the check-valves geometry of the afflux element that is furnished with check-valves guarantees that the fluid via check-valves is communicated with between the first and second check-valves through holes.
Waste chamber is formed by the waste chamber in the inner surface that is arranged on the fluid side element at least in part.
If the afflux element is not fluid-tight to the connection of fluid side element, for the mixed occurrence guaranteeing not have fluid in the afflux recess, drain tank is arranged between any two adjacent afflux recesses, rhone is parallel to any two adjacent afflux recesses.
For guaranteeing simply also can connect and removably connect fast between pumping installations and the stocking system, be connected with positive connector, and seal member, the sealing parts are fixed in the groove of positive connector, negative connector forms the chamber that holds positive connector, and seal member is slightly larger than the chamber, so when positive connector is contained in the negative connector, the inwall of seal member engagement cavity.
Description of drawings
Fig. 1 has shown whole system;
Fig. 2 has shown whole microdialysis probe;
Fig. 3 A﹠amp; 3B has shown whole micro-fluid chip;
Fig. 4 A﹠amp; 4B has shown the pipe that is connected with passage fluid in the micro-fluid chip;
Fig. 5 has shown the stocking system that comprises fluid;
Fig. 6 has shown bottom and the afflux element of stocking system;
Fig. 7 has shown the rough schematic of fluid storage section;
Fig. 8 A-8C has shown fluid storage section, space, full and at system's run duration;
Fig. 9 A﹠amp; 9B has shown two kinds of forms of waste liquid chamber;
Figure 10 has shown the block diagram of base station;
Figure 11 has shown the feature of drainage channel;
Figure 12 has shown the pump connection;
Figure 13 has shown the analytic unit system;
Figure 14 has shown the analysis micro-fluid chip;
Figure 15 has shown the afflux micro-fluid chip;
Figure 16 has shown the filter that filters in the recess;
Figure 17 has shown the reducer set;
Figure 18 has shown the reducer that inserts in the passage;
Figure 19 A and 19B have shown another selection of the afflux element of stocking system; With
Figure 20 A and 20B have shown another selection of valve.
The specific embodiment
It below is the detailed description of the preferred embodiments of the present invention.
Fig. 1 has shown the system (1) of the concern material of the medium that is used for measurement such as gas or fluid, and wherein in more specific examples, described medium is blood or bodily tissue.In a preferred embodiment of the invention, system (1) comprises base station (2), this base station (2) comprises the interchangeable fluidic component with fluid and optionally has pump installation, and electronic unit, this electronic unit comprises for the computer that stores and may deal with data and is used for the display of display measurement value.Be connected to civil power, perhaps optionally, portable computer especially comprises its oneself power supply, such as battery or fuel cell optimum system choosing.
Base station (2) is communicated with analytic unit (3) fluid by first fluid communication line (4), this first fluid communication line (fluid communication link) (4) preferably in the medical injected system field the commercially available flexible pipe of common type of service.Analytic unit (3) is preferably tied up arm or the wrist of the patient under monitoring, may pass through patch, and comprises the sensing device of analyzing for carrying out material concentration.Be used for being communicated with analytic unit (3) fluid by second fluid communication line (7) from the material gathering-device (5) of tissue (6) collection of material.Electrical interconnection (8) is guaranteed one or more operations that analytic unit is connected with power supply, and the numeral that will measure or analog data are transferred to the base station and/or from the base station from analytic unit.In specific embodiments of the present invention, this can be substituted by radio communication.
Fluid communication line road (4) is included in the set of a plurality of single tubes (408) in the common coating, as illustrating after a while.
Material gathering-device (5) is the structure that can collect from medium (6) any type of paying close attention to material, but in a preferred embodiment of the invention, it is commercially available microdialysis probe, or a kind of like this probe, wherein: infusion liquid is transferred to the first side of semipermeable membrane and the second side of this semipermeable membrane contacts with medium (6).When infusion liquid during along membrane flow, because they diffuse through film from medium (6), so it collects related substances, and this is rich in the infusion liquid of material fluid, is called sample fluid now, then takes out from film to be used for further analyzing.The exemplary embodiments of this probe has been described among the WO9413195A1.
Fig. 2 has shown the simple view of this probe (5), the wherein end (11) of tubulose semipermeable membrane (10) sealing, and near-end (12) is around connecting fluid in front conduit (13) and rear fluid conduit systems (14).Perfusion of fluid is supplied to film inside (15) by the fluid in front conduit, and flows out by the rear fluid conduit systems.(13) are sent to rear (14) fluid conduit systems from the place ahead owing to perfusion of fluid, and it collects the material that sees through the film diffusion from surrounding medium (6).Thereby, be rich in material perfusion of fluid, be called sample fluid, leave by rear fluid conduit systems (14).
Conduit (13,14) is the commercially available fluid migration pipe of standard preferably, and its size is at micron order, as the coated glass pipe, inside diameter ranges at 5-50 μ m and the external diameter scope at 500-1000 μ m.Yet, also can use other material.Conduit (13,14) can be arranged to single pipe, perhaps comprises the single tube of two conduits (13,14) side by side, perhaps can be the concentric system of a conduit in another.
Replace tubular film (10), can adopt in a conduit (13,14) and window.
Fig. 3 A has shown whole micro-fluid chip (20), and wherein substrate (21) has groove on a surface, forms flow path (22).Although it is called as plate, can adopt to have the arbitrary shape that at least one is suitable for forming the surface of flow path.
Substrate (21) preferably wherein forms the substrate of flow path.It can be made by polymer material, include but not limited to, polystyrene (PS), polymethyl methacrylate (PMMA), polyethylene terephthalate (PETG), cyclic olefine copolymer (COC), and/or any appropriate polymer material.Optionally, substrate can be made by other suitable material of non-polymeric body.Can use any appropriate kind technology in substrate, to form flow path, such as etching or hot-forming, perhaps can use the injection molding technology to make substrate, in the case, in substrate, form flow path during the manufacture process.Optionally, can form the first flow path with own known any other appropriate technology in the prior art.Flow path will normally be formed in the surface portion of substrate.
By utilizing top board (23) covered substrate (21), make flow path (22) fluid-tight, wherein the first top board can be the size plate similar to the size of substrate (21), perhaps thin foil, and align with substrate (21), make thus flow path (22) form passage (26).Top board can be the material identical with first substrate, or other suitable material, as above-mentioned, and in a preferred embodiment, it has general plane and smooth surface, may have the through hole (25) that aligns with flow path (22), realize that passage (26) is to extraneous path.
Preferably, top board by laser weld, ultrasonic bonding, thermal weld or arbitrarily other welding method be connected to substrate, but can use arbitrarily other method, as glueing joint by any known means or bonding.It can be connected to the whole surf zone that substrate does not have flow path, perhaps only centers on the edge of flow path.
Fig. 3 B has shown the specific embodiments of similar whole micro-fluid chip (20), wherein top board (23) is the mirror image of substrate (21), also comprise flow path (22b), therefore when two plates (21,23) connect, flow path in the top board aligns with the flow path (22a) of substrate (21), the passage (26) that forms is partly in substrate (21), partly in top board (23).
Fig. 4 A illustrates the side view of whole chip (20), its mesopore (30) penetrates the side of substrate (21), hole (31) penetrates the bottom of substrate (21), and the hole (25) on hole (32) and Fig. 3 A penetrates top board (23).Below, any this type of produce path from passage (26) to the external world, penetrate substrate (21) or top board (23) or both holes (30,31,32) and be referred to as opening.
The pipe that picture forms first fluid communication line (4) is connected to opening in the following manner: they are pressed towards top board (23) or substrate (23), image tube (33) is pressed towards the side of substrate (21) respectively, and inner flow passage is alignd with opening (30).Some fluid encapsulation material also can be inserted between pipe and substrate or the top board, to produce from managing inner fluid-encapsulated connection to passage (22).Optionally, tube portion ground or fully penetrate opening, image tube (35) pass opening (32) or pipe (34) inserts in the those widened sections (36) of openings (31).
Fig. 4 B has shown the method that multi-lumen tube (37) is connected to micro-fluid chip (20), as seen have two passages such as top view, wherein be connected to the first passage of micro-fluid chip (20) end-opening at least one chamber (38) fluid, and at least one of other chamber is connected to second channel by the opening of a side at pipe (37), but may utilize some plugs (40) in the end-the opening part sealing.
Fig. 5 has shown the stocking system that comprises pressure structure (100).The critical piece of pressure structure (100) be upper element (perhaps on the pressure side element) (100a), lower element (perhaps fluid side element) (100b), paper tinsel or film (120) and afflux element (130).
On the pressure side element (100a) has first group of shape or geometry (101-105), and fluid side element (100b) has second group of shape or geometry (111-115), first and second groups of geometries are outside profile in the plate that consists of main body (100a, 100b), first group of geometry of upper main body roughly becomes mirror image at second group of geometry of size and dimension up and down main body.The combination internal volume of the inner volume of first group of geometry (101) and first group of geometry (102-105) is roughly the same, and accordingly, the combination internal volume of the internal volume of second group of geometry (111) and second group of geometry (112-115) is roughly the same.
On the pressure side element (100a) has inner the first pattern recess (141, see for example Fig. 7), with the adapter (311) that pump connects (310) that is connected internally to of first group of geometry (101-105), sees Figure 12.These recesses can be separately connected to adapter (311), but preferably, only one first group geometry (101-105) is directly connected to adapter (311), and first group of geometry is connected to each other by the first pattern recess.
The paper tinsel of flexible material or film (120) have been positioned on the pressure side between the element (100a) and fluid side element (100b), and wherein flexibility is interpreted as: easily bending of material and not damaged, but needn't have any obvious elasticity.Film (120) has part (121-125), and its form fit is to first group and second group of geometry (101-105,111-115), and wherein shape is preferably by vacuum mo(u)lding and/or punching press or punch die formation.
Optionally, for the barometric gradient of guaranteeing the film both sides can be with the liquid extruding storage compartment, in another embodiment, film (120) can comprise flexible portion, its other parts than film have more elasticity, flexible portion is between the chamber of alignment, and wherein flexible portion is suitable at least one that substantial deformation becomes two chambers being arranged on each side of flexible portion.
Element (100b, 120) preferably is connected 121-125 by paper tinsel or film (120) being thermally welded to the upper second group of geometry (111-115) that center on of fluid side element (100b) with membrane portions) the edge connection.But can use arbitrarily other connected mode, as bonding, Laser Welding or ultrasonic bonding.
Preferably, on the pressure side element (100a) also is connected to film (120), in itself and the surperficial relative surface that is connected to fluid side element (100b), this preferably realizes by the ultrasonic bonding around edge (106,107), but also can use the arbitrarily method of other Connection Element, as bonding or laser weld.
Preferably, all fluid side geometries (112-115) are equipped with the recess (117) of the second pattern, this recess (117) has and penetrates the on the pressure side reservoir through hole (119) of element (100b), wherein the second at least part of pattern recess (117) aligns with protrusion (127) in edge (107), and as seen the second pattern recess (117) of part is positioned at second group of geometry (112-115) inboard, as scheme upper.Second group of geometry (111) has the waste material recess (116) that aligns with edge protrusion (126), wherein this waste material recess (116) has two independent parts, first's waste material recess has the first check-valves through hole (118a), and second portion waste material recess has the second check-valves through hole (118b).
The edge protrudes (126) around waste material recess (116), the first and second check-valves through hole (118a, 118b), and a plurality of valve through holes (128) are gone back through flow body side member (100b), its mode is: the edge protrudes free island section or the connecting portion (108) that (126) comprise the flexible membrane (120) that covers the second through hole (128), every a junction (108) covers a pair of valve through hole (128), its mode is: another of each valve through hole (128) and valve through hole (128) is paired, and connecting portion (108) produces fluid and is communicated with between them.
Afflux element (130) is connected on the pressure side element (100b) in the surface opposite with film (120).Afflux element (130) has the first afflux recess pattern (131) and the second afflux recess (133) that is formed in the surface, and wherein the first afflux recess (131) is connected to reservoir through hole (119) and valve through hole (128).Recess (131,133) can have the recess of mirror image in the surface of fluid side element (100b), when afflux element (130) is connected 100b with the fluid side element) when connecting, form passage.The first and second check-valves through holes (118a, 118b) are communicated with inside (132) fluid of the check-valves geometry (143) that wherein is furnished with check-valves (142).
Because the first afflux recess pattern (131) is connected to valve through hole (128), inside and the fluid between the second afflux recess (133) of therefore having set up second group of geometry (112-115) connect.In the same manner, the second portion of waste material recess (116) is connected in the second through hole (128), and the fluid of setting up between in the inside of the second pattern geometries (110) and the second afflux recess (133) connects.
Two elements (130,100b) preferably connect by ultrasonic bonding, laser weld, perhaps connect two objects with any other known way.The first afflux recess (133) comprises fluid openings (134), perhaps in the side of element (100b) and/or (130), as scheme upper finding, perhaps by one in one upper surface in element (100b) or (130) or the lower surface.
Valve (135) is positioned to connecting portion (108) that first end (136) presses flexible membrane (120) downwards to lower element (100b), stops thus anyly to enter by the fluid of valve by hole (128).Second end (137) of valve (135) passes otch (138).Valve (135) is preferably made by the soft material of some cardinal principle, as rubber.When default became work, valve (135) was removed, and preferably irreversibly removes, and discharged thus entering by the fluid of valve by hole (128).
On the pressure side element (100a), fluid side element (100b) and afflux element (130) preferably are equipped with pin and hole, when element (100a, 100b) connects, pin fits into corresponding hole, thereby guarantees the abundant alignment of element, and obtains stable connection.
Fig. 6 has shown the afflux element (130) that is connected to film (120) and fluid side element (100b) and element (100a) on the pressure side.
Two check-valves through holes (118a) and (118b) between fluid be communicated with by check-valves (142) and realize, its only guarantee to flow can be from check-valves by hole (118b) to (118a), and can not be conversely.Check-valves (142) is the commercially available duckbill valve of standard preferably, but also can use arbitrarily other check-valves.Check-valves (142) is arranged in check-valves shape or the geometry (143), it has inside (132) and passes through hole (118a, 118b) fluid communication with check-valves, and check-valves (142) is positioned in the check-valves geometry (143), and its mode is: fluid only can flow to check-valves through hole (118b) through check-valves (142) from check-valves through hole (118b).
If pipe, will insert for example recess (133) as single pipe (408, see for example Figure 15), then optionally can introduce through hole (144), wherein can insert by glue or other sticky material so that pipe is fixed in the recess.
Fig. 7 has shown the on the pressure side side view of the combined system of element (100a), flow element (100b) and film (120).When element (100a, 100b) connected, first group of geometry (101-105) alignd with second group of geometry (111-115), formed compartment (231-235) (visible compartment (231) on Fig. 9 A and 9B).Membrane portions (122-125) is separated into (perhaps pressure) chamber (242-245) and lower (perhaps fluid) chamber (252-255) with compartment (232-235), and membrane portions (122-125) adopts mode airtight or fluid-tight to make pressure chamber (242-245) and fluid cavity (252-255) sealing.
Fluid is given to the inside of fluid cavity (252-255) by the entrance (not shown), wherein entrance is to enter first group of geometry (102-105), obtain the opening that is connected with the fluid in the external world.Entrance is preferably equipped with spin locking screw thread (lure lock taps), is used for the device of conveyance fluid is connected to fluid chamber (252-255).Subsequently, entrance is closed, and preferably by utilizing thermal weld fusing spin locking screw thread, perhaps seals them with any alternate manner that seals this opening.
Fig. 8 A is side view, illustrates in the compartment (232) that is formed by first group of geometry (102) and second group of geometry (112), this figure also illustrates the first and second pattern recesses (117,141).Flexible membrane (120) is clipped between two elements (100a, 100b), thereby membrane portions (122) is divided into two chambeies (242) and (252) with compartment (232), as mentioned above, each chamber has leads to extraneous entrance, also as the above, chamber (242) is by the first pattern recess (141) in element (100a) surface on the pressure side, and chamber (252) are by the second pattern recess (117) in fluid side element (100b) surface.
In Fig. 8 B, compartment (232) is shown as that it is fluid-filled, and this fluid is in the fluid cavity (252) that is limited by membrane portions (122) and shape (112).The gas of picture air, perhaps some fluids are given by the first pattern recess (141) and are sent into pressure chamber (242), the barometric gradient of membrane portions (122) both sides is risen, and described barometric gradient guarantees that the fluid in the fluid cavity (252) is extruded the second pattern recess (117).
Fig. 8 C has shown identical compartment (232), and wherein because gas or liquid in charged pressure chamber (242), therefore a large amount of fluids have been extruded fluid cavity (252).
Fig. 9 A has shown the waste material compartment (231) that is used for storing waste liquid, it adopts to first group of geometry (101) mode similar with the compartment (232-235) of second group of geometry (111) and designs, the waste material compartment is separated into two chambers by membrane portions (121), waste chamber (241) and empty chamber (dummychambe) (251).Preferably, waste liquid imports waste chamber (251) by waste material recess (116), as in the illustrated embodiment of the present invention, yet, also can use opposite situation.Empty chamber (241) then is " virtual ", does not produce obvious counter-pressure on membrane portions (121).
Preferably, have contact free to outside atmospheric pressure by the airport (260) in first group of geometry (101), guarantee that empty chamber (241) is in than under the lower internal pressure of waste chamber (251).In the present embodiment, membrane portions (121) is guaranteed not have in the waste chamber (251) fluid to pass through airport (260) to be leaked in the environment, because it makes waste chamber (251) sealing relative to empty chamber (241).Selectively, by utilizing fluid-tight but any this type of airport (260) of film (261) sealing that can see through air can be avoided membrane portions (121), as shown in Fig. 9 B.
In certain embodiments of the invention, flow rate will for the pressure of regulating system, be regulated thus in " void " chamber.By in some way to the pressurization of the second Room, can realize it.Check-valves (142) is guaranteed not reflux to turn back to the second afflux recess (133) from waste chamber (251).
Figure 10 has shown the schematic representations of base station (2), it comprises pressure structure (100), pumping installations (202), soft copy (201), monitoring arrangement (204) and the energy (205) optionally, as battery or fuel cell.Yet, in the preferred embodiment of the invention, obtain the energy from civil power.
Interchangeable fluid section, be also referred to as wet end (200), consist of pressure structure (100), analytic unit (3), probe (5), with the first and second fluid communication line road (4) and (8), but in certain embodiments of the invention, also comprise especially pumping installations (202) and/or the energy (205).
Soft copy (201) at first is computer (203) and monitoring arrangement (204).Computer is mainly used in the Storage and Processing measurement data, but can carry out in addition other possibility task, such as set information and the information that monitors purpose, for example patient of storage system.Monitoring arrangement (204) preferably may have the standard monitor of touch screen.
The base station further comprise all field of electronic devices known to the skilled, in this electric device needed electronics and machinery.
Pumping installations is preferably sent air or some other gas or liquor pump into compressor in the pressure chamber (242-245) with certain scalable fixed rate and pressure.Arbitrarily other conceivable pumping mode also may be used on system, as fluid (gas or liquid) being extruded machinery or the electrical system of flexible container in the pressure chamber (242-245).
Wet end (200) is connected to or inserts in the base station (2) with any-mode well known by persons skilled in the art, in the cavity in the shell (or box) that puts it into base station (2), the shape of its cavity is designed to hold with fixing and firm mode upper element (100a) and the lower element (100b) of connection.
An importance of native system is that it provides following possibility: for example, the patient that wet end (200) is housed can shift between several base stations (2) of inserting wet end (200), and monitoring beginning or continuation.When moving to another place from the three unities, patient can not feel to extract probe (5) and insert again the misery of new probe, and can keep identical probe (5) and remaining wet end (200).Advantageously, wet end (200) can also comprise the device for the data of the set information of storage such as acquired measurement result and/or system, the wherein advantageously digital microchip of this device.Selectively, this data can directly wirelessly transmission between single base station.
The parts that another main aspect of the present invention is wet end (200) do not comprise metal or are a small amount of metal at least, and it does not produce with for example MRI-scanning and disturbs.
Figure 11 has shown the feature that is particularly useful for afflux element (130), but it also can be applicable on the pressure side and fluid side element (100a, 100b).Afflux element (130) is welded to fluid side element (100b) in the following manner: any two the first adjacent afflux recesses (131) are separated by welding by both sides (double welding), because this is in the situation that single welding can not fluid-tight provide extra safety.Then still exist the second welding will prevent the chance that the fluid in the first afflux recess (131) mixes.
Further security feature is introduced into the preferred embodiment of system, as its on figure shown in, wherein sump pit (300) forms along the side of the first afflux recess (131).Figure has shown the cross section of afflux element (130), two the first afflux recesses (131) have been shown, has sump pit (300) between them, afflux element (130) is arrived in the zone welding (301) of lower element (100b) between groove (131) and sump pit (300), or connects with some alternate manners.
Sump pit (300) is guaranteed can " be captured " by sump pit (300) by closely not welding the fluid that leaks, and be bled into adjacent the first afflux recess (131) at it and remove in observable mode before, may be by it be discharged to the external world from system.Can discover thus the leakage that in afflux element (130), occurs, and detection wet end (200) is replaced.
Figure 12 has shown the pump connection (310) to wet end (200), and its Air is preferred pressor substance to delivering in the pressure chamber (242-245), but also can adopt arbitrary gas or liquid.Pump connects (310) and is shown as two parts system, wherein positive connector (311) is equipped with O shape circle (312), and this O shape circle (312) is fixed in the breach (313) in the following manner: the part of O shape circle in breach (313) top and its slightly larger in diameter in the internal diameter of negative connector (314).When positive connector (311) is positioned at negative connector (314) inside, O shape circle is guaranteed the fully stable connection of being connected with fluid-tight with respect to the friction of the inwall of negative connector (314), realize that thus the fluid between manometer tube (315) and the pressure entrance (316) connects, air intake is communicated with recess (141) fluid and arrives the being seen pressure chamber of Fig. 8 A-8C (242-245) by the there.Positive connector (311) can be one integrated part in the element (100a, 100b, 130), but preferably is connected to the independent parts of pressure elements (100a).
An advantage is to keep analytical equipment near the medium of patient or investigation, and wherein analytical equipment comprises analytic unit (3), second fluid communication line (7) and material gathering-device (5).This is because the response time of system during measuring minimized, and because general patient's comfort level, wherein only this analysis part is connected to patient, and the degree of freedom of motion only is subjected to the length restriction of first fluid communication line (4) and electrical communication circuit (8).
Figure 13 has shown the preferred embodiment of the design of analytic unit, wherein analytic unit shell (330) is made of three parts, analytic unit outer casing bottom (330a), analytic unit cover top portion (330b), and analytic unit supporting construction (330c).System is with following principle work: reagent is added to the sample fluid that comprises related substances, to produce some detectable effects, thereby analytic unit comprises analysis micro-fluid chip (331), be also referred to as little laboratory, wherein reagent fluid is mixed into sample to obtain characterizing observable and measurable effect of some materials concentration in fluid, and wherein effect is that optics is detectable in a preferred embodiment.
Afflux micro-fluid chip (332) distributing fluids in system is analyzed micro-fluid chip (331) such as reagent fluid is given to deliver to, and optionally, waste liquid is discharged from analytic unit.In a preferred embodiment, the afflux micro-fluid chip also perfusion of fluid is given deliver to material gathering-device (5) to inner catheter (13), and receive sample fluid from fluid conduit systems (14) backward, it is assigned to analyzes micro-fluid chip (331).
Analytic unit supporting construction (330c) is positioned between analytic unit cover top portion (330b) and the analytic unit outer casing bottom (330a), and is designed with and adds deep (337).Sensor outer housing (336) comprises sensor outer housing bottom (336a) and sensor outer housing top (336b), and is arranged in and adds deep (337).Fluid section (331) and (332) are pressed towards analytic unit outer casing bottom (330a) in the inboard opposite surface with adding deep (337) of analytic unit supporting construction (330c), keep it to fix, advantageously, use fluid section (331,332), the roughly parts (can be rubber blanket, rubber washer or foam) of softness between analytic unit supporting construction (330c) and/or the analytic unit outer casing bottom (330a).
Analytic unit supporting construction (330c) and sensor outer housing bottom (336a) equipment are fenestrate, the first window (339) in the analytic unit supporting construction (330c), with the second window (338) in the sensor outer housing bottom (336a), be positioned to: when analytic unit is combined in a time-out, two windows alignment.Packing ring, liner or foam (341), preferably rubber or elastomeric by between analytic unit supporting construction (330c) and sensor outer housing bottom (336a), centers on window (338,339) with relatively especially external light source sealing.The sensor (333) that is enclosed in thus between the sensor outer housing bottom (336a) and sensor outer housing top (336b) only receives the light that passes window (338,339).Slide or plate (350) can be positioned at window.
Three analytic unit housing parts (330a, 330b, 330c) preferably edgewise edge connect by ultrasonic bonding, but also can adopt arbitrarily other method, such as bonding these parts.Similarly, two sensor outer housing parts (336a, 336b) preferably edgewise edge connect by ultrasonic bonding, but also can adopt arbitrarily other method, as bonding these parts.
As above described in a preferred embodiment, the measurement of material is according to optical detection, sensor outer housing (336) inside that does not therefore importantly have external light source to see through micro-fluid chip (331,332) or place sensor.Therefore, to connect be by first fluid communication line (4) to shell (330) only fluid of being designed to from the external world to the internal flow part (331,332).Only is the conductive communication circuit (8) that sensor (333) is connected to base station (2) to other extraneous connection.The first and second fluid communication line roads (4,7) and electrical communication circuit (8) are equipped with respectively plug (343,344,345), are used for sealed entry (346,347,348).
One in the major part of analytic unit is micro-fluid chip, and its execution obtains characterizing the observable of the concentration of something in fluid and the chemical reaction of measurable optical effect.
Figure 14 has shown the decision design of analysis micro-fluid chip (331), this design is identical with the design of general micro-fluid chip (20), have analytic substrate (370) and analyze top board (371), be surrounded by analysis vat system (372,375,377,379,381,382) therebetween.In the drawings, two parts (370,371) are not connected.Perfusion of fluid enters analysis vat (372) by the analysis chip opening (373) of analyzing in the top board (371).The first reagent fluid enters analysis vat part (375) by the analysis chip opening (374) of analyzing in the top board (371), and locates to mix at mixing point (376) with perfusion of fluid.Analysis vat (372) extends to the first circuitous section (377), the fluid that mixes at this place is free to be mixed mutually, and arrive the second mixing point (378) at it and react before, and mix with the second reagent fluid that enters from analysis vat part (379) and analysis chip opening (380).Analysis vat (372) extends in the second circuitous section (381), the fluid that mixes at this place is free to be mixed mutually, and arrive the 3rd circuitous section (382) at them and react before, the 3rd circuitous section (382) aligns with window (339,338), so sensor (333) has the visual angle of observing the detectable reaction of optics that occurs in the 3rd circuitous section.The first top board (371) is transparent in its zone that covers the 3rd circuitous section at least therefore.Fluid, be waste liquid at present, leave and analyze microchip (331) by analyzing opening (383).
Figure 15 has shown the preferred embodiment of afflux micro-fluid chip (332), it adopts the mode identical with general micro-fluid chip (20) to design, comprise afflux substrate (400) and afflux top board (401), these two plates (400,401) do not connect among the figure.A plurality of afflux grooves (402-407) are connected with single tube (408) fluid.Afflux groove (402-407) is connected with one group of afflux chip opening (411-413) fluid again.In illustrated embodiment of the present invention, one in the afflux groove (406) with one in the single tube (408) forward fluid conduit systems (13) that is connected to the material gathering-device (5) that is communicated with perfusion of fluid.Selectively, perfusion of fluid is all walked around analytic unit, and one in the pipe (408) is directly connected to forward fluid conduit systems (13).
By afflux chip opening (410) and analysis chip opening (373), the afflux groove in the example illustrated (407) is at the backward fluid conduit systems (14) of material gathering-device (5) and analyze and produce fluid between the analysis vat (372) in the micro-fluid chip (331) and connect.
Afflux groove (402-407) preferably is made of the flow path in the afflux substrate (400), and as described above, this flow path aligns with mirror image flow path in the afflux top board (401).
Optionally, the forward fluid conduit systems (13) of material gathering-device (5) and/or backward fluid conduit systems (14) directly be connected to and analyze micro-fluid chip (331), wherein afflux micro-fluid chip (332) will pour into and sample fluid is assigned to and analyzes micro-fluid chip (331) and from analyzing micro-fluid chip (331) distribution.
Two micro-fluid chips (331,332) and the filter between them (among 420, Figure 16 as seen) connect together, and its mode is: register is communicated with to produce fluid between the groove of two micro-fluid chips.Then example system among the figure makes afflux chip opening (410) align with analysis chip opening (373), afflux chip opening (411) aligns with analysis chip opening (374), afflux chip opening (412) aligns with analysis chip opening (380), and afflux chip opening (413) aligns with analysis chip opening (383).
Filter can selectively be located, such as the reference flow direction, just front at afflux micro-fluid chip (332) or may be just at the second afflux recess (133) afterwards, preferably it must be inserted in current limiter (501) before, below describes current limiter (501).
Two micro-fluid chips preferably connect in the mode of the end to the top, wherein the relative afflux top board (401) of analytic substrate (370) is located, but optionally, its can for the end to end mode, wherein analysis and afflux substrate (370,400) are located relative to each other, perhaps push up the top mode, and wherein analysis and afflux top board (371,401) are located relative to each other, perhaps push up end mode, wherein analyze relatively afflux substrate (400) location of top board (371).
Two micro-fluid chips (331,332) connect by ultrasonic bonding, thermal weld, splicing or any alternate manner of connecting two elements.
Figure 16 has shown a connection of two openings (421,422), wherein afflux substrate (400) is analyzed top board (371) location relatively, and filter recess or depression (423,424) form and alignment around opening (421,422).Filter (420) is positioned at and filters between depression (423,424) and two micro-fluid chips (331,332), is used for removing foul, pollutant, the microorganism of fluid and other material that may exist.Two filter depression (423,424) have increased the working region of filter.Filtering material is microporous PE S preferably, but also can the application of any suitable filter.
The optimal way of the single flow rate of regulating system is to introduce current limiter or flow restriction element in system, and wherein current limiter advantageously can be that interior cross-sectional area is significantly less than single tube (408), the first and second afflux recesses (131-133), afflux micro-fluid chip (132) and analyzes the afflux chip of micro-fluid chip (131) and the tube portion of analysis chip groove (402-407,372,375,377-379,381,382).The natural selection of this current limiting element can be commercially available silica-based microporous pipe on the market of standard, perhaps capillary tube, capillary tube has following character: for any given pressure reduction, by selecting the capillary tube of appropriate length and diameter, flow rate can be fixed on required value.
The multiple different embodiment that insert current limiter are possible, such as their being imported in first or second afflux recess (131-133) or as shown in figure 17, limitations set (500) is introduced first fluid communication line (4), wherein current limiter (501) inserts each single tube (408), increase total flow resistance of single tube (408), reduce thus flow rate.Yet, the preferred embodiments of the present invention are, current limiter (501) is inserted in the groove of afflux microchip (332), perhaps insert in the groove of analyzing micro-fluid chip (331), as show top view seen in fig. 18 of micro-fluid chip (502) and groove (503), wherein current limiter (501) is arranged in groove (503) and fixing by more one or more cohesive material plugs (504), plug (504) also is used for the fluid that seal groove flows, and forces it to pass through current limiter (501).
System in the preferred embodiment works in the following ways: the container of perfusion of fluid from base station (2) is by the forward fluid conduit systems (13) of the single tube (408) in the first fluid communication line (4) to probe (5), selectively by one in micro-fluid chip (331) or (332).In probe (5), when related substances saw through film (10) diffusion, they were collected by sample fluid.This is rich in the perfusion of fluid of material, is sample fluid now, enters the first circuitous groove (372) of analyzing micro-fluid chip (331), as previously mentioned, selectively, at first by one in the groove of afflux micro-fluid chip (332).
Sample fluid is mixed with the plurality of reagents fluid-phase subsequently.Reagent fluid from base station (2) by some single tubes (408) the first fluid communication line (4), by the opening of picture (374,380) and the slot part of picture (375,377), enter the analysis micro-fluid chip, and mix with sample fluid at the mixing point of picture (376,378).Circuitous reactive moieties (377,381) guarantees that reacting fluid fully mixes with sample fluid if having time and reacts.
Last circuity part (382) passes through the position that window (338) is surveyed at detectable optical effect by sensor (333).The data that sensor send to be measured are to base station (2), preferably by electrical communication circuit (8) or pass through wireless transmission.
Sample fluid, be waste liquid at present, leave analysis micro-fluid chip (331) by opening (383), preferably by one in the pipe of afflux micro-fluid chip (332) and fluid communication line road (4), get back to base station (2), locate it at this and be stored in certain bag, container or the chamber (231).Optionally, the direct guiding system of waste liquid.
Base station (2) comprises can process and store the computer of data, preferably also comprises the monitor for video data.Computer installation (2) also can adopt certain methods control sensor (333) and/or flow rate.
Flowing of fluid produced by the pumping installations (202) that is included in the base station (2), wherein the pumping installations in the preferred embodiment is the type of fluid storage in fluid pouch or chamber (252-255), each described fluid pouch or chamber (252-255) have at least one flexible sides or wall, with a pressure communication in the pressure chamber (232-235).Optionally, all fluid chamber (252-255) are positioned in the common pressure chamber.The pressor substance such as gas is filled in the inside of pressure chamber then, and when pressor substance made flexible sides or the relative fluid extruding of wall, the fluid in the fluid chamber was squeezed in the fluid communication line road (4) thus.
First fluid communication line (4) is a plurality of single flexible pipes (408, see Figure 15) preferably, and is known such as medical filling system field, and preferably, by consisting of as materials such as PE, PUR, PA.Single tube (408) is assembled in by in the common big envelope or shell made as materials such as PVC, rubber, PUR.In order to ensure the correct installation of pipe, especially between system's installation period, single tube preferably can be coated different colors, may also have different external diameters, is possible with only a kind of permutation and combination of installing of guaranteeing pipe.
Figure 19 A has shown the selectivity form of the pressure structure seen in Fig. 5 and 6 for example; wherein afflux element (130) protective cowl (601) of being managed (600) and protecting tube (600) substitutes; possibly, described protective cowl (601) is fixed on the pressure side element (100b) with pipe.Pipe substitutes at least the first and second afflux recesses (131,133), and fluid is connected to storage through hole (119).In preferred illustrated embodiment, pipe (600) is to extend to the single flexible pipe (408) that stores through hole (119) from common big envelope.
In the present embodiment, the valve bonnet element (602) that comprises check valve structure (143) is connected on the pressure side element (100b).Valve bonnet element (602) and on the pressure side the system of element (100b) can have recess (116,133), opening (134) and through hole (118), as the system of the embodiment seen in Fig. 5 and 6, and work in the same manner.
Figure 19 B illustrates the identical systems that Figure 19 A shows with top view, and wherein dotted line represents to have the rear side of the system of pipe (600) and protective cowl (601).The upper front side of view comprises second group of geometry (111-115), the first pattern recess (117), it produces from second group of geometry (112-115) inner by storing through hole (119) to the fluid connection of pipe (600), waste material recess (116) and have the valve bonnet element (602) of check valve structure (143).
Figure 20 A and 20B have shown the selection form of valve (135), are particularly suited for the embodiment seen in Figure 19 A and the B.The clamping element (650) that comprises two shanks (651) and have the pivoting member (652) of press element (653) is releasably connected to the structure (654) that pipe (600) does not have protective cowl (601) to locate.It is lower that structure (654) is positioned at pipe, and comprise the end (656) of compatible portion (655) to hold and to cooperate press element (653).In two shanks (651) each comprises the part (657) that clamping element (650) is fastened to structure (654), and when clamping element (650) is fixed to structure (654), pipe (600), is communicated with to prevent any fluid by pipe (600) between end (656) and compatible portion (655) by pinching.When system is set to work, two shanks (651) are pressed together around pivotable member (652), shown in arrow (658) among Figure 20 B, so that they are discharged from structure (653), and clamping element (650) then removes, and the fluid in the releasing tube (600) is communicated with thus.
Claims (16)
1. analytic unit (3) that is used for the system (1) of analysing fluid, described analytic unit (3) comprise for the first fluid communication line (4) of pressure structure (100) communication of fluid of base station (2), second fluid communication line (7) with material gathering-device (5) communication of fluid, and sensing device, described sensing device is suitable for providing the data of content of material in the expression fluid, wherein, analytic unit shell (330) cover envelope described analytic unit (3), described analytic unit (3) and described analytic unit shell (330) are in outside, base station (2), wherein, the described sensing device of described analytic unit shell (330) cover envelope, described sensing device comprises therein analyzes micro-fluid chip (331) and optical pickocff (333), described analysis micro-fluid chip (331) has and comprises at least one analysis vat (372,375,377,379,381,382) analysis vat system, and wherein, at least one analysis vat (372) of described analysis micro-fluid chip (331) comprises circuity part (377,381,382).
2. analytic unit according to claim 1, wherein, the flow resistance that described first fluid communication line (4) has is less than described second fluid communication line (7).
3. analytic unit according to claim 1, wherein, described first fluid communication line (4) is shorter than described second fluid communication line (7).
4. analytic unit according to claim 1, wherein, at least a portion (382) of described analysis vat system (372,375,377,379,381,382) is covered by transparent top (371).
5. analytic unit according to claim 1 further comprises the afflux micro-fluid chip (332) that is positioned at analytic unit shell (330), and described afflux micro-fluid chip (332) has afflux chip groove (402-407).
6. analytic unit according to claim 5, wherein, at least one in the described afflux chip groove (402-407) is communicated with described first fluid communication line (4) fluid.
7. according to claim 5 or 6 described analytic units, wherein, at least one in the described afflux chip groove (402-407) is communicated with at least one analysis vat (372,375,377,379,381,382) fluid of described analysis micro-fluid chip (331).
8. analytic unit according to claim 7, wherein, described afflux micro-fluid chip (332) comprises at least one afflux chip opening (410-413), described at least one afflux chip opening (410-413) aligns with at least one analysis chip opening (373,374,380,383) of described analysis micro-fluid chip (331), provides thus the fluid between the chip middle slot to be communicated with.
9. analytic unit according to claim 8 further comprises the filter (420) that is arranged between described afflux micro-fluid chip (332) and the described analysis micro-fluid chip (331).
10. according to claim 8 or 9 described analytic units, wherein, at least one in the described afflux chip opening (410-413,373,374,380,383) has depression (424).
11. analytic unit according to claim 8, wherein, in described analysis micro-fluid chip (331) and the described afflux micro-fluid chip (332) at least one comprises at least one groove (402-407,372,375,377,379,381,382), and the slot part of the flow resistance of the increase of providing is provided described at least one groove.
12. analytic unit according to claim 11, wherein, the flow resistance of described increase is provided by a capillary (501), and described capillary tube (501) is arranged among of described at least one groove (402-407,372,375,377,379,381,382).
13. analytic unit according to claim 1, wherein, at least one in described the first and second fluid communication line roads (4,7) provides described analytic unit (3) to described base station (2) and/or removably connecting to described material gathering-device (5).
14. analytic unit according to claim 1, it is suitable for receiving pressure fluid via described first fluid communication line (4).
15. analytic unit according to claim 1, it is made by one or more material monolithics that allow NMR (Nuclear Magnetic Resonance)-imaging scanning.
16. analytic unit according to claim 1 further comprises data processing equipment (203), described data processing equipment is suitable for deal with data so that the information about content of material in the fluid to be provided.
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CN102782476A (en) * | 2010-01-13 | 2012-11-14 | 弗劳森有限公司 | Microfluidic system comprising a light emitting device |
CN109561858A (en) * | 2016-08-26 | 2019-04-02 | 心脏起搏器股份公司 | The system and method for determining abnormal plasma glucose event using glucose replacement |
DK181117B1 (en) * | 2021-05-12 | 2023-01-10 | Flowsion As | Micro-dialysis probe with reinforcing tube |
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CN1534290A (en) * | 2003-04-01 | 2004-10-06 | 中国科学院电子学研究所 | Multifunction microanalysis system platform |
CN1673750A (en) * | 2004-03-26 | 2005-09-28 | 生命扫描有限公司 | Microfluidic analytical system with position electrodes |
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DE69024364T2 (en) | 1989-10-17 | 1996-07-11 | British Tech Group | REINFORCED CHEMILUMINESCENCE ASSAY |
DE4130742A1 (en) * | 1991-09-16 | 1993-03-18 | Inst Diabetestechnologie Gemei | METHOD AND ARRANGEMENT FOR DETERMINING THE CONCENTRATION OF INGREDIENTS IN BODY LIQUIDS |
DE4401400A1 (en) | 1994-01-19 | 1995-07-20 | Ernst Prof Dr Pfeiffer | Method and arrangement for continuously monitoring the concentration of a metabolite |
WO1999039629A1 (en) | 1998-02-04 | 1999-08-12 | Arizona Board Of Regents, A Body Corporate Of The State Of Arizona, Acting For And On Behalf Of Arizona State University | Chemical sensors having microflow systems |
DE10010587A1 (en) | 2000-03-03 | 2001-09-06 | Roche Diagnostics Gmbh | System for the determination of analyte concentrations in body fluids |
US20070292310A1 (en) | 2004-05-17 | 2007-12-20 | Danfoss A/S | Microanalysis Apparatus with Constant Pressure Pump System |
WO2006018022A1 (en) * | 2004-08-19 | 2006-02-23 | Danfoss A/S | Micro-analysis system |
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CN1534290A (en) * | 2003-04-01 | 2004-10-06 | 中国科学院电子学研究所 | Multifunction microanalysis system platform |
CN1673750A (en) * | 2004-03-26 | 2005-09-28 | 生命扫描有限公司 | Microfluidic analytical system with position electrodes |
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