EP1093578A1 - Micro-flow module for chemical analysis - Google Patents
Micro-flow module for chemical analysisInfo
- Publication number
- EP1093578A1 EP1093578A1 EP98910665A EP98910665A EP1093578A1 EP 1093578 A1 EP1093578 A1 EP 1093578A1 EP 98910665 A EP98910665 A EP 98910665A EP 98910665 A EP98910665 A EP 98910665A EP 1093578 A1 EP1093578 A1 EP 1093578A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- chip
- module according
- microflow module
- microflow
- thin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000004458 analytical method Methods 0.000 title abstract description 10
- 239000000126 substance Substances 0.000 title abstract description 7
- 238000010438 heat treatment Methods 0.000 claims description 20
- 239000010409 thin film Substances 0.000 claims description 18
- 229910052710 silicon Inorganic materials 0.000 claims description 6
- 239000010703 silicon Substances 0.000 claims description 6
- 239000011521 glass Substances 0.000 claims description 5
- 238000009413 insulation Methods 0.000 claims description 4
- 239000000853 adhesive Substances 0.000 claims description 2
- 230000001070 adhesive effect Effects 0.000 claims description 2
- 230000000712 assembly Effects 0.000 claims description 2
- 238000000429 assembly Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 8
- 230000008569 process Effects 0.000 abstract description 5
- 238000000646 scanning calorimetry Methods 0.000 abstract description 5
- 238000011835 investigation Methods 0.000 abstract description 3
- 230000008859 change Effects 0.000 abstract description 2
- 239000010410 layer Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000007788 liquid Substances 0.000 description 7
- 239000012491 analyte Substances 0.000 description 5
- 238000001514 detection method Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000010292 electrical insulation Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 2
- 238000005842 biochemical reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000005530 etching Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229910016312 BiSb Inorganic materials 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- VNNRSPGTAMTISX-UHFFFAOYSA-N chromium nickel Chemical compound [Cr].[Ni] VNNRSPGTAMTISX-UHFFFAOYSA-N 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011810 insulating material Substances 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000002346 layers by function Substances 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910001120 nichrome Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000007704 wet chemistry method Methods 0.000 description 1
Classifications
-
- 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
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N25/00—Investigating or analyzing materials by the use of thermal means
- G01N25/20—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity
- G01N25/48—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity on solution, sorption, or a chemical reaction not involving combustion or catalytic oxidation
- G01N25/4873—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity on solution, sorption, or a chemical reaction not involving combustion or catalytic oxidation for a flowing, e.g. gas sample
-
- 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
- B01J2219/00783—Laminate assemblies, i.e. the reactor comprising 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
- B01J2219/00819—Materials of construction
- B01J2219/00824—Ceramic
- B01J2219/00828—Silicon wafers or 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
- B01J2219/00819—Materials of construction
- B01J2219/00831—Glass
-
- 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
- B01J2219/00873—Heat exchange
-
- 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
- B01J2219/00889—Mixing
Definitions
- the invention relates to a microflow module, in particular for calorimetric measurements in the context of research, quality control and on a laboratory scale and for other analytical tasks.
- Measuring apparatuses, evaluation units and sampling devices for the applications mentioned are known in principle and are offered commercially. With the measuring method of scanning calorimetry it is possible, for example, to recognize the temperature at which a sample is converted or reacted and how large the amount of heat required for this, which is a quantity which is necessary to be known for the stated purposes. Compared to purely optical measurement methods for the same or similar purposes, the method mentioned has the advantage that optically non-transparent samples are also accessible for measurement. According to the prior art, thermostatted chambers, which can optionally be pressurized with a defined pressure, are used to take the measurement sample. A typical sample chamber of the type mentioned is e.g. can be found in the brochure of BAHR The ⁇ noanalysis GmbH DSC301 4/94.
- a sample receiver and sensor for scanning calorimetry in particular differential scanning calorimetry, which includes a heating element and a sample receiving area, one with a recess provided support frame has a membrane-shaped thin support layer, on which a layer arrangement consisting of at least one sensor arrangement and an electrically heatable thin metal layer structure, which are separated from one another by an electrical insulation layer, is applied and provide this with a further layer receiving the sample to be examined is.
- this device has a significantly improved time constant in relation to a single measurement compared to the otherwise known devices, it, like the other known calorimeters, only allows a very low sample throughput.
- thermocouples are provided in the vicinity of the channel outlet, where the beads mentioned also collect and in fact the biochemical reaction is only catalyzed there, which locally heats up the liquid.
- This microbiosensor is not very suitable for analyzing chemical reactions which are induced, for example, by mixing two reactants present in solution, since it does not allow the reaction to be recorded in its entirety. This applies in particular to very fast chemical reactions which, when using the I-shaped channel, may have taken place before the sample volume has even reached the detectable channel area. An analysis of the reaction kinetics is not possible with this microbiosensor.
- the invention has for its object to provide a microflow module for chemical analysis, the fast sample change and thus inexpensive investigations of fast-running processes time-resolved and with small time constants and optionally also the possibility of performing a scanning calorimetry offers and can be used as a transducer for miniaturized analysis of a wide range of substances.
- the microflow module contains a first chip, into which an extended channel area with a Y-shaped branched input area, to which two input channels adjoin, is introduced and the first chip is connected to cover a second chip, which is provided on the channel side with at least one thermosensitive thin-film element, preferably in the form of a thermopile.
- FIG. 1 shows a first assembly of the microflow module
- FIG. 2 shows a second assembly of the microflow module
- FIG. 3 shows a lateral section of the complete microflow module along a section plane A-A according to FIG. 2.
- the microflow module comprises a first chip 1, as indicated in plan view in FIG. 1, which preferably consists of glass or silicon.
- An elongated channel region 10 is etched into this chip 1 by wet chemistry; the etching depth in the example is 100 ⁇ m with a chip 1 thickness of 500 ⁇ m.
- the stretched channel area 10 is followed by a Y-shaped branched input area 11 with two input channels 12, 13, which is produced in the same etching step.
- the sum of the area cross sections of the input channels 12, 13 should preferably correspond to the area cross section of the extended channel area 10.
- the extended channel region 10 is essentially above to assign its extension length on both sides to a chamber 14 filled with a gas in the assembled state.
- the microflow module comprises a second chip 2, which is shown in plan view with its essential components in FIG. 2.
- This chip 2 can also be made of glass or silicon again. With a view to achieving a good signal-to-noise ratio and the greatest possible sensitivity, the most advantageous choice is glass for the first chip 1 and silicon for the second chip 2.
- thermosensitive thin-film element 21 is formed by three thermopiles 211, 212, 213, each of which consists of 48 BiSb / Sb thermocouple pairs.
- thermopiles are arranged with respect to the channel 10 on the chip 2 such that the hot contact points 214 arranged symmetrically to the longitudinal axis of the channel essentially capture the channel 10, whereas the cold contact points 215 in heat sink areas of the microflow module, in the example on the support frame 27, are arranged.
- twenty-three thermocouples are on one side and twenty-four thermocouples on the opposite side of the channel, one thermocouple forming the contact between the two thermocouple areas.
- Each of these thermopiles 211, 212, 213 is furthermore assigned, separated by the electrical insulation layer 22, an electrical thin-film heating element 23 such that it only covers the channel region 10.
- each thin-film heating element is formed by a meandered NiCr layer.
- the thin-film heating element 25 is preferably designed such that it also covers the areas of the input channels 12, 13. All of the last-mentioned electrical assemblies 211 to 213, 23 and 25 are covered with a final second insulation layer 29.
- This layer 29 is designed as a lacquer layer and serves to protect the metallic functional layers against mechanical and chemical influences and to avoid electrical coupling between the hot contact points via the liquid.
- the two chips 1 and 2 mentioned are connected to one another by an adhesive 28, as indicated in a section along the plane AA in FIG. 2. Anodic bonding can also be considered for the connection.
- the input channels 12, 13 are connected to corresponding supply lines, not shown.
- a microflow module designed in this way can be calibrated and used as described below.
- the microflow module is calibrated in such a way that distilled water is passed through the two channels 12, 13 at a defined flow rate into the extended channel area 10.
- the following procedure is carried out for each of the thermopiles 211, 212, 213 provided in the example: a defined heating power is applied to the thin-film heater assigned to each heating element and the response signal of the associated thermopile is recorded. This process is repeated for different heating powers, which are typically between 1 ⁇ W - 1 mW, and different flow rates, which in the example are between 0.1 - 50 ⁇ l / min.
- calibration curves or calibration hyper surfaces are obtained for each thermopile, which represent the thermoelectric signal as a function of the heating power fed in and the flow rate.
- Kahbrier curves can be used in the analysis of chemical reactions for the evaluation of individual thermopile signals in order to determine the power fed in by the reaction from the signal level.
- the calibration of the Thermopiles if they are connected in series to be able to evaluate an integral signal.
- thermopiles 211, 212, 213 are to be connected in series in this example.
- the reagents are mixed in the Y-shaped entrance area and a chemical reaction begins.
- the heat that is converted is integrally detected by the thermopiles, a thermal equilibrium being established over time; the initially rising thermoelectric signal saturates.
- the microflow module is to be used as a scanning calorimeter.
- a liquid to be examined for characteristic temperatures, phase transitions, crystallization processes or the like is fed through the input channels 12, 13 to the device.
- the liquid is heated more and more by a linearly increasing, optionally sinusoidal or other modulated electrical heating power application of the thin-film heaters 23 and 25 and the associated thermoelectric signal is detected.
- This signal shows a proportional increase in the thermoelectric signals following the heating power with slight deviations from the linearity at the temperatures corresponding to a specific heating power at which heat is consumed or released by physicochemical processes. The location of these deviations over time corresponds to the associated heating power and temperature.
- thermoelectric signal with the linearly interpolated undisturbed signal as the baseline.
- a reactant in solution should flow in through the first input channel, while a liquid, such as distilled water, which is initially free of reactants, is fed in through the second input channel.
- This second input channel is provided with a supply hose, which is provided with a T-branching piece, not shown, to which a reservoir with an analyte liquid is connected, in such a way that analyte volumes defined in a timed manner can be added to the carrier stream.
- analyte volumes With sufficiently small analyte volumes and a low flow rate, the entire chemical reaction takes place in the channel region 10 and is therefore detectable in its entirety.
- analyte volumes there are defined analyte volumes in this mode of operation, so that here, in addition to a statement about the detected concentration, one can also obtain information about the amount of substance detected.
- thermopiles used in the example have the advantage over thermoresistive measuring elements, the alternative use of which is also possible within the scope of the invention, that they do not have to be addressed with an electrical signal.
- thermoresistive measuring elements the alternative use of which is also possible within the scope of the invention, that they do not have to be addressed with an electrical signal.
- Example used thermopile has an expansion in the direction of
- thermopiles Channel longitudinal axis of 3.2 mm, each covering a channel volume of 0.64 ⁇ l with the channel geometry provided here.
- the spacing of the thermopiles from one another is chosen so that analyzer volumes up to the named size are not at all
- thermoelectric signals of each individual thermopile are read out individually, which means that the time and location of the flow rate are also resolved
- the thin-film heating element 25 With the help of the thin-film heating element 25 provided, extremely fast chemical reactions at low flow rates can be simulated, in which the sample volume forms the first thermopile Reached the point in time at which the simulated reaction would have practically been completed.
- the thin-film heating element 25 can advantageously also be used when performing the scanning calorimetry described above, in order to be able to couple in a greater overall power. In addition, its use offers the possibility of thermally activating chemical reactions and then subsequently thermoelectrically recording them, as described above.
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Combustion & Propulsion (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Organic Chemistry (AREA)
- Investigating Or Analyzing Materials Using Thermal Means (AREA)
Abstract
Description
Mikroflußmodul zur chemischen AnalytikMicroflow module for chemical analysis
Die Erfindung betrifft einen Mikroflußmodul, insbesondere für kalorimetrische Messungen im Rahmen von Forschung, Qualitätskontrolle und im Labormaßstab und für andere analytische Aufgaben.The invention relates to a microflow module, in particular for calorimetric measurements in the context of research, quality control and on a laboratory scale and for other analytical tasks.
Meßapparaturen, Auswerteeinheiten und Probenaπfhahmevorrichtungen für die genannten Anwendungen sind grundsätzhch bekannt und werden kommerziell angeboten. Mit der Meßmethode der Scanning-Kalorimetrie läßt sich bspw. erkennen, bei welcher Temperatur sich eine Probe umwandelt oder reagiert und wie groß die dazu erforderliche Wärmemenge ist, was für die genannten Anwendungszwecke eine notwendig zu wissende Größe darstellt. Gegenüber rein optischen Meßmethoden für gleiche oder ähnliche Zwecke hat die genannte Methode den Vorteil, daß auch optisch nicht transparente Proben einer Messung zugänglich sind. Gemäß dem Stand der Technik finden zur Meßprobenaufhahme thermo- statisierte Kammern, die ggf. wahlweise mit einem definierten Druck beaufschlagbar sind, Anwendung. Eine typische Probenkammer genannter Art ist z.B. dem Prospekt der Firma BAHR Theπnoanalyse GmbH DSC301 4/94 entnehmbar. Neben dem relativ kostenaufwendigen Geräteaufbau haftet solchen Lösungen im wesentlichen der Nachteil an, daß die recht voluminöse Probenkammerausbildung, mit großen Massen und isolierenden Materiahen, hohe parasitäre Wärmekapazitäten bedingen, die sich in einer zeitlichen Trägheit des Gesamtsystems bemerkbar machen.Measuring apparatuses, evaluation units and sampling devices for the applications mentioned are known in principle and are offered commercially. With the measuring method of scanning calorimetry it is possible, for example, to recognize the temperature at which a sample is converted or reacted and how large the amount of heat required for this, which is a quantity which is necessary to be known for the stated purposes. Compared to purely optical measurement methods for the same or similar purposes, the method mentioned has the advantage that optically non-transparent samples are also accessible for measurement. According to the prior art, thermostatted chambers, which can optionally be pressurized with a defined pressure, are used to take the measurement sample. A typical sample chamber of the type mentioned is e.g. can be found in the brochure of BAHR Theπnoanalyse GmbH DSC301 4/94. In addition to the relatively expensive construction of the device, such solutions essentially have the disadvantage that the rather voluminous design of the sample chamber, with large masses and insulating materials, necessitates high parasitic heat capacities, which are noticeable in the inertia of the overall system over time.
Aus DE 44 38 785 AI ist eine als Analyse- und Dosiersystem bezeichnete Vorrichtung bekannt, bei der die eigentliche Analyse erst in einer nicht zum Dosiersystem gehörigen externen weiteren Baugruppe erfolgt, wobei zur Detektion keine thermischen Transducer zum Einsatz gelangen. Das dort vorgeschlagene System ist ein Reaktor- und Dosiersystäm, bei dem die vorgesehenen thermischen Elemente ausschließlich zur Ansteuerung von Fluidaktoren dienen. Aus der DE 44 29067 AI ist ein Probenaufhehmer und Sensor für die Scanning-Kalorimetrie, insbesondere differentielle Scanning- Kalorimetrie, bekannt, der ein Heizelement und einen Probenaumahmebereich beinhaltet, wobei ein mit einer Ausnehmung versehener Trägerrahmen eine membranförmig ausgebildete dünne Trägerschicht aufweist, auf der eine Schichtanordnung, bestehend aus wenigstens einer Sensoranordnung und einer elektrisch beheizbaren dünnen MetaUschichtstruktur, die voneinander durch eine elektrische Isolationsschicht getrennt sind, aufgebracht ist und diese mit einer weiteren, die zu untersuchende Probe aufnehmenden Schicht versehen ist. Diese Vorrichtung besitzt zwar gegenüber den sonst bekannten Vorrichtungen eine wesentlich verbesserte Zeitkonstante bezogen auf eine Einzelmessung, ermöglicht aber, wie auch die anderen bekannte Kalorimeter, nur einen sehr geringen Probendurchsatz.From DE 44 38 785 AI, a device known as an analysis and metering system is known, in which the actual analysis is carried out only in an external, additional module which is not part of the metering system, no thermal transducers being used for detection. The system proposed there is a reactor and metering system in which the thermal elements provided serve exclusively to control fluid actuators. From DE 44 29067 AI a sample receiver and sensor for scanning calorimetry, in particular differential scanning calorimetry, is known, which includes a heating element and a sample receiving area, one with a recess provided support frame has a membrane-shaped thin support layer, on which a layer arrangement consisting of at least one sensor arrangement and an electrically heatable thin metal layer structure, which are separated from one another by an electrical insulation layer, is applied and provide this with a further layer receiving the sample to be examined is. Although this device has a significantly improved time constant in relation to a single measurement compared to the otherwise known devices, it, like the other known calorimeters, only allows a very low sample throughput.
Weiterhin beschreiben Xie, Mecklenberg, Danielsson, Ohmn, Winquist in "Microbiosensor based on an integrated thermopile", Analytica Chimica Acta 299 (1994), S. 165-170 einen πiiniaturisierten Biosensor zur Erfassung und Untersuchung enzymatisch katalysierter biochemischer Reaktionen, bei denen die katalysierten Enzyme auf kleine Kügelchen immobilisiert sind, welche sich in einem Untersuchungsraum befinden, der als I-förmiger Flußkanal gebildet ist. Innerhalb dieses Kanals sind Thermoelemente vorgesehen, die von der Probenflüssigkeit umspült werden. Dabei sind die heißen Kontaktstellen der Thermoelemente in der Nähe des Kanalauslaß vorgesehen, wo sich auch die genannten Kügelchen sammeln und tatsächlich auch nur dort die biochemische Reaktion katalysiert wird, was lokal zur Aufheizung der Flüssigkeit führt. Zur Analytik chemischer Reaktionen, die bspw. durch Mischung zweier in Lösung vorliegender Reaktanden induziert werden, ist dieser Mikrobiosensor wenig geeignet, da er die Reaktion nicht in ihrer Gesamtheit erfassen läßt. Dies gilt insbesondere für sehr schnelle chemische Reaktionen, die bei Verwendung des I-förmigen Kanals schon abgelaufen sein können, bevor das Probenvolumen überhaupt den detektiven Kanalbereich erreicht hat. Eine Analytik der Reaktionskinetik ist mit diesem Mikrobiosensor nicht möglich.Furthermore, Xie, Mecklenberg, Danielsson, Ohmn, Winquist in "Microbiosensor based on an integrated thermopile", Analytica Chimica Acta 299 (1994), pp. 165-170 describe a miniaturized biosensor for the detection and investigation of enzymatically catalyzed biochemical reactions in which the catalyzed Enzymes are immobilized on small spheres, which are located in an examination room, which is formed as an I-shaped flow channel. Thermocouples are provided within this channel and the sample liquid flows around them. The hot contact points of the thermocouples are provided in the vicinity of the channel outlet, where the beads mentioned also collect and in fact the biochemical reaction is only catalyzed there, which locally heats up the liquid. This microbiosensor is not very suitable for analyzing chemical reactions which are induced, for example, by mixing two reactants present in solution, since it does not allow the reaction to be recorded in its entirety. This applies in particular to very fast chemical reactions which, when using the I-shaped channel, may have taken place before the sample volume has even reached the detectable channel area. An analysis of the reaction kinetics is not possible with this microbiosensor.
Der Erfindung liegt die Aufgabe zugrunde, einen Mikroflußmodul zur chemischen Analytik zu schaffen, der einen schnellen Probenwechsel und damit preiswerte Untersuchungen schnell ablaufender Prozesse zeitaufgelöst und mit kleinen Zeitkonstanten ermöglicht und wahlweise zugleich die Möglichkeit der Durchführung einer Scanmng-Kalorimetrie bietet und der als Transducer für die miniaturisierte Analyse eines breiten Substanzspektrums einsetzbar ist.The invention has for its object to provide a microflow module for chemical analysis, the fast sample change and thus inexpensive investigations of fast-running processes time-resolved and with small time constants and optionally also the possibility of performing a scanning calorimetry offers and can be used as a transducer for miniaturized analysis of a wide range of substances.
Die Aufgabe wird durch die Merkmale des ersten Patentanspruchs gelöst. Weitere vorteilhafte Ausbildungen sind durch die nachgeordneten Ansprüche erfaßt. Wesentüch im Rahmen der Erfindung ist, daß der Mikroflußmodul einen ersten Chip enthält, in den ein ausgestreckter Kanalbereich mit einem Y-förmig verzweigtem Eingangsbereich, an den sich zwei Eingangskanäle anschließen, eingebracht sind und der erste Chip mit einem zweiten Chip abdeckend verbunden ist, der kanalseitig mit wenigstens einem thermosensitiven Dünnschichtelement, bevorzugt in Form einer Thermosäule, versehen ist.The object is achieved by the features of the first claim. Further advantageous developments are covered by the subordinate claims. It is essential in the context of the invention that the microflow module contains a first chip, into which an extended channel area with a Y-shaped branched input area, to which two input channels adjoin, is introduced and the first chip is connected to cover a second chip, which is provided on the channel side with at least one thermosensitive thin-film element, preferably in the form of a thermopile.
Die Erfindung soll nachstehend anhand eines schematischen Ausführungsbeispiele näher erläutert werden. Es zeigen:The invention will be explained in more detail below with the aid of a schematic exemplary embodiment. Show it:
Fig. 1 eine erste Baugruppe des Mikroflußmoduls, Fig. 2 eine zweite Baugruppe des Mikroflußmoduls und Fig. 3 einen seitlichen Schnitt des vollständigen Mikroflußmoduls entlang einer Schnittebene A-A gemäß Fig. 2.1 shows a first assembly of the microflow module, FIG. 2 shows a second assembly of the microflow module, and FIG. 3 shows a lateral section of the complete microflow module along a section plane A-A according to FIG. 2.
Der Mikroflußmodul umfaßt einen ersten Chip 1, wie in Fig. 1 in Draufsicht angedeutet, der bevorzugt aus Glas oder Silizium besteht. In diesen Chip 1 ist naßchemisch ein ausgestreckter Kanalbereich 10 eingeätzt; die Ätztiefe beträgt dabei im Beispiel 100 μm bei einer Dicke des Chips 1 von 500 μm. An den ausgestreckten Kanalbereich 10 schließt sich ein Y-förmig verzweigter Eingangsbereich 11 mit zwei Eingangskanälen 12, 13 an, der im gleichen Ätzschritt hergestellt wird. Die Summe der Flächenquerschnitte der Eingangskanäle 12, 13 soll dabei bevorzugt dem Flächenquerschnitt des ausgestreckten Kanalbereiches 10 entsprechen. Jedoch sind auch andere Geometrien, insbesondere düsenähnlich wirkende Querschnittsverengungen der Eingangskanäle in Richtung des Y-förmigen Eingangsbereichs denkbar, wenn man gezielt turbulente Strömungsabschnitte schaffen will. Zur weiteren Erhöhung der Empfindlichkeit des vollständigen Mikroflußmoduls ist weiterhin vorgesehen, dem ausgestreckten Kanalbereich 10 im wesentlichen über seine Erstreckungslänge beidseitig je eine, im zusammengebauten Zustand mit einem Gas gefüllte Kammer 14 zuzuordnen. Weiterhin umfaßt der Mikroflußmodul einen zweiten Chip 2, der mit seinen wesentlichen Baugruppen in Figur 2 in Draufsicht dargestellt ist. Dieser Chip 2 kann ebenfalls wieder aus Glas oder Silizium gefertigt sein. Im Hinblick auf die Erzielung eines guten Signal-Rausch- Verhältnisses und einer größtmöglichen Empfindlichkeit ist am vorteilhaftesten die Wahl von Glas für den ersten Chip 1 und von Silizium für den zweiten Chip 2. Dabei wird im Falle der Verwendung von Silizium für den zweiten Chip 2 dieser mittels bekannter Stmkturierungsschritte so ausgebildet, daß ihm eine membranbildende Ausnehmung 26 (vgl. Fig. 3) derart gegeben ist, daß die Membran mindestens den ausgestreckten Kanalbereich 10 überdeckt, bevorzugt jedoch größer ausgebildet ist, und ein als Wärmesenke wirkender Trägerrahmen 27 verbleibt. Auf diesen Chip 2 ist auf der, im zusammengebauten Zustand, dem Kanal 10 zugewandten Seite wenigstens ein thermosensitives Dünnschichtelement 21 und ein zu diesem durch eine erste Isolationsschicht 22 getrenntes elektrisches Heizelement 23 vorgesehen. Im Beispiel ist das thermosensitive Dünnschichtelement 21 durch drei Thermosäulen 211, 212, 213 gebildet, die jeweils aus 48 BiSb/Sb-Thermoschenkelpaarungen bestehen. Diese Thermosäulen sind in bezug auf den Kanal 10 so auf dem Chip 2 angeordnet, daß die heißen Kontaktstellen 214 symmetrisch zur Kanallängsachse angeordnet den Kanal 10 im wesentlichen mittig erfassen, wohingegen die kalten Kontaktstellen 215 in Wärmesenkenbereichen des Mikroflußmoduls, im Beispiel auf dem Trägerrahmen 27, angeordnet sind. Dabei liegen im Beispiel dreiundzwanzig Thermoelemente auf der einen und vierundzwanzig Thermoelemente auf der gegenüberliegenden Kanalseite, wobei ein Thermoelement den Kontakt zwischen den beiden Thermoelementbereichen bildet. Jeder dieser Thermosäulen 211, 212, 213 ist weiterhin, getrennt durch die elektrische Isolationsschicht 22, ein elektrisches Dünnschichtheizelement 23 so zugeordnet, daß dieses ausschließlich den Kanalbereich 10 überdeckt. Jedes Dünnschichtheizelement ist im Beispiel durch eine mäandrierte NiCr- Schicht gebildet. Außerdem ist zumindest über dem Gebiet des Y-förmigen Eingangsbereiches 11 ein weiteres Dünnschichtheizelement 25 vorgesehen. Für die weiter unten beschriebenen Einsatzfälle des Mikroflußmoduls wird das Dünnschichtheizelement 25 bevorzugt jedoch so ausgeführt, daß es auch die Bereiche der Eingangskanäle 12, 13 überdeckt. Alle letzt genannten elektrischen Baugruppen 211 bis 213, 23 und 25 sind mit einer abschließenden zweiten Isolationsschicht 29 überdeckt. Diese Schicht 29 ist als Lackschicht ausgeführt und dient als Schutz der metallischen Funktionsschichten gegen mechanische und chemische Einflüsse sowie zur Vermeidung eines elektrischen Überkoppelns zwischen den heißen Kontaktstellen über die Flüssigkeit. Beide genannten Chips 1 und 2 sind, wie in Fig. 3 in einem Schnitt entlang der Ebene A-A nach Fig. 2 angedeutet, miteinander durch eine Verklebung 28 verbunden. Ebenso kann für die Verbindung ein anodisches Bonden in Betracht kommen. Die Eingangskanäle 12, 13 werden mit entsprechenden, nicht dargestellten Zuleitungen verbunden.The microflow module comprises a first chip 1, as indicated in plan view in FIG. 1, which preferably consists of glass or silicon. An elongated channel region 10 is etched into this chip 1 by wet chemistry; the etching depth in the example is 100 μm with a chip 1 thickness of 500 μm. The stretched channel area 10 is followed by a Y-shaped branched input area 11 with two input channels 12, 13, which is produced in the same etching step. The sum of the area cross sections of the input channels 12, 13 should preferably correspond to the area cross section of the extended channel area 10. However, other geometries are also conceivable, in particular cross-sectional constrictions of the inlet channels in the direction of the Y-shaped inlet area, if the aim is to create turbulent flow sections in a targeted manner. To further increase the sensitivity of the complete microflow module, it is also provided that the extended channel region 10 is essentially above to assign its extension length on both sides to a chamber 14 filled with a gas in the assembled state. Furthermore, the microflow module comprises a second chip 2, which is shown in plan view with its essential components in FIG. 2. This chip 2 can also be made of glass or silicon again. With a view to achieving a good signal-to-noise ratio and the greatest possible sensitivity, the most advantageous choice is glass for the first chip 1 and silicon for the second chip 2. In this case, if silicon is used for the second chip 2 this is formed by means of known structuring steps in such a way that it is given a membrane-forming recess 26 (cf. FIG. 3) such that the membrane covers at least the extended channel region 10, but is preferably larger, and a support frame 27 which acts as a heat sink remains. At least one thermosensitive thin-film element 21 and an electrical heating element 23 separated from it by a first insulation layer 22 are provided on this chip 2 on the side facing the channel 10 in the assembled state. In the example, the thermosensitive thin-film element 21 is formed by three thermopiles 211, 212, 213, each of which consists of 48 BiSb / Sb thermocouple pairs. These thermopiles are arranged with respect to the channel 10 on the chip 2 such that the hot contact points 214 arranged symmetrically to the longitudinal axis of the channel essentially capture the channel 10, whereas the cold contact points 215 in heat sink areas of the microflow module, in the example on the support frame 27, are arranged. In the example, twenty-three thermocouples are on one side and twenty-four thermocouples on the opposite side of the channel, one thermocouple forming the contact between the two thermocouple areas. Each of these thermopiles 211, 212, 213 is furthermore assigned, separated by the electrical insulation layer 22, an electrical thin-film heating element 23 such that it only covers the channel region 10. In the example, each thin-film heating element is formed by a meandered NiCr layer. In addition, there is another thin-film heating element at least over the area of the Y-shaped entrance area 11 25 provided. For the applications of the microflow module described below, however, the thin-film heating element 25 is preferably designed such that it also covers the areas of the input channels 12, 13. All of the last-mentioned electrical assemblies 211 to 213, 23 and 25 are covered with a final second insulation layer 29. This layer 29 is designed as a lacquer layer and serves to protect the metallic functional layers against mechanical and chemical influences and to avoid electrical coupling between the hot contact points via the liquid. The two chips 1 and 2 mentioned are connected to one another by an adhesive 28, as indicated in a section along the plane AA in FIG. 2. Anodic bonding can also be considered for the connection. The input channels 12, 13 are connected to corresponding supply lines, not shown.
Ein derart ausgebildeter Mikroflußmodul kann wie nachstehenden beschrieben geeicht und verwendet werden.A microflow module designed in this way can be calibrated and used as described below.
Die Kalibrierung des Mikroflußmoduls erfolgt derart, daß durch die beiden Kanäle 12, 13 destilliertes Wasser mit einer definierten Flußrate in den ausgestreckten Kanalbereich 10 geleitet wird. Für jede der im Beispiel vorgesehenen Thermosäulen 211, 212, 213 wird folgender Vorgang durchgeführt: der pro Heizelement zugeordnete Dünnschichtheizer wird mit einer definierten Heizleistung beaufschlagt und das Anwortsignal der zugehörigen Thermosäule erfaßt. Dieser Vorgang wird für unterschiedliche Heizleistungen, die typischerweise zwischen 1 μW - 1 mW liegen, und unterschiedliche Flußraten, die im Beispiel zwischen 0,1 - 50 μl/min liegen, wiederholt. Auf diese Weise erhält man für jede Thermosäule Kalibrierkurven, respektive Kalibrier- Hyperflächen, die das thermoelektrische Signal in Abhängigkeit von der eingespeisten Heizleistung und der Flußrate darstellen. Diese Kahbrierkurven sind bei der Untersuchung chemischer Reaktionen für die Auswertung einzelner Thermosäulensignale heranziehbar, um aus der Signalhöhe die durch die Reaktion eingespeiste Leistung zu ermitteln. In gleicher Weise, wie oben beschrieben, erfolgt die Kalibrierung der Thermosäulen, wenn diese in Serie geschaltet sind, um ein integrales Signal auswerten zu können.The microflow module is calibrated in such a way that distilled water is passed through the two channels 12, 13 at a defined flow rate into the extended channel area 10. The following procedure is carried out for each of the thermopiles 211, 212, 213 provided in the example: a defined heating power is applied to the thin-film heater assigned to each heating element and the response signal of the associated thermopile is recorded. This process is repeated for different heating powers, which are typically between 1 μW - 1 mW, and different flow rates, which in the example are between 0.1 - 50 μl / min. In this way, calibration curves or calibration hyper surfaces are obtained for each thermopile, which represent the thermoelectric signal as a function of the heating power fed in and the flow rate. These Kahbrier curves can be used in the analysis of chemical reactions for the evaluation of individual thermopile signals in order to determine the power fed in by the reaction from the signal level. In the same way as described above, the calibration of the Thermopiles, if they are connected in series to be able to evaluate an integral signal.
In einem Beispiel der Verwendung des Mikroflußmoduls wird durch die Eingangskanäle 12, 13 je ein Strom einer in Lösung befindlichen Reagenz in den Kanalbereich 10 geleitet. Die Thermosäulen 211, 212, 213 sollen in diesem Beispiel in Serie geschaltet sein. Im Y-förmigen Eingangsbereich findet die Vermischung der Reagenzien statt, und eine chemische Reaktion beginnt zu starten. Die dabei umgesetzte Wärme wird durch die Thermosäulen integral detektiert, wobei sich im Laufe der Zeit ein thermisches Gleichgewicht einstellt; das zunächst ansteigende thermoelektrische Signal verläuft in eine Sättigung. Je geringer dabei die eingestellte Flußrate gewählt wird, womit die Verweilzeit eines bestimmten Volumens der Mischung sich verlängert, desto länger ist die Erfassung der in diesem Volumen ablaufenden Reaktion und um so größer ist die erfaßbare Wärmemenge und damit das thermoelektrische Signal und desto geringer ist das Detektionslimit für gering konzentrierte Reagenzien.In one example of the use of the microflow module, a stream of a reagent in solution is passed through the input channels 12, 13 into the channel region 10. The thermopiles 211, 212, 213 are to be connected in series in this example. The reagents are mixed in the Y-shaped entrance area and a chemical reaction begins. The heat that is converted is integrally detected by the thermopiles, a thermal equilibrium being established over time; the initially rising thermoelectric signal saturates. The lower the selected flow rate, which increases the dwell time of a certain volume of the mixture, the longer the detection of the reaction taking place in this volume and the greater the amount of heat that can be detected and thus the thermoelectric signal and the lower the detection limit for low-concentration reagents.
In einem weiteren Ausführungsbeispiel soll der Mikroflußmodul als Scanning-Kalorimeter Verwendung finden. Dazu wird eine auf charakteristische Temperaturen, Phasenübergänge, Kristallisationsvorgänge o.a. zu untersuchende Flüssigkeit durch die Eingangskanäle 12, 13 der Vorrichtung zugeführt. Die Flüssigkeit wird durch eine linear ansteigende, wahlweise sinusförmig oder anderes modulierte elektrische Heizleistungsbeaufschlagung der Dünnschichtheizer 23 und 25 immer mehr erwärmt und das zugehörige thermoelektrische Signal erfaßt. Dieses Signal zeigt einen der Heizleistung folgenden proportionalen Anstieg der thermoelektrischen Signale mit leichten Abweichungen von der Linearität bei den einer bestimmten Heizleistung entsprechenden Temperaturen, bei denen durch physikochemische Vorgänge Wärme konsumiert oder freigesetzt wird. Die Lage dieser Abweichungen über der Zeit korrespondiert jeweils mit der zugehörigen Heizleistung und dieser zugehörigen Temperatur. Die konsumierte oder freigesetzte Wärme ergibt sich als Integral des thermoelektrischen Signals mit dem linear interpolierten ungestörten Signal als Basislinie. In einer weiteren Verwendung des Mikroflußmoduls soll durch den ersten Eingangskanal ein Reaktand in Lösung einströmen, während durch den zweiten Eingangskanal eine zunächst reaktandenfreie Flüssigkeit, wie destilliertes Wasser, zugeführt wird. Dieser zweite Eingangskanal ist mit einem Zufuhrungsschlauch, der mit einem nicht näher dargestellten T- Verzweigungsstück, an das ein Reservoir mit einer Analytflüssigkeit angeschlossen ist, derart versehen, daß zeitlich getaktet definierte Analytvolumina dem Trägerstrom zugegeben werden können. Diese Analytproben kommen im Y-förmigen Eingangsbereich mit der durch den ersten Eingangskanal zugeführten Reaktandenlösung zur Vermischung. Bei hinreichend kleinen Analytvolumina und kleiner Flußrate läuft die gesamte chemische Reaktion im Kanalbereich 10 ab und ist somit in ihrer Gesamtheit detektierbar. Im Gegensatz zu oben beschriebenen Verwendungen des Mikroflußmoduls liegen bei dieser Betriebsweise definierte Analytvolumina vor, so daß hier neben einer Aussage über die detektierte Konzentration auch eine über die detektierte Stoffmenge erhalten werden kann.In a further exemplary embodiment, the microflow module is to be used as a scanning calorimeter. For this purpose, a liquid to be examined for characteristic temperatures, phase transitions, crystallization processes or the like is fed through the input channels 12, 13 to the device. The liquid is heated more and more by a linearly increasing, optionally sinusoidal or other modulated electrical heating power application of the thin-film heaters 23 and 25 and the associated thermoelectric signal is detected. This signal shows a proportional increase in the thermoelectric signals following the heating power with slight deviations from the linearity at the temperatures corresponding to a specific heating power at which heat is consumed or released by physicochemical processes. The location of these deviations over time corresponds to the associated heating power and temperature. The heat consumed or released is the integral of the thermoelectric signal with the linearly interpolated undisturbed signal as the baseline. In a further use of the microflow module, a reactant in solution should flow in through the first input channel, while a liquid, such as distilled water, which is initially free of reactants, is fed in through the second input channel. This second input channel is provided with a supply hose, which is provided with a T-branching piece, not shown, to which a reservoir with an analyte liquid is connected, in such a way that analyte volumes defined in a timed manner can be added to the carrier stream. These analyte samples are mixed in the Y-shaped input area with the reactant solution supplied through the first input channel. With sufficiently small analyte volumes and a low flow rate, the entire chemical reaction takes place in the channel region 10 and is therefore detectable in its entirety. In contrast to the uses of the microflow module described above, there are defined analyte volumes in this mode of operation, so that here, in addition to a statement about the detected concentration, one can also obtain information about the amount of substance detected.
Die im Beispiel eingesetzten Thermosäulen haben gegenüber thermoresistiven Meßelementen, deren alternativer Einsatz im Rahmen der Erfindung aber ebenso möglich ist, den Vorteil, daß sie nicht mit einem elektrischen Signal angesprochen werden müssen. Jeder der imThe thermopiles used in the example have the advantage over thermoresistive measuring elements, the alternative use of which is also possible within the scope of the invention, that they do not have to be addressed with an electrical signal. Everyone in the
Beispiel eingesetzten Thermosäulen hat eine Ausdehnung in Richtung derExample used thermopile has an expansion in the direction of
Kanallängsachse von 3,2 mm, wobei sie jeweils bei der hier vorgesehenen Kanalgeometrie ein Kanalvolumen von 0,64 μl überdecken. Die Beabstandung der Thermosäulen voneinander ist so gewählt, daß Analyvolumina bis hinauf zu genannter Größe zu keinemChannel longitudinal axis of 3.2 mm, each covering a channel volume of 0.64 μl with the channel geometry provided here. The spacing of the thermopiles from one another is chosen so that analyzer volumes up to the named size are not at all
Zeitpunkt wesentliche Teile zweier benachbarter Thermosäulen erfassen.Capture essential parts of two neighboring thermopiles at the time.
Unter dieser Voraussetzung ist eine Einzelauslesung der thermoelektrischen Signale jeder einzelnen Thermosäule gegeben, wodurch weiterhin eine flußratenabhängige zeit- und ortsaufgelösteUnder this condition, the thermoelectric signals of each individual thermopile are read out individually, which means that the time and location of the flow rate are also resolved
Analyse der Reaktionskinetik ermöglicht wird.Analysis of the reaction kinetics is made possible.
Mit Hilfe des vorgesehenen Dünnschichtheizelementes 25 können äußerst schnelle chemische Reaktionen bei geringen Flußraten simuliert werden, bei denen das Probenvolumen die erste Thermosäule zu einem Zeitpunkt erreicht, zu dem die simulierte Reaktion praktisch schon vollständig abgelaufen wäre. Das Dünnschichtheizelement 25 kann vorteilhaft auch bei Durchführung der oben beschriebenen Scanning- Kalorimetrie Verwendung finden, um eine größere Gesamtleistung einkoppeln zu können. Darüber hinaus bietet sein Einsatz die Möglichkeit chemische Reaktionen thermisch zu aktivieren und sie dann, wie oben beschrieben, im weiteren thermoelektrisch zu erfassen.With the help of the thin-film heating element 25 provided, extremely fast chemical reactions at low flow rates can be simulated, in which the sample volume forms the first thermopile Reached the point in time at which the simulated reaction would have practically been completed. The thin-film heating element 25 can advantageously also be used when performing the scanning calorimetry described above, in order to be able to couple in a greater overall power. In addition, its use offers the possibility of thermally activating chemical reactions and then subsequently thermoelectrically recording them, as described above.
Die beispielhaft aufgezeigten vielfältigen Einsatzgebiete des erfindungsgemäßen Mikroflußmoduls verdeutlichen die Multivalenz der geschaffen Vorrichtung. The diverse fields of application of the microflow module according to the invention shown by way of example illustrate the multivalency of the device created.
BezuεszeichenlisteBezuεszeichenliste
1 erstes Chip1 first chip
10 ausgestreckter Kanalbereich10 stretched channel area
11 Y-förmig verzweigter Eingangsbereich11 Y-shaped branched entrance area
12, 13 Eingangskanäle12, 13 input channels
14 gasbefüllte Kammern14 gas-filled chambers
2 zweites Chip2 second chip
21 thermosensitives Dünnschichtelement21 thermosensitive thin-film element
211, 212,211, 212,
213 Thermosäulen213 thermopiles
214 heiße Kontaktstellen der Thermosäulen214 hot contact points of the thermopiles
215 kalte Kontaktstellen der Thermosäulen215 cold contact points of the thermopiles
22 erste elektrische Isolationsschicht22 first electrical insulation layer
23 den Thermosäulen zugeordnetes elektrisches23 electrical associated with the thermopiles
DünschichtheizelementThin layer heating element
25 elektrisches Dünnschichtheizelement25 electrical thin-film heating element
26 membranartige Ausnehmung26 membrane-like recess
27 Trägerrahmen27 support frame
28 Verklebung, Bondung28 bonding, bonding
29 zweite Isolationsschicht29 second insulation layer
A-A Schnittebene A-A cutting plane
Claims
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19707044 | 1997-02-21 | ||
DE19707044A DE19707044C1 (en) | 1997-02-21 | 1997-02-21 | Microflow module for calorimetric measurements |
PCT/EP1998/000836 WO1998037408A1 (en) | 1997-02-21 | 1998-02-13 | Micro-flow module for chemical analysis |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1093578A1 true EP1093578A1 (en) | 2001-04-25 |
Family
ID=7821124
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98910665A Withdrawn EP1093578A1 (en) | 1997-02-21 | 1998-02-13 | Micro-flow module for chemical analysis |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1093578A1 (en) |
JP (1) | JP2001513882A (en) |
DE (1) | DE19707044C1 (en) |
WO (1) | WO1998037408A1 (en) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6703246B1 (en) * | 1999-07-06 | 2004-03-09 | The Dow Chemical Company | Thermal method and apparatus |
WO2004097373A2 (en) * | 2003-04-28 | 2004-11-11 | Univ Arizona | Thermoelectric biosensor for analytes in a gas |
JP4380264B2 (en) * | 2003-08-25 | 2009-12-09 | カシオ計算機株式会社 | Bonding substrate and substrate bonding method |
DE10355126A1 (en) * | 2003-11-24 | 2005-06-30 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Method and device for measuring the heat released in chemical or physical reactions |
FR2894668B1 (en) * | 2005-12-08 | 2008-01-18 | Univ Maine | CALORIMETER FOR STUDYING A CONTINUOUS CHEMICAL REACTION |
JP4851831B2 (en) * | 2006-04-07 | 2012-01-11 | 学校法人明治大学 | Micro calorimetry apparatus and micro calorimetry method |
DE102007019695B4 (en) | 2007-04-24 | 2009-08-13 | Analytik Jena Ag | Cuvette for the optical analysis of small volumes |
CH702328A2 (en) | 2009-12-01 | 2011-06-15 | Acl Instr Ag | Heat flow calorimeter. |
DE102012003863B3 (en) * | 2012-02-22 | 2013-03-07 | Technische Universität Bergakademie Freiberg | Device, useful for determining effect of nanoparticle materials on living cells by measuring thermal power production of cells using chip-calorimeter, comprises flow measurement chamber, permanent magnet, pivot device, and thermopile |
EP2972259B1 (en) * | 2013-03-15 | 2021-12-08 | The Charles Stark Draper Laboratory, Inc. | System and method for a microfluidic calorimeter |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4408352C2 (en) * | 1994-03-12 | 1996-02-08 | Meinhard Prof Dr Knoll | Miniaturized substance-recognizing flow sensor and method for its production |
DE4429067C2 (en) * | 1994-08-17 | 2002-11-28 | Inst Physikalische Hochtech Ev | Sampler and sensor for scanning calorimetry |
DE4438785C2 (en) * | 1994-10-24 | 1996-11-07 | Wita Gmbh Wittmann Inst Of Tec | Microchemical reaction and analysis unit |
-
1997
- 1997-02-21 DE DE19707044A patent/DE19707044C1/en not_active Expired - Fee Related
-
1998
- 1998-02-13 WO PCT/EP1998/000836 patent/WO1998037408A1/en not_active Application Discontinuation
- 1998-02-13 JP JP53623198A patent/JP2001513882A/en active Pending
- 1998-02-13 EP EP98910665A patent/EP1093578A1/en not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of WO9837408A1 * |
Also Published As
Publication number | Publication date |
---|---|
JP2001513882A (en) | 2001-09-04 |
DE19707044C1 (en) | 1998-08-06 |
WO1998037408A1 (en) | 1998-08-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0938383B1 (en) | Device for carrying out research on cell specimens and similar material | |
DE69923704T2 (en) | SENSOR FOR DIFFERENTIAL THERMOANALYSIS | |
DE602004005547T2 (en) | Method and system for monitoring a fluid flow | |
DE69319427T2 (en) | ANALYSIS OF MEASURING THE FLOW RESISTANCE | |
DE60208313T2 (en) | Microelectronic detector on a chip | |
DE60012962T2 (en) | SENSORS AND TRANSFORMERS WITH FREESTANDING BOOM | |
DE60105717T2 (en) | Parallel gas chromatograph with microsensor matrix | |
DE10058394C1 (en) | Methods for biochemical analysis and associated arrangement | |
DE10122133B4 (en) | Integrated microsystem | |
DE60023917T2 (en) | SENSOR FOR A MICROFLUIDIC MACHINING SYSTEM | |
EP0988526B1 (en) | Device for detecting biochemical or chemical substances by fluorescence excitation and method for its production | |
DE19707044C1 (en) | Microflow module for calorimetric measurements | |
EP1780290A2 (en) | Apparatus for amplifying nucleic acids | |
DE102017102026A1 (en) | Calorimeter with diffusion-welded block | |
DE69033904T2 (en) | ANALYSIS DEVICE | |
DE19819537A1 (en) | Analysis and diagnostic tool | |
DE69635160T2 (en) | DEVICE FOR MAGNIFYING SENSOR ELECTRICITY | |
Venkadesh et al. | Advanced multi-functional sensors for In-situ soil parameters for sustainable agriculture | |
DE10321472A1 (en) | Fluidic module, used as multi-functional micro-reaction module for chemical reactions, has fluid zone between one side permeable to infrared and side with infrared reflective layer for on-line analysis | |
EP1674866A1 (en) | Device for the thermostatic control of a measuring cell used in an analyser, and measuring cell which is insertable into the analyser and can be replaced. | |
DE69806375T2 (en) | METHOD AND APPARATUS FOR MEASURING ENTHALPY CHANGES BY MEANS OF A DIFFERENTIAL THERMAL ANALYSIS APPARATUS (DTA APPARATUS) WORKING WITH QUASI-ISOTHERMAL HEATING PROCESS | |
Montes et al. | Determination of pesticides using a low-temperature co-fired ceramic microfluidic platform | |
DE4429067C2 (en) | Sampler and sensor for scanning calorimetry | |
DE102009033420B4 (en) | Device for determining the oxygen content in a gas | |
DE102016222035A1 (en) | Microfluidic device and method for analyzing samples |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19990826 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DK ES FI FR GB IT LI NL SE |
|
17Q | First examination report despatched |
Effective date: 20040525 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20040901 |