EP1622715A1

EP1622715A1 - Component used in microprocess control

Info

Publication number: EP1622715A1
Application number: EP04728110A
Authority: EP
Inventors: Dirk Schmalz; Heinz Allmann; Michael HÄBERL; Hans Muntermann; Michael Schmelz; Frank Schwarz; Reiner Funck; Astrid Lohf
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 2003-05-09
Filing date: 2004-04-17
Publication date: 2006-02-08
Also published as: WO2004098768A1; US20070077179A1; JP2006526492A

Abstract

The invention relates to a component used in microprocess control that comprises at least one process control microfluidic element (4) and microfluidic channel connections (9) and that is provided with a thermally insulating housing (1) surrounding the microfluidic element (4). The microfluidic channel connections (9) are guided through the housing (1). Linking elements for linking individual housings (1) are disposed on the housing (1) in such a manner that the respectively assigned microfluidic channel connections (9) can be sealingly interlinked. The microfluidic element (4) is interposed between a connection block (3) and a heat transfer block (2), and the temperature of the heat transfer block (2) and the connection block (3) and thus of the microfluidic element (4) can be controlled. A linking element for interlinking individual housings (1) has a conical screw (21) with a threaded section (22) and a conically tapered section (23). A locking pin (18) with a bore (19) adapted to the conical screw (21) and projecting from a first of the housings (1) to be interlinked is introduced into a recess (20) of a second housing (1) which recess is adapted to the locking pin (18). The locking pin is tightly pressed into said recess by means of the conical screw (21) whose conically tapered section (23) is engaged with the bore (19) of the locking pin (18).

Description

Micro processing module

The invention relates to a microprocessing module that has at least one process engineering microfluidic element.

In recent years, fluid technology has become increasingly miniaturized, so that the controlled use of small amounts of fluid in the microliter range and below is increasingly becoming research and development

Production purposes in chemical, pharmaceutical and biological fields is used. Various microreactor elements have been developed that allow, for example, mixing, separating, tempering and analyzing the smallest amounts of liquid or gas. Complete microreaction systems not only allow a very effective and cost-effective production or analysis of chemical substances, but also make it possible for the first time not possible reaction processes that are only possible due to a changed fluid dynamics that occurs when such miniaturized microfluidic structures are used.

The manufacture of a microreaction system is due to the small dimensions of the individual structures and

Connections very complex. The microreaction system is complex to handle and can be used easily damaged in everyday laboratory work. Modular microprocessing systems, which consist of interconnectable, individual modules, each of which can contain one or more process steps, have been developed especially for the needs in research institutions. A complex microreaction engineering system can be built up from the individual modules, which contain microfluidic elements such as pumps, mixers or analysis devices. _The individual modules are much cheaper to manufacture and can be replaced in the event of damage without having to replace the entire microreaction system.

The individual components have fluidic and possibly further connections, which must be connected to one another or to external device connections when a microreaction system composed of several components is set up. The previously known microreaction modules of this type do not, however, have any universal uses. and standardized connections for the fluidic and, for example, electrical connections. Even if only uniform components from a certain system provider are used, the lengthy connection technology makes it a long time

Construction time necessary. Especially for research purposes, however, a frequently changing experimental setup, ie a changed arrangement of individual modules, is necessary and leads to a high expenditure of time during use. Furthermore, in many reaction and analysis processes, complex control mechanisms for specifically influencing the temperature of individual or all process steps of a microreaction are necessary. Most microprocessing systems can be cooled and / or heated under certain conditions, for example in a regulated heating bath. The targeted temperature control of only individual process steps is not possible in this way. It is also conceivable to completely separate the individual microreaction modules and to set them up independently of one another in a temperature-controlled manner. However, this leads to a high space requirement and a complex and fault-prone connection technology via fluid connections that are often not thermally controlled.

This delays and makes it more difficult to replace individual modules or to modify an experimental setup.

It is therefore an object of the present invention to design a microprocessing module in such a way that extensive thermal insulation of the individual modules is ensured and at the same time a quick connection, in particular of the fluid connections of the individual modules, is possible.

This object is achieved according to the invention by a microprocessing module with at least one process engineering microfluidic element and with microfluidic channel connections, the microprocessing module being arranged in a thermally insulating housing which Microfluid channel connections are passed through the housing and connecting elements for connecting individual housings are arranged on the housing, so that the respectively assigned microfluid channel connections can be tightly connected to one another.

By arranging the microprocessing module in a thermally insulating housing, the individual building blocks of a complex microreaction system composed of several building blocks are thermally decoupled from one another, so that a targeted temperature control of the individual microfluidic elements of the microprocessing building block is possible. The housing has connections arranged on the outside, so that respectively assigned connections are also connected to one another when two housings are connected to one another. While a simple contacting of the connections is sufficient for electrical connections, for example, fluid connections can and must be tightly connected to one another by using suitable connection devices. It has been shown that a tight fluid connection can be established using commercially available fluid connections even with a slight contact pressure of the interconnected housings. The mechanical and fluidic connection technology can be largely integrated into the housing, so that projecting connection or connection elements can be avoided, which would otherwise be exposed to increased mechanical stress in everyday laboratory work.

It is preferably provided that the microfluidic element is essentially completely thermally conductive Material is surrounded. The microfluidic element can, for example, be accommodated in a metal block which is arranged in the interior of the insulating housing. The good thermal conductivity of the metal block ensures a uniform temperature control of the microfluidic element contained therein, with the surrounding housing achieving thermal insulation of the individual microfluidic elements. Such a construction of a thermally controllable microfluidic element, which is thermally decoupled from other components by means of an insulating housing, enables a much more precise temperature control that is independent of one another for individual process steps, as can hardly be achieved with microreaction modules that are separated from one another only by individual insulation layers such as plastic films ,

According to an advantageous embodiment of the inventive concept, it is provided that the thermally conductive. Material is aluminum or copper and the housing could be made of any other suitable material such as ceramic or a plastic that meets the requirements. These materials have sufficient thermal properties for most requirements, are easy to process and are sufficiently resistant for use in everyday laboratory work.

It is advantageously provided that the microfluidic element between a connection block in the

Connection block arranged fluid connections and an arm transfer block with facilities for Temperature control is arranged. The microfluidic element can be arranged between these two blocks, which are preferably made of aluminum or copper and can be detachably connected to one another, in such a way that, apart from the respective connections, it is completely removed from the one used

Material with a high thermal conductivity is surrounded. In the individual blocks, all connections and contacts for the ikrodfluid element and the temperature control are integrated. By inserting the microfluidic element, usually a

Micro reaction chip, and the subsequent connection of the connection block to the heat transfer block, the microfluidic element is connected to all fluid and, for example, electrical connections in the surrounding blocks, without the individual connections having to be made manually in each case. Of course, differently designed microfluidic elements, which are not necessarily produced in the form of a chip, can also be used, the shape of the connection block or of the heat transfer block in each case matching the microfluidic

Element is adjusted.

The individual connection connections in the connection block are connected to the connections arranged in the housing via hoses and lines. If the microfluidic element malfunctions, it can be removed and replaced without further effort, in particular without the manual loosening and reconnection of connections and connecting lines. Different connection blocks or

Heat transfer blocks are used, their shape and Connection arrangement is adapted to different geometries of microfluidic elements.

According to one embodiment of the inventive concept, it is provided that the connection block has devices for

Has temperature control. An electrical heater, in particular a resistance heater or a fluid-operated heat exchanger with a predeterminable fluid temperature, which are arranged in the heat exchanger block and, if appropriate, in the connection block, can be considered. Temperature control by one or more Peltier elements, by inductive or microwave heating can also be used. It is also possible to combine different possibilities of temperature control with one another, or to apply them at different times simultaneously or depending on the reaction method just carried out.

It is preferably provided that the temperature of the microfluidic element can be regulated. For this purpose, one or more sensors for temperature measurement are arranged in the immediate vicinity of the microfluidic element. The connection block and the heat exchanger block can have sufficiently small dimensions in order to cause only a low thermal inertia when the temperature changes due to the low heat capacity of the blocks. This enables fast, effective temperature control within a wide temperature range, which enables both the production of the smallest quantities of chemicals and rapid parameter screening for experimental tests. According to a further embodiment of the inventive concept, it is provided that sensors such as pressure, flow, conductivity, temperature, optical or pH sensors are arranged on the microfluidic element in the housing. About appropriate, through that

The individual sensors can be connected to external measuring devices through connecting lines which are guided through the housing and provided with detachable connections _. and supply them with measured values. Since the individual sensors are located inside the housing and can be activated if necessary, undesired influencing of a reaction taking place in the microfluidic element is largely ruled out. The arrangement of the individual sensors, which does not have to be changed even when changing a microfluidic element, remains reproducible over many test series and enables reliable and repeatable measurements.

It is also provided that microfluidic components such as valves, check valves or pumps are arranged on the microfluidic element and / or the microfluidic channel connections. Such microfluidic components enable controlled reaction control and fluid flow control within the microprocessing module, or the microfluidic element, which is largely independent of an external fluid supply or subsequent process steps.

It is advantageously provided that a

Connection element for connecting individual housings has a conical screw which has a locking pin with a bore adapted to the conical screw, which protrudes from a first of the housings to be connected, releasably pressed firmly into a recess of a second housing adapted to the locking pin. When connecting two housings, the locking pin of one housing is first inserted into the recess, usually a bore, of the second housing, and is firmly attached with a conical screw that can be screwed to the second housing and whose conically tapering section protrudes through the bore of the locking pin connected to the second housing. The arrangement of the bore in the locking pin and the design of the conical section of the conical screw are coordinated with one another such that as the conical screw is increasingly screwed into the second housing, the

Locking pin and the associated first housing are pressed increasingly firmly against the second housing. In this way, a defined contact pressure of the two housings can be achieved with simple means, which also ensures a reliable and tight connection of the associated ones

Ensures fluid connections of the two housings.

An embodiment of the inventive concept provides that the housing has protrusions and recesses on the side faces for a form-fitting arrangement of individual housings relative to one another. In addition to the locking pin, projections and recesses adapted to them facilitate the precise positioning of the housings to be connected relative to one another. This ensures that the associated fluid connections and, if necessary, electrical connections, even when a connection between two housings is established quickly Contactings are reliably and tightly connected or manufactured. In addition, this type of connection ensures that the side faces of two housings to be connected are not mixed up.

It is advantageously provided that the microprocessing module on the bottom surface of the housing has devices for releasably fastening the microprocessing module on a base plate. Although the connection technology of the individual housings in many cases enables a reliable connection of several housings with each other and thus the construction of a complex microreaction system without any additional aids, it may be useful for certain applications to fix the individual micro process engineering components on a common base plate. The common base plate can on the one hand contribute to an additional secure connection of the individual microprocessing components to one another and, on the other hand, enables the attachment of further components, such as, for example, external measuring devices which are used together with the microreaction system.

Further development of the inventive concept are

Subject of further subclaims. An embodiment of the invention is explained below with reference to the drawing. It shows:

Fig. 1 shows the basic structure of a microprocessing module, the individual Components are shown exploded for better illustration and

Fig. FIG. 2 shows a structure of a complex micro-process engineering system from several interconnected micro-process engineering components according to FIG. 1.

Fig. 1 shows an embodiment of a microprocessing module, the individual

Components are shown in an exploded view. During the assembly of the individual components, the microprocessing module is usually held upside down, as shown in FIG. 1.

In the embodiment shown, the microprocessing module has a housing 1, which is made of polyaryl ether ketone (PEEK) due to the desired thermal insulation properties. The housing 1 could also be made of any other suitable thermally insulating material such as ceramic or a plastic that meets the requirements. In the interior of the housing 1 are a heat exchanger block 2 and

Connection block 3 arranged, between which there is a microreaction chip 4. The microreaction chip 4 as a concrete example for any microfluidic element has fluid channels (not shown), the characteristic dimensions of which are in the micrometer range.

The microreaction chip 4 is usually by means of known shaping or structure-forming Process made from a thin glass plate or a silicon chip. Furthermore, other types of microreaction chip 4 are known and conceivable, in which microreaction chip 4 is made of metal or plastic. There are different versions of

Microreaction chips 4 or very generally known microfluidic elements which enable process engineering operations such as dosing, tempering, reactions, mixing, staying, extracting, separating, evaporating or rectifying.

In order to ensure the fastest possible and uniform temperature control of the microreaction chip 4, a material with high thermal conductivity, such as copper or aluminum, is usually used for the heat transfer block 2 and the connection block 3.

Due to the manufacturing process, the heat transfer block 2 consists of a base block 5, the meandering grooves 6 for

Passing a tempering medium. The meandering grooves 6 are covered by a sealing plate 7. On the side facing the connection block 3, the closure plate 7 has a cutout 8 which is adapted to the dimensions of the microreaction chip 4.

There are several in the connection block 3

Microchannel fluid connections 9 are arranged in such a way that the common, different microreaction chips 4 can each be contacted fluidically. Commercial connection systems are used, which at Establish a sufficiently tight fluidic connection using the appropriate contact pressure.

After inserting the microreaction chip 4 into the recess 8, the connection block 3 and the heat transfer block 2 are firmly screwed together. Supply lines for the temperature control medium 10 and heating cartridges 11 are connected to the arm transfer block 2 from the outside through the housing 1 by correspondingly adapted bores. In this way, the temperature of the microfluidic element is achieved by means of a temperature control device operated electrically or with a fluid heat transfer medium is controllable.

In the exemplary embodiment shown, the

Heat exchanger block 2 has a further recess 12 for receiving a sensor 13. Due to its embedding in the heat transfer block 2, the sensor 13 is brought to the same temperature as the microreaction chip 4, so that largely unadulterated measurements are possible.

The microchannel fluid connections 9 are connected via a hose 14, which is only indicated schematically, to fluid connections 15 arranged in the side walls of the housing 1. Not shown are further electrical connections between the connection block 3 or the heat exchanger block 2 and the outside of the housing 1, which can be used, for example, for energy transmission or control and evaluation of further measuring devices. To contact these electrical, not shown

Connection can on the outside of the housing 1 additional connections such as Single plug connections, collective plug connections or terminal strips can be provided.

Also not shown is the possibility of arranging displays on the outside of the housing in the form of LEDs or LCD displays, which can display measured states and properties in the interior of the housing without the need for external measuring and display devices.

The housing 1 has projecting guide pins 16 and bores 17 adapted to them. When connecting two housings 1, the guide pins 16 of a first housing 1 must be inserted into the bores 17 of a second housing 1, thereby ensuring a precise and reliable alignment of the individual housings 1 with one another.

A locking pin 18, which is fixedly connected to the first housing 1 and has a bore 19 running transversely to its longitudinal axis, is inserted into a bore 20 adapted to it in the side wall of the second housing 1. A conical screw 21 with a threaded section 22 and a conically tapering section 23 is screwed to the second housing 1 such that the conically tapering section 23 with the

Bore 19 of the locking pin 18 of the first housing 1 is brought into engagement and increasingly presses the locking pin 18 and the associated first housing 1 to the second housing 1. The individual microprocessing modules can consequently be connected to one another in a simple manner by screwing in or loosening the conical screw 21 be separated from each other. The contact pressure required for a tight connection of the respectively assigned fluid connections 15 of two housings 1 can be ensured by correspondingly screwing in the conical screw 21.

To protect against environmental influences, the housing 1 can be closed with a base plate 24 which is screwed to the housing 1.

In the exemplary embodiment shown in FIG. 2 of a complex microreaction system built from a plurality of microprocessing components, seven microprocessing components are each connected to one another. Via the guide pins 16 and the associated bores 17, further microprocessing modules can be connected in a simple manner to the microreaction system shown, the locking pin 18 and the associated housing 1 of the newly added microprocessing module being fixed by screwing in the conical screw 21 and each associated fluid connections 15 are tightly connected.

The connection technology shown enables complex microreaction systems to be set up solely by assembling the individual microprocessing components. It can be useful for various applications to attach the individual micro process engineering components on a common base plate. The individual housings 1 are then locked via the respective base plates 24, which fit into the recesses in the base plate positioned and, if necessary, additionally attached.

Claims

Microprocess engineering component

1. Microprocessing module with at least one process engineering microfluidic element (4) and with microfluidic channel connections (9), the microprocessing module being arranged in a thermally insulating housing (1) which

Microfluid channel connections (9) are guided through the housing (1) and connecting elements for connecting individual housings (1) are arranged on the housing (1) so that the respectively assigned microfluid channel connections (9) can be tightly connected to one another.

2. Microprocessing module according to claim 1, characterized in that the microfluidic element (4) is substantially completely surrounded by thermally conductive material.

3. Microprocessing module according to claim 1 or 2, characterized in that the thermally conductive material is aluminum or copper and the housing (1) made of thermally insulating material, in particular

Plastic such as polyaryl ether ketone (PEEK) or ceramic.

4. Micro process engineering component according to one of the preceding claims, characterized in that the microfluidic element (4) is arranged between a connection block (3) in the connection block (3) - 11

Microfluid channel connections (9) and a heat transfer block (2) with devices for temperature control is arranged.

5. Microprocessing module according to claim 4, characterized in that the connection block (3) has devices for temperature control.

6. The microprocessing module according to one of the preceding claims, characterized in that the temperature of the microfluidic element (4) can be controlled by means of a temperature control device operated electrically and / or with a fluidic heat transfer medium.

7. Microprocessing module according to one of the preceding claims, characterized in that the temperature of the microfluidic element (4) is adjustable.

8. Micro process engineering module according to one of the preceding claims, characterized in that sensors such as pressure, flow, conductivity, pH or optical sensors are arranged on the microfluidic element (4) in the housing (1).

9. Micro process engineering component according to one of the preceding claims, characterized in that microfluidic components such as valves, check valves or pumps on the microfluidic

Element (4) and / or the microfluidic channel connections (9) are arranged.

10. Micro process engineering module according to one of the preceding claims, characterized in that a connecting element for connecting individual housings (1) has a conical screw (21), which has a

Locking pin (18) with a bore (19) adapted to the conical screw (21) and protruding from a first of the housings (1) to be connected, releasably fixed. pressed into a recess (20) of a second housing (1) adapted to the locking pin (18).

11. Microprocessing module according to one of the preceding claims, characterized in that the housing (1) has protruding formations and recesses on the side faces for a form-fitting arrangement of individual housings (1) relative to one another.

12. The microprocessing module according to claim 11, characterized in that the housing (1) has projecting guide pins (16) and bores (17) adapted to them.

13. Microprocessing module according to one of the preceding claims, characterized in that the microprocessing module on the bottom surface of the housing (1) has devices for releasably fastening the microprocessing module on a base plate.