Device having a specific support structure for receiving, analysing and treating samples.

The invention relates to a micromechanical structure for purposes of biotechnology, so particular disease and hunger, for purposes of biotechnology, genetic engineering, cell research, for the pharmaceutical industry, for healing and exploring particular hitherto incurable diseases, also for agricultural research to new sources of food and to develop energy sources and restore the environment. For the purposes of medicine, for example, blood tests but also of tissues or cells, such as antibody, Antigenimmobilisierung for the production of monoclonal antibodies for the production of antibiotics, insulin, but also for remedy sera, bacteria and other substance investigations and comparative experiments. Always there is the task of a safe kontollierten dealing with the particular substance, during and after an investigation, reaction or the like, particularly when the substances may constitute a danger to the environment.

In order to fulfill the purposes mentioned, in particular to combat disease and hunger in the world, it is necessary to be able to handle in investigations, reactions, tests, comparative studies and test series with particularly hazardous substances safe even if the amounts of substance yet are so low.

Object of the invention is to provide a clean, safe storage and handling of substances that are dangerous or can be - whether before, during or after an investigation, reaction, test or the like - to facilitate or ensure.

This object is achieved by a microstructure according to claim 1. This microstructure has many advantages. They can be manufactured in large quantities at low cost. It is suitable for the secure storage of a variety of substances as a sample for testing, for treatment, for studies, for comparison, for reactions etc.. The arrangement of suitable cavities each other in the structure in the manner of a matrix or array allows simple process control, simple examination and implementation of desired reactions of desired small amounts of substances and their targeted treatment and investigation. The structure of the cavities consists of inert material, ie it changes in the investigations, treatments not, the cavities are reliably closed and are not attacked by most pollutants.

Training and further developments of the invention are given in further claims and in the description and drawing of an embodiment. Combinations of these features must be the invention. In the drawings:<ul><li>Figure 1 is a structure with a single cavity and a particular surface orientation of the crystalline material.</li><li>FIG. 2 is a modification of Figure 1;</li><li>FIG. 3 is a structure of crystalline material;</li><li>Fig. 4 shows a structure in a modification of Figure 3;</li><li>5 shows a structure in a constructive modification of FIG. 1;</li><li>. Fig. 6 shows a modification of Figure 2 or 4, wherein a structured part in the middle between two thereof arranged in different parts (sandwich structure);</li><li>. Fig. 7 shows a modification of Fig 6 with in bottom plate and top plate additionally arranged facilities;</li><li>8 shows a further modification of FIG 6 or 7 with additional layers or plates..;</li><li>9 is a version with measuring or detecting means. </li><li>10 shows a structure with measuring and detecting device, and optionally storage.</li><li>11 shows a device with a biosensor, in particular field effect transistor.</li><li>FIG. 12 is a modification of the embodiment of Fig. 11;</li><li>13 is a means for detecting certain substances in fluids.</li><li>14 is a device for automatic examination with documentation of the test results.</li><li>FIG. 15 is a heat exchanger in particular plate cooler;</li><li>Fig. 16 is a plan view of FIG. 15;</li><li>Fig. 17 is a modification of FIG. 15 and</li><li>Fig. 18 is a plan view of Fig. 17.</li></ul>

Referring to FIG. 1, a structure 1 of walls with one, preferably a plurality of cavities therein for receiving small amounts of substance, and the block is completed by a cover 3. Block 1 and cover 3 are made of crystalline material, such as semiconductor material. Similarly to the closure of the container according to the invention with a second mask is generated a counterpart = lid 3 which corresponding elevations 4 to the wells having 2, since the masks are geometrically identical. The masking technique allows a high precision in the manufacture; it is known from the semiconductor technology.

The abovementioned technique a crystal directional anisotropic etching process is advantageous to use, as this will enable, lisieren taking advantage of the self-limiting effect of (111) crystal planes, wells with high geometric precision and very narrow tolerances rea. The container in Fig. 1 can be produced in (100) silicon, wherein the laterally defining (111) planes forms an angle of 54.7 ° to the wafer surface. However, the invention is not limited to above-mentioned etching. Other known types of transfers of wells in semiconductor or similar crystalline material can be applied, such as laser-drilling.

The cover 3 can be provided with an elevation 4, which has the same 54.7 ° inclination to the crystal surface as the container block 1 in the region 2, thereby properly tight manner. This is true even if the lid has a plurality of protrusions, and the block 1 has a plurality of recesses second If there is insufficient accuracy of fit, the surveys produced by etching and depressions on the cover 3 and Block 1 for individual applications of particularly dangerous substances, a circumferential seal can also be used. Fig. 5 shows an embodiment, which in turn corresponds to the 54.7 ° bevel collecting 4 of the lid and form with another one closure. In addition, adhesives or other bonding techniques to increase the tightness can be applied. In particular, a laser beam in the seam welding method can be applied on the peripheral rim of the lid. A plurality of cavities 2 is not limited in the block of the container size, training and distribution.

The cavities 2 (and the elevations 4) may, in particular square, rectangular, be circular, oval or diamond-shaped. You can down taper or expand towards - see Figure 1 and Figure 2 -.. Or keep the same cross-section, if they are bored, for example using a laser beam (Fig. 4). You can also have other cross sections or shapes (openings, channels form).

An additional layer or plate 5 serves as a support or intermediate support (removably) advantageously of the same material, such as silicon or the like, as the bottom of the container, also hermetically sealed manner.

The worked out from a block of material structure 1 forms advantageously (for mass production), a flat plate with through cavities 2 such openings, channels or the like desired shape wet chemically etched with advantage of silicon while the cover 3 and the bottom 5 of this material of the structure 1 preferably well connected, in particular hermetically sealed lockable material such as glass, quartz glass, ceramic or silicon plastic or silicon metal composite material.

In FIG. 6, as shown, the bottom 5 or to the structure 1 side coated with a layer 7, for example, a filter layer, a sedimentation layer, an inert, or catalytic or otherwise reacting layer of a material, or even absorbent material can be. A nonwoven fabric or other large pore or provided with large open area non-woven fabric, fiber laminate, foam or similar permeable structure may be used depending on the application (collecting, storing, reacting). It may be an inert support or an active carrier material which is used for the layer 7 and below could against if valves or other devices (see Fig. 8) are arranged. Block 1 with the cavities 2 includes these distributed advantageous to a grid in XY on the surface of the preferred silicon crystal as an array or in matrix form (see. FIG. 3), so that they filled eg by means of automatic devices with substances fumigated seeded, diluted, destitute, sucked or the like., mixed or can be made to react. The feed or sampling elements are then programmatically line by line, until the entire surface is scanned, as is known in automatic analyzers or handling machines or robots for medical or other research purposes.

The material of the block 1 must be inert in each case relative to the substance being examined, treated, diluted, to be mixed or to be brought to a reaction or is tested for its absence (composition or anti-tests).

Depending on the purpose for which the invention is applied, the cavities for the investigation or storage (storage containers) can be designed more in particular, in which the cavities 2 are only part of trial or examination or reaction chambers in block - see Fig. 7. the matrix or array arrangement in the XY direction is maintained as described above and also the substantially sandwich-like structure of FIG. 6. in addition is 8 or 9 associated with a more appropriate recess in the cover plate 3 and the bottom plate each of the cavity, the total seen the chamber volume or volume of the cavity 2 substantially increased. Can now take place feed or discharge of a medium in the plane, for example if the same to-medium all chambers or to be discharged.

As a rule, for the purposes of the aforementioned substances as solids are examined in a fluid; it can also gases into a liquid or gas or liquid to be examined in a solid. This applies in particular for immune reactions, for assaying enzymes or microorganisms. It can be found in one or more properties such as flow, density, surface or boundary effects, special characteristics of particles, permeability, friction, adhesion at or analyzes of substances / mixtures chemical or physical properties or its amendment. It can be a storage under certain conditions such as pressure or vacuum are investigated over a certain time in the simplest case, or by external influence, a response, or the lack of response to be investigated. External influences may include: radiation, heat treatment, application of reagents, measuring the change of material properties in heat, cold, steam, humidity or supplied materials / particles, by applying electrical / electrochemical, or magnetic means, by application of sound, infrasound, ultrasound , Furthermore, colorimetric, spectrophotometric or fluororometrische studies, for example using as reagent Reagenzpapieren can be carried out as a layer 7th Heating and / or cooling elements can be guided through the plates 3 and 5 of the chambers, 2 10 and 11, for example in the form of each tempered media in channels or it can thermocouples, in particular Peltier elements may be disposed at least partially in the area of ​​these cavities. Substances can be used with fluorescent labels, radioactive labels or enzyme labels with carriers or without carriers, bonded or separable, organic or inorganic, with cells or cell fragments, gel or other for the detection of microorganisms, bacteria, viruses and other things, but also to detection of cancer, for the determination of individual substances in the blood or to determine the pH value, blood sugar, blood cholesterol or for the detection of narcotics or other blood. The appropriate test methods, in particular biological / medical, Chemical composition / physical are known, especially in blood test, to test sera etc. Even research methods for other body fluids such as lymph, urine, etc. are known, depending on whether small particles labeled or unlabeled, organic / be inorganic, used with or without a carrier of a known type, fluoroscopy are recommended using X-rays, but also investigations with the aid of gamma rays, visible light infrared or ultraviolet light (optical process). Evaluation by means of optical fibers are shown for example in Fig. 9 and 10. In tests of the flow properties of substances or substance mixtures is advantageous, as shown in FIG. 8 to control the inflow, outflow or both (flow rate) with the help of micro-valves 12 and 13 in the cover or base 5 of the block 1 with the microcavities second The micro valves themselves are known per se (see for example, EP 0250948 A2). They are preferably in the same array or in the same matrix arranged in XY direction as the cavities 2 in block 1 and thereby give a simple evaluation possibility for respective investigations. In the bottom 5 7 may be arranged as shown in Fig. 6 is a layer. Below the bottom 5 is still a further support part or end plate 14 be arranged, which includes a detecting means such as photo-elements in the same array arrangement for analysis to a microprocessor (not shown here). can forward. The lines for supply and removal of substances, reagents, etc. are not shown, nor is the radioactive sources which advantageously from above, ie above the lid 3, radiate in Fig. 8. The parts 3 and 5 can also be 8 in Fig. Advantageously glass, quartz or silicon ceramic or a silicon composite material and at least partially transparent, at least partially reflective. Top or bottom may be possibly replaced by foil strips of opaque material, at least partially, for example, may also be on the cover 3, if it contains the microvalves, another plastic film can be adhered, which causes a hermetically sealed closure, but are pierced by a hollow needle can. Films or layers may be optically opaque or out, they can be designed as heating layers 10 or heat sink 11 or formed specular / nichtspiegelnd, permeable to certain wavelengths filternd, partially transparent or similar for optical purposes. Also, carbon or diamond layers and / or mask layers that are time- or partially kavitätenabdeckend usable.

The micro-valves can be controlled and driven in a conventional manner or as described in the manner as described in German Patent Application P 38 11 052.0-31. The reaction in the cavities can then be effected by moving for example on piezoelectric routes, magnetic, electrostatic or similar. In this case, a nutrient solution, a mutant, a Reganz or the like diluted, enriched, are dosed and the residence time are controlled by respective closing and opening of the microvalves. The heat treatment or cooling treatment can be by means of Peltier elements, heat pipes, Thomson-Joule coolers or the like performed.

As sensors, arranged in the same array in the lowest layer, in turn, silicon sensors are preferred, especially for the study of physical or chemical properties such as black and white or gray scale, contrast, turbidity, transmittance, transparency, reflection, conductivity, resistance, capacitance, pressure, strain , temperature volume, quantity, time, etc. in order to evaluate the measured values ​​are passed on to a microprocessor or microcomputer, not shown. The readout can follow in a conventional manner, if the evaluation is carried out visually, eg the type of P 38 17 153.8-33.

The storage and documentation of the data of the measurement or test program and the storage of, for example patient data disease or data or data from sera or pharmaceuticals can be carried out on the same chip (lowermost layer in Fig. 8 to 10). The storage can be either with the aid of an optical memory take place, for example, according to DE-OS 3,804,751 with amorphous silicon as a storage medium (bubble memory) or as an integrated semiconductor memory device (DE-OS 38 17 153) or a RAM device (P 37 01 295.9-52). Referring to FIG. 9, it is possible in a simple manner in an optical or optoelectronic evaluation using an optical waveguide 15, which passes through the micro-chamber or cavity 2 in block 1 or comes close to it and is etched in interesting area of ​​his coat and eg is coated to achieve a response in particular substrate.

Modifications of the embodiment of FIG. 9 are manifold possible, especially for photoelectric or other photoelectric evaluation not only by means of optical fibers. The light guides are preferably V-grooves, at the bottom thereof disposed adjacent fixed and not only continuously available but also cut obliquely corresponding to the inclination of the pit, and at least partial surfaces 15a, 15b of the light guide 15 (sectional area) or the V-pit are reflective , The arrangement parallel to the pit across the pit from above or below 90 degrees, 180 degrees or the like occur. The optical fibers are taken out and are for evaluation to photocells, such as line sensors or arrays, connected for the purpose of analog or preferably digital readout. The readout can be done in rows and ranks, described for example by scanning using a photo-electric line sensor as described in DE-OS 3,804,200. Here, an optical bus can be used. A suitable optical data system is described in DE-PS 3 619 778. transmitters and receivers, in particular diodes may be integrated into the structural unit. The mines are in their V-angle (slope adjustable or changeable, see DE-OS 3,613,181). An integrated optical waveguide and their structure and applications are described in the journal Laser and Optoelectronics, no. 4, 1986, pages 323 to 336. On page 338 of the same journal are also described applications of optical fiber sensors in medicine.

In Fig. 10 is a block 1 with the bottom 5 and the lid 3 is shown with microcavities 2, in particular extends through recesses in the cover 3 and bottom 5 - similar to that of Fig. 7 - but above the in-array arrangement microcavities 2 each treatment openings, valves, supply and discharge organs, window, dopant ranges are merited, etc. according to the chamber volume in the lid 3, while, for example, an array of photoelectric cells or a CCD array or a MOS field-effect transistor is arranged in the bottom 5 of the reading and evaluating, for example, is connected via the aforementioned optical or an electrical bus to an evaluation unit, in particular with microprocessors of the microcomputer. A light pen 16 scans rows and row by row, the array from, for example, in binary code 8x8 microcavities or cells or 10x10 for direct digital interrogation. Instead of the light pen 16 may also be a piezoelectric, a capacitive, magnetic or electrical sensors are used. The pin 16 is then ready for application of a voltage, power or light irradiation or the like suitable to the window 17 in the lid 3 into the chambers 2 of the block 1 to the direct read-out, for example via a CCD array in the same arrangement as the microcavities or cells, indicated here by the CCD cells 17 '. In the same manner may also be arranged a MOSFET or a RAM device. The readout can be carried out with devices of integrated optics, especially contactless and two-dimensionally (see DE-OS 3,605,018 or US Patent No. 4,778,989.). Instead of the light pen 16 also an ion-selective measuring electrode could be used as a replaceable sensor element, in particular for measuring the cones activities in liquids and on tissue surfaces. Such ion-selective measuring systems are known and commercially available. They are based on a pure electric evaluation principle in contrast to the embodiment of FIG. 9, for example, is used for the optical determination of the catalytic enzyme activity of a substance sample, wherein the conditioned by the emzymatische reaction change of spectral properties of an enzyme substrate or its reaction products are detected per unit time. The enzyme substrate is associated with the exposed portion of a light guide with which the sample substance to be measured is brought into contact.

In the embodiment of FIG. 10 is an evaluation by means of a CCD array, for example, to DE-OS 3,817,153 or by means of semiconductors to DE-OS 3,715,674 or by means of liquid crystal elements is recommended, such as in DE- PS 3602796 describes. With such elements, a direct storage of test or analysis result is possible at any time specifically interrogated, even after individual microcavities.

In Figs. 11 and 12, the properties to be examined adapted optronic / electronic sensors are shown, which are generally known under the term "biosensors". Such biosensors generally operate with field-effect transistor 18 in silicon technology. Together, the biosensor produced thereby has a biological component to the surface that is connected to the gate of the transistor. This biological component or reagent or enzyme substrate 19 must be capable of respectively desired reaction. Then you can after the workspace is optimally set, by means of one or more voltage sources U1, U2, impose voltage eg when R to drain and source and measure corresponding changes in ion activity. The measurement 12 may also be photoelectrically with the aid of light conductors between the transmitter and receiver, such as diodes, lasers, integrated in FIG.. A biosensor of the kind here at issue is described in DE-PS 3,634,573.

In FIG. 13, a sensor is shown purely schematically on a silicon wafer 20, wherein a sensor chip 21 is reacted with the substance sample, such as a soil sample, a liquid sample, a food sample or a tissue sample with contaminants therein whose proportion is to be determined, for example. It can also be an oxygen demand or oxygen content or the like can be determined. The sensor is a conventional Termistor- or conductivity sensor. Also, sound or ultrasound or infra-sound sensors are suitable if the sample is to be hereby applied. Miniature microphones are known.

In Fig. 14, the embodiment of an automatic test machine is shown. A microcomputer or microprocessor assumes control of the test sequence according to a predetermined test program. The program can be contained in replaceable an external memory, eg in a PROM or EPROM, or an erasable read-write memory. Patient data, data of the test materials, the reagents, etc. are also interchangeable and after a test, the test results in the microcomputer or microprocessor are also stored, in particular in a memory for random access and the recording itself documenting, for example, as a CCD image, thermal imaging piezoresistive or on magnetic tape, electrostatic or ferroelectric etc.

In the embodiment of Fig. 14, a film carrier 23 is shown adhered to the macro chip from a Vielzehl individual chips in FIGS. 1 to 5 or releasably attached, wherein said film carrier has a transport perforation 24, the film with the usual film transports, such as controlled Maltese cross from roll to roll over a treatment period of the program, and from station to station 25, that is here to lead IX. Initially, one or more substances to the test program will be introduced into the microcavities of the chips in Station I. In station II then there is a reaction, either with or without treatment, and after a reaction time is measured automatically and transported to the test station III, as necessary, carry out further tests, the test results are automatically assigned to the individual cavities, optionally individual Probesubstanzherkünften, and patients. The self-documentation and storage takes place in the microcomputer or microprocessor 22 for automatic test control and test applications.

The invention further describes an apparatus for a micromechanical heat exchanger, especially Joule-Thomson cooler.

In the prior art are on the market various types of miniaturized heat exchangers, such as Joule-Thomson coolers. All are characterized by very high unit cost.

A available on the market Joule-Thomson cooler (eg Fa. Hymatik) has a very long metal coil that is wound on the surface of a cone. The overall arrangement is located in a dewar housing, the expanded gas flows back over a large area on which is provided with cooling fins metal spiral between the Dewar wall and conical surface.

Another arrangement of WA Little (AIP Proceedings of Future Trends in Superconductive Electronics;. P 421, University of Virginia, Charlottesville, in 1978, published, consisting of several, glued glass plates have been incorporated into the lateral cooling channels These coolers are. ineffective, because owing to the poor heat conductivity of the glass, the efficiency of the heat exchanger is limited.

The invention has as its object, a miniature heat exchanger, in particular to provide Joule-Thomson cooler which can be manufactured economically and increased exchanger power results.

This object is achieved by providing, in contrast to known, in this minicoolers the flow channels a plate heat exchanger are arranged vertically in a thin substrate. This substrate is (sandwiched) enclosed by two cover plates are incorporated in the connecting channels which connect the vertical channels of the substrate, seen in cross section, to a meander. The individual lines of the heat exchanger are on the substrate (viewed from above) arranged in spiral form. In the center of the substrate is an expansion chamber, in which the main cooling power is generated. The highly compressed gas meanders on the heat exchanger coil from the outside inwards, expands in the central expansion chamber, and is then passed in countercurrent over channels having substantially enhanced cross-section of the spiral to the outside again, which is already pre-cools the incoming gas. In order to maintain the large radial temperature gradient across the substrate and to keep the losses as small as possible by heat conduction in the substrate and in the cover plates, vertical separation channels are incorporated between the various arms of the spirals. The overall arrangement is provided above and below with two insulating with the lowest possible heat conduction (eg glass). It can be directly connected to the central plate (sandwich) and glass cover plates.

The invention is particularly suitable for cooling of infrared CCD's. The cooling medium is a highly compressed gas (eg nitrogen) is used, which can be achieved as a limiting temperature of the boiling point of the gas (in the central expansion chamber).

The invention is explained below with reference to embodiments shown in the drawing. Show it<ul><li>FIG. 15 is a cross section through a heat exchanger as a Joule-Thomson cooler in the high-pressure channels</li><li>Fig. 16 top plan view of an elementary cell heat exchanger of the Joule-Thomson cooler in the area of ​​the central silicon wafer,</li><li>Fig. 17 is a cross section through the Joule-Thomson cooler in the area of ​​the low pressure channels,</li><li>FIG. 18 is an overall arrangement of the elementary heat exchanger cells and the expansion chamber in the center of the silicon wafer.</li></ul>

In the following an embodiment of the Joule-Thomson cooler is described. The overall arrangement consists of three processed silicon wafers 1, 1a, 1b, which are connected to each other and two cover plates, for example of glass 3.5, which in turn are connected to the silicon wafer of FIG. 1.

Fig. 15 shows a cross section of the overall assembly by the smaller cooling channels 26. In the upper and lower silicon wafers are etched recesses 27, which close the channels of the central silicon wafer to meanders. These wells are also etched in (110) silicon wafers, where the depth is limited independently by crystallography. Etching is anisotropic in a batch process.

In the central silicon wafer vertical channels 26 are incorporated, leading the forward and backward flowing gas and are used simultaneously by the thin partition walls as a heat exchanger. An elementary cell of this heat exchanger is shown in Fig. 16. The inner, smaller channels 26 lead the compressed (eg, typically 50-100 bar), hinströmende gas. The outer, large channels 29 are interconnected so as to form a channel with a large cross section for the reverse flow, expanded gas. The partitions in the outer region 28 have only task is to ensure the most effective possible heat exchange and mechanical stability. The more lined walls between high- and low-pressure channels 30 must absorb the entire pressure difference and at the same time allow a good heat transfer. The special geometry of the channels in this configuration is determined by the crystalline structure of the silicon, with vertical (111) planes of (110) wafers.

Fig. 17 shows a cross section through the outer area of ​​the channels 29 for the gas flowing back. Here the outer silicon discs 1a and 1b are completely etched to obtain the largest possible cross-section of the meander of the expanded gas.

The overall arrangement of the individual heat exchange cells on the central silicon wafer is shown in Fig. 18. The cells are arranged side by side and spirally performed from the outer region to the center of the disc. At the disk center is an expansion chamber 31, in which the cooling power is generated. eg can immediately above this chamber similar to a cooling silicon chip Semiconductor or IC's are arranged. The individual spiral arms are each thermally isolated by separation channels 32, 33rd

The novel micromechanical Joule-Thomson cooler is distinguished from existing systems in particular by the fact that he can be with the known batch process method of micromechanics, how they are applied in the manufacture of semiconductor devices manufactured considerably cheaper. Furthermore, a very good swirling of the gas and thus a high efficiency of the heat exchanger is to be expected due to the vertical arrangement of the cooling channels and the frequent meanders. Furthermore, a fluid to be cooled semiconductor chip are integrated directly into the system or overall arrangement, so that the cooling capacity is made at the chip without partitions.

The invention is not limited to the use of a particular medium for heat exchange. In addition, the management of the media is not restricted to the exemplary embodiment. Even heat pipes (heat pipes) are applicable.