DE102021120976A1 - microplate - Google Patents

Abstract

The invention relates to a microtiter plate (3) for the analysis of a large number of liquid or pasty samples (4) provided as drops using nuclear magnetic resonance of the samples (4), comprising a base plate (5) with a large number of in the base plate ( 5) introduced wells (6) or a plurality of first elevations (7) for receiving the samples (4), - a cover (8), which is designed such that the samples (4) between the wells (6) or first Elevations (7) of the base plate (5) and the cover (8) can be included, and- at least one sensor component (9), which is designed to emit light influenced by the nuclear magnetic resonances of the samples (4), the at least one The sensor component (9) is at least partially in contact with the samples (4) and forms at least part of the base plate (5) and/or the cover (8), the base plate (5) and/or the cover (8) being at least area of at least one Sensor component (9) for the excitation light and the emitted light are transparent.

Description

The invention relates to a microtiter plate and a measuring device for the analysis of a large number of liquid or pasty samples provided as drops using nuclear magnetic resonance.

Nuclear magnetic resonance spectroscopy (NMR spectroscopy) allows the investigation of the electronic environment of individual atoms and their interactions with neighboring atoms. The components of samples and the structures of molecules can be determined using NMR spectroscopy. NMR spectroscopy also forms the basis of magnetic resonance tomography, which is often used in the medical or biological field to examine tissues and organs.

Many atomic nuclei have a non-zero nuclear spin and thus a magnetic moment as rotating charge carriers, such as ¹ H or ¹³ C atoms. In a static magnetic field, the nuclear spins perform a precession movement, the so-called Larmor precession, around the axis of the constant magnetic field. The atomic nuclei change the orientation of their nuclear spins to the magnetic field through the absorption or emission of alternating magnetic fields when these are resonant with the Larmor frequency. This effect is also known as nuclear magnetic resonance. The possible magnetic angular momentum quantum states of the nuclear spins are equidistant and dependent on the Larmor frequency. The frequency and duration of the Larmor precession depend on the respective nuclear spin and its spatial and chemical environment. The detection of the Larmor precessions based on the Larmor frequencies thus enables a very precise determination of the chemical composition of the sample and the spatial structure of the molecules contained in the sample.

The alternating magnetic field is usually generated by a magnetic coil. In conventional NMR spectroscopy, inductive methods are often used to detect nuclear magnetic resonances. The sample is often surrounded by an induction coil in which an electrical voltage is generated by the alternating magnetic fields emitted by the nuclear spins occurring. Typically, strong static magnetic fields of up to 25 T are used to polarize the nuclear spins in order to obtain a preferred polarization of nuclear spins aligned in the same way and thus a magnetization that can be measured with conventional magnetic field sensors. A miniaturization of the NMR measuring devices is thus usually not possible. The sample to be examined is usually placed in a long glass tube. The required sample volume is a few milliliters. However, this is a major disadvantage, particularly in the life sciences sector, since the available sample volumes are often in the microliter range. For example, often only a few microliters of sample can be extracted from cell cultures or tissue points.

A newer generation of magnetic field sensors falls into the field of so-called quantum sensors, in which a wide variety of quantum effects are used to determine various physical and/or chemical measured variables. In the field of industrial process automation, such approaches are of particular interest with regard to the increasing efforts towards miniaturization while at the same time increasing the performance of the respective sensors.

Quantum sensors are based on the fact that certain quantum states of individual atoms can be very precisely controlled and read out. In this way, for example, precise and low-interference measurements of electric and/or magnetic fields and gravitational fields with resolutions in the nanometer range are possible. In this context, various spin-based sensor arrangements have become known, for which atomic transitions in crystal bodies are used to detect changes in movements, electric and/or magnetic fields or gravitational fields. In addition, various systems based on quantum-optical effects have also become known, such as quantum gravimeters or optically pumped magnetometers, the latter in particular being based on gas cells, among other things.

For example, in the field of spin-based quantum sensors, various devices have become known which use atomic transitions, for example in various crystal bodies, in order to detect even small changes in movements, electric and/or magnetic fields or gravitational fields. Typically, diamond with at least one silicon or nitrogen vacancy center, silicon carbide with at least one silicon vacancy or hexagonal boron nitride with at least one vacancy color center is used as the crystal body. In principle, the crystal bodies can have one or more defects.

Another sub-area in the field of quantum sensors relates to gas cells, in which atomic transitions and spin states can be queried optically to determine magnetic and/or electrical properties, among other things. A gaseous alkali metal is usually present in the gas cell and a buffer gas. Magnetic properties of a surrounding medium can be determined by Rydberg states generated in the gas cell. For example, gas cells are used in quantum-based standards that provide physical quantities with high precision. So they have long been used in frequency standards or atomic clocks, such as from the EP 0 550 240 B1 known.

It is therefore the object of the present invention to specify a device by means of which the nuclear spin resonances of small sample volumes, e.g. less than 100 μl, can be detected in a simple manner.

• - eine Bodenplatte mit einer Vielzahl von in die Bodenplatte eingebrachten Vertiefungen oder einer Vielzahl von ersten Erhebungen zur Aufnahme der Proben,
• - einen Deckel, welcher derart ausgestaltet ist, dass die Proben zwischen den Vertiefungen oder den ersten Erhebungen der Bodenplatte und dem Deckel einschließbar sind, und
• - mindestens eine Sensorkomponente, welche dazu ausgestaltet ist, unter einem Anregungslicht ein von den Kernspinresonanzen der Proben beeinflusstes Licht zu emittieren, wobei die mindestens eine Sensorkomponente zumindest teilweise in Kontakt mit der Proben steht und zumindest einen Teil der Bodenplatte und/oder des Deckels bildet, wobei die Bodenplatte und/oder der Deckel zumindest im Bereich der mindestens einen Sensorkomponente für das Anregungslicht und das emittierte Licht transparent sind.

The object is first achieved according to the invention by a microtiter plate for the analysis of a large number of liquid or pasty samples provided as drops using nuclear magnetic resonances of the samples, comprising

• - a base plate with a large number of depressions made in the base plate or a large number of first elevations for receiving the samples,
• - a lid, which is designed in such a way that the samples can be enclosed between the depressions or the first elevations of the base plate and the lid, and
• - at least one sensor component, which is designed to emit a light influenced by the nuclear magnetic resonances of the samples under an excitation light, wherein the at least one sensor component is at least partially in contact with the sample and forms at least part of the base plate and/or the cover, wherein the base plate and/or the cover are transparent at least in the area of the at least one sensor component for the excitation light and the emitted light.

Using the microtiter plate according to the invention, a large number of samples can be analyzed in a simple manner using their nuclear spin resonances. When excited with an excitation light, the at least one sensor component emits a light which is influenced, in particular dependent, on the nuclear spin resonances of the respective sample. The light is, for example, a fluorescent light. In particular, the intensity of the light or a relative distance between two intensity peaks is influenced by the nuclear magnetic resonance of the respective sample. The emitted light is detected outside of the microtiter plate, at least one chemical and/or physical property of the respective sample being determined on the basis of the detected light. The at least one sensor component is part of the base plate and/or the cover. The at least one sensor component can be configured in one piece or in multiple pieces; in both cases the at least one sensor component is in contact with each of the samples.

In one configuration, the at least one sensor component is at least one crystal body with at least one defect. With appropriate optical excitation, crystal bodies with at least one defect show a fluorescence signal which is dependent, among other things, on a magnetic field present on the crystal body. The nuclear spin resonances of the respective sample influence the magnetic field applied to the at least one sensor component, so that at least one chemical and/or physical property of the respective sample can be determined using the fluorescence signal. This requires direct contact between the respective sample and the at least one sensor component. The crystal body with the at least one defect leads to an improvement in the measurement accuracy of the detection of the nuclear magnetic resonances of the respective sample and thus the at least one chemical and/or physical property of the respective sample due to its high sensitivity to magnetic fields. In addition, the fluorescence signal, in particular the intensity of the fluorescence signal, can be used to determine the magnetic flux density, the magnetic susceptibility, the magnetic permeability or another variable related to at least one of these variables.

In a further development, the crystal body is a diamond with at least one silicon vacancy center or nitrogen vacancy center, silicon carbide with at least one silicon vacancy center or hexagonal boron nitride with at least one vacancy color center.

The at least one sensor component is preferably designed as a layer, with the layer being arranged in the area of the cover and/or in the area of the base plate. For example, the layer is applied using a CVD or PVD method. The layer can be configured as a single, continuous layer that extends across all samples, or one layer can be applied to the respective areas of the samples.

The at least one sensor component is advantageously designed as a layer, with the crystal body being arranged in the area of the cover and/or in the area of the base plate, with the at least one defect in an area of the crystal body facing the samples personal is arranged. Since the at least one defect emits light that is influenced by the nuclear spin resonances of the respective sample, it must be arranged adjacent to the samples.

In a further development, the cover is made of glass, with the at least one sensor component being applied as a layer to a surface of the cover facing the base plate.

In another embodiment, the lid has a large number of second elevations, the second elevations being cup-like or dome-like, such that the second elevations can be inserted into the depressions in the base plate or such that the samples can be positioned between the first elevations and the second elevations are. In particular, very small volumes of the respective sample are thus clamped and held between the first elevations and the second elevations or between the depressions and the second elevations.

In a further development, the depressions, the first elevations, the cover and/or the second elevations are designed in a defined area in such a way that the samples, due to their hydrophilicity or their hydrophobicity or lipophilicity/lipophobia and/or ultraphobia and/or their surface tension in the defined area can be positioned. The defined area is equipped with a property, for example, which conflicts with a property of the cover and/or the base plate. The respective sample is thus preferably retained in the defined area. Thus, the bottom plate and its first elevations or depressions can have hydrophilic properties, whereas the defined area has lipophilic properties. A sample with more lipophilic properties will therefore preferentially arrange itself in the defined area. For a hydrophilic sample, such as an aqueous sample, the properties of the bottom plate and the defined area could be reversed accordingly. Ultraphobic properties repel both hydrophilic and lipophilic samples.

In a further development, at least one spacer is provided, with the at least one spacer being designed in such a way that a defined layer thickness of the samples can be set between the cover and the base plate.

The base plate can preferably be produced from a polymer resin by means of an injection molding process and/or an embossing process. The at least one sensor component is usually arranged on the microtiter plate in a separate step.

In one embodiment, the samples each have a volume of less than 100 μl, in particular less than 10 μl.

• - eine Halterung für die Aufnahme einer Mikrotiterplatte nach mindestens einem der vorherigen Ansprüche,
• - mindestens eine Anregungseinheit für die Anregung der mindestens einen Sensorkomponente mittels des Anregungslichts,
• - mindestens eine Detektionseinheit für die Detektion des von der mindestens einen Sensorkomponente emittierten Lichts, und
• - eine Auswerteeinheit, welche anhand des detektierten Lichts mindestens eine chemische und/oder physikalische Eigenschaft der Proben ermittelt.

The object on which the present invention is based is furthermore achieved according to the invention by a measuring device for the analysis of a large number of liquid or pasty samples provided as drops using nuclear magnetic resonances of the samples, comprising

• - a holder for receiving a microtiter plate according to at least one of the preceding claims,
• - at least one excitation unit for exciting the at least one sensor component by means of the excitation light,
• - at least one detection unit for detecting the light emitted by the at least one sensor component, and
• - an evaluation unit which determines at least one chemical and/or physical property of the samples based on the detected light.

Using the measuring device according to the invention, a respective sample is analyzed in a simple manner on the basis of its nuclear spin resonance. For this purpose, the microtiter plate is placed in a holder which encompasses the microtiter plate, for example, on one or more of its side surfaces and/or its bottom surfaces. The at least one excitation unit emits an excitation light, which is guided to the at least one sensor component. The light emitted by the at least one sensor component is guided to the at least one detection unit. When guiding the excitation light and the emitted light, at least one optical element can optionally be used, such as a mirror, a prism, a filter, or an optical fiber. As a rule, the emitted light, which is influenced by the respective nuclear spin resonances of the sample, is detected separately. To achieve this, a single excitation unit and a single detection unit can be used, for example, which individually excite the respective samples one after the other and detect the emitted light by making either the microtiter plate and/or the excitation unit and the detection unit movable. Alternatively, for example, a large number of excitation units and detection units can be used in order to be able to analyze a defined number of samples at the same time.

In one configuration, an alternating frequency source is provided for exciting the at least one sensor component and/or the samples. The introduction of alternating fields can be used to carry out typical excitation-query sequences known from NMR spectroscopy, such as the spin-echo method or the so-called XY8N sequence, in which the magnetization of the nuclear spins is specifically set and observed using the alternating field. With the help of these sequences, rapidly changing magnetic fields can also be precisely detected by different components of the respective sample that are present in the area of the at least one sensor component. However, the respective sample can also be excited using the alternating field in order to increase the sensitivity of the analysis of the nuclear magnetic resonances. The alternating frequency antenna can be a microwave antenna, for example.

In a development, an inductor is provided which is designed to induce a preferential polarization of the nuclear spins of the samples. In a further development, the inductor is a magnetic field device that generates a magnetic field at least in a region of the samples and in a region of the at least one sensor component. The magnetic field is in particular static. Instead of a magnetic field device, the inductor can be based on other methods of hyperpolarization, e.g. in the form of para-hydrogen introduced into the samples. It is also possible to configure the inductor as a laser source and/or microwave source and thus to induce a preferred polarization in the electron spins of the at least one sensor component and then to transfer this preferred polarization of the electron spins to the nuclear spins of the samples. In particular, the excitation unit can be used as the laser source. The first and/or second microwave source can be used both to induce a preferred polarization of the nuclear spins of the samples and to excite the at least one sensor component.

• 1: ein vereinfachtes Energieschema für ein negativ geladenes NV-Zentrum im Diamant.
• 2a-b: eine erste Ausgestaltung der erfindungsgemäßen Mikrotiterplatte.
• 3a-b: eine zweite Ausgestaltung der erfindungsgemäßen Mikrotiterplatte.
• 4a-b: eine dritte Ausgestaltung der erfindungsgemäßen Mikrotiterplatte.
• 5a-c: eine vierte Ausgestaltung der erfindungsgemäßen Mikrotiterplatte.
• 6: eine erste Ausgestaltung des erfindungsgemäßen Messgeräts.

In the following, the invention is based on the figures 1 - 6 be explained in more detail. They show:

• 1 : a simplified energy scheme for a negatively charged NV center in diamond.
• 2a-b : a first embodiment of the microtiter plate according to the invention.
• 3a-b : a second embodiment of the microtiter plate according to the invention.
• 4a-b : a third embodiment of the microtiter plate according to the invention.
• 5a-c : a fourth embodiment of the microtiter plate according to the invention.
• 6 : a first embodiment of the measuring device according to the invention.

In 1 A simplified energy scheme for a negatively charged nitrogen vacancy (NV) center in diamond is shown to exemplify the excitation and fluorescence of a vacancy in a crystalline body. The following considerations can be transferred to other crystal bodies with corresponding defects.

In diamond, each carbon atom is typically covalently bonded to four other carbon atoms. A nitrogen vacancy center (NV center) consists of a defect in the diamond lattice, i.e. an unoccupied lattice site, and a nitrogen atom as one of the four neighboring atoms. In particular, the negatively charged NV ^- centers are important for the excitation and evaluation of fluorescence signals. In the energy scheme of a negatively charged NV center there is a triplet ground state ³ A and an excited triplet state ³ E, each of which has three magnetic substates m _s =0,±1. Furthermore, there are two metastable singlet states ¹ A and ¹ E between the ground state ³ A and the excited state ³ E. In the absence of an external magnetic field, a splitting of the two states m _s = +/-1 from the ground state m _s =0 occurs which is called the zero field splitting Δ and which depends on the temperature T.

Excitation light 1 from the green range of the visible spectrum, e.g. excitation light 1 with a wavelength of 532 nm, excites an electron from the ground state ³ A into a vibrational state of the excited state ³ E, which emits a fluorescence photon 2 returns to the ³ A ground state with a wavelength of 630 nm. This fluorescence signal is a measure of the zero field splitting Δ and can be used to determine and/or monitor the temperature T.

An applied magnetic field with a magnetic field strength B leads to a splitting (Zeeman splitting) of the magnetic sub-states, so that the ground state consists of three energetically separated sub-states, each of which can be excited. However, the intensity of the fluorescence signal depends on the respective magnetic substate from which the excitation took place, so that the distance between the fluorescence minima can be used, for example, to calculate the magnetic field strength B using the Zeeman formula. The magnetic field strength B is modified by the nuclear spins of the respective sample 4 or results from them.

Other options for evaluating the fluorine are within the scope of the present invention zenzsignals provided, such as the evaluation of the intensity of the fluorescent light, which is also proportional to the applied magnetic field. An electrical evaluation, in turn, can be carried out, for example, via photocurrent detection of magnetic resonance (PDMR for short). In addition to these examples of evaluating the fluorescence signal, there are other options which also fall within the scope of the present invention.

In the figures 2a-b a first embodiment of the microtiter plate 3 according to the invention is shown. In this embodiment, the base plate 5 has a large number of first elevations 7 and the cover 8 has a large number of second elevations 10 between which the samples 4 are accommodated. The samples each have, for example, a volume of less than 100 μl, in particular less than 10 μl. The second elevations 10 are designed in the manner of a dome, for example, alternatively they are designed in the manner of a bowl. Optionally, at least one spacer 12 is arranged between the cover 8 and the base plate 5, which is designed in such a way that a defined layer thickness 13 of the samples 4 between the cover 8 and the base plate 5 can be set. The base plate 5 is produced from a polymer resin, for example by means of an injection molding process and/or an embossing process.

The at least one sensor component 9 is configured as a multiplicity of sensor components 9, for example. The sensor component 9 forms part of the second elevations 10 of the cover 8 and is at least partially in contact with the samples 4 when the microtiter plate is closed, i.e. when the cover 8 is placed on the base plate 5, so that the sensor components 9 are one of the Nuclear magnetic resonances of the respective sample 4 emit light influenced. The at least one sensor component is, for example, at least one crystal body with at least one defect, such as in particular a diamond with at least one silicon defect center or nitrogen defect center, silicon carbide with at least one silicon defect center or hexagonal boron nitride with at least one defect color center. For the sake of clarity, the samples 4 are hatched in these and the following figures.

In the figures 3a-b a second embodiment of the microtiter plate 3 according to the invention is shown. In this embodiment, a layer 9a of the sensor component 9 is provided in the area of the cover 8 , which layer faces the samples 4 and the base plate 5 . For example, the cover 8 is made of glass. Alternatively, the layer 9a is arranged in the area of the base plate 5 . Optionally, the first elevations 7 are configured in a defined area 11 in such a way that the samples 4 can be positioned in the defined area due to their hydrophilicity or their hydrophobicity or lipophilicity/lipophobicity or ultraphobicity or their surface tension. Correspondingly, a defined area 11 can also be arranged on the depressions 6 and/or the cover 8 and/or the second elevations 10 .

In the figures 4a-b a third embodiment of the microtiter plate 3 according to the invention is shown. In this embodiment, the base plate 5 has indentations 6 which are partially formed by the sensor components 9 . The cover 8 also has second elevations 10 which can be inserted at least partially into the depressions 6 so that the samples 4 can be positioned between the depressions 6 and the second elevations 10 .

In the figures 5a-b a fourth embodiment of the microtiter plate 3 according to the invention is shown. In this embodiment, the at least one sensor component 9 is arranged both in the area of the cover 8 as a layer 9a and in the area of the base plate as part of the depressions 9 . The samples 4 are in contact with two sensor components 9, as a result of which the sensitivity of the analysis of the samples 4 is increased. In 5c the cover 8 is shown as an example with the layer 9a of the sensor component 9 . The crystal body 9b is arranged in the area of the cover 8 and/or in the area of the base plate 5, the at least one defect 9c being arranged in an area of the crystal body 9b facing the samples 4. Depending on the manufacturing method of the layer 9a, it is possible to control the distribution of the at least one defect 9c in the crystal body 9b and to ensure that these 9b are preferably arranged in a region of the layer 9a facing the samples 4.

In 6 shows a first embodiment of the measuring device 14 according to the invention for the analysis of a multiplicity of liquid or pasty samples 4 provided as drops on the basis of their nuclear magnetic resonances. The microtiter plate 3 is held in a holder 15 . The base plate 5 and/or the cover 8 are transparent at least in the area of the at least one sensor component 9 for the excitation light of the excitation unit 16 and the light emitted by the at least one sensor component 9 . For example, the at least one excitation unit 16 is arranged above the microtiter plate 3 in order to excite the at least one sensor component 9 from above. The detection unit 17 is designed to detect the light emitted by the at least one sensor component 9 and is arranged below the microtiter plate 3, for example. the yesterday The bright line indicates the path of the excitation light from the excitation unit 16 to the sensor component 9 and the path of the emitted light from the sensor component 9 to the detection unit 17 .

In this embodiment, an excitation unit 16 and a detection unit 17 are provided, which can be moved relative to the microtiter plate, so that each of the samples 4 can be analyzed individually one after the other. However, several excitation units 16 and several detection units 17 can also be provided in order to analyze several samples 4 simultaneously. Furthermore, the measuring device 14 has an evaluation unit 18 which uses the light detected by the detection unit 17 to determine at least one chemical and/or physical property of the samples 4 .

An alternating frequency source 19 is optionally arranged in the measuring device 14, which is designed to excite the at least one sensor component 9 and/or the samples 4. Furthermore, the measuring device 14 includes, for example, an inductor 20 which is designed to induce a preferential polarization of the nuclear spins of the respective sample 4 . For example, in the inductor 20 there is a magnetic field device which generates a magnetic field at least in a region of the samples 4 and in a region of the at least one sensor component 9 .

Reference List

1

excitation light

2

fluorescent light

3

microplate

4

rehearse

5

bottom plate

6

indentations

7

first surveys

8th

Lid

9

sensor component

9a

layer

9b

crystal body

9c

void

10

second surveys

11

defined area

12

spacers

13

layer thickness

14

gauge

15

bracket

16

excitation unit

17

detection unit

18

evaluation unit

19

alternating frequency source

20

inductor

QUOTES INCLUDED IN DESCRIPTION

This list of documents cited by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Patent Literature Cited

• EP 0550240 B1 [0008]

Claims (15)

Microtiter plate (3) for the analysis of a large number of liquid or pasty samples (4) provided as drops using nuclear spin resonances of the samples (4), comprising - a base plate (5) with a large number of depressions (6) made in the base plate (5) or a large number of first elevations (7) for receiving the samples (4), - a cover (8) which is designed in such a way that the samples (4) can be enclosed between the depressions (6) or the first elevations (7) of the base plate (5) and the cover (8), and - at least one sensor component (9) which is designed to emit light influenced by the nuclear magnetic resonances of the samples (4) under an excitation light, the at least one sensor component (9) being at least partially in contact with the samples (4) and forms at least part of the base plate (5) and/or the cover (8), the base plate (5) and/or the cover (8) being transparent at least in the region of the at least one sensor component (9) for the excitation light and the emitted light are. microtiter plate claim 1 , wherein the at least one sensor component (9) is at least one crystal body with at least one defect. microtiter plate claim 2 wherein the crystalline body is diamond having at least one silicon vacancy center or nitrogen vacancy center, silicon carbide having at least one silicon vacancy center, or hexagonal boron nitride having at least one color vacancy center. Microtiter plate according to at least one of Claims 1 - 3 , wherein the at least one sensor component (9) is designed as a layer (9a), the layer (9a) being arranged in the area of the cover (8) and/or in the area of the base plate (5). microtiter plate claim 2 , wherein the at least one sensor component (9) is designed as a layer (9a), the crystal body (9b) being arranged in the area of the cover (8) and/or in the area of the base plate (5), the at least one defect ( 9c) is arranged in a region of the crystal body (9b) facing the samples (4). Microtiter plate according to at least one of Claims 1 - 5 , wherein the cover (8) is made of glass, wherein the at least one sensor component (9) is applied as a layer (9a) to a base plate (5) facing surface of the cover (8). Microtiter plate according to at least one of Claims 1 - 6 , wherein the cover (8) has a plurality of second elevations (10), the second elevations (10) being cup-like or dome-like in design, such that the second elevations (10) can be inserted into the depressions (6) of the base plate (5). are or in such a way that the samples (4) can be positioned between the first elevations (7) and the second elevations (10). microtiter plate claim 7 , The depressions (6), the first elevations (7), the cover (8) and / or the second elevations (10) in a defined area (11) are designed such that the samples (4) due to their hydrophilicity or their hydrophobicity or lipophilicity/lipophobicity and/or ultraphobicity and/or their surface tension can be positioned in the defined area (11). Microtiter plate according to at least one of Claims 1 - 8th , wherein at least one spacer (12) is provided, wherein the at least one spacer (12) is designed such that a defined layer thickness (13) of the samples (4) between the cover (8) and base plate (5) can be adjusted. Microtiter plate according to at least one of Claims 1 - 9 , wherein the base plate (5) can be produced from a polymer resin by means of an injection molding process and/or an embossing process. Microtiter plate according to at least one of Claims 1 - 10 , wherein the samples (4) each have a volume of less than 100 μl, in particular less than 10 μl. Measuring device (14) for the analysis of a large number of liquid or pasty samples (4) provided as drops using nuclear spin resonances of the samples (4), comprising - a holder (15) for receiving a microtiter plate (3) according to at least one of the preceding claims, - at least one excitation unit (16) for exciting the at least one sensor component (9) by means of the excitation light, - at least one detection unit (17) for detecting the light emitted by the at least one sensor component (9), and - An evaluation unit (18) which uses the detected light to determine at least one chemical and/or physical property of the samples (4). measuring device claim 12 , With an alternating frequency source (19) for exciting the min at least one sensor component (9) and/or the samples (4) is provided. Measuring device according to at least one of the Claims 12 - 13 , wherein an inductor (20) is provided, which is designed to induce a preferential polarization of the nuclear spins of the samples (4). measuring device Claim 14 , wherein the inductor (20) is a magnetic field device which generates a magnetic field at least in a region of the samples (4) and in a region of the at least one sensor component (9).

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