DE102014101172A1 - Arrangement for an optical measuring system for determining a sample and sample chamber arrangement - Google Patents

Abstract

The application relates to an arrangement for an optical measuring system for determining a sample (1a), having a sample chamber (1), an immersion fluid (6) which is accommodated in the container (2) and in heat-conducting contact with the sample chamber (1) and the sample (1a) arranged therein is an optical component (9) of an optical measuring device, a further optical component (8) and a temperature control device (3) associated with the immersion fluid (6), which are thermally insulated from the optical component (9) and is set up to temper the immersion fluid (6) in the fluid volume (2) and hereby the sample (1a) to be determined in the sample chamber (1), wherein the optical component (9) and / or the further optical component (8) parts an optical measuring device which is adapted to determine a sample (1a) in the sample chamber (1) by means of an optical tweezers.

Description

The invention relates to an arrangement for an optical measuring system for determining a sample and a sample chamber arrangement.

background

In optically determining a sample, an optical measuring device is usually used to examine the sample. In this case, fluidic samples are arranged in a sample chamber which is optically transparent for light of at least one measurement wavelength, so that the measurement light can be irradiated onto the sample.

As an optical measuring device, a device can be used with which the sample to be determined is examined in the sample chamber using optical tweezers. Such a device is for example from the document DE 10 2010 027 721 A1 known. In general, optical tweezers are photonic devices that can be used to manipulate even the smallest objects, especially for holding or moving objects. Typically, laser light is used for this purpose. Lenses of the measuring device are used to focus the laser light and to detect measuring signals. The sample chamber, in which the sample to be determined is located, must be optically transparent to the measuring light, at least in the region of chamber windows through which the measuring light propagates.

Summary

The object of the invention is to specify an improved arrangement for an optical measuring system for determining a sample and a sample chamber arrangement in which the provision of the sample in a sample chamber with desired measuring properties is ensured in a simple and efficient manner. In particular, a measurement-specific temperature of the sample in the sample chamber is to be improved.

The object is achieved by an arrangement for an optical measuring system for determining a sample according to the independent claim 1. According to a further aspect, a sample chamber arrangement according to claim 11 is provided. Advantageous embodiments are the subject of dependent subclaims.

According to one aspect, an arrangement is provided for an optical measuring system for determining a sample, in particular a liquid sample. A sample chamber is provided which is optically transparent for light of a measuring wavelength and is adapted to receive a sample to be determined. The sample chamber is optically transparent for light of one measurement wavelength. The optical transparency may be formed for one or more measurement wavelengths in the visible range and / or other optical wavelength ranges.

The assembly includes a container having an opening receiving an immersion fluid that is in heat-conducting contact with the sample chamber and the sample disposed therein. In the case of an immersion liquid, for example immersion oil, water or glycerol can be used. The use of the immersion fluid can serve a variety of purposes, including, for example, adjusting optical properties such as a desired resolution or suppressing interfering reflections. If such an adaptation or optimization of optical properties takes place when using the immersion fluid, it is also possible to speak of an optical coupling mediated by the immersion fluid between the optical component and the sample chamber.

Furthermore, an optical component of an optical measuring device is provided, which is introduced via the opening in the container and arranged opposite one side of the sample chamber, such that the optical component is in contact contact with the immersion fluid and coupled thereto to the sample chamber.

The arrangement has a temperature control device associated with the immersion fluid, which is thermally insulated from the optical component and arranged to temper the immersion fluid in the fluid volume and, via this, the sample to be determined in the sample chamber. The thermal insulation here means that tempering device and optical component, with the exception of a possible thermal contact via the immersion liquid, are thermally separated. In particular, there is no heat transfer from the temperature control device to the optical component via other apparatus elements of the arrangement. For this purpose, thermally isolating or insulating components can be provided in the construction of the apparatus, which are arranged in the structure between tempering and optical component.

The thermal insulation of the temperature control relates in particular to the tempering, which provides heat and / or cooling energy for tempering. The thermal insulation with respect to the tempering device can be formed at least for one or more housing parts and / or optically active elements which can be arranged in the housing formed by the housing parts of the optical component

According to a further aspect, a sample chamber arrangement for determining a sample by means of an optical measuring device is provided. The arrangement has a sample chamber and a container. The container associated with the sample chamber is configured to receive an immersion fluid. Through an opening of the container, a section of an optical component of an optical measuring device for forming a coupling mediated by the immersion fluid to the sample chamber can be introduced here. The immersion fluid is in heat-conducting contact with the sample chamber and the sample disposed therein upon introduction into the container. A temperature control device associated with the immersion fluid is provided, which is set up to heat the immersion fluid in the fluid volume and, via this, the sample to be determined in the sample chamber, whether to heat it and / or to cool it. The sample chamber is optically transparent to light of a measurement wavelength which is used for the optical determination, at least in the region of optical sample chamber windows.

For the irradiation of the measuring light when determining the sample, the sample chamber has at least one optical window, for example a glass window. It is provided that the sample chamber is formed with plane-parallel plates, which are connected by spacers. The plane-parallel plates can for example consist of glass. The sample chamber may extend over the optical component opposite in a sample plane surface.

The sample chamber and the container can be arranged on a carrier and thermally decoupled therefrom by means of a heat coupling. For example, the heat coupling may be formed with bearing elements which are arranged between sample chamber / container and the carrier, for example bearing elements made of a silicone material.

On an opposite side of the sample chamber and opposite thereto, a further optical component can be arranged, which is assigned to the optical measuring device or another optical measuring device and which is in touching contact with a further immersion fluid and couples thereto via the sample chamber. The optical component and / or the further optical component may be a lens. The further immersion fluid can be the immersion fluid or a different immersion fluid. The further optical component can also be thermally insulated from the tempering device, with no heat coupling to the immersion fluid being present.

The optical component and / or the further optical component may be parts of an optical measuring device that is set up to determine a sample in the sample chamber by means of optical tweezers. The technology of determining a sample, such as a biological or biochemical sample, such as cells or cell particles, using optical tweezers is known per se in various embodiments.

A further embodiment provides that the temperature control device is set up to directly temper the immersion fluid by a temperature control element in contact with the immersion fluid. In the various embodiments, the temperature control device can be configured for heating and / or cooling the sample to be determined. In the event that in particular a heating device is provided with the tempering device, the tempering element is a heating element. The tempering element can be completely or partially immersed in the immersion fluid in the fluid volume. As a result, a direct physical contact between immersion fluid and tempering be made.

The tempering device can be set up to temper the immersion fluid indirectly by the tempering element being in indirect heat-conducting contact with the immersion fluid. Alternatively or additionally, immersion fluid and tempering element may be in indirect contact. This is a heat-conducting contact which is free of contact contact between immersion fluid and tempering element, but ensures heat conduction between tempering element and immersion fluid. The indirect, thermally conductive contact between immersion fluid and tempering element may comprise one or more thermally conductive materials.

An embodiment provides that the tempering is arranged on and / or within a wall of the container. One or more tempering elements, for example heating elements, can be formed on the wall of the container or accommodated in it. For example, a heating wire can be integrated in the wall material. However, an arrangement of such a heating wire or a heating sleeve on the outer surface of the wall of the fluid volume may alternatively or additionally be provided.

The opening may be disposed opposite the sample chamber in an open-topped container. The container may be formed as an open-topped container. The opening may be sized in size to limit insertion of the optical component in the container. In this way, the wall surrounding the opening form a stop for the optical component to prevent it from penetrating too far into the container. In this case, the opening can be adapted in terms of its cross-sectional shape to the outer shape of the optical component in the region of the section which is displaced into the container.

An embodiment can provide that a further temperature control device, which is set up to thermally couple the sample in the sample chamber, is additionally arranged on the optical component and / or the further optical component and is thermally coupled thereto. In this embodiment, a supplementary tempering takes place via the optical component and / or the further optical component in that these are heated and / or cooled, in particular the respective component housing. In one embodiment, a heating sleeve can be provided, which is placed on the outside of the optical component and / or the further optical component.

The sample chamber may be implemented as a flow chamber or flow cell. The sample chamber can be flowed through in the measuring operation of the sample to be determined. In this case, the sample chamber can be embodied opposite to the optical component and the further optical component as a closed chamber, such that the optical component and further optical component are arranged opposite a wall section of the sample chamber. Inlet and outlet for the introduction and removal of the sample chamber flowing through the sample can be arranged in the region of lateral boundaries of the sample chamber. But also the formation of inflows and outflows on a flat side of the sample chamber can be provided, expediently outside of the region of the sample chamber, in which the optical component and further optical component are opposed.

A further development can provide that wall sections of the container are arranged on an outer surface of the sample chamber. By means of the wall sections arranged on the outer surface of the sample chamber, for example, one or more side walls of the container can be formed. An adhesive bond can be produced between the wall sections of the container and the sample chamber, for example by means of gluing or welding. The wall portions of the container may be integrally formed with the sample chamber as a whole or parts thereof. In one embodiment, the container consists of wall sections which are applied to the outer surface of the sample chamber.

In one embodiment, it can be provided that one or more wall sections of the container are formed by the sample chamber. For example, the bottom of the container may be formed by wall sections of the sample chamber.

It may be an integrated unit with the sample chamber and the container formed. The integrated unit can be made in one piece.

Description of exemplary embodiments

Embodiments will be explained in more detail with reference to a drawing. Hereby show:

1 a schematic representation of a sample chamber arrangement in section,

2 a schematic representation of an arrangement with a sample chamber and an optical measuring device in section and

3 a schematic representation of the arrangement 2 in section, wherein the sample chamber is arranged on heat-decoupling bearing elements.

1 shows a schematic representation of a sample chamber arrangement with a sample chamber 1 , by means of an upper and a lower, for each application optically transparent sample carrier 4 . 7 , For example, coverslips is formed. The sample chamber 1 is with the help of a sealant 5 between the sample carriers 4 . 7 produced. This can for example consist of fat or a parafilm. The sample carriers 4 . 7 and the seal 5 form a wall of the sample chamber 1 ,

It is also possible to manually or automatically a sample 1a in situ in the sample chamber 1 bring in, ie in the in the sample chamber 1 formed volumes for receiving the sample to be determined.

On the upper sample carrier 4 is a designed as a container fluid volume 2 arranged, which is an immersion liquid 6 absorbs, for example, water. However, another immersion liquid which is optically transparent at the wavelength of light used for examination may be used. The bottom of the fluid volume 2 is in the embodiment shown by the sample chamber 1 formed, namely the upper sample carrier 4 , Side walls of the fluid volume are directly upright on the sample chamber 1 ,

In the walls of the fluid volume 2 is a tempering device 3 arranged, in particular for heating the immersion liquid 6 serves. Over the upper sample carrier 4 becomes heat energy, with the help of the tempering device 3 in the immersion liquid 6 is generated, by means of heat conduction to the sample chamber 1 and finally to the test 1a transfer. The formation of possible lateral temperature gradients can thus be minimized. There is an indirect transfer of heat and / or cooling power from the temperature control 3 about the immersion liquid 6 into the sample 1a instead of. The sample 1a itself is from the tempering device 3 separated. So it will not be the sample 1a actively heated, nor even a sample must be present in order to trigger the heating or cooling process itself. Both in the fluid volume 2 containing the immersion liquid 6 contains, as well as in the immersion liquid 6 even any instrument can be located, for example a microscope objective, a pipette or an additional sensor for monitoring the temperature.

The position of the temperature control device 3 is not on an assembly in the wall of fluid volume 2 limited. The immersion liquid 6 can also be tempered directly by a heating and / or a cooling element is disposed in the liquid.

In the 1 If necessary, it may be a bit easier to maintain. The heater serves in this context only as a heat source for heating the liquid in the container, which in turn transmits the heat absorbed by the heater to the sample. The geometry of the container itself is also arbitrary and can be adapted to the shape of the sample or the sample carrier.

2 shows a schematic representation of an apparatus for determining a sample by means of an optical measuring device using optical tweezers, the arrangement of 1 is being used.

Below the sample chamber 1 a lens 8th arranged, the optically by means of an immersion agent 8a , for example, immersion oil, is coupled. This lens 8th serves to generate the optical traps (tweezers) and at the same time as an imaging system for the microscopic observation of the sample 1a ,

Above the sample chamber 1 is, partially submerged in the temperature-controlled immersion liquid 6 , a lens designed as a condenser lens 9 arranged. The objective 9 is through an opening 2a the fluid volume 2 introduced herein.

The objective 9 On the one hand serves the correct illumination of the sample 1a On the other hand, it forms the signal to be measured in a manner known per se on a detector system (not shown). Both lenses 8th . 9 form a temperature sink, so that to improve the efficiency of the lenses 8th . 9 optionally with a heating jacket can be heated to reduce the temperature gradient. The heating jacket (not shown) may be external to one or both lenses, for example 8th . 9 be put on. In principle, the respective functions of the lenses 8th . 9 also be exchanged, that is, the optical trap is generated by the upper lens and the lower lens is for detection.

3 a schematic representation of the arrangement 2 on average, the sample chamber 1 is arranged on heat-decoupling bearing elements. To the heat coupling of the sample 1a in the sample chamber 1 To keep the rest of the measuring apparatus as low as possible, are as storage elements heat insulators 10 intended. In a similar way, the lenses can 9 and / or the other lens 8th with insulators 10a thermally decoupled from the environment. These thermal insulators may for example consist of silicone.

The use of the sample chamber arrangement 1 has been described above by way of example in connection with optical components embodied as lenses, in particular with reference to a sample determination by means of optical tweezers. Without further ado, other applications may involve other optical components in which an optically active element couples to the sample chamber via the immersion liquid. The arrangement can also be configured for other examination methods.

The features disclosed in the above description, the claims and the drawings may be important both individually and in any combination for the realization of the various embodiments.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been 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.

Cited patent literature

• DE 102010027721 A1 [0003]

Claims (13)

Arrangement for an optical measuring system for determining a sample ( 1a ), with - a sample chamber ( 1 ), which is optically transparent and arranged for light of a measuring wavelength, a sample to be determined ( 1a ), - a container ( 2 ), which has an opening ( 2a ), - an immersion fluid ( 6 ) contained in the container ( 2 ) and in heat-conducting contact with the sample chamber ( 1 ) and the sample arranged therein ( 1a ), - an optical component ( 9 ) of an optical measuring device, which passes over the opening ( 2a ) in the container ( 2 ) and one side of the sample chamber ( 1 ) is arranged opposite, such that the optical component ( 9 ) in contact with the immersion fluid ( 6 ) and via this to the sample chamber ( 1 ), and - one of the immersion fluid ( 6 ) associated tempering device ( 3 ) separated from the optical component ( 9 ) is thermally isolated and furnished, the immersion fluid ( 6 ) in the fluid volume ( 2 ) and on this the sample to be determined ( 1a ) in the sample chamber ( 1 ) to temper. Arrangement according to claim 1, characterized in that on an opposite side of the sample chamber ( 1 ) and this opposite another optical component ( 8th ) which is associated with the optical measuring device or another optical measuring device and which is in touching contact with a further immersion fluid ( 8a ) and via this to the sample chamber ( 1 ) couples. Arrangement according to claim 1 or 2, characterized in that the optical component ( 9 ) and / or the further optical component ( 8th ) Are parts of an optical measuring device that is set up, a sample ( 1a ) in the sample chamber ( 1 ) by means of optical tweezers. Arrangement according to at least one of the preceding claims, characterized in that the temperature control device ( 3 ), the immersion fluid ( 6 ) directly by a tempering in contact with the immersion fluid ( 6 ) stands. Arrangement according to at least one of the preceding claims, characterized in that the temperature control device ( 3 ), the immersion fluid ( 6 ) indirectly by the tempering in indirect, thermally conductive contact with the immersion fluid ( 6 ) stands. Arrangement according to claim 5, characterized in that the tempering on and / or within a wall of the container ( 2 ) is arranged. Arrangement according to at least one of the preceding claims, characterized in that the opening ( 2a ) in an open-topped container ( 2 ) of the sample chamber ( 1 ) is arranged opposite one another. Arrangement according to at least one of the preceding claims, characterized in that on the optical component ( 9 ) and / or the further optical component ( 8th ) and thermally coupling thereto a further temperature control device is arranged, which is adapted to the sample ( 1a ) in the sample chamber ( 1 ) in addition to tempering. Arrangement according to at least one of the preceding claims, characterized in that the sample chamber ( 1 ) is designed as a flow chamber. Arrangement according to at least one of the preceding claims, characterized in that wall sections of the container ( 2 ) on an outer surface of the sample chamber ( 1 ) are arranged. Arrangement according to at least one of the preceding claims, characterized in that one or more wall sections of the container ( 2 ) from the sample chamber ( 1 ) are formed. Arrangement according to at least one of the preceding claims, characterized in that an integrated structural unit with the sample chamber ( 1 ) and the container ( 2 ) is formed. Sample chamber arrangement for a determination of a sample ( 1a ) by means of an optical measuring device, comprising: - a sample chamber ( 1 ) which is optically transparent to light of a measuring wavelength, - a container ( 2 ), in which an immersion fluid ( 6 ) and into which a portion of an optical component ( 9 ) of an optical measuring device for forming a coupling to the sample chamber ( 1 ) via an opening ( 2a ) is insertable, wherein the immersion fluid ( 6 ) after introduction into the container ( 2 ) in heat-conducting contact with the sample chamber ( 1 ) and the sample arranged therein ( 1a ), and - one of the immersion fluid ( 6 ) associated tempering device ( 3 ), which is set up, the immersion fluid ( 6 ) in the container ( 2 ) and on this the sample to be determined ( 1a ) in the sample chamber ( 1 ) to temper.

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