DE102015007029A1 - Fluid sampling device and its manufacture, fluid analysis device and optical measurement method - Google Patents

Abstract

The invention relates to a fluid sampling device for arrangement in a fluid analysis device according to the invention, comprising a channel device surrounding a channel internal volume through which a fluid sample in the channel direction (S) is flowable, wherein the channel direction is perpendicular to the channel cross section and wherein the channel means at least one in channel direction between a first optical waveguide having a first outer surface to form a first evanescent field (f1), and a second optical waveguide having a second outer surface to form a second evanescent Feld (f2), at least one interface device for connecting the at least one first and at least one second optical waveguide with the interface device of the fluid analysis device, wherein the first outer surface and second outer surface each extending between the first channel cross-section (A1) and second channel cross-section (A2) and are arranged along this channel portion and in contact with the channel internal volume to allow the penetration of the first and second evanescent field in the channel internal volume of the channel portion. The invention further relates to this fluid analysis device, the fluid sampling device manufacturing method, and an optical measurement method for measurement on the fluid sampling device.

Description

The invention relates to a fluid sampling device for a fluid analysis device, to this fluid analysis device for this fluid sampling device, to the production thereof, and to an optical measurement method for measurement on the fluid sampling device.

State of the art

In classical methods for fluid analysis of a fluid sample, in particular in blood analysis, the sedimentation of the fluid sample by gravitational effects plays a negative role, because they provide concentration inhomogeneities in the fluid sample, which falsify the measurements depending on the flow.

From the DE 44 37 758 B4 For example, an image analysis method and a flow particle image analyzer are known wherein images generated by an imaging device are analyzed by particles dissolved in a flowing fluid.

From the DE 692 30 420 T2 For example, a multiple signal output reference system for an evanescent wave sensor is known, which is designed for analysis of analytes applied thereto, such as molecules or antibodies. In such methods, an evanescent wave at the interface between the optical device and the analyte enters the analyte at a depth of usually less than one wavelength. Due to the interaction between evanescent wave and analyte, a metrological quantitative and / or qualitative statement about the analyte is possible.

The EP 0 810 026 B1 describes a method and apparatus for performing blood cell analysis combining impedance analysis, scattered light analysis, fluorescence analysis and flow cytometry techniques to analyze a whole blood sample.

All such methods operate at high equipment cost to achieve a very good mix of all particles in the fluid with uniform as possible statistical distribution of all particles with a mostly additional method. Sedimentation or segregation is undesirable because they falsify the measurement results and statistical evaluations.

Tasks

The invention has for its object to provide a simple fluid sampling device, their preparation, and a fluid analysis device for fluid analysis of the fluid sample, in particular blood analysis, and a fast, secure optical measurement method.

Another object is to avoid light scattering effects that occur in the fluid analysis by often common in the prior art lighting arrangements, which u. a. the problem of blood cell destroying hemolysis in the determination of the concentrations of hemoglobin derivatives in optical lactate determination is avoided.

A further object is to provide a simple fluid sampling device consisting of a few components that are as similar as possible, which is simple and inexpensive to produce and easy to store.

These objects are achieved by the fluid sampling device according to claim 1, the fluid analyzing device according to claim 7 and the optical measuring method according to claim 13 and the manufacturing method according to claim 14.

description

The fluid sampling device according to the invention is arranged for arrangement in a fluid analysis device according to the invention and comprises: a channel device surrounding a channel internal volume through which a fluid sample is flowable in the channel direction, wherein the channel direction is perpendicular to the channel cross-section and wherein the channel means at least one in the channel direction a first optical waveguide having a first outer surface for forming a first evanescent field, a second optical waveguide having a second outer surface for forming a second evanescent field - at least one interface device for connecting the at least one first and at least one second optical waveguide to the interface device of the fluid analysis device, - wherein the first outer surface and zw Each outer surface extending between each of the first channel cross-section (A1) and second channel cross-section (A2) and are arranged along this channel portion and in contact with the channel inner volume to allow the penetration of the first and second evanescent field in the channel internal volume of the channel portion.

The fluid which can be analyzed by means of the fluid sampling device is preferably a non-Newtonian fluid, in particular an aqueous particle suspension, in particular a biological fluid, in particular blood. The fluid sampling device is preferably configured to achieve a laminar flow of the fluid.

Preferably, the fluid sampling device is made of plastic or plastic. The first outer surface of the first optical waveguide and the second outer surface of the second optical waveguide are preferably formed as permeable as possible for the evanescent field to be formed there. The first optical waveguide and / or the second optical waveguide may consist of plastic or glass. Preferably, the fluid sampling device consists essentially of the first and the second optical waveguide, and at least one channel wall element, which may in particular be film-like or may consist of film. A carrier substrate for this component can be provided. It can consist of the interface device for connecting the at least one first and at least one second optical waveguide to the interface device of the fluid analysis device in at least one surface portion of the first and second optical waveguide, can be coupled into the light or can emerge from the light. Such a compact construction is preferred in order to achieve low manufacturing costs of the fluid sampling device. Preferably, the fluid sampling device is a disposable article. This ensures a simple and sterile measurement environment.

But it is also possible to form the fluid sampling device as a reusable article, in particular sterilizable -. B. autoclavable - is formed.

The first and / or the second optical waveguide is a transparent to infrared and / or visible light component, which may be a fiber, tube, a rod or a plate member that can transport light over short or long distances. The light pipe is achieved by reflection at the interface of the optical waveguide either by total reflection due to a lower refractive index surrounding the light guide medium or by (partial) mirroring of the interface. The first and / or the second optical waveguide may be made of glass or plastic or comprise such materials. The first and / or the second optical waveguide are preferably formed substantially straight, but may also be formed bent at least in sections, in particular, they can follow the direction of the channel section.

The first optical waveguide and the second optical waveguide preferably run parallel to one another in the channel section and are preferably spaced apart by at least one channel wall element, in particular a planar connecting element or a planar connection, such that the optical waveguides and the at least one channel wall element form the channel section. For the measuring principle, it is only necessary for the first optical waveguide and the second optical waveguide to be arranged differently with respect to a gravitational field, so that particle measurment on the second outer surface results in a different measurable influencing of the respective evanescent field compared to the first outer surface. The first optical waveguide and the second optical waveguide can also be arranged inclined relative to one another at least in sections.

There may be more than two optical fibers arranged along the channel section. This can improve the measurement quality.

Preferably, the at least one channel wall element is a planar connection, in particular a foil which in particular comprises the optical waveguides or acts on both sides. Thereby, the production of the fluid sampling device becomes inexpensive.

Preferably, the channel section is arranged for sedimentation of particles contained in the fluid between the first outer surface and the second outer surface. For this purpose, the channel section has in particular a suitable size of the channel cross-section, in particular of the first and second channel cross-section, which allows the sedimentation of the particles.

Preferably, the fluid sampling device has more than two optical waveguides, which are arranged in particular along the channel section. The first and / or second or the further optical waveguide can be formed as a channel wall element and / or can be arranged within the channel section.

The fluid sampling device preferably has a fluid interface device for connecting the channel device to a fluid movement device, in particular a pump. This fluid interface device may comprise at least one attachment portion, e.g. As a mounting flange, and optionally a sealant, for. B. an O-ring.

The fluid analysis device according to the invention for receiving at least one fluid sampling device according to the invention comprises: at least one receiving device for receiving the fluid sampling device, an optical measuring device for measuring a light transmitted through the at least one first optical waveguide of the fluid sampling device and measuring at least one of the at least one a second optical waveguide of the fluid sample device of transmitted light (LT2) is set up, and at least one interface device for connecting the optical measuring device with the interface device of the fluid sampling device.

The optical measuring device is preferably configured to control the light (LS1) to be conducted in the at least one first optical waveguide of the fluid sampling device and the light (LS2) to be guided into the at least one second optical waveguide of the fluid sampling device. This function can also be taken over by a preferably provided electronic control device of the fluid analysis device.

Preferably, the fluid analysis device, in particular the optical measuring device, comprises: at least one first light source for coupling light (LS1, LS2) into the first and / or the second optical waveguide of the fluid sampling device; At least one light detector for detecting the light (LT1, LT2) passed through the first and / or the second optical waveguide of the fluid sampling device and the light (LT1, LT2) modified by the absorption of the first and / or the second evanescent field, and preferably: an electronic control device in order to generate at least one measuring signal depending on the coupled-in light and the changed light.

The at least one first light source and / or at least one second light source may each be an LED, in particular an LED having a color spectrum comprising several wavelengths, for example a light source. With white light. The light source can also be substantially monochromatic, and z. B. be a laser diode.

The emission of the light (LS1) introduced into the at least one first optical waveguide and the emission of the light (LS2) introduced into the at least one second optical waveguide preferably take place simultaneously, but can also take place overlapping in time or successively. The detection of the light (LT1) transmitted by the at least one first optical waveguide and the detection of the light (LT2) transmitted by the at least one second optical waveguide are preferably carried out simultaneously, but can also take place overlapping in time or successively.

The at least one first light detector and / or the at least one second light detector may be a photodetector, for. B. be a photomultiplier or a photodiode.

Preferably, the fluid analysis device, in particular its receiving device, is adapted to align the fluid sampling device in a gravitational field generated by gravity or by centrifugation to effect sedimentation of particles contained in the fluid between the first outer surface and the second outer surface in the gravitational field. For this purpose, the fluid analysis device, in particular its receiving device, for. Example, have a positioning means by means of which arranged in the receiving device fluid sampling device is held immobile in the gravity field or adjusted.

Preferably, the fluid analysis device has a fluid movement device, by means of which the optical waveguides are movable in the direction of flow of the fluid of the fluid sample in their relative position to the gravitational field. The fluid movement device is preferably a fluid transport device, in particular a pump, for. B. a pump for continuous delivery, in particular a continuously conveying rotary pump, in particular an impeller pump, axial pump, gear pump; or preferably centrifugal pump.

The electronic control device preferably has an A / D converter device and / or a digital data processing device, in particular a CPU or microprocessor, and / or a data storage device.

The electronic control device is preferably set up to detect the light which has passed through the first optical waveguide and the light changed by the absorption of the first evanescent field as a first measuring signal and the light which has passed through the second optical waveguide and is changed by the absorption of the second evanescent field to capture the second measurement signal. Preferably, the electronic control device has an evaluation device to compare the first measurement signal and the second measurement signal, in particular time-dependent and / or in particular by forming a difference from the first and second measurement signal. In this way, the measurement of the evanescent field can take place.

Preferably, the electronic control device is configured to detect the change in the first measurement signal caused by the penetration of particles contained in the fluid into the first evanescent field and / or the change in the second caused by the penetration of particles contained in the fluid into the second evanescent field Detect measurement signal. Preferably, the electronic control device, in particular the evaluation device, is adapted to determine a time average of the particular time-dependent first and / or second measurement signal. Preferably, the electronic control device, in particular the evaluation device, is set up to analyze the first and / or the second measurement signal in order to determine the frequency (s) of penetration of the particles contained in the fluid to detect the first and / or second evanescent field, in particular to compare these frequencies and / or to evaluate statistically.

Preferably, the fluid analysis device has a fluid movement device, with which the fluid can be transported as fluid flow through the channel device of the fluid sampling device, wherein in particular the electronic control device of the fluid analysis device is designed to control the fluid flow caused by the fluid movement device. However, the fluid movement device can also be provided as a separate device with respect to the fluid analysis device and / or the fluid sampling device, which device is connected to the fluid analysis device and / or the fluid sampling device in order to convey the fluid.

The invention also relates to a fluid analysis device according to the invention, on which a fluid sampling device according to the invention is arranged, in particular such that it can be replaced by the user by means of another fluid sampling device. As a result, it is possible to use a fluid analysis device having a plurality of fluid sampling devices, which is advantageous in particular when the fluid sampling devices can be produced inexpensively or are disposable. However, the fluid sampling device can also be inseparably connected to the fluid analysis device by the user, as it is permanently fixed in the receiving device.

The invention also relates to a method for optical measurement on a fluid sample in the fluid sample device according to the invention, at least comprising the steps of: introducing the fluid sampling device into a fluid analysis device; Orienting the fluid sampling device in a gravity field to allow sedimentation of the particles contained in the suspension, moving the fluid sample through the channel means of the fluid sampling device, during which movement the sedimentation of the particles takes place in the fluid; - During a period of sedimentation: detection, in particular time-dependent detection, of the first optical fiber of the fluid sampling device and changed by the absorption of the first evanescent field changed light as the first measurement signal and detection, in particular time-dependent detection of the passed through the second optical fiber of the fluid sampling device and by the absorption of the second evanescent field changed light as a second measurement signal, - optionally: evaluation of the first and second measurement signal by an electronic evaluation device. Preferred embodiments of the method can be found in the description of the fluid sampling device according to the invention or the fluid analysis device according to the invention.

In particular, the invention relates to the use of the fluid sampling device according to the invention or the fluid analysis device according to the invention or the measuring method according to the invention for the purpose of blood analysis.

The fluid sampling device according to the invention is set up to receive a fluid sample, and is preferably configured to enable an optical measuring method according to the invention in combination with a fluid analysis device according to the invention. The use of an optical analysis method has the advantage over chemical methods that it solves environmentally-friendly analytical tasks.

The fluid sampling device according to the invention is preferably designed for laminar flowing fluids, in particular suspensions, preferably blood.

The fluid sampling device according to the invention is preferred for a measurement method according to the invention for non-Newtonian fluids, such. B. blood suitable, but not limited thereto.

The fluid analysis device according to the invention is preferably designed to receive at least one fluid sampling device each with sensor, measuring and analysis units, orient in the gravitational field and connect with interfaces to perform a sampling and evaluation and for the fluid sample of the respective fluid sampling device a particular controllable flow generator unit with more Provide interfaces to each channel of a fluid sample.

The optical measuring method according to the invention makes use of the limited penetration depth of evanescent fields of VIS and IR radiation into a fluid sample flowing in the fluid sampling device according to the invention, in combination with the effect of inertial forces. In this case, the weight force in the gravitational field of the earth, generally referred to as gravitational component with a centrifugal component, and / or additional artificial inertial forces, such as centrifugal forces, which are generated mechanically, are used.

In the present case, the term gravitation is assumed to be simplified from top to bottom of a fall direction, without reference being made to orientation in space. It is important in this consideration that this can also be done by changing the relative position of a device or parts of the device to the gravitational field.

The fluid sampling device according to the invention preferably consists essentially of a first, in a longitudinal direction S extending optical waveguide and a second optical waveguide which extends parallel to the second optical waveguide and preferably maintains a defined distance thereto. The two optical waveguides are preferably connected by at least one planar connection, which is preferably the optical waveguides, for. B. hose-like, surrounds. Preferably, the channel is between the optical waveguides and the flat connection. The area connection can z. B. be formed of two wall-like surfaces which enclose the channel between them.

The flat connection is preferably a foil or of a foil-like material, and is preferably made of plastic or has plastic.

The channel section receives the fluid sample. Preferably, via interfaces at both distal ends of the channel portion of the fluid sampling device, both the fluid sample can be introduced into the fluid sampling device, as well as with a flow, in particular a laminar flow, acted upon.

The fluid sampling device orients the fluid sample in a gravitational field, e.g. B. gravitation in the gravitational field of the earth or an artificial gravity field. The channel cross-section is defined perpendicular to the flow direction and preferably defined by height times width of the channel portion. The height is preferably defined perpendicular to the flow direction between the outer surfaces of the optical waveguides and the width is preferably defined perpendicular to the flow direction between the channel walls. In this case, preferably, the amount of the height of the channel portion is higher than the amount of the width of the channel portion. As a result, particles in the laminar flow-exposed fluid sample flowing between the optical waveguides in the channel section, depending on their mass and the exposure time in the channel section in the direction of gravity in the direction of at least one arranged below optical waveguide sedimented.

The fluid sampling device is formed in a first embodiment as a cuboid tube with inner cuboid channel portion, wherein the first and second outer surface of the optical waveguide delimiting the upper and lower surfaces of the cuboid channel internal volume and a planar connecting element, in particular film, the two side surfaces of the cuboid channel internal volume limits ,

In a second embodiment, the first and second optical fibers in the flow direction of the fluid change their relative position to the gravitational field in that the fluid analysis device comprises a rotating means, by means of which the fluid sampling device can be rotated by a rotational angle α, in particular a = 180 ", about its flow direction axis In particular, the previously upper optical waveguide can become the lower optical waveguide and vice versa. In this way, permanent particles deposits on the corresponding lower optical fiber can be avoided. In addition, it is also possible to measure in this way, temporarily or exclusively, without fluid flow present in the channel direction.

In a third embodiment, the upper and lower optical waveguides change their relative position to the gravitational field in that the channel device, in particular the channel section, in particular the first and the second optical waveguide of the fluid sampling device, is U-shaped, in which case on the upper Optical waveguide comes to rest in an antiparallel position of the upper optical waveguide and thus the lower optical waveguide comes to lie completely supreme. In this case, the channel device may also have a meander-shaped structure with a multi-directional change in direction S of the channel device.

The fluid analysis device according to the invention is preferably also configured to optionally change the fluid sampling device in a gravitational field, e.g. As well as mechanical way, by changing or orientation of a layer of the fluid sampling device, for. B. by rotating about one or more axes of the fluid sampling device to effect. This can z. B. a rotation device may be provided, on which the fluid analysis device is mounted, wherein the centrifugal force caused by the gravitational field in the direction perpendicular to the rotational direction is formed.

The sedimentation or segregation of a fluid sample mentioned in the prior art as undesirable is required for the optical measuring method according to the invention using the fluid sampling device according to the invention and a fluid analysis device.

Although the measuring method according to the invention can also be used for a wide variety of non-Newtonian fluids, the measuring principle is explained below using the example of a blood analysis.

When using the sedimentation effects in laminar flowing blood samples, as a fluid sample, according to the measuring method according to the invention, it is exploited that blood consists essentially of plasma (55%) and the erythrocytes (44%). The other substances are to be ignored in the first place. The density of the erythrocytes is about 1076 kg / m ³ , which is slightly larger than that of the plasma with 1028 kg / m ³ , which leads to sinking rates of 1 .mu.m / s to 3 .mu.m / s.

By way of example, starting from a volume flow of a blood sample of 1 μl / s (60 μl / min) and a channel cross-section of the fluid sampling device of 0.1 mm × 1 mm, a flow rate of the fluid of 1 cm / s results. In this case, the channel of the fluid sampling device in which the fluid sample is received is aligned in the gravitational field so that the vector of the gravitational acceleration parallel to lateral boundaries in the direction of an optical waveguide, here referred to as lower optical waveguide shows. At such a flow rate results after one to three centimeters for the upper optical waveguide an erythrocyte free zone. Taking into account the quantum physical effect, in which the total reflected light in the optical waveguides depending on the frequency, z. B. at a wavelength of about 600 nm to about 1000 nm, about 1 to 3 microns penetrates into the adjacent medium, resulting after a short enema no more optical interaction with the erythrocytes of the blood in this area. The evanescent radiation field of the upper optical waveguide can therefore only interact with the blood plasma. For the lower optical fiber the situation looks completely different. Here, the erythrocytes are on the ground and can interact with the evanescent field of the lower optical fiber. This means that in this area radiation (IR or VIS) is absorbed frequency-specifically, for example, by the various hemoglobin derivatives. For both regions of the fluid sample, top and bottom, there is virtually no disturbing scattering. Thus, the problem of blood cell-destroying hemolysis in the determination of the concentrations of hemoglobin derivatives can be solved.

Another problem in the optical lactate determination is also solved because it can be measured in the upper erytrozytenfreien range without having to change the blood sample.

In a further embodiment, the fluid sampling device according to the invention is guided by a helical rotation of the channel through 180 ° about the axis in the flow direction in order to reverse segregation.

In a further embodiment, the fluid sampling device according to the invention is achieved by an anti-parallel guidance of the channel after a 180 ° U-turn in the plane, whereby z. B. can adjust the original erythrocyte distribution again.

Multiple inversions of the gravitational field effect on the fluid in the course of the flow, z. B. by a partially helical rotation of the channel by 180 ° or by a meandering channel course are possible depending on the problem.

Likewise, the fluid sampling device according to the invention as a whole in its position to a gravity field is absolutely and temporally variable by the fluid analysis device.

Overall, a provision, measurement and analysis of fluid samples is made possible by the invention in a simple and reliable manner.

Preferably, the fluid analysis device according to the invention, in particular the fluid sampling device, is designed as a portable device, so that it is easy for the user to carry and transport manually. Such portable devices are particularly suitable for near-patient laboratory diagnostics (English: point of care testing).

The invention also relates, in particular, to a method for producing the fluid sampling device according to the invention, comprising the steps of: providing the first and second optical waveguides, preferably by injection molding these optical waveguides from a plastic, which may be or may be polycarbonate in particular; Providing the interface device which is suitable for connecting the at least one first and at least one second optical waveguide to the interface device of the fluid analysis device; Formation of the channel means of the fluid sampling device; - Optional: providing at least one channel wall element, which may consist in particular of plastic; Preferably, assembling the optical waveguides, the interface device, and preferably the at least one channel wall element, to form the channel device of the fluid sampling device.

Further advantages, features and applications of the present invention will become apparent from the following description taken in conjunction with the figures. Show it:

1a A fluid sampling device according to the invention in a lateral cross-sectional view according to a first exemplary embodiment

1b The fluid sampling device of the invention 1a in frontal cross-sectional view

1c A detail of 1b , showing the evanescent fields of the optical fibers

2a . 2 B and 2c In each case, another fluid sampling device according to the invention according to a further exemplary embodiment in frontal cross-sectional view

3a A schematic side view of the fluid analysis device according to the invention according to an embodiment.

3b The fluid analysis device as in 3a in which the fluid sampling device according to the invention the 1a to 1c is used.

4 A schematic view of the fluid analysis device of 3b arranged on a rotation device for generating a gravitational field.

5 Schematic representation of the optical measuring method according to the invention according to an embodiment.

6 Schematic representation of the manufacturing method according to the invention according to an embodiment.

1 shows the fluid sampling device 1 , which is substantially cuboid, and which is adapted for placement in a fluid analysis device 100 , as in 3a and 3b shown. The fluid sampling device 1 has a channel device 10 which surrounds a channel internal volume, shaded gray in the figure, through which a fluid sample 6 in the channel direction S is flowable. The channel direction S is perpendicular to the channel cross section A and the channel device has a channel section extending in the channel direction between the first channel cross section A1 and the second channel cross section A2 11 on. The fluid sampling device 1 is preferably used for blood analysis, and is set up to form a laminar blood flow as possible. The blood is in first approximation a suspension 6 of particles 6a , namely blood cells, in aqueous fluid, namely blood serum.

The fluid sampling device 1 has a first optical waveguide 2 on, the first outer surface 2a to form a first evanescent field f1. The fluid sampling device 1 also has - perpendicular to the channel direction S the first optical fiber opposite - a second optical waveguide 3 on top of a second outer surface 3a to form a second evanescent field f2. The optical fibers can be made of glass. The length of the two straight and parallel to each other extending optical waveguide in the here constant channel direction S corresponds in this case the length of the channel section 11 and substantially the length of the channel means 10 ,

The fluid sampling device 1 has an interface device ( 12 . 13 . fourteen . 15 ) for connecting the at least one first ( 2 ) and at least one second ( 3 ) Optical waveguide with the interface device ( 112 . 113 . 114 . 115 ) of the fluid analysis device 100 on. The interface device of the fluid sampling device includes the planar end surface 12 of the first optical waveguide 2 , which serves the entry of the light ES1, the planar end face fourteen of the second optical waveguide 3 , which serves the entrance of the light ES2, which is the planar end face 13 of the first optical waveguide 2 , which serves the exit of the light ET1 and the planar end face 15 of the second optical waveguide 3 , which serves the exit of the light ET2. The planar endface can. The planar end face is here in each case perpendicular to the channel direction S, which also corresponds to the - here constant - direction of the optical waveguide near the respective end face. However, the planar end face can also lie at an angle other than 90 ° to this channel direction S, and in particular can be parallel to this direction S. In the latter case, one can use an optical grating or prism, or other optical means, to couple the light in the desired direction into the optical fiber to give the light pipe and the desired total reflection at the outer surfaces of the optical fiber.

The first outer surface 2a and second outer surface 3a each extend between the first channel cross-section A1 and second channel cross-section A2 and along this channel section 11 and are disposed in contact with the channel internal volume to allow penetration of the first and second evanescent fields into the channel internal volume of the channel portion. The concentration change caused by the sedimentation of the particles in the fluid along the length in the direction S of the channel section in the vicinity of the outer surfaces 2a and 3a the optical waveguide causes the frequency with which the particles, in particular erythrocytes, reach the range of the evanescent field in which they can be changed for B. touch the respective outer surface. As a result, the evanescent field of the first and second optical waveguides are influenced in different ways, which in turn can be measured by measuring the light transmitted through the first optical waveguide 2 transmitted light LT1 and measurement by the second optical fiber 3 transmitted light LT2 detected and can optionally be evaluated.

The channel section 11 is for sedimentation of particles contained in the fluid 6a between the first outer surface 2a and the second outer surface 3a in particular by having a suitable cross-sectional area and in particular a suitable channel height, here parallel to the direction of gravitational acceleration g. A channel height is particularly suitable if it allows a different formation of the particle concentration at the first and second outer surface due to the sedimentation.

The fluid sampling device here has a fluid interface device ( 16 . 17 ) for connecting the channel device 10 to a fluid movement device 124 on. The fluid interface device has a connection flange 16 for the entry of the fluid and a connection flange 17 for the discharge of the fluid.

The first fiber optic cable 2 and the second optical fiber 3 are by two plate-like and here planar channel wall elements 4 interconnected or spaced apart. These channel wall elements 4 are preferably formed as a plastic film. The two optical fibers and the two channel wall elements 4 here form the channel section. This is particularly apparent from the cross-sectional view in FIG 1b recognizable, which is perpendicular to the channel direction S.

It is also possible and preferred that the optical fibers do not, as in 1a and 1b to be seen as wall elements of the channel section 11 are formed, but are arranged in a channel section, which consists of several, in particular integrally connected, channel wall elements ( 4 '; 4 ''; 4 ''' ), as in the embodiments of the alternative fluid sampling devices ( 1'; 1''; 1''' ) in the 2a . 2 B and 2c is shown.

2a shows the fluid sampling device 1' , which has a substantially cuboid channel portion, wherein a first optical waveguide is arranged as a plate-shaped member in the channel direction S, and in this case is arranged planar on the inside of the upper boundary wall of the channel portion. A second optical waveguide is arranged perpendicular to the channel direction S opposite the first optical waveguide as a plate-shaped component in the channel direction S, and in this case is arranged planar on the inside of the upper boundary wall of the channel section. Compared to the fluid sampling device 1 of the 1b the first and second outer surfaces are enlarged.

2 B shows the fluid sampling device 1'' , which has a substantially cuboid channel portion, in which two first optical waveguides 2 '' are arranged as cuboid and rod-shaped components in the channel direction S within the channel inner volume, and in this case substantially - at least not over its entire length in the channel direction S - not arranged directly on the inside of the upper boundary wall of the channel section. Two second optical fibers 3 '' are perpendicular to the channel direction S the first optical waveguides opposite to each other as cuboid and rod-shaped components in the channel direction S, and arranged in this case substantially - at least not over its entire length in the channel direction S - not directly on the inside of the lower boundary wall of the channel section. Compared to the fluid sampling device 1 of the 1b the first and second outer surfaces are enlarged by exposing substantially the entire outer surface of an optical waveguide to the channel internal volume and allowing contact by particles.

2c shows the fluid sampling device 1''' , which has a substantially cuboid channel portion, in the seven first optical waveguide 2 ''' are arranged as cuboid and rod-shaped components in the channel direction S within the upper half of the channel inner volume and in the seven second optical waveguide 3 ''' are arranged as cuboid and rod-shaped components in the channel direction S within the lower half of the channel inner volume. The optical waveguides are here substantially along the entire inner side of the lateral channel wall elements 4 ''' arranged, and optionally additionally provided at the top and bottom, whereby a higher resolution in the formation of a sedimentation-induced gradient of the particle concentration along the gravitational field is made possible.

3a shows the fluid analysis device 100 for receiving a fluid sampling device 1 , The fluid analysis device 100 has a base 120 which carries the components of the fluid analysis device. The fluid analysis device 100 has a receiving device 121 for receiving the fluid sampling device. In principle, the fluid analysis device could also have a plurality of recording devices and be set up for simultaneous measurement at a plurality of fluid sampling devices. The recording device 121 holds the fluid sampling device in position and aligns it in the gravity field so that the height of the channel device 10 or the channel section 11 parallel to the gravitational field, here the gravitation in direction g. As a result, the sedimentation takes place under a defined acceleration, namely the gravitational acceleration g. Preferably, the receiving device has a locking device (not shown), z. B. a clamping device formed by sprung locking elements, by means of which the fluid sampling device is held by the user releasably in the receiving device.

The fluid analysis device 100 has an optical measuring device 123 on, for measuring a through first optical fiber 2 the fluid sampling device 1 transmitted light LT1 and for measuring one through the second optical fiber 3 the fluid sampling device 1 transmitted light LT2 is set up. The fluid analysis device 100 also indicates the interface device ( 112 . 113 . 114 . 115 ) for connecting the optical measuring device 123 with the interface device ( 12 . 13 . fourteen . 15 ) of the fluid sampling device 1 on. The Interface elements ( 112 . 113 . 114 . 115 ) are present planar end surfaces of the light guide of the light pipe system 123a , Optionally, lenses or other means for beam guidance may be provided on these interface elements.

The optical measuring device 123 has a light source designed as an LED 125 on, in defined intensity over a light pipe system 123a on the interface elements 112 and 114 the fluid analysis device 100 and to the interface elements 12 and fourteen the fluid sampling device 1 is distributed. The optical measuring device 123 here has two photodetectors 126 on, independently from the first optical fiber 2 via the interface elements 13 and 113 emerging light LT1 and that from the second optical fiber 3 via the interface elements 15 and 115 measuring light leakage LT2. The measuring signals are - optionally: from the electrical control device 122 digitized and - evaluated. This is done taking into account the nature of the emitted light LS1 and LS2, here also from the electrical control device 122 is controlled.

The fluid analysis device 100 is adapted to the fluid sampling device 1 in one produced by gravity - or by centrifugation (see 4 ) To align gravity field to sedimentation of particles contained in the fluid in the gravitational field 6a between the first outer surface 2a and the second outer surface 3a to effect. Optionally, the fluid analysis device 100 a rotating device (not shown) around the received fluid sampling device 1 controlled to rotate in the gravity field and so change the direction of sedimentation or reverse.

Preferably, the fluid analysis device 100 a fluid movement device 124 on, here a pump, with which the fluid 6 through the channel device 10 the fluid sampling device 1 as fluid flow is transportable, in particular the electronic control device 122 the fluid analysis device 100 is designed to, by the fluid movement device 124 to control caused fluid flow. The fluid movement device 124 is via a fluid line system 124a to the fluid interface device ( 116 . 117 ) of the fluid analysis device 100 connected. The fluid interface device ( 116 . 117 ) can spigot 116 . 117 have, with the connecting flanges 16 . 17 the fluid interface device ( 16 . 17 ) of the fluid sampling device are fluid-tight connectable.

The optical interface device and the fluid interface device of the fluid sampling device 1 and the fluid analysis device 100 are here, and according to a preferred embodiment, arranged so that the fluid sampling device by the user is releasably connectable to the fluid analysis device.

The gravity field can, as in 4 shown to be produced by centrifugation by z. B. the fluid analysis device 100 with inserted fluid sampling device 1 on a rotating device 130 which rotates about an axis of rotation R and an alternative acceleration field 1' generated, which is dominated by the centrifugal force g '.

• – Einbringen der Fluidprobenvorrichtung (1) in eine Fluidanalysevorrichtung; (201)
• – Orientieren der Fluidprobenvorrichtung (1) in einem Schwerefeld, um die Sedimentation der in der Suspension enthaltenen Partikel zu ermöglichen, (202)
• – Bewegen der Fluidprobe durch die Kanaleinrichtung der Fluidprobenvorrichtung, wobei während dieser Bewegung die Sedimentation der Partikel im Fluid stattfindet; (203)
• – während eines Zeitabschnitts der Sedimenation: Erfassung, insbesondere zeitabhängige Erfassung, des durch den ersten Lichtwellenleiter der Fluidprobenvorrichtung gelangten und durch die Absorption des ersten evaneszenten Feldes veränderten Lichts als erstes Messsignal und Erfassung, insbesondere zeitabhängige Erfassung, des durch den zweiten Lichtwellenleiter der Fluidprobenvorrichtung gelangten und durch die Absorption des zweiten evaneszenten Feldes veränderten Lichts als zweites Messsignal; (204)
• – optional: Auswertung des ersten und zweiten Messsignals durch eine elektronische Auswertungseinrichtung (205).

This in 5 schematically shown embodiment of the method according to the invention 200 for optical measurement on a fluid sample in suspension 6 in the fluid sampling device according to the invention 1 has the steps:

• Introduction of the fluid sampling device ( 1 ) in a fluid analysis device; ( 201 )
• Orienting the fluid sampling device ( 1 ) in a gravitational field to allow sedimentation of the particles contained in the suspension, ( 202 )
• Moving the fluid sample through the channel means of the fluid sampling device, during which movement the sedimentation of the particles takes place in the fluid; ( 203 )
• - During a period of sedimentation: detection, in particular time-dependent detection, of the first optical fiber of the fluid sampling device and changed by the absorption of the first evanescent field changed light as the first measurement signal and detection, in particular time-dependent detection of the passed through the second optical fiber of the fluid sampling device and by the absorption of the second evanescent field changed light as a second measurement signal; ( 204 )
• Optional: evaluation of the first and second measuring signals by an electronic evaluation device ( 205 ).

• – Bereitstellen der ersten und zweiten Lichtwellenleiter (301);
• – Bereitstellen der Schnittstelleinrichtung, die geeignet ist zur Verbindung des mindestens einen ersten und mindestens einen zweiten Lichtwellenleiters mit der Schnittstelleneinrichtung der Fluidanalysevorrichtung; (302)
• – Ausbildung der Kanaleinrichtung der Fluidprobenvorrichtung; (303)
• – optional: Bereitstellen mindestens eines Kanalwandelements, das insbesondere aus Kunststoff bestehen kann; (304)
• – vorzugsweise: Assemblieren der Lichtwellenleiter, der Schnittstelleinrichtung und vorzugsweise des mindestens eines Kanalwandelements, um die Kanaleinrichtung der Fluidprobenvorrichtung auszubilden (305).

This in 6 schematically shown embodiment of the method according to the invention 300 for producing a fluid sampling device according to the invention 1 has the steps:

• Providing the first and second optical waveguides ( 301 );
• Providing the interface device which is suitable for connecting the at least one first and at least one second optical waveguide to the interface device of the fluid analysis device; ( 302 )
• Formation of the channel means of the fluid sampling device; ( 303 )
• - Optional: providing at least one channel wall element, which may consist in particular of plastic; ( 304 )
• Preferably, assembling the optical waveguides, the interface device and preferably the at least one channel wall element in order to form the channel device of the fluid sampling device ( 305 ).

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 4437758 B4 [0003]
• DE 69230420 T2 [0004]
• EP 0810026 B1 [0005]

Claims (15)

Fluid sampling device ( 1 ; 1'; 1''; 1''' ) for placement in a fluid analysis device ( 100 ) according to claim 7, comprising a channel device ( 10 ) surrounding a channel internal volume through which a fluid sample ( 6 ) in the channel direction (S) is flowable, wherein the channel direction is perpendicular to the channel cross-section and wherein the channel means at least one in channel direction between a first channel cross-section (A1) and a second channel cross-section (A2) extending channel portion ( 11 ), a first optical waveguide ( 2 ; 2 '; 2 ''; 2 ''' ), which has a first outer surface ( 2a ) for forming a first evanescent field (f1), and a second optical waveguide ( 3 ; 3 '; 3 ''; 3 ''' ), which has a second outer surface ( 3a ) to form a second evanescent field (f2), at least one interface device ( 12 . 13 . fourteen . 15 ) for connecting the at least one first ( 2 ) and at least one second ( 3 ) Optical waveguide with the interface device ( 112 . 113 . 114 . 115 ) of the fluid analysis device, wherein the first outer surface ( 2a ) and second outer surface ( 3a ) each extend between the first channel cross section (A1) and the second channel cross section (A2) and along this channel section ( 11 ) and in contact with the channel internal volume to allow penetration of the first and second evanescent fields into the channel internal volume of the channel section. Fluid sampling device according to claim 1, characterized in that the first optical waveguide and the second optical waveguide parallel to each other and by at least one planar connection ( 4 ; 4 '; 4 ''; 4 ''' ) are spaced such that the optical fibers ( 2 . 3 ) and the at least one planar connection form the channel section. Fluid sampling device according to claim 2, characterized in that the at least one planar connection ( 4 ; 4 '; 4 ''; 4 ''' ) is a film, in particular the optical waveguides ( 2 . 3 ) or applied on both sides. Fluid sampling device according to one of the preceding claims, characterized in that the channel section ( 11 ) for the sedimentation of particles contained in the fluid ( 6a ) between the first outer surface ( 2a ) and the second outer surface ( 3a ) is set up. Fluid sampling device according to one of the preceding claims, characterized in that the fluid sampling device comprises more than two optical waveguides, which are arranged in particular along the channel portion. Fluid sampling device according to any one of the preceding claims, characterized in that the fluid sampling device (a fluid interface device 16 . 17 ) for connecting the channel device ( 10 ) to a fluid movement device ( 124 ) having. Fluid analysis device ( 100 ) for receiving at least one fluid sampling device ( 1 ; 1'; 1''; 1''' ) according to one of the preceding claims 1 to 6, comprising at least one receiving device ( 121 ) for receiving the fluid sampling device, an optical measuring device ( 123 ) arranged to measure a light (LT1) transmitted through the at least one first optical waveguide of the fluid sampling device and to measure a light (LT2) transmitted through the at least one second optical waveguide of the fluid sampling device, and at least one interface device ( 112 . 113 . 114 . 115 ) for connecting the optical measuring device to the interface device of the fluid sampling device. Fluid analysis device according to claim 7, characterized in that the fluid analysis device is adapted to align the fluid sampling device in a gravitational field generated by gravity or by centrifugation in order to determine in the gravitational field the sedimentation of particles ( 6a ) between the first outer surface ( 2a ) and the second outer surface ( 3a ) to effect. Fluid analysis device according to claim 7 or 8, characterized in that the fluid analysis device comprises a rotating device, by means of which the fluid sampling device ( 1 ) or the optical fibers ( 2 . 3 ) are movable in their relative position to the gravitational field. Fluid analysis device according to claim 7, 8 or 9, characterized in that the fluid analysis device comprises: - at least one first light source ( 125 ) in order to couple light (LS1, LS2) into the first and / or the second optical waveguide of the fluid sampling device, - at least one light detector ( 126 ) to detect the light (LT1, LT2) passed through the first and / or the second optical waveguide of the fluid sampling device and the light (LT1, LT2) changed by the absorption of the first and / or the second evanescent field, and 122 ) in order to generate at least one measuring signal depending on the coupled-in light and the changed light. Fluid analysis device according to claim 10, characterized in that the fluid analysis device comprises a fluid movement device ( 124 ), with which the fluid can be transported through the channel device of the fluid sampling device as a fluid flow, wherein in particular the electronic control device ( 122 ) of the fluid analysis device is designed to control the fluid flow caused by the fluid movement device. Fluid analysis device according to one of claims 7 to 11, on which a fluid sampling device according to one of claims 1 to 6 is arranged. Procedure ( 200 ) for optical measurement on a fluid sample in suspension ( 6 ) in the fluid sampling device ( 1 ) according to claim 1, at least with the steps - introducing the fluid sampling device ( 1 ) in a fluid analysis device; ( 201 ) - orienting the fluid sampling device ( 1 ) in a gravitational field to allow sedimentation of the particles contained in the suspension, ( 202 Moving the fluid sample through the channel means of the fluid sampling device, during which movement the sedimentation of the particles takes place in the fluid; ( 203 ) - during a period of sedimentation: detection, in particular time-dependent detection, of the first optical waveguide of the fluid sampling device and changed by the absorption of the first evanescent field changed light as the first measurement signal and detection, in particular time-dependent detection, of the second optical fiber of the fluid sampling device arrived and by the absorption of the second evanescent field changed light as a second measurement signal; ( 204 ) - Optional: Evaluation of the first and second measurement signal by an electronic evaluation device. Process for producing the fluid sampling device according to one of claims 1 to 6. Use of the fluid sampling device according to one of claims 1 to 6 or the fluid analysis device according to any one of claims 7 to 12 or the method according to claim 13 for blood analysis.

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