Reaction vessel

Abstract

The present invention provides a container for use in analyzing samples, the container comprising a housing, a lid closing a first end of the housing, a stator disposed within the housing for receiving a rotor, and a shaft having a first end to which a magnetic shaft drive is fixed and an opposing second end covered by the rotor, the rotor and stator spaced apart by a ring-shaped gap of constant radius, the shaft extending within a first bearing attached to the shaft at an axial portion disposed between the magnetic shaft drive and the rotor, the first bearing being fixed to the lid.

Description

[Technical field]

[0001] The present invention relates to an apparatus, which is a reaction vessel suitable for exerting a predetermined shear force on a liquid sample, a method for manufacturing the reaction vessel, and a process for exerting a predetermined shear force on a sample, preferably including optical analysis of the sample passing through a portion of the reaction vessel.

[0002] The reaction vessel comprises a rotor extending on bearings, preferably just one bearing, the rotor having an axle with a drive at one end and adapted to receive rotational torque from a drive motor which may be located adjacent to the drive or at a distance from the drive. Preferably, the bearing is located at a distance from the height of the liquid sample placed in the vessel, such that the bearing does not come into contact with the liquid.

[0003] The reactor vessel includes a stator coaxially disposed with a rotor, and a predetermined gap is formed between the rotor and the stator, and a predetermined shear stress can be applied to the liquid, the shear stress being proportional to the rotational frequency of the rotor, the radius of the rotor, and the viscosity of the liquid, and inversely proportional to the gap width between the rotor and the stator.

[0004] The reaction vessel allows the liquid sample to circulate when driven by the rotation of the rotor, and the vessel shape is designed such that the maximum shear stress is applied to the liquid at the smallest gap width between the rotor and the stator.

[0005] The reaction vessel is preferably provided with a detection portion arranged at its lower end, which is at least partially light-transmitting, e.g. for light to illuminate the internal volume of the reaction vessel and for detecting radiation passing through and / or emitted from the internal volume of the reaction vessel. [Background technology]

[0006] WO2012 / 110570A1 shows diagrammatically a reaction vessel in which a rotor extends on an axle that extends on a bearing located in a lid covering the vessel and a second bearing located in the bottom of the lid, the rotor having a conical shape parallel to the vessel bottom which tapers conically. In an alternative example, the vessel extends on a sleeve located in the top half of a cylindrical vessel, the rotor extends into a tube open at both ends, the tube being located in the bottom half of the vessel spaced from the rotor and spaced from the vessel bottom.

[0007] WO2016 / 001334A1 shows a reaction vessel in which a stator is inserted spaced from the vessel wall and spaced from a central rotor. The rotor is cylindrical with a chamfered periphery. The stator has an extension below the part surrounding the rotor, and the light source and detector are oriented at 90° to each other and 45° to a common central axis and are directed into the space formed by the extension. Summary of the Invention

[0008] It is an object of the present invention to provide an alternative reaction vessel suitable for exerting a shear stress on a liquid, and an alternative process for exerting a shear force on a liquid using a reaction vessel. Preferred objects are to provide a reaction vessel configured to effectively exert a shear force on the entire volume of liquid contained in the vessel, and to provide a vessel that allows optical detection of a representative portion of the liquid.

[0009] The present invention achieves this object by the features of the claims, in particular by providing a reaction vessel suitable for subjecting the entire volume of a liquid contained therein to a shear force, said vessel being configured for circulating the liquid through the vessel, a housing having a first end for connection to a lid and an opposing second end closed by a bottom wall, the second end comprising a detector having at least one window, preferably two windows, in the housing wall, the windows being optically transparent and preferably planar, the detector preferably being disposed adjacent the bottom wall; a lid closing the first end of the housing, the lid preferably having a recess coaxially disposed with the housing, and preferably having a cylindrical side wall that clamps to the cylindrical portion of the first end of the housing; a stator disposed within the housing and having a cylindrical inner surface for receiving the rotor at a fixed distance, the cylindrical surface having a first open end cross section and an opposing second end cross section, the outer surface of the stator being spaced from the housing by at least three, preferably four, webs connecting the stator to the housing at spaced intervals, the webs preferably extending only along a stator retaining portion of the housing; Optionally, the stator has an opening in its second end cross section directly adjacent to or spaced from the sensing portion; Preferably, an extension pipe is connected to the second end cross section of the stator, the extension pipe having a constant cross section or a cross section tapering towards the detection portion and terminating directly adjacent to the detection portion or at a distance from the detection portion, the distance may extend along the second portion of the nozzle holder; a rotor having or consisting of a cylindrical portion disposed within a stator, the rotor and the stator being separated by a ring-shaped gap of constant radius, the rotor covering a second end of the shaft and having a flat front face and a chamfered or rounded periphery or a second end having a rounded front face, the rotor having at its first end a terminal peripheral collar extending across the radius of the cylindrical rotor portion and across the cylindrical surface of the stator, the collar accordingly extending across the ring-shaped gap formed between the rotor and the stator; A shaft having a first end to which a magnetic shaft drive is fixed and an opposing second end covered by a rotor, the shaft extending into a first bearing arranged on the shaft at an axial portion arranged between the magnetic shaft drive and the rotor, the first bearing being fixed to the lid, preferably the first end of the shaft being a free end and arranged in a recess in the lid, the free end of the shaft and the recess in the lid forming a second bearing which is a friction bearing; Equipped with The shaft, the magnetic shaft drive, the first and second bearings through which the shaft extends, the rotor, the stator, preferably the extension of the stator and / or the detector are arranged coaxially.

[0010] A constant radius ring gap between the cylindrical rotor portion and the cylindrical stator portion defines an annular gap having a constant cross section.

[0011] Typically, the rotor, the rotor's peripheral collar, the stator, the optional extension pipe, and the first and optional second bearings, as well as the magnetic shaft drive, are coaxial with the shaft, and preferably all components of the vessel are coaxial with a common longitudinal axis, for example the longitudinal axis of the shaft.

[0012] In a detector having two windows, the windows are preferably arranged at 90° and more preferably parallel to each other on opposite sides of the housing wall.

[0013] Typically, the stator is spaced apart from the housing, the space from the housing to the stator forming a channel for the liquid to flow in the space from one end of the stator, e.g. its first end section, to the other end of the stator, e.g. its second end section, or to the opening of the extension pipe opposite the stator. The extension pipe is therefore also spaced apart from the housing. Since there is no relative movement between the stator and the housing in the space forming the channel for the liquid, the shear forces in this channel are significantly smaller, e.g. substantially no shear forces compared to the shear forces occurring between the rotor and the stator, so that in the channel between the stator and the housing, the liquid can return to the gap between the rotor and the stator without experiencing any associated shear forces. Preferably, the space from the housing to the stator is at least as large as the radius of the ring-shaped gap between the rotor and the stator in order to generate maximum shear forces between the rotor and the stator and to avoid large shear forces when the liquid passes through the space between the stator and the housing. The extension pipe is disposed coaxially with the nozzle holding portion of the housing, and preferably the extension pipe is disposed at a fixed distance from the nozzle holding portion of the housing.

[0014] Preferably, the cross-sectional area of ​​the extension pipe is at least as large as the cross-sectional area of ​​the annular gap between the rotor and the stator. Preferably, the extension pipe is circular in each of its cross-sections or heights.

[0015] The webs connecting the stator to the housing at the spaced apart positions may be formed by one of the stator and the housing with a clamp connection between the webs and the respective other of the stator and the housing, or the webs may be integrally formed with both the stator and the housing, for example by additive manufacturing using a 3D printer, fused dummy modeling (FDM) techniques. The embodiment in which the stator, optionally an extension pipe connected to the second end of the stator, and the housing including the connecting webs are integrally formed has the advantage that the stator is less likely to warp and warp, as compared to a stator clamped in the housing by, for example, a web.

[0016] Preferably, the rotor is spaced from the first bearing so that the shaft is not covered by this spacing. The spacing of the first bearing from the rotor reduces contamination of the first bearing by liquid contacting the rotor.

[0017] Preferably, the housing has a diameter, in the part between the height of the lid or the first bearing, e.g. the first bearing arranged in the lid, and the height of the rotor, which is smaller than the outer or inner diameter of the stator and / or smaller than the diameter of the rotor, in particular smaller than the diameter of the peripheral collar of the rotor. Such a part with a smaller diameter is also interchangeably referred to as the collar part of the housing. Preferably, in the collar part, in particular the part covering the part between the lid or the first bearing, e.g. the first bearing arranged in the lid, and the rotor, the shaft is not covered by either the first bearing or the rotor. In the process with the vessel, preferably the liquid is poured into the housing up to the smallest cross section of the collar part, preferably to a height that completely fills the annular gap between the rotor and the stator.

[0018] The housing preferably has a recess at its first end, preferably of cylindrical cross section, for receiving the cylindrical side wall of the lid, for example, preferably with a friction fit, optionally including mating grooves and ridges on the exterior of the cylindrical side wall of the lid with grooves and ridges on the interior surface of the recess at the first end of the housing.

[0019] Optionally, the housing has an enlarged inner cross section, e.g. is widened, in a part at the height of the peripheral collar of the rotor compared to a part at the height of the second end of the stator and / or compared to a cross section of the housing part between the height of the lid or the height of the first bearing, e.g. the first bearing arranged in the lid, and the height of the rotor. The enlargement of the inner cross section of the housing at the height of the peripheral collar of the rotor has the advantage of guiding the liquid flow, which is moved radially outward by the rotating rotor, in particular by the rotating peripheral collar, into the gap between the stator and the housing, e.g. to generate a return flow of liquid to the second end cross section of the stator or to a cross-sectional opening of an extension pipe arranged on the opposite side of the rotor and / or on the opposite side of the stator.

[0020] The shaft is preferably a cylindrical stainless steel rod, or alternatively, the shaft may be a cylindrical rod of high performance plastic.

[0021] Preferably, the first bearing is fixed, for example clamped, to the lid, for example the first bearing is clamped in a recess formed by the cylindrical side wall of the lid. The first bearing may be a bore in a plate, which provides a friction bearing for the shaft, optionally with only radial guidance and / or without axial guidance. The magnetic shaft drive preferably comprises or consists of a holder comprising a magnet, which is fixed to the shaft, for example by a clamp. The holder preferably has a recess for holding a magnet, preferably a pair or two pairs of magnets. Along the shaft, the magnetic shaft drive is preferably arranged between the lid forming a second bearing for the first end of the shaft and the first bearing fixed to the lid, for example by clamping in a recess formed by the side wall of the lid, whereby the magnetic shaft drive holds the shaft between the first bearing and the second bearing, also in the case where the first bearing is a bore allowing axial sliding of the shaft. To restrain axial movement of the shaft in the first bearing, the magnetic shaft drive can be fixed to the shaft in a position where the magnetic shaft drive is located adjacent to the first bearing, for example where the magnetic shaft drive contacts the first bearing, with the first end of the shaft extending into the second bearing and the front face of the shaft contacting the recess in the lid with sufficient clearance to allow rotation of the shaft. Preferably, the magnet is a neodymium magnet, for example a cylindrical magnet located in a hole in the holder. Alternatively, other high performance magnets can be used, including high performance composite magnets manufactured by injection molding.

[0022] Preferably, the shaft is a cylindrical metal rod, the magnet of the magnetic shaft drive is a neodymium magnet, and all other components of the vessel are preferably made of a light-transmitting synthetic resin, such as polystyrene, polyethylene, polylactic acid, polyethylene terephthalate, polycarbonate, or acrylic-butadiene-styrene, or nylon.

[0023] Preferably, the synthetic resin components, fixed together, for example by clamping with surfaces that slide against each other when the components are attached, have a groove perpendicular to their common longitudinal axis, for example perpendicular to the longitudinal axis of the shaft, the groove being manufactured by additive manufacturing, for example by 3D printing, preferably liquid resin 3D printing, for example using high-precision fused molding (FDM) techniques.

[0024] The magnetic shaft drives can be driven by correspondingly arranged magnets, preferably a magnetic drive having the same number of magnet pairs as there are shaft drives.

[0025] Preferably, the first bearing is connected to the lid, for example by a clamp, preferably in a recess formed by the cylindrical side wall of the lid, and the lid is connected to the first end of the housing by a clamp, whereby no additional fastening means are required, for example the container can be provided as a separate element that is simply connected by a clamp, without additional adhesives, sealing or mechanical fastening devices.

[0026] The container is a housing having a detector portion at a second end thereof with at least one, preferably at least two, light-transmitting windows, the housing including a stator and having at a first end thereof a recess for receiving a lid; As a separate part, a lid connected to a first bearing including a shaft having a rotor fixed to a second end and a magnetic shaft drive fixed to a first end, the lid being clampable to the first end of the housing; may be provided as a combination of

[0027] The reaction vessel has the advantage that it is configured to exert shear forces between the rotor and stator, pumping the liquid by rotating the rotor and resulting in homogeneous treatment of the entire liquid in the vessel, so that a liquid representative of the entire liquid is present at the detection portion of the housing. A peripheral collar extending over the radius of the cylindrical rotor portion upon rotation can generate sufficient centrifugal forces on the liquid to pump the liquid so that it circulates through the gap between the rotor and stator and returns through the channel formed by the spacing between the housing and the stator.

[0028] The pumping action is provided only by the rotation of the rotor, and thus the drive element of the vessel, e.g. the rotating element, is preferably composed of a rotor arranged at the second end of the shaft and a shaft drive arranged at the first end of the shaft. Moreover, the vessel has the advantage that the shear force can be controlled by controlling only the rotation speed of the rotor, by exerting a large shear force on the liquid mainly only between the rotor and the stator, and the vessel is configured to avoid the occurrence of relevant shear forces outside the ring gap defined between the rotor and the stator. Thus, the vessel is configured to subject the liquid to maximum shear forces only in the ring gap between the rotor and the stator. The vessel is configured to circulate the entire volume of the liquid through the ring gap between the rotor and the stator when the rotor is rotated, and to convert the native structure prion protein to the aggregated state only in the ring gap between the rotor and the stator, and the flow of liquid through the vessel outside this ring gap does not provide a shear force sufficient to significantly affect the conversion of the native structure prion protein to the aggregated state.

[0029] The ring gap between the rotor and the stator is preferably in the range of 0.2-0.5 mm and / or in the range of 5%-30% of the rotor radius. The shear stress is proportional to the rotor rotation frequency, the rotor radius and the viscosity of the liquid, and inversely proportional to the gap width between the rotor and the stator.

[0030] Preferably, at least two containers are arranged parallel to one another and connected to one another, the housing and the connection therebetween being integral, e.g. manufactured in one piece, more preferably the material of the housing and the connection therebetween being continuous, wherein the at least two containers parallel to one another and connected to one another are arranged such that their light-transmitting windows are arranged in a common plane, e.g. their windows are arranged in a plane parallel to the straight line of the rows in which the containers are arranged in the device.

[0031] Furthermore, the present invention provides an analytical process in which a liquid sample is injected into a container, preferably by injecting the sample into a housing and / or a stator, then placing a rotor in the stator, preferably a rotor mounted on a shaft extending on a first bearing fixed to the lid, and placing the lid on a first end of the housing, rotating a magnetic shaft drive to rotate the rotor, optically detecting the sample in a detection section of the housing, and preferably transmitting the detection result or a medical indication derived from the detection result to a donor of the sample. The donor of the sample may be a medical research institution, a physician, or a patient from whom the sample was taken. Furthermore, the analytical process may be used to determine the effect of a compound on its efficacy in inhibiting or reversing the formation of aggregated structure prion protein by adding the compound to a sample or an aliquot of the sample and comparing the rate of formation of aggregated structure prion protein during the process. Thus, the process may be used to analyze samples from patients by adding a compound suspected to have activity against the formation of aggregated structure prion protein to a sample from a particular patient in order to detect the efficacy of the compound in at least delaying the formation of aggregated structure prion protein in the donor's sample. The efficacy of a compound in delaying the formation of aggregated prion protein includes preventing, inhibiting, suppressing, and / or reversing the formation of aggregated prion protein. Here, the process can be used to select compounds for their efficacy in delaying, e.g., inhibiting, suppressing, preventing, or reversing the formation of aggregated structure prion protein for a particular patient sample. In general, the sample can be liquid or solid biomaterial, e.g., solution, serum, tissue, obtained from a patient. The patient can be a human patient, or an animal or tissue culture, particularly for research. The process can be an in vitro process or assay, and can be used, e.g., as a translational assay system during drug discovery.

[0032] A process using the device of the present invention can also be utilized to screen and select compounds for their activity and efficacy in inhibiting, suppressing or reversing the formation of aggregated prion protein, the process comprising the steps of injecting a liquid sample comprising native prion protein and / or aggregated prion protein to detect compounds having activity in retarding the formation of aggregated prion protein, adding at least one compound to be screened into the housing and placing the rotor inside the stator, rotating the magnetic shaft drive to rotate the rotor, and optically detecting the sample in the detection portion of the housing.

[0033] The invention will now be explained in more detail by way of examples and with reference to the drawings. [Brief description of the drawings]

[0034] [Figure 1] FIG. 1A is a cross-sectional view of an embodiment of a container, FIG. 1B is a cross-sectional view rotated 90° relative to the horizontal at the indicated height B, FIG. 1C is a cross-sectional view rotated 90° relative to the horizontal at the indicated height C, and FIG. 1D is a cross-sectional view of the housing of FIG. 1A rotated 90° relative to the vertical, with some components of the embodiment shown in FIG. 2 removed from FIG. 1A. [Diagram 2] FIG. 2 is a cross-sectional view of a portion of the embodiment. [Diagram 3] FIG. 3 is an enlarged cross-sectional view of FIG. 2. [Figure 4] 2 shows the results of measuring the formation of aggregated prion protein produced in the vessel of FIG. 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0035] Generally, each feature described with reference to the drawings is a separate feature of the container of the present invention and is independent of other features.

[0036] 1A-D show a housing 1 having a first end 2 and an opposing second end 3, closed by a bottom wall 4. A detection portion 5 is disposed at the second end 3 of the housing 1, the detection portion 5 having at least one, preferably two opposing light-transmitting windows 6 (FIGS. 1C, 1D). Optionally, the bottom wall 4 has a bottom window 4a of light-transmitting material, the central portion of which is surrounded by a non-transmitting bottom wall forming a bottom opening 4b.

[0037] Disposed within the housing 1 is a stator 10 which extends from a first open end section 11 to an opposing second open end section 12 and has a cylindrical inner surface 15. Connected to the second end section 12 is an extension pipe 13 which tapers towards the second end 3 of the housing 1. The extension pipe 13 functions to guide liquid flowing along the extension pipe 13 and the stator 10 through the detection section 5.

[0038] Preferably, as shown with respect to the extension pipe 13, the extension pipe 13 tapers towards the second end 3 of the housing 1 to form a nozzle.

[0039] The stator 10 is disposed in the housing and spaced apart by webs 14. The stator 10 extends along a stator retaining portion 8 of the housing 1, and preferably the webs 14 extend along the stator retaining portion 8 between the housing 1 and the stator 10.

[0040] The rotor 20 is coaxially disposed inside the stator 10, and the spacing between the rotor 20 and the cylindrical inner surface of the stator 11 forms a ring-shaped gap where shear forces are applied to the liquid as the rotor 20 rotates. The rotor as a cylindrical portion 21 disposed within the stator 10, and the cylindrical portion 21 at its first end 22 has a peripheral collar 23 that extends over a radius of the cylindrical rotor portion 21. The rotor collar 23 according to a preferred embodiment also extends into the ring-shaped gap between the rotor 20 and the stator 10.

[0041] The opposing second end 24 of the rotor has a flat front surface 25 with a circumferential bevel 26 .

[0042] The rotor 20 is arranged at the second end 32 of the shaft 30. Opposite the second end 32, the first end 31 of the shaft 30 carries a magnetic shaft drive 33 including at least two magnets 34. The magnetic shaft drive 33 is fixed to the shaft 30 which extends in a first bearing 35, which is optionally axially displaceable. In the embodiment shown, the magnetic shaft drive 33 has a flat front face 36 which can frictionally extend into an adjacent flat front face 37 of the first bearing 35, thereby limiting the axial movement of the shaft 30. The first bearing 35 is held by a clamp inside a cylindrical part 41 of a lid 40, which is clamped to the first end 2 of the housing 1. The lid 40 also closes the cross section of the first end 2 of the housing 1.

[0043] In the embodiment shown, all elements are coaxially disposed relative to the longitudinal axis 39 of the shaft 30 .

[0044] 1A and 1D show the housing 1 with a collar 82 between the first end 2 of the housing and the stator retainer 8. From the first end 2, the collar 82 tapers along a first portion 82a to a reduced cross-section of the housing 1, and from the stator retainer 8, the collar 82 tapers along a second portion 82b to a reduced cross-section of the housing 1. The collar 82 provides a threshold for the movement of liquid from the stator retainer 8 towards the first end 2 of the housing 1. Preferably, the liquid is injected into the housing up to the reduced cross-section of the collar 82, for example reaching an approximate liquid fill level 91 at the reduced cross-section of the collar 82.

[0045] The part of the housing 1 where the extension pipe 13 is arranged is also referred to as the nozzle holding part 83 of the housing. Preferably, the extension pipe 13 is connected only to the stator 10, i.e. without a web extending between the extension pipe 13 and the nozzle holding part 83. Preferably, the first part 83a of the nozzle holding part 83 extends due to the axial extension of the extension pipe 13 and is spaced at a certain distance from the extension pipe 13, and the second part 83b of the nozzle holding part 83 adjacent to the first part 83a of the housing 1 may taper towards the second end 3 of the housing 1. Here, the second part 83b of the nozzle holding part 83 connects the first part 83a to the second end 3 of the housing 1 across the part where the extension pipe 13 does not extend.

[0046] 2 shows the lid 40 in an enlarged view with a first bearing 35 clamped to a cylindrical portion 41 of the lid 40. A shaft 30 extends into the first bearing 35 and its first end 31 is attached by a clamp to a magnetic shaft drive 33. In a preferred embodiment, the first end 31 of the shaft 30 terminates in a convex front face 38 that extends into a corresponding recess 42 in the lid, with which the front face 38 of the shaft 30 forms a second bearing 50.

[0047] FIG. 3 shows an enlarged cross-sectional view of FIG.

[0048] In general, the drawings show an embodiment of a container according to the invention, where the container is provided as two separate elements, each of which is pre-assembled to be connected to one another to form a sealed reaction container by clamping a lid 40 to the second end 2 of the housing 1, whereby the lid 40 positions the rotor 20 coaxially within the stator 10 while closing the cross-section open and extended by the second end 2 of the housing 1.

[0049] For the analytical process of the present invention, it is preferred to inject the liquid sample into the housing 1 before the lid 40 is attached to the housing.

[0050] Example: Analytical process for detecting the effect of shear forces on a sample by optical detection As a typical sample, recombinant aggregated prion protein derived from a shear-force-induced reaction of recombinant native prion protein was mixed with 1.5 mg / ml native structure human α-synuclein in PBS containing 1% Triton X-100 at a dilution of 1 / 100000, together with a postmortem brain homogenate sample from a synucleinopathic patient (positive control). The buffer composition and procedural details were similar to previous disclosures WO2012 / 110570A1 and WO2016 / 001334A1. The fluorophore used for detection of aggregated prion protein was thioflavin T. As a negative control, the same reaction composition was used without the addition of recombinant aggregated prion protein. The vessels generally corresponded to FIG. 1. The gap width between the stator and rotor was 0.3 mm and the rotor diameter was 3 mm. The treatment frequency used was 400 revolutions per second (400 Hz), corresponding to a shear rate of 12570 per second and a shear stress of 11.2 Pascals, and the reaction temperature was set at 30°C. Overall, the reaction was followed for 15 hours, corresponding to 180 cycles of treatment and rest. In each cycle, the treatment was applied for 3 seconds, followed by a resting phase of 297 seconds. To detect the formation of aggregated prion protein, the fluorescence signal of Thioflavin T was accumulated in the resting phase of each cycle. For each of the positive and negative controls, data traces for 15 replicas were recorded.

[0051] In the positive control, aggregated prion protein was formed after about 4 hours (±0.5 hours). In the negative control, aggregated prion protein started to form after about 14 hours in some replicas, but most replicas showed no signs of aggregated prion formation during the observation time. The measurement results are shown in Figure 4 along with the positive control (left) and the negative control (right). The formation of aggregates occurred in a reproducible manner, so the individual measurements overlap.

[0052] In general, detection can be measured by a change in fluorescence of a fluorescent dye added to the mixture through the detection portion of the container, the dye being specific to the aggregated structure of the prion protein. Typical dyes are, for example, thioflavin T, thioflavin S, Congo Red, thiophene-based amyloid ligands such as luminescent conjugated polythiophenes (LCPs), polythiophene acetic acid (PTAA), and luminescent conjugated oligothiophenes (LCOs), Pittsburgh compound B, aminonaphthalene 2-cyanoacrylate (ANCA) probes, pegylated phenylbenzoxazole derivatives, pinacyanol, chrysamine G, and dyes including at least one of the following scaffolds: chalcone, flavone, aurone, stilbene, diphenyl-1,2,4-oxadiazole, diphenyl-1,3,4-oxadiazole, benzothiazole, benzoxazole, benzofuran, imidazoviridine, benzimidazole, quinoline, and naphthalene.

[0053] Alternatively, native conformation prion protein can be labeled with a fluorescent dye, for example by coupling the fluorescent dye directly to the native conformation prion protein or via an intermediate spacer, such as a fluorescent derivative that contains a reactive chemical group, such as an isothiocyanate (which reacts with primary amines, e.g., lysine), a succinyl imide ester (which reacts with amino groups to form an amide bond, e.g., the N-terminal amino acid), or a maleimide (which reacts with free sulfhydryl groups, e.g., cysteine). Such fluorescent derivatives include cyanines, fluoresceins, rhodamines, Alexa fluorophores, Dylight fluorophores, ATTO-Tec dyes, BODIPY dyes, SETA dyes, SeTau dyes, and DYOMICS dyes. [Explanation of symbols]

[0054] 1. Housing 2. First end of housing 3 Second end of the housing 4 Bottom wall 4a Bottom window 4b Bottom opening 5. Detection section 6 Window section 7 Cylindrical section 8 Stator retaining part of the housing 10 Stator 11 First end cross section of stator 12 Second end cross section of stator 13 Extension pipe 14. Web 15 Cylindrical inner surface of stator 16 Opening 20 Rotors 21 Rotor cylindrical part 22 first end of rotor 23 Rotor Color 24 Second end of rotor 25 Front of rotor 26 Bevel 30 Shaft 31 first end of shaft 32 Second end of shaft 33 Magnetic Shaft Drive 34 Magnet 35 First bearing 36 Front of magnetic shaft drive 37 Front of first bearing 38 Front of shaft 39 Longitudinal axis 40 Lid 41 Cylindrical part of lid 42 Lid recess 50 Second bearing 82 Housing color part 82a First part of collar 82b Second part of collar 83 Nozzle holder of housing 83a: First end of nozzle holder 83b second end of nozzle holder 91 Proper Liquid Fill Level

Claims

1. A container for use in analyzing a sample, comprising: a housing (1) having a first end (2) for connection to a lid (40) and an opposing second end (3) closed by a bottom wall (4), said second end (3) comprising a detection part (5) having at least one light-transmissive window (6) in the housing wall; a lid (40) closing said first end (2) of said housing (1); a stator (10) having a cylindrical surface (15) for receiving a rotor (20) at regular intervals, disposed inside said housing (1), said cylindrical surface (15) having a first open-end cross section (11) and an opposing second-end cross section (12), and an outer surface of said stator (10) being spaced apart from said housing (1); a rotor (20) having a cylindrical part (21) disposed inside said stator (10), said rotor (20) and said stator (10) being separated by a ring-shaped gap of a constant radius, and said rotor (20) having a second end (24) covering said second end (32) of said shaft (30); a shaft (30) having a first end (31) to which a shaft drive (33) is fixed and an opposing second end (32) covered by said rotor (20), extending into a first bearing (35) disposed on said shaft (30) at a shaft part disposed between said magnetic shaft drive (33) and said rotor (20), said first bearing (35) being fixed to the lid (40); comprising said shaft (30), said magnetic shaft drive (33), said first bearing (35), said rotor, said stator, and / or said detection part being integrally formed; said container having at least two webs (14) connecting said stator (10) to said housing (1) at a distance; said rotor (20) having, at its first end (22), a terminal circumferential collar (23) extending over the radius of said cylindrical part (21) and extending onto said cylindrical surface (15) of said stator (10); said shaft drive (33) being a magnetic body, the container.

2. The stator (10), the housing (1), and the web (14) that spaces the stator (10) from the housing (1) are integrally formed, the container according to claim 1.

3. The detection unit (5) has two window portions (6) in opposing wall portions, the window portions (6) being light transmissive and planar, the container according to claim 1.

4. The detection unit (6) is disposed adjacent to the bottom wall (4), the container according to claim 1.

5. The lid (40) has a cylindrical portion (41) of a side wall that forms a recess disposed coaxially with the housing (1), the cylindrical side wall being clamped to the cylindrical portion (7) of the first end portion (2) of the housing (1), the container according to claim 1.

6. The stator (10) has a second end cross-section (12) opening (16) directly adjacent to the detection unit (5) or spaced apart from the detection unit (5), the container according to claim 1.

7. An extension pipe (13) is connected to the second end cross-section (12) of the stator (10), the extension pipe (13) having a terminal directly adjacent to the detection unit (5) or spaced apart from the detection unit (5), the container according to claim 1.

8. The extension pipe (13) has a cross-section that tapers towards the detection unit (5) or has a constant cross-section, the container according to claim 7.

9. The rotor (20) has, at its second end (24), a flat front surface (25) and a chamfered or rounded periphery (26) or a rounded front surface (25), the container according to claim 1.

10. The first end portion (31) of the shaft (30) is a free end disposed within the recess (42) of the lid (40), the free end of the shaft (31) and the recess (42) of the lid (40) forming a second bearing (50) that is a friction bearing, the container according to claim 1.

11. An element provided with the housing (1), a stator (10) disposed inside the housing (1), the detection unit (5), and the lid (40) connected to the first bearing (35) as a separate element, wherein the shaft (30) extends within the first bearing (35), and a magnetic shaft drive (33) disposed between the first bearing (35) and the lid (40) is attached to the first end (31) thereof, the first end (31) of the shaft (30) is a free end disposed within a recess (42) of the lid (40), the free end (31) of the shaft and the recess (42) of the lid (40) form a second bearing (50), and the rotor (20) is attached to the second end (32) of the shaft (30). The container according to claim 1.

12. The container according to claim 11, wherein the housing (1) has a cylindrical portion at its first end (2) adapted to receive the lid (40) by snap fit.

13. A process for analyzing a patient-derived sample to detect the presence of aggregated prion protein using the container according to any one of claims 1 to 12, the process comprising injecting the sample and native prion protein into the housing, placing the rotor within the stator, rotating the magnetic shaft drive to rotate the rotor, optically detecting the sample at the detection unit of the housing, and transmitting the detection result or a medical sign derived from the detection result to the provider of the sample.

14. The process for analyzing a patient-derived sample according to claim 13, comprising adding the compound to the patient-derived sample to detect the efficacy of a compound that at least delays the formation of aggregated prion protein in the sample of the provider.

15. A process for screening a compound for an activity of suppressing the formation of aggregated prion protein, using the container according to any one of claims 1 to 12, the process comprising: injecting a liquid sample comprising a native prion protein and / or an aggregated-structured prion protein to detect a compound having an activity of delaying the formation of the aggregated prion protein; adding at least one compound to be screened within the housing; disposing the rotor within the stator; rotating the magnetic shaft drive to rotate the rotor; and optically detecting the sample at the detection portion of the housing.

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