SAMPLE HOLDER FOR ANALYZING SOLID FORM PROPERTIES OF A SUBSTANCE

Abstract

A sample holder (1) for containing a substance in a solid form screening process comprises a body (2) with a sidewall portion (21), a bottom portion (22) and a hollow interior limited by the sidewall portion (21) and the bottom portion (22). The bottom portion (22) is made of a thermoplastic polyimide. The sample holder (1) allows for providing a high quality analysis of solid form properties of a substance and an efficient and safe processing of the substance.

Claims

1. A sample holder for containing a substance in a solid form screening process, comprising: a body with a sidewall portion, a bottom portion and a hollow interior limited by the sidewall portion and the bottom portion, wherein the bottom portion is made of a thermoplastic polyimide.

2. The sample holder according to claim 1, wherein the sidewall portion and the bottom portion are one single piece made of the thermoplastic polyimide.

3. The sample holder according to claim 1, wherein the body is essentially circular cylindrical.

4. The sample holder according to claim 1, wherein the bottom portion of the body has a thickness of about 150 micrometer or less, of about 100 micrometer or less, of about 50 micrometer or less, or of about 25 micrometer.

5. The sample holder according to claim 1, wherein in the interior of the body the bottom portion and the sidewall portion form an essentially right angle.

6. The sample holder according to claim 1, wherein the sidewall portion of the body has a protruding section in which an outer diameter of the sidewall portion exceeds an outer diameter of the sidewall portion outside the protruding section.

7. The sample holder according to claim 6, wherein the protruding section of the sidewall portion forms a lower step.

8. The sample holder according to claim 6, wherein the protruding section of the sidewall portion forms an upper step.

9. The sample holder according to claim 1, wherein the sidewall portion of the body has a thickness in a range of between about 400 micrometer and about 1500 micrometer, of between about 600 micrometer and about 1200 micrometer, or of between about 700 micrometer and about 1000 micrometer.

10. The sample holder according to claim 6, wherein the sidewall portion of the body has a thickness in a range of between about 400 micrometer and about 1500 micrometer, of between about 600 micrometer and about 1200 micrometer, or of between about 700 micrometer and about 1000 micrometer, and wherein the thickness of the protruding section of the sidewall portion of the body is about 400 micrometer to about 200 micrometer bigger than outside the protruding section.

11. The sample holder according to claim 1, comprising a cap adapted to be arranged on the body to close the interior of the body.

12. The sample holder according to claim 11, wherein the cap is made of the thermoplastic polyimide.

13. The sample holder according to claim 11, wherein the cap has a first mating structure and the body has a second mating structure (213), wherein the first mating structure (311, 312, 313) pressure-fits the second mating structure (213) when the cap (3; 30; 39) closes the body (2; 20; 29).

14. A multi-well plate having a plurality of wells, wherein each of the plurality of wells has a bottom made of a thermoplastic polyimide, wherein the wells are shaped to receive and hold a sample holder according to claim 1.

15. A method of analyzing solid form properties of a substance, comprising solidifying the substance, obtaining the solidified substance in one of the wells of the multi-well plate according to claim 14, and analyzing the solidified substance in the well of the multi-well plate by transmission X-ray diffraction comprising providing X-ray from a top of the well through the solidified substance and a bottom of the well, and evaluating the X-ray which passed the solidified substance and the bottom of the well.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The sample holder and the process according to the invention are described in more detail herein below by way of exemplary embodiments and with reference to the attached drawings, in which:

[0040] FIG. 1 shows a top view on a body of an insert as a first embodiment of a sample holder according to the invention;

[0041] FIG. 2 shows a cross sectional view of the body of FIG. 1 along the line A-A of FIG. 1;

[0042] FIG. 3 shows a top view on a cap of the sample micro-vessel of FIG. 1;

[0043] FIG. 4 shows a cross sectional view of the cap of FIG. 3 along the line B-B of FIG. 3;

[0044] FIG. 5 shows a side and partially cross sectional view of the sample micro-vessel of FIG. 1;

[0045] FIG. 6 shows detail C of FIG. 5;

[0046] FIG. 7 shows detail D of FIG. 5;

[0047] FIG. 8 shows an exploded perspective view of an embodiment of a multi-well plate according to the invention equipped with inserts identical to the inserts of FIG. 1 to FIG. 7 in a preparing arrangement;

[0048] FIG. 9 shows an exploded side view of the multi-well plate of FIG. 8;

[0049] FIG. 10 shows a top view of the multi-well plate of FIG. 8;

[0050] FIG. 11 shows a cross sectional view of the multi-well plate of FIG. 8 along the line E-E of FIG. 10;

[0051] FIG. 12 shows detail F of FIG. 11;

[0052] FIG. 13 shows an exploded side view of the multi-well plate of FIG. 8 in an analyzing arrangement;

[0053] FIG. 14 shows a cross sectional view of the multi-well plate of FIG. 13 along the line E-E of FIG. 10;

[0054] FIG. 15 shows detail G of FIG. 14;

[0055] FIG. 16 shows a cross sectional view of the body of FIG. 1 equipped with a stopper;

[0056] FIG. 17 shows a cross sectional view of a second embodiment of a sample holder according to the invention;

[0057] FIG. 18 shows a cross sectional view of a third embodiment of a sample holder according to the invention; and

[0058] FIG. 19 shows a graphic of the background characteristics of thermoplastic polyimide compared to a conventional polyimide, i.e. poly (4,4-oxydiphenylene-pyromellitimide).

DESCRIPTION OF EMBODIMENTS

[0059] In the following description certain terms are used for reasons of convenience and are not intended to limit the invention. The terms right, left, up, down, under and above refer to directions in the figures. The terminology comprises the explicitly mentioned terms as well as their derivations and terms with a similar meaning. Also, spatially relative terms, such as beneath, below, lower, above, upper, proximal, distal, and the like, may be used to describe one element's or feature's relationship to another element or feature as illustrated in the figures. These spatially relative terms are intended to encompass different positions and orientations of the devices in use or operation in addition to the position and orientation shown in the figures. For example, if a device in the figures is turned over, elements described as below or beneath other elements or features would then be above or over the other elements or features. Thus, the exemplary term below can encompass both positions and orientations of above and below. The devices may be otherwise oriented (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein interpreted accordingly. Likewise, descriptions of movement along and around various axes includes various special device positions and orientations.

[0060] To avoid repetition in the figures and the descriptions of the various aspects and illustrative embodiments, it should be understood that many features are common to many aspects and embodiments. Omission of an aspect from a description or figure does not imply that the aspect is missing from embodiments that incorporate that aspect. Instead, the aspect may have been omitted for clarity and to avoid prolix description. In this context, the following applies to the rest of this description: If, in order to clarify the drawings, a figure contains reference signs which are not explained in the directly associated part of the description, then it is referred to previous or following description sections. Further, for reason of lucidity, if in a drawing not all features of a part are provided with reference signs it is referred to other drawings showing the same part. Like numbers in two or more figures represent the same or similar elements.

[0061] FIG. 1 shows a top view of a body 2 of an insert 1 as a first embodiment of a sample holder according to the invention. The body 2 has a right circular sidewall portion 21 and a flat circular bottom portion 22. The sidewall portion 21 has an upper cap receiving section 213 and a protruding section 212 radially extending beyond the cap receiving section 213.

[0062] In FIG. 2 the body 2 is shown in a cross sectional side view. Thereby, it can be seen that the body 2 has an interior and that the bottom portion 22 is essentially perpendicular to the sidewall portion 21. At its inner side, the sidewall portion 21 is straight. Thus, in the interior of the body 2, the bottom portion 22 and the sidewall portion 21 form an essentially right angle.

[0063] The sidewall portion 21 further has a pipe like lower section 211. The protruding section 212 of the sidewall portion 21 laterally projects over the lower section 211 and the cap receiving section 213 to an identical extent. More particular, the lower section 211 abruptly passes over into the protruding section 212 thereby forming a lower step 2122 at the bottom end of the protruding section 212. Similarly, the cap receiving section 213 abruptly passes over into the protruding section 212 thereby forming an upper step 2121 at the top end of the protruding section 212. The lower step 2122 and the upper step 2121 each have a horizontal abutting surface wherein the abutting surface of the lower step 2122 is downwardly oriented and the abutting surface of the upper step 2121 is upwardly oriented.

[0064] The entire body 2 is rotational symmetric around a longitudinal axis 24. It is completely made of a preferably amorphous thermoplastic polyimide (TPI). The protruding section 212 is embodied in the sidewall portion 21 by varying its thickness in an axial direction. For example, in the embodiment shown in FIG. 1 and FIG. 2, a thickness of the sidewall portion 21 is 1 millimeter (mm) in the protruding section 212 and 0.7 mm outside the protruding section 212, i.e., in the cap receiving section 213 and the lower section 211. Thus, the protruding section 212 laterally projects over the lower section 211 and the cap receiving section 213 by 0.3 mm.

[0065] As can be seen in FIG. 2, the bottom portion 22 is comparably thin, for example, 0.05 mm thick. At its top end the body 2 has a free opening 23 wherein in the upper part of the cap receiving section 213 the interior is slightly expanding. Thus, the inner surface of the sidewall portion 21 has an outwardly tapering part 2131 at the opening 23. For example, the height of the body 2 amounts to about 14 mm wherein the cap receiving section 213 is about 0.9 mm thereof and the protruding section is about 3 mm thereof. The inner diameter of the body 2 is, e.g., about 6.25 mm and the outer diameter is about 8.25 mm at the protruding section 213 and about 7.4 mm outside the protruding section 213.

[0066] FIG. 3 shows a top view of a cap 3 of the insert 1. The cap 3 has a sidewall portion 31 surrounding a circular window portion 32. The sidewall portion 31 has a right circular cylinder section 313 and plural gripping projections 314 outwardly extending from the cylinder section 313 at various heights. It further, includes a radial section 312 inwardly extending from the cylinder section 313.

[0067] In FIG. 4 the cap 3 is shown in a cross sectional side view. Thereby, it can be seen that the radial section 312 of the sidewall portion 31 of the cap 3 perpendicularly extends from the interior surface of its cylinder section 313. Thus, it horizontally extends. At its inner end, the radial section 312 passes over into an inwardly narrowing arrow section 311 which directly surrounds the window portion 32.

[0068] The entire cap 3 is one piece made of the TPI which is also used in the body 2. It has a vertical axis 33. The window portion 32 is comparably thin, for example, it has a thickness of about 0.05 mm. The whole cap has a height of about 2 mm, for example. An inner diameter of the cylinder section 313 of the sidewall portion 31 corresponds to the outer diameter of the cap receiving section 213 of the sidewall portion 21 of the body 2. For example, it is about 7.8 mm which is about 0.2 mm bigger than the outer diameter of the cap receiving section 213. Since the arrow section 311 at its lateral end side is higher than the radial section 312 it axially or vertically projects over the radial section 312 in an upward and downward direction. Thereby, the outer side of the arrow section 311 forms together with the top and bottom sides of the radial section 312 and the inner side of the cylinder section 313 a body recess.

[0069] FIG. 5 shows the complete insert 1 wherein the cap 3 is mounted onto the body 2. The axis 24 of the body 2 together with the axis 33 of the cap 3 form an axis 11 of the insert 1. Thereby, the cap receiving section 213 of the sidewall portion 21 of the body 2 is arranged in the body recess of the cap 3. In more detail, the top end of the cap receiving section 213 abuts the bottom side of the radial section 312 of the sidewall portion 31 of the cap 3 and the upper step 2121 of the protruding section 212 of the sidewall portion 21 of the body 2 abuts the bottom end of the cylinder section 313 of the sidewall portion 31 of the cap 3.

[0070] In FIG. 6 and FIG. 7 sections of the insert 1 are shown in more detail. Thereby, it can be seen that the vertical outer side of the arrow section 311 of the cap 3 abuts the tapering part 2131 of the inner surface of the sidewall portion 21. When the cap 3 and the body 2 are pressed together, the arrow section 311 slides along the inclined surface of the tapering part 2131 such that the cap 3 or a specific section thereof is slightly deformed. Like this, the cap 3 can tightly close the body 2.

[0071] FIG. 8 and FIG. 9 show an embodiment of a multi-well plate 4 according to the invention. The multi-well plate 4 comprises a cover plate 41, a main plate 43 and, in the preparing arrangement of the multi-well plate shown in FIGS. 8-12, a solid plate 44. The main plate 43 is equipped with a label 432 mounted to a cross side. The solid plate 44 is screwed bottom up to the main plate 43 by means of screws 422. Then the cover plate 41 is screwed top down to the main plate 43 by means of screws 421.

[0072] As can be best seen in FIG. 10, the multi-well plate 4 has ninety-six wells 46 formed by bores in the cover plate 41 and bores in the main plate 43. The wells 46 are arranged in eight rows each having twelve wells 46. Turning back to FIG. 8 and FIG. 9, each well 46 has one insert 1 wherein the bottom portion 22 of the body 2 of the insert 1 forms the bottom of the well 46. Thus, the bottoms 22 of the wells 46 are made of the preferably amorphous thermoplastic polyimide. Each of the bodies 2 is provided with one cap 3 of the insert 1 wherein the caps 3 are grouped to handling units having two rows each with eight caps 3 connected together.

[0073] As can be seen in FIG. 11 and FIG. 12 in more detail each of the bores in the main plate 43 is shaped to receive and hold one of the inserts 1. In the main plate 43 the wells 46 have dimensions fitting to the inserts 1. Particularly, the inner surfaces of the wells 46 are adapted to mate to the outer surfaces of the inserts 1. In more detail, the wells 46 in the main plate 43 have widened upper ends to receive the protruding sections 212 of the bodies 2 of the inserts 1. Thereby, the widened upper ends have horizontal contact surfaces which abut the lower surfaces 2121 of the protruding sections 212.

[0074] In the cover plate 41 the bores forming the wells 46 are downwardly tapering. In particular, in the cover plate 41 the wells 46 have inclined inner side surfaces 411 which form a conus angle of about 30. Such conical shape gives space to X-ray irradiation. Furthermore, the cover plate 41 presses the caps 3 on the bodies 2 such that the inserts 1 are tightly closed.

[0075] In contrast to FIGS. 8-12, in which the multi-well plate is shown in a preparing arrangement, FIGS. 13-15 show the multi-well plate 4 in an analyzing arrangement. In particular, instead of the solid plate 43 an aperture plate 45 is screwed bottom up to the main plate 43 by means of the screws 422. The aperture plate 45 comprises a plurality of conical bores 451 which are downwardly widening. The bores 451 are arranged at the aperture plate 45 such that each well 46 is equipped with one of the bores 451.

[0076] The multi-well plate 4 can specifically be used for analyzing solid form or crystallization properties of substances in an embodiment of a method according to the invention. Thereby, for preparing the substances powders, solvents and reagents are provided into the bodies 2 of the inserts 1 which are positioned in the wells 46 of the multi-well plate 4 in its preparing arrangement. More particularly, the solid plate 44 is screwed bottom up to the main plate 43 and the bodies 2 of the inserts 1 are positioned top down into the wells 46. Then, the powders and solvents are provided into the bodies 2 and the caps 3 are placed onto the bodies 2. Finally, the cover plate 41 is screwed top down to the main plate 43 such that the caps 3 are pressed onto the bodies 2 and, thereby, the inserts 1 are tightly closed.

[0077] Inside the inserts the powder and the solvent are mixed and prepared such that the substances result in a solid form. For example, the substances can be crystallized inside the inserts 1. Such preparing may include equilibration for example by the help of a stirrer, cooling, anti-solvent addition, lyophilizing, reactive crystallization, precipitation or evaporation.

[0078] After solidification or preparation, the solid plate 44 is replaced by the aperture plate 45 resulting in the multi-well plate 4 being in its analyzing arrangement. Then, the moist solidified substances are analyzed by transmission X-ray diffraction. In particular, an X-ray beam is provided from an appropriate source above the cover plate 41 into the wells 46 and inserts 1 through the solidified substances and the bottoms 22 and out of the bores 451 of the aperture plate 45. For allowing to completely illuminate the whole wells 46 by the X-ray beam having a line focus, the multi-well plate 4 is rotated (+/approx. 180). To further reduce statistical effects on the intensity distribution the wells 46 are tilted to a max. of 15 during the measurement. As mentioned above, the inclined surfaces 411 of the bores of the cover plate 41 allow for preventing to shade the wells 46.

[0079] Below the multi-well plate 4 a detector is arranged which detects the X-ray passing the bottoms 22 of the wells 46. The detected X-ray is then evaluated and conclusions about the solid form properties of the solidified substances are drawn. Additionally, the moist crystallized substances inside the inserts 1 are microscopically measured for gathering further information.

[0080] Then, the system is prepared for a drying step which includes removing the caps 3 from the bodies 2 for allowing evaporation. The crystallized substances are dried and the caps 3 are mounted to the bodies again. Thereafter, the dried solid substances are analyzed by transmission X-ray diffraction and microscopic inspection again.

[0081] After analyzing the substances, the inserts 1 can be rearranged in accordance with the results of the analysis. As shown in FIG. 16 the inserts 1 are then tightly closed. In particular, the caps 3 are removed from the bodies 2 and, instead, elastic stoppers 5 are pressed top in the bodies 2. Like this, the inserts 1 are tightly closed. Then, the inserts 1 are positioned in a storage multi-well plate where they can be stored.

[0082] FIG. 17 shows a cross-sectional view of a sample carrier 10 as a second embodiment of a sample holder according to the invention. The sample carrier 10 has a body 20 and a cap 30. The body 20 comprises an L-shaped sidewall portion 210 and a circular bottom portion 220. The bottom portion 220 is positioned on a horizontal section of the sidewall portion 210. It is made of a preferably amorphous TPI.

[0083] The cap 30 of the sample carrier 10 has a sidewall portion 310 surrounding a circular window portion 320. The window portion 320 is made of the preferably amorphous TPI. The sidewall portion 310 is hook-shaped wherein a vertical section of the sidewall portion 210 of the body 20 is received in the hook. Between the horizontal section of the sidewall portion 210 of the body 20 and a central section of the sidewall portion 310 of the cap 30 a ring shaped spacing screen 40 is arranged. A through hole of the spacing screen 40 is limited by the bottom portion 220 of the body 20 and the window portion 320 of the cap 30 such that an interior 60 is formed in between.

[0084] Between the sidewall portion 210 of the body 20, the sidewall portion 310 of the cap 30 and the spacing screen 40 an O-ring 50 is clamped which seals the interior 60 of the sample carrier 10.

[0085] In FIG. 18 another sample carrier 19 as a third embodiment of a sample holder according to the invention is shown. The sample carrier 19 has a body 29 and a cap 39. The body 29 comprises a partially L-shaped sidewall portion 219 and a circular bottom portion 229. The sidewall portion 219 and the bottom portion 229 are one piece made of a preferably amorphous TPI.

[0086] The cap 39 of the sample carrier 19 has a sidewall portion 319 surrounding a circular window portion 329. The sidewall portion 319 and the window portion 329 are one piece made of the preferably amorphous TPI. The sidewall portion 319 is partially hook-shaped wherein a vertical section of the sidewall portion 219 of the body 29 is received in the hook. Between a horizontal section of the sidewall portion 219 of the body 29 and a central arm section of the sidewall portion 319 of the cap 39 a flat sealing ring 49 is arranged. Between the bottom portion 229 of the body 29, the window portion 329 of the cap 39 and the sealing ring 49 an interior 59 of the sample carrier 19 is formed. FIG. 19 shows graphs of measurement results of the background characteristics of thermoplastic polyimide (TPI) and of poly (4,4-oxydiphenylene-pyromellitimide) which is known in the art under the trademark Kapton. More particularly, in the example shown in FIG. 19 background properties of a 0.13 mm thick foil made of TPI are compared to background properties of a 0.125 mm thick foil made of Kapton. Thereby, the TPI graph 91 and a Kapton graph 92 result each showing the measurement results of the respective foil.

[0087] As can be derived from FIG. 19 the TPI foil is X-ray amorphous and shows no characteristic peaks as Kapton foil does. Due to the absence of such broad peaks in comparison to Kapton foil, the TPI foil is essentially better suitable for analytical applications. In addition, it consists of the same low X-ray background properties comparable to Kapton foil and also provides the same good stability properties for preparation/protection purposes for analytical testing.

[0088] This description and the accompanying drawings that illustrate aspects and embodiments of the present invention should not be taken as limitingthe claims defining the protected invention. In other words, while the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. Various mechanical, compositional, structural, electrical, and operational changes may be made without departing from the spirit and scope of this description and the claims. In some instances, well-known circuits, structures and techniques have not been shown in detail in order not to obscure the invention. Thus, it will be understood that changes and modifications may be made by those of ordinary skill within the scope and spirit of the following claims. In particular, the present invention covers further embodiments with any combination of features from different embodiments described above and below.

[0089] The disclosure also covers all further features shown in the Figs. individually although they may not have been described in the afore or following description. Also, single alternatives of the embodiments described in the figures and the description and single alternatives of features thereof can be disclaimed from the subject matter of the invention or from disclosed subject matter. The disclosure comprises subject matter consisting of the features defined in the claims or the exemplary embodiments as well as subject matter comprising said features.

[0090] Furthermore, in the claims the word comprising does not exclude other elements or steps, and the indefinite article a or an does not exclude a plurality. A single unit or step may fulfil the functions of several features recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. The terms essentially, about, approximately and the like in connection with an attribute or a value particularly also define exactly the attribute or exactly the value, respectively. The term about in the context of a given numerate value or range refers to a value or range that is, e.g., within 20%, within 10%, within 5%, or within 2% of the given value or range. Components described as coupled or connected may be electrically or mechanically directly coupled, or they may be indirectly coupled via one or more intermediate components. Any reference signs in the claims should not be construed as limiting the scope.