DEVICES AND METHODS FOR MEASURING VISCOELASTIC CHANGES OF A SAMPLE
20230251175 · 2023-08-10
Inventors
Cpc classification
G01N2011/002
PHYSICS
G01N33/86
PHYSICS
G01N11/162
PHYSICS
International classification
C12Q1/56
CHEMISTRY; METALLURGY
Abstract
The present invention provides an apparatus for use in viscoelastic analysis, for example in coagulation testing of sample liquids, such as blood and/or its elements. In the apparatus for use in viscoelastic analysis, the rotating means are provided below the cup, pin and cup receiving element. The present invention further provides capacitive detection means and temperature control devices, which may be used in the apparatus for use in viscoelastic analysis. The present invention further provides a method of performing viscoelastic analysis, e.g. coagulation analysis, on a sample using the devices and apparatuses.
Claims
1. A capacitive detection means for detecting variations in a rotation around a vertical axis caused by blood coagulation, comprising: a rotatable capacitor element capable of rotating around the vertical axis; at least one fixed capacitor element; and an electrical circuit, which is preferably connected to the at least one fixed capacitor element; wherein each of the capacitor elements comprises at least one electrically conductive element, which does not have a circular shape with the vertical axis as a center, and wherein the rotatable capacitor element and the at least one fixed capacitor element are arranged such that the at least one electrically conductive element of the rotatable capacitor element faces the at least one electrically conductive element of the at least one fixed capacitor element; wherein the electrical circuit is capable of detecting a rotation of the rotatable capacitor element around the vertical axis of at least +/−2° with an accuracy of at least 0.2° in a time frame of at most 5 seconds.
2. The capacitive detection means according to claim 1, wherein at least one of the capacitor elements comprises an electrically non-conductive support, which preferably extends essentially perpendicularly to the vertical axis and wherein the at least one electrically conductive element of said at least one of the capacitor elements is disposed on the support.
3. The capacitive detection means according to claim 1, wherein the at least one fixed capacitor element is arranged essentially in parallel to the rotatable capacitor element.
4. The capacitive detection means according to claim 1, wherein rotatable capacitor element has essentially a plate-like, disk-like or cylindrical shape.
5. The capacitive detection means according to claim 1, wherein the at least one fixed capacitor element comprises a sine oscillator electrode (S), a cosine oscillator electrode (C), and a pickup electrode (P).
6. The capacitive detection means according to claim 5, wherein the at least one fixed capacitor element comprises at least three sine oscillator electrodes (S), at least three cosine oscillator electrodes (C), and at least three pickup electrodes (P).
7. The capacitive detection means according to claim 1, further comprising at least one ground electrode (G) located on the at least one fixed capacitor element (i) between a sine oscillator electrode (S) and a pickup electrode (P); or (ii) between a cosine oscillator electrode (C) and a pickup electrode (P).
8. The capacitive detection means according to claim 1, wherein the rotatable capacitor element can be attached to a shaft of an apparatus for measuring the coagulation characteristics of a sample, which shaft is rotatable around the vertical axis, such that a rotation of the shaft causes a rotation of the rotatable capacitor element and/or vice versa.
9. A capacitive detection means for detecting variations in a rotation around a vertical axis caused by blood coagulation, comprising: a rotatable dielectric element, which is capable of rotating around the vertical axis and which does not have a circular shape with the vertical axis as center; two fixed capacitor elements; and an electrical circuit, preferably connected to a fixed capacitor element; wherein each of the two fixed capacitor elements comprises at least one electrically conductive element; the two fixed capacitor elements are arranged such that the electrically conductive elements of the capacitor elements face each other; and the dielectric element is at least partially placed between the two fixed capacitor elements; wherein the electrical circuit is capable of detecting a rotation of the rotatable dielectric element around the vertical axis of at least +/−2° with an accuracy of at least 0.2° in a time frame of at most 5 seconds.
10. The capacitive detection means according to claim 9, wherein the capacitor elements comprise an electrically non-conductive support, which preferably extends essentially perpendicularly to the vertical axis and at least one electrically conductive element disposed on the support.
11. The capacitive detection means according to claim 9, wherein the two fixed capacitor elements are arranged in an essentially parallel manner to each other and to the rotatable dielectric element.
12. The capacitive detection means according to claim 9, wherein the capacitor elements have essentially a plate-like or disk-like shape.
13. The capacitive detection means according to claim 9, wherein the capacitor elements comprise at least one sine oscillator electrode (S), at least one cosine oscillator electrode (C), and/or at least one pickup electrode (P).
14. The capacitive detection means according to claim 13, wherein the upper capacitor element comprises a pickup electrode (P) and the lower capacitor element comprises a sine oscillator electrode (S), and a cosine oscillator electrode (C).
15. The capacitive detection means according to claim 14, wherein the upper capacitor element comprises at least three pickup electrodes (P) and the lower capacitor element comprises at least three sine oscillator electrodes (S), and at least three cosine oscillator electrodes (C).
16. The capacitive detection means according to claim 13, wherein the upper capacitor element comprises a sine oscillator electrode (S) and a cosine oscillator electrode (C) and the lower capacitor element comprises a pickup electrode (P).
17. The capacitive detection means according to claim 16, wherein the upper capacitor element comprises at least three sine oscillator electrodes (S) and at least three cosine oscillator electrodes (C) and the lower capacitor element comprises at least three pickup electrodes (P).
18. The capacitive detection means according to claim 9, wherein the rotatable dielectric element can be attached to a shaft of an apparatus for measuring the coagulation characteristics of a sample, which shaft is rotatable around the vertical axis, such that a rotation of the shaft causes a rotation of the rotatable dielectric element and/or vice versa.
19. The capacitive detection means according to claim 9, wherein the dielectric element has essentially a disk-like or plate-like shape.
20. An apparatus for measuring the coagulation characteristics of a sample comprising the capacitive detection means according to claim 9.
21. A temperature control device for controlling the temperature of a cup and/or of a cup receiving element while measuring the coagulation characteristics of a sample in a thromboelastic measurement apparatus, comprising: a heater comprising an electromagnetic radiation emitting element emitting radiation with an emission maximum in the wavelength range from 300 to 3,000 nm; a temperature sensing element for contactless measurement of thermal radiation in the wavelength range from more than 3,000 nm to 30,000 nm; and optionally, controlling means for activating or deactivating the heater depending on the temperature measured by the temperature sensing element, which has preferably an accuracy of at least +/−3° C.
22. The temperature controlling device according to claim 21, wherein the electromagnetic radiation emitting element is a diode.
23. The temperature controlling device according to claim 22, wherein the diode is an LED or a near-IR diode.
24. The temperature controlling device according to claim 21, wherein the temperature sensing element is a pyro-electric detector, a photoresistor, or a photodiode.
25. The temperature controlling device according to claim 21, wherein the controlling means comprise a feedback loop for the heater current, voltage, or pulse width.
26. An apparatus for measuring the coagulation characteristics of a sample comprising the temperature control device according to claim 21.
27. The apparatus according to claim 26, further comprising a capacitive detection means for detecting variations in a rotation around a vertical axis caused by blood coagulation, the capacitive detection means comprising: a rotatable capacitor element capable of rotating around the vertical axis; at least one fixed capacitor element; and an electrical circuit, which is preferably connected to the at least one fixed capacitor element; wherein each of the capacitor elements comprises at least one electrically conductive element, which does not have a circular shape with the vertical axis as a center, and wherein the rotatable capacitor element and the at least one fixed capacitor element are arranged such that the at least one electrically conductive element of the rotatable capacitor element faces the at least one electrically conductive element of the at least one fixed capacitor element; wherein the electrical circuit is capable of detecting a rotation of the rotatable capacitor element around the vertical axis of at least +/−2° with an accuracy of at least 0.2° in a time frame of at most 5 seconds.
Description
BRIEF DESCRIPTION OF THE FIGURES
[0227] In the following a brief description of the appended figures will be given. The figures are intended to illustrate the present invention in more detail. However, they are not intended to limit the subject matter of the invention in any way.
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EXEMPLARY EMBODIMENTS
[0239] In the following, the present invention is illustrated in various exemplary embodiments. However, the present invention shall not to be limited in scope by the specific embodiments described in the following. The exemplary embodiments are given to enable those skilled in the art to more clearly understand and to practice the present invention. The present invention, however, is not limited in scope by the exemplary embodiments, which are intended as illustrations of selected aspects of the invention only, and methods which are functionally equivalent are within the scope of the invention. Indeed, various modifications of the invention in addition to those described herein will become readily apparent to those skilled in the art from the foregoing description, accompanying figures and the exemplary embodiments below. All such modifications fall within the scope of the appended claims.
[0240]
[0241] In the first preferred exemplary embodiment shown in
[0242] According to the first preferred exemplary embodiment shown in
[0243] During coagulation testing the blood sample typically forms a blood clot. After formation of the clot between cup (202) (e.g., a cuvette) and pin (203), the clot itself is stretched by the movement of the cup (202) relative to the pin (203). The detection of the characteristic parameters of the clot is based on the mechanical coupling of cup (202) and pin (203) by the clot. During a viscoelastic measurement, the pin (203) is fixed and the cup (202) rotates gently and slowly around the axis (212) by means of the elastic coupling element (208) and the cup receiving element (210). The movement of the cup (202) can be measured by various methods, for example by means of capacitive detection means (211), such as capacitor plates. In operation, the pin (203) is stationary and the rotatable shaft (206) and cup (202) placed in the cup receiver (210) are rotated back and forth by the elastic element (208, e.g. a spring wire), for example in an angular range of about ±5°. The rotation is transmitted by the coupling of the shaft (206) to the cup receiving element (210). When the blood clot forms an increasing torque acts against the oscillating movement of the cup (202), such that the cup/cup receiving element is oscillating in a decreased angular range of <±5°. This decrease in angular (oscillating) movement can be detected by suitable detection means (211) disposed below the pin (203) and cup (202)/cup receiving element (210).
[0244] This first preferred exemplary embodiment shown in
[0245] Another advantage of the first preferred exemplary embodiment shown in
[0246] In contrast to the existing measurement technologies, in the preferred embodiment shown in
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[0248] Thus, in contrast to the prior art apparatus shown in
[0249] In addition, the placement of the rotation means, such as the bearing (307) and/or the spring (308) below the cup/cup receiving element enables new movement detection means due to the resulting available space at the lower end of the shaft (306), similarly to the embodiment in
[0250] In summary, also the second embodiment of the present invention as depicted in
[0251]
[0252] Preferably, the rotatable capacitor element (411a) is attached to the lower end of the shaft (406), such that shaft (406) is essentially perpendicular to the rotatable capacitor element (411a). The rotatable capacitor element (411a) has electrically conductive elements (shaded areas in the capacitor element (411a) shown in
[0253] In parallel to the rotatable capacitor element (411a) another capacitor element (411b) is provided. In general, a capacitor element refers in particular to one or more conductive elements arranged on a support. Said capacitor element (411b) can also be obtained by, for example, etching PCB material or by applying metal to a support material, such as ceramics. Said capacitor element (411b) is fixed, while the rotatable capacitor element (411a) follows the rotating movement of shaft (406). In other words, rotatable capacitor element (411a) typically rotates with the rotating shaft. Said fixed capacitor element (411b) is electrically connected to a circuitry, while the conductive elements on rotatable capacitor element (411a) are electrically insulated from all other parts and from each other. The movement of the shaft (406) can thus be detected by the relative movement of the capacitor element (411a) (which rotates with shaft (406)) in respect to the fixed capacitor element (411b).
[0254] The fixed capacitor element (411b) may for example comprise three kinds of electrodes: Sine oscillator (S), Cosine oscillator (C), and Pickup electrode (P). The electrodes S and C can then be connected to a rectangular oscillating voltage with a 90°-phase shift between S and C. Other phase shifts and/or a frequency shift between the two signals are also possible. Depending on the angular position of shaft (406) and the corresponding exact position of the conductive element on the connected disk, the capacitance C.sub.SP from electrode S to electrode P and the capacitance C.sub.CP from electrode C to electrode P is changed in opposite directions. Accordingly, the actual angle of the rotatable conductive element can be calculated from the difference of C.sub.SP and C.sub.CP after scaling to the sum of C.sub.SP and C.sub.CP. This scaling provides high insensitivity to external mechanical distortions like distance changes, vibrations, tilting of the axis, and the like.
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[0256] Said charge fluctuations on electrode P can be amplified by a charge amplifier (15) and detected synchronously to the initial alternating voltages at electrodes S and C in a synchronized detector (16). In this way, two voltages U.sub.S and U.sub.C are generated and subsequently send through separated low-pass filters to reduce noise. Both resulting voltage signals, X and Y, allow calculation of a signal proportional to the angular displacement D of the capacitor element (11a) by D=(X−Y)/X+Y). To provide this signal as recordable data stream, the initial signals X and Y could be also digitized in an ADC (analog/digital converter) and then further processed digitally.
[0257] Other configurations in the fixed array of conductive electrodes are also conceivable without changing the general measurement principle. For example, one sine oscillator electrode (S) could be combined with two pickup electrodes (P1 and P2) at each side of S, separated again by ground electrodes to prevent directly induced charge fluctuations without the loop way via the rotatable conductive elements. In this case, the angular movement of said conductive elements would result in charge increase at one of the two pickup electrodes and in charge decrease at the other pickup electrode.
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[0259] In summary, there is a high variability in number, arrangement and symmetry of employed electrodes. As a general principle, the precision and insensitivity against external distortions is improved by increasing the electrode number for each type S, C, and P from 1 to at least 3.
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[0263] A heating (719), in particular a radiation element, which emits electromagnetic radiation in the wavelength range below 3 μm (3000 nm), more preferably below 1 μm (1000 nm), is placed in close vicinity (preferably not more than 75 mm distance) of the shaft (706) and/or the cup-receiving element (710). Such a radiation element (719) may be, for example, a light emitting diode (preferably having a wavelength range 450-780 nm), a near-IR diode (preferably having a wavelength range 780-1500 nm), or a UV diode (preferably having a wavelength range 300-450 nm). A portion of the emitted energy (indicated by the dotted arrow in
[0264] The upper cut-off of the spectral range of emitted radiation (wavelength of 3 μm, preferably 1 μm) is important, because the emitted radiation should not interfere with the spectral range of thermal radiation according to Planck's law. This law describes that thermal radiation is emitted only in the range above 3 μm for an (ideally black) body at a temperature between 30 and 40°. The thermal radiation (as indicated by the dotted arrow in
[0265] For example, a near-IR diode with emission maximum around 850 nm (2 W total power, OSRAM SSH4715AS) was used as a heating (719) and a pyro-electric detector with spectral sensitivity between 5.5 and 14 um (MELEXIS MLX 90615) was used as temperature sensor (719). Shaft (706) and cup receiving element (710) were blackened by conventional blackboard color to increase absorption of thermal radiation. Non-movable surrounding metal parts were heated to 37° C. by 2 conventional thermo-resistors (5 W power in total) and controlled to maintain this value by a conventional thermo-regulation consisting of said thermo-resistors and a thermocouple as sensor. The IR diode enabled additional heating of the cup receiving element and the cup from 35.5° C. (as achieved by thermal radiation from the surrounding non-movable parts) to 37° C. (as required to perform a thromboelastometric measurement at typical body temperature) within less than 30 seconds. An alternative radiation source, a light emitting diode with emission maximum at 660 nm (CREE, Xlamp XP, XPEPHR-L 1-0000-00901) and an average output power of 0.35 W, was also able to heat the cup receiving element (710) and cup (702) from 35.5° C. to 37° C. with less than 30 seconds. The maximum achievable temperature difference between surrounding metal parts and cup was about 16° C. for the diode emitting at 850 nm maximum and about 12° C. for the diode emitting at 660 nm maximum.