JP2005300540A - Calibration auxiliary means - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an ICG standard that is stable for a long time, does not require any special preparation before use, and can be used easily, and to provide a method for manufacturing the standard. <P>SOLUTION: A calibration auxiliary means is assembled in the following manner. First, a reference standard substance 6 is prepared by dissolving an ICG coloring matter and albumin protein into water. Then, a carrier sheet 1 made of a fleece material is dipped into water and then is dried. After the carrier sheet 1 is dried, a thin layer made of a coloring matter combined with protein and is adjusted precisely is formed on the surface of the fleece material. The carrier sheet 1 and a packing sheet 2 are piled up and are inserted into a plastic card. In this case, plastic layers 4a, 4b can be piled up so that they can be adhered by a frame region 5, for example, by welding or by using an adhesive. Then, the plastic card is sterilized, and is packaged by a sealed package. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a calibration aid for fluorescence measurement.

  An important area in application to fluorescence measurements is that of quantifying non-invasive tissue perfusion in patients. A non-invasive tissue perfusion imaging and quantification system is described in US Pat. The patient injects indocyanine green (ICG, a fluorescent dye exhibiting maximum absorption in the near infrared region) into the patient, and irradiates the target tissue using an irradiation source that emits irradiation light in the near infrared region. Monitored by a digital camera. From the fluorescence signal of the tissue of interest (that is, light emitted from a fluorescent dye contained in blood flowing through the tissue), the perfusion state of the tissue is determined using an appropriate algorithm as disclosed in Patent Document 1. be able to. Furthermore, Patent Document 2 discloses an apparatus that uses ICG measurement for determining tissue perfusion during surgery.

  Advantageously, an external fluorescent standard is used during the measurement. This reference material is placed beside the tissue of interest, and emits a predetermined constant fluorescence signal when the material is irradiated, and this fluorescence signal is recorded together with the fluorescence signal of the tissue of interest.

By using a fluorescent standard, various measurements can be directly compared and the measurement results can be normalized based on a predetermined signal intensity of the fluorescent standard. The use of fluorescent standards can further correct for changes in measurement conditions during measurement (changes in ambient light intensity, changes in camera exposure parameters, changes in irradiation parameters, etc.).
European Patent Application No. 1210906A2 German Patent No. 10,059,070C1

  To make the criteria as described above, the dried pure ICG dye is usually dissolved in water or methanol prior to use. Using this liquid sample, in vitro fluorescence measurement can be performed as described above. However, this measurement takes a long time. Since ICG is not stable when exposed to atmospheric moisture and light, it is necessary to prepare a standard product immediately before use, which is a major disadvantage when used in emergency surgery. Further, the absorption and fluorescence properties of such a lysed pure standard sample are not equal to the properties of the protein-bound dye after injection into the patient, eg, the maximum absorption wavelength is shifted from 780 nm to 805 nm.

  Since pure ICG powder exhibits different absorption and fluorescence properties than dissolved ICG, dried pure ICG dye cannot be used as a standard as described above. Furthermore, the properties of dried ICG vary with ambient humidity.

  Accordingly, an object of the present invention is to provide an ICG standard product that is stable for a long time and does not require special preparation before use, and is easy to use. Furthermore, an object of the present invention is to provide a method for producing such a standard product.

  According to one aspect of the present invention, the object of the present invention can be realized by a calibration auxiliary means as defined in claim 1, which can be used as an external standard as described above. . Preferred embodiments of the calibration aid can be configured as defined in any one of claims 2-14. According to a particularly convenient embodiment of the present invention, the calibration aid is sealed with packaging material, and thus sealed so that the calibration aid is made sterile before it is actually used as a disposable means. keep. Such a calibration kit as further defined in claim 15 can be stored for a long period of time without exposing the patient to the risk of infection.

  Each of the calibration aids or calibration kits of the type described herein can be used with a commercially available angiographic system, such as Applicant's IC-VIEW® system, or a similar system, respectively. . In accordance with the present invention, calibration aids such as those described herein can also be used as fluorescent or absorption standards used in other methods using injectable display dyes.

  According to the invention, a calibration aid of the type described above can be produced using the method defined in claim 16. A preferred embodiment of the method may be configured as defined in any one of claims 17-23.

  In most embodiments, the porous support structure is flat and preferably made from a fibrous sheet material (woven or non-woven), the porous support structure being a sponge-like material, bulk zeolite, various types of Sintered materials or other porous materials can be included. In general, a carrier structure having a large surface area per unit volume, preferably 40,000 [1 / m], more preferably 200,000 [1 / m], ie a specific surface area, is relevant to the present invention. And the carrier structure material preferably has a porosity of more than 80%.

  In the following description, the present invention will be described by way of non-limiting examples with reference to the accompanying schematic drawings. Note that the scale of the attached drawings is not based on the actual size.

  The calibration assisting means shown in FIGS. 1 to 3 are configured as easy-to-handle card-like objects, fleece carrier sheet 1, backing sheet 2 made of white paper with display 3 printed thereon, and 2 stacked exactly in frame area 5. Two transparent plastic layers 4a and 4b are provided. Preferably, the calibration aid is provided as a disposable sterile product and is housed in a foam bag covered with Tyvek® or other packaging material that has the function of preventing contamination of the outer surface of the calibration aid. Packaged as a single device.

  The carrier sheet 1 made of fleece can be composed of polyvinyl alcohol fibers cross-linked with a chemical substance. This type of fleece product is commercially available, for example from Freudenberg Hauhaltprodukte KG. The carrier sheet 1 is packed with a standard reference material 6 containing albumin protein and an ICG fluorescent dye.

The backing sheet 2 made of white paper extends beyond the fleece carrier sheet 1. Among these, commercially available paper of 80 g / m ² is a material suitable for the backing sheet 2. However, the backing sheet 2 can also be made of a plastic material. Preferably, the backing sheet 2 exhibits a certain degree of transparency to electromagnetic radiation in a certain spectral range, and the irradiation in this spectral range excites the reference standard material 6 to emit fluorescence, and this fluorescence Light is emitted. Therefore, the calibration assisting means can be used as a standard of high irradiation intensity when viewed from the front and as a standard of low irradiation intensity when viewed from the back. When the plastic card is turned over, the light irradiation intensity is attenuated by the backing sheet 2, so that the second reference irradiation intensity level can be provided.

  The display 3 can include handling instructions and other identification means. Therefore, the standard product used can be easily recorded by a camera that is also used for fluorescence measurement.

  PVC films such as those available from Klockner Pentaplast (eg Pentafood LM 176) are suitable materials for the transparent plastic layers 4a, 4b, but other Materials can also be used. In this way, the reference standard substance 6 is shielded from moisture, so that it is stable for a long period of time. Since the dye of the reference standard substance 6 binds to the protein, the light characteristics are the same as those of the dye when introduced into the patient.

  The calibration auxiliary means can be assembled as follows.

  First, a standard reference material 6 is prepared by dissolving ICG dye and albumin protein in water. Next, the carrier sheet 1 is immersed in water and dried. After the carrier sheet 1 is dried, a thin layer made of a dye combined with protein and adjusted with high accuracy is formed on the surface of the fleece material. The carrier sheet 1 and the backing sheet 2 are stacked and inserted into the plastic card. In this case, the plastic layers 4a, 4b can be closely stacked, for example, by welding or using an adhesive so that the plastic layers 4a, 4b are in close contact with each other in the frame region 5.

  The plastic card is then sterilized and packaged in a sealed package.

  The calibration aid is sterilized and can be used during surgery. However, the calibration auxiliary means should not be placed on the tissue itself in order to prevent the phenomenon that the fluorescence signal emitted from the tissue interferes with the fluorescence signal emitted from the reference standard 6. Usually, the calibration assistance means needs to be placed close to the tissue of interest (for example, on an operating table close to the patient). Opaque material that does not transmit near-infrared light first (eg, opaque sterile drape or abdominal pad) when the calibration aid cannot be placed near the patient because the reference material standards are far from the tissue of interest And then a calibration aid must be placed on this opaque material.

  The calibration aid is configured so that it can be used alone during the fluorescence measurement (usually during a measurement of about 8 minutes) and needs to be discarded after the measurement.

It is a top view of the front of the calibration assistance means by this invention. It is a top view of the back surface of the calibration assistance means of FIG. FIG. 3 is a cross-sectional view of the calibration assisting means of FIGS. 1 and 2 perpendicular to the drawing plane of FIGS. 1 and 2 along the broken line A-A ′ of FIGS. The individual layer thicknesses are enlarged at a large magnification for clarity.

Explanation of symbols

1 Carrier sheet 2 Backing sheet 3 Display 4a, 4b Plastic layer 5 Area frame

Claims (23)

A porous carrier structure (1) having a front and a back surface, and a dried reference standard material (6) that adheres to at least part of the surface of the carrier structure and contains a fluorescent dye.
A calibration auxiliary means for measuring fluorescence.   The calibration auxiliary means according to claim 1, wherein the fluorescent dye contains indocyanine green.   The calibration auxiliary means according to claim 1 or 2, wherein the reference standard (6) further contains albumin protein.   4. Calibration assistance means according to any one of the preceding claims, wherein the porous carrier structure (1) is a fibrous carrier sheet.   Calibration aid means according to claim 4, wherein the fibrous carrier sheet (1) comprises a fleece material.   The calibration assisting means according to claim 4 or 5, wherein the fibrous carrier sheet contains polyvinyl alcohol fibers.   The calibration assistance means according to any one of the preceding claims, further comprising a backing sheet (2) that at least partially covers the back surface of the carrier structure (1).   The calibration assistance means according to claim 7, wherein the backing sheet (2) is arranged such that the backing sheet extends beyond the carrier structure in at least one direction.   9. Calibration assisting means according to claim 7 or 8, wherein the backing sheet (2) comprises a display (3) printed on the backing sheet.   10. Calibration assistance means according to any one of claims 7 to 9, wherein the backing sheet (2) comprises a paper material.   Furthermore, it comprises at least one transparent plastic layer (4a, 4b) configured to function as a moisture barrier for protecting the carrier structure so that the carrier structure (1) is not exposed to moisture. The calibration auxiliary means according to any one of claims 1 to 10.   12. Calibration aid according to claim 11, wherein the plastic layer (4a, 4b) comprises a PVC film material.   13. Auxiliary calibration means according to any one of the preceding claims, wherein the front surface of the carrier structure (1) extends over an area of 100 to 5000 square millimeters.   14. Calibration assistance means according to any one of the preceding claims, wherein the entire outer surface of the calibration assistance means is sterilized.   A calibration kit comprising the calibration assistance means of claim 14 and packaging material sealing said calibration assistance means and configured to maintain the outer surface of said calibration assistance means in a sterile condition. A method of manufacturing a calibration aid for fluorescence measurement comprising:
Providing a porous support structure (1) having a front and a back surface;
-Preparing a solution by dissolving the fluorescent dye in a hydrophilic solvent;
Immersing the carrier structure (1) in the solution; and-drying the carrier structure (1) to remove the hydrophilic solvent from the carrier structure (1).   17. The method of claim 16, further comprising dissolving albumin protein in the hydrophilic solvent before immersing the carrier structure (1) in the solution.   The method of claim 16 or 17, wherein the hydrophilic solvent comprises water.   19. A method according to any one of claims 16 to 18, further comprising the step of at least partially covering the back surface of the carrier structure (1) with a backing sheet.   20. The method of claim 19, wherein the back surface of the carrier structure (1) is covered by the backing sheet (2) such that the backing sheet (2) extends in at least one direction beyond the carrier structure (1). .   The method further comprises the step of printing an indication (3) on the backing sheet (2) before the step of at least partially covering the back surface of the carrier structure (1) with the backing sheet (2). Item 19. The method according to Item 19 or 20.   22. The method according to any one of claims 16 to 21, further comprising the step of stacking the carrier structure (1) and at least two layers (4a, 4b) of transparent plastic material to form a card-like object. the method of.   23. A method according to any one of claims 16 to 22, further comprising the step of sterilizing the outer surface of the calibration aid.

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