JP6283327B2 - Measuring method, measuring apparatus and program - Google Patents

Description

  The present invention relates to a measuring method, a measuring apparatus, and a program for measuring a volume of an aqueous solution of a medicine filled in a needle-like recess of a mold forming a microneedle.

  In recent years, as a new dosage form capable of administering drugs such as insulin, vaccine (Vaccines), and hGH (human growth hormone) into the skin without pain, a micro-needle array (hereinafter referred to as MNA) Abbreviated). MNA includes drugs and biodegradable microneedles (also called microneedles or microneedles) arranged in an array. By affixing this MNA to the skin, each microneedle pierces the skin, the microneedle is absorbed in the skin, and a drug contained in each microneedle can be administered into the skin.

  As a manufacturing method of such MNA, MNA is filled with a drug aqueous solution containing a drug or the like in each needle-shaped recess of a mold (mold) having a large number of needle-shaped recesses, which is an inverted type of MNA, and dried. A method is known in which MNA is peeled from a mold after forming (see Patent Documents 1 and 2). When manufacturing MNA, it is necessary to strictly control the amount of drug administered into the skin from MNA. For this reason, in the manufacturing process of MNA, the amount of the drug contained in MNA is quantified.

  In the method for producing MNA described in Patent Document 3, MNA is dissolved in water and the amount of the drug contained in MNA is measured. However, in the method described in Patent Document 3, it is necessary to perform destructive measurement, which causes a problem that the produced MNA is destroyed.

  Here, the amount of the medicine supplied into the skin by the MNA depends on the volume (volume) of the aqueous solution of medicine filled in each needle-like recess of the mold. For this reason, the volume of the drug aqueous solution filled in each needle-shaped recess of the mold is measured, and the volume of the drug aqueous solution in each needle-shaped recess is quantified, thereby quantifying the amount of drug contained in the MNA. Can be achieved.

  As a method for measuring the volume of the aqueous drug solution filled in each needle-shaped recess of the mold, for example, the weight of the mold before filling with the aqueous drug solution and the weight of the mold after filling with the aqueous drug solution can be measured with a high-precision electronic balance. A method for measuring and measuring the volume of the aqueous drug solution based on the weight difference before and after filling and the density of the aqueous drug solution is known. According to the method of measuring with this high-precision electronic balance, it is possible to perform nondestructive measurement of the volume of the aqueous drug solution filled in each needle-like recess of the mold.

JP2013-162982A JP2012-254952A JP 2011-224332 A

  However, when performing a measurement using the above-described high-accuracy balance, it is necessary to prepare a high-accuracy electronic balance having a measurement range and resolution suitable for measurement. For example, the case where the weight of the mold is 800 mg and this mold is filled with 2 mg of a chemical aqueous solution will be described as an example. In this case, if the allowable range of variation in the 2 mg capacity is ± 3% of 2 mg, this allowable range is ± 0.06 mg. Therefore, the high-precision electronic balance needs to have a resolution of 0.01 mg. However, the weight of the mold is 800 mg, which is much larger than the weight of the aqueous drug solution, and there is a difference of about 400 times, so that the measurement range of the high-precision electronic balance needs to ensure 800 mg. For this reason, it is actually difficult to prepare a high-performance electronic balance that achieves both a measurement range (800 mg) and resolution (0.01 mg), and the needle-shaped recess is filled based on the weight difference before and after filling. The volume of the aqueous drug solution could not be measured with high accuracy. In addition, the method using a high-precision electronic balance requires that molds be set on the high-precision electronic balance one by one, so efficient MNA production in the MNA manufacturing process (eg, roll-to-roll production) Not suitable for.

  Moreover, in the measurement using the above high-accuracy balance, the volume of the aqueous drug solution for each needle-like concave portion of the mold cannot be measured individually. As a result, it is not possible to measure the variation in the volume of the aqueous drug solution for each needle-like recess. For this reason, development of the technique which can carry out the nondestructive measurement of the capacity | capacitance of the chemical | medical-agent aqueous solution for every acicular recessed part of a mold at high speed and high precision was desired. At this time, in the manufacturing process of MNA, since it is common to manufacture while switching MNAs of a plurality of types of drugs such as insulin and vaccine, it is desired to develop a measurement technique independent of the type of drug. .

  Patent Document 2 discloses a method of measuring each length of the colored portion by observing the blue microneedle peeled off from the mold with a video microscope by coloring each MNA microneedle in blue. Has been. Since the shape of each needle-like recess of the mold is known, the individual volume (capacity) of the microneedle in each needle-like recess is obtained based on the measurement result of the length of the microneedle in each needle-like recess. However, since this method is intended for measurement of microneedles after drying, it can be performed regardless of the type of drug, but it can be applied to the measurement of the volume of the aqueous drug solution filled in the individual needle-like recesses of the mold. Can not.

  The present invention has been made in view of such circumstances, and provides a measurement method, a measurement apparatus, and a program capable of nondestructively measuring the volume of an aqueous solution of a drug for each needle-like recess of a mold at high speed and with high accuracy. The purpose is to do.

  A measurement method for achieving the object of the present invention measures the volume of an aqueous solution of a medicine filled in a needle-shaped recess of a light-transmitting mold in which a plurality of needle-shaped recesses that are inverted types of microneedles are formed. In the measurement method, the transmitted light image obtained by imaging the transmitted light of the parallel light emitted from the second surface opposite to the first surface by the perpendicular incidence of the parallel light to the first surface of the mold filled with the aqueous solution The acquisition step for acquiring the liquid, the transmitted light image acquired in the acquisition step is analyzed, the non-formation region of the needle-like concave portion, the first wall surface portion in the aqueous solution of the needle-like concave portion, and the liquid of the aqueous solution of the needle-like concave portion The liquid indicating the boundary between the liquid surface and the second wall surface portion from the image pattern in the transmitted light image formed by the transmitted light of the parallel light respectively incident on the second wall surface portion on the first surface side from the surface Liquid surface feature line for detecting surface feature line for each needle-like recess Has a step out, and the detection result of the liquid level feature line detection step, based on the shape of the known needle-like recess, and capacity calculation step of calculating the capacity of each needle-like recess, the.

  According to the present invention, paying attention to the difference in the angle of refraction of parallel light refracted by the first wall surface portion and the second wall surface portion of each needle-shaped recess, the volume of the aqueous solution of the drug in each needle-shaped recess is reduced. Can be measured.

  In the measurement method according to another aspect of the present invention, the transmitted light is incident on the non-formation region, travels straight through the mold, and is emitted from the first region of the second surface and on the first wall surface portion. The second transmitted light that is incident and refracted by the first wall surface portion and is emitted from the second region corresponding to the needle-like concave portion of the second surface, and the first transmitted light incident on the second wall surface portion and the second wall surface portion. And the third transmitted light that is refracted at a refraction angle larger than the light and exits from a portion of the first region, and the image pattern includes the first transmitted light and the third transmitted light that exit from the portion of the first region. A first image formed by the combined light; a first transmitted light emitted from a portion different from a part of the first region; and a second image formed by the second transmitted light emitted from the second region. The liquid level feature line detecting step is based on the position of the boundary between the first image and the second image. Detecting the liquid level characteristic line. Thereby, the boundary of the liquid level for every needle-shaped recessed part and a 2nd wall surface part is detectable.

  In the measurement method according to another aspect of the present invention, the first image is an annular image that surrounds the outer periphery of the second image and becomes brighter than the second image. In the liquid surface characteristic line detection step, the annular liquid surface is detected. Detect feature lines. Thereby, the boundary of the liquid level for every needle-shaped recessed part and a 2nd wall surface part is detectable.

  In the measurement method according to another aspect of the present invention, prior liquid level feature line detection is performed in advance to detect the liquid level characteristic lines of the first and second liquid levels that are parallel to the first surface and have different liquid level heights. The first radius from the center of the needle-shaped recess of the liquid level feature line of the first liquid level detected in the step, and the center of the needle-shaped recess of the liquid level feature line of the second liquid level A pre-radius detecting step for detecting a second radius from the first, a first liquid surface height from the second surface to the center of the first liquid surface, and a second liquid from the second surface to the center of the second liquid surface. A preliminary liquid level detection step for detecting the surface height in advance, and the volume calculation step includes a plurality of liquid level feature lines from the center of the needle-shaped recess based on the detection result of the liquid level feature line detection step. A third radius detecting step for detecting a third radius to each of the points; a detection result of the third radius detecting step; A third liquid level height detecting step for detecting a third liquid level height from the second surface to each of the plurality of points based on the detection results of the radius detection step and the preliminary liquid level height detection step; And a calculation step for calculating a capacity in the needle-shaped recess based on the detection results of the third radius detection step and the third liquid level height detection step and the known shape of the needle-shaped recess. Thereby, based on the detection result of the liquid surface characteristic line for each needle-shaped recess, the volume of the aqueous solution of the drug in the needle-shaped recess can be detected for each needle-shaped recess.

In the method according to another aspect of the present invention, the first radius and R _H, the second radius and R _L, the first liquid level height and D _H, the second liquid level height and D _L, When the third radius for each of a plurality of points is R _X , the third liquid level for each of the plurality of points is D _X, and D _H > D _L , the third liquid level height detection step is as follows: Using the formula (1), D _X = [(R _X −R _L ) × (D _H −D _L )] / (R _H −R _L ) + D _L (1), The third liquid level is detected. Thereby, the third liquid level height can be detected from the detection result of the third radius detection step.

  In the measurement method according to another aspect of the present invention, an incident step in which parallel light is perpendicularly incident on the first surface, an imaging step in which transmitted light emitted from the second surface is imaged by an imaging unit and a transmitted light image is generated, and The acquisition step acquires a transmitted light image from the imaging unit. Thereby, a transmitted light image can be acquired.

  In the measuring method according to another aspect of the present invention, the imaging step images the transmitted light using an imaging unit focused on the second surface. Thereby, the parallel light transmitted through the mold can be captured by the imaging unit.

  A measuring apparatus for achieving the object of the present invention measures the volume of an aqueous solution of a medicine filled in a needle-like recess of a light-transmitting mold in which a plurality of needle-like recesses that are inverted types of microneedles are formed. In the measuring apparatus, a transmitted light image obtained by imaging the transmitted light of the parallel light emitted from the second surface opposite to the first surface by the perpendicular incidence of the parallel light to the first surface of the mold filled with the aqueous solution The acquisition unit for acquiring the image, the transmitted light image acquired by the acquisition unit is analyzed, the non-formation region of the needle-like recess, the first wall surface portion in the aqueous solution of the needle-like recess, and the liquid of the aqueous solution of the needle-like recess The boundary between the liquid surface and the second wall surface portion is shown based on the image pattern in the transmitted light image formed by the transmitted light of the parallel light respectively incident on the second wall surface portion on the first surface side from the surface. A liquid surface characteristic line detection unit that detects a liquid surface characteristic line for each needle-like recess; Comprising a detection result of the liquid level feature-ray detecting unit, based on the shape of the known needle-like recess, and the capacity calculation section for calculating the capacity of each needle-like recess, the.

  The measuring apparatus according to another aspect of the present invention includes an incident unit that vertically enters parallel light on the first surface, and an imaging unit that captures the transmitted light emitted from the second surface and generates a transmitted light image. The acquisition unit acquires a transmitted light image from the imaging unit.

  A program for achieving the object of the present invention is a means for measuring the volume of an aqueous solution of a medicine filled in a needle-shaped recess of a light-transmitting mold in which a plurality of needle-shaped recesses that are inverted types of microneedles are formed. As a program for causing a computer to function as a parallel light emitted from a second surface opposite to the first surface by vertical incidence of parallel light on the first surface of the mold filled with the aqueous solution An acquisition unit that acquires a transmitted light image obtained by imaging the transmitted light of the sensor, and a transmitted light image acquired by the acquisition unit is analyzed to form a non-formation region of the needle-like concave portion and a first wall surface portion in the aqueous solution of the needle-like concave portion And the liquid surface based on the image pattern in the transmitted light image formed by the transmitted light of the parallel light respectively incident on the second wall surface portion that is closer to the first surface than the liquid surface of the aqueous solution of the needle-shaped recess. Indicates the boundary with the second wall Calculates the capacity of each needle-shaped recess based on the liquid surface feature line detection unit that detects the surface feature line for each needle-shaped recess, the detection result of the liquid surface feature line detection unit, and the shape of the known needle-shaped recess. Function as a capacity calculator.

  The measuring method, measuring apparatus, and program of the present invention can perform nondestructive measurement of the volume of an aqueous solution of a drug for each needle-shaped recess of a mold at high speed and with high accuracy.

It is the schematic of the measuring apparatus which measures the capacity | capacitance of the chemical | medical-agent aqueous solution with which the acicular recessed part of the mold was filled. It is sectional drawing of a mold. It is explanatory drawing for demonstrating the state change of the chemical | medical solution aqueous solution with which each acicular recessed part of a mold was filled. It is explanatory drawing for demonstrating acquisition of the transmitted light pattern image by a measuring apparatus. (A) is sectional drawing of the mold in which parallel light injects, (B) is explanatory drawing for demonstrating the optical path (traveling direction) of the transmitted light of the parallel light which permeate | transmits a mold. (A) is sectional drawing of the acicular recessed part of a mold, (B) is a graph for demonstrating the intensity distribution (transmitted light intensity distribution) of the transmitted light of the parallel light which permeate | transmits a mold. (A) is sectional drawing of the acicular recessed part from which the capacity | capacitance of chemical | medical agent aqueous solution differs, (B) is an enlarged view of the area | region M in (A), (C) is shown to FIG. 6 (B). It is the enlarged view to which the transmitted-light intensity | strength of the boundary part of the left side in the figure of the partial area | region B1, B2 expanded was expanded. It is the enlarged view to which a part of transmitted light pattern image shown in FIG.4 (C) was expanded. (A), (B) is the front view of the transmitted light pattern image in case the liquid level in a needle-shaped recessed part is parallel with respect to a 1st surface, and sectional drawing of a mold, (C), (D ) Are a front view of a transmitted light pattern image and a cross-sectional view of a mold when the liquid level in the needle-like recess is inclined with respect to the first surface. It is a block diagram which shows the electric constitution of an image processing system. (A) is sectional drawing of the mold in which the 1st liquid level is formed in each acicular recessed part, (B) is a cross section of the mold in which the 2nd liquid level is formed in each acicular recessed part. (C) is a front view of a transmitted light pattern image generated by imaging the transmitted light of the mold shown in (A), and (D) is an image of the transmitted light of the mold shown in (B). It is a front view of the transmitted light pattern image generated in this way. (A) is explanatory drawing for demonstrating the measurement of the liquid level characteristic line radius of a 1st liquid level, (B) is description for demonstrating the measurement of the liquid level characteristic line radius of a 2nd liquid level. FIG. It is explanatory drawing for demonstrating the detection of the liquid level height of a 1st liquid level, and the detection of the liquid level height of a 2nd liquid level. (A) is explanatory drawing for demonstrating the detection process of the liquid surface characteristic line radius by a radius detection part, (B) is for demonstrating the detection process of the liquid level by a liquid level height detection part. It is explanatory drawing of. It is explanatory drawing for demonstrating the liquid level height calculation process by a liquid level height detection part. It is the graph showing the relationship between the capacity | capacitance of the chemical | medical-agent aqueous solution with which it filled in the needle-shaped recessed part, and elapsed time immediately after filling. It is a flowchart which shows the flow of a process of measurement and storage of prior measurement data. It is a flowchart which shows the flow of the measurement process of the capacity | capacitance of the chemical | medical-agent aqueous solution for every acicular recessed part.

[Overall configuration of measuring device]
FIG. 1 is a schematic view of a measuring apparatus 10 according to the measuring method and measuring apparatus of the present invention. The measuring device 10 measures the volume of a drug aqueous solution 18 that is an aqueous solution of the drug 16 (see FIG. 3) filled in the needle-like recess 14 of the mold 12.

  As shown in FIG. 1, the measuring apparatus 10 is roughly divided into a surface light source 21 corresponding to an incident part of the present invention, an interference filter 22, an imaging unit 25 including a lens 23 and an imaging element 24, and an image processing system 26. And comprising. Although not shown, the measurement apparatus 10 is provided with a stage that supports the mold 12 between the interference filter 22 and the imaging unit 25.

  FIG. 2 is a cross-sectional view of the mold 12. As shown in FIG. 2, the mold 12 is a flat plate mold used for manufacturing an MNA 29 in which microneedles 28 are arranged in an array. The mold 12 is made of silicon rubber in the present embodiment, and has light transmittance. In the mold 12, a plurality of needle-like recesses 14 that are the inverted types of the microneedles 28 are formed in an array (see FIG. 4A).

  Corresponding to the shape of the microneedle 28, the needle-like recess 14 has a conical shape that gradually tapers from the first surface 12a of the mold 12 toward the second surface 12b opposite to the first surface 12a. Yes. For this reason, the wall surface of the acicular recessed part 14 turns into an inclined surface. In addition, in this embodiment, it forms so that the inclination angle of the opening vicinity part by the side of the 1st surface 12a of the needle-shaped recessed part 14 may become smaller than the inclination angle of another part among the wall surfaces of the needle-shaped recessed part 14. Yes.

  Each needle-like recess 14 of the mold 12 is filled with the aqueous drug solution 18 from the first surface 12a side. In addition, the code | symbol 18a in a figure is the liquid level of the chemical | medical agent aqueous solution 18 with which the needle-shaped recessed part 14 was filled.

  A plurality of communication holes 31 are formed in the second surface 12b of the mold 12 so as to communicate with the needle-like recesses 14 respectively. The mold 12 is set on the above-described stage with the first surface 12a facing upward in the drawing and the second surface 12b facing downward in the drawing after the filling of each of the needle-shaped recesses 14 with the aqueous drug solution 18.

  After filling each needle-shaped recess 14 with the aqueous drug solution 18, the mold 12 is dried to evaporate water from the drug aqueous solution 18 in each needle-shaped recess 14 to solidify the drug 16 (see FIG. 3). A microneedle 28 is formed in each needle-like recess 14. As a result, the MNA 29 is formed on the first surface 12 a of the mold 12, and the MNA 29 is peeled from the mold 12.

  FIG. 3 is an explanatory diagram for explaining a state change of the aqueous drug solution 18 filled in each needle-like recess 14 of the mold 12. Here, FIG. 3 (A) shows a state immediately after filling the needle-shaped recess 14 with the pharmaceutical aqueous solution 18, FIG. 3 (B) shows a state in which the mold 12 is being dried, and FIG. 3 (C) shows a mold. 12 is a state after drying.

  As shown in FIGS. 3 (A) to 3 (C), after filling each needle-shaped recess 14 with the drug aqueous solution 18, the mold 12 is dried, so that the liquid drug in each needle-shaped recess 14 is dried. Water evaporates from the aqueous solution 18 and finally the drug 16 is solidified, and solid microneedles 28 are formed in each needle-like recess 14. As a result, the MNA 29 is formed on the first surface 12a of the mold 12 as shown in FIG.

  The microneedle 28 is a crystal of the drug 16 contained in the drug aqueous solution 18. For this reason, the optical characteristics (refractive index, light absorption rate, etc.) of the microneedle 28 vary depending on the type of the drug 16 contained in the drug aqueous solution 18.

  On the other hand, in the pharmaceutical aqueous solution 18, water accounts for about 80%, the proportion of the pharmaceutical 16 is several percent, and the rest is a HES (hydroxyethyl starch) solution or the like. Accordingly, since the aqueous drug solution 18 is 95% water, HES solution, etc., the water determines the optical characteristics of the aqueous drug solution 18. For this reason, even if the kind of the medicine 16 in the medicine aqueous solution 18 changes, the optical characteristics of the medicine aqueous solution 18 do not change greatly.

  Therefore, the measuring device 10 pays attention to the water contained in the pharmaceutical aqueous solution 18 and measures the volume (volume) of the pharmaceutical aqueous solution 18 filled in each needle-like recess 14. The measurement time by the measuring device 10 is before the water contained in the drug aqueous solution 18 evaporates and the drug 16 solidifies. Specifically, immediately after filling the drug aqueous solution 18 into the needle-shaped recess 14 (FIG. 3A )) And during the drying of the mold 12 (see FIG. 3B).

  In addition, when measuring during drying of the mold 12 shown to FIG. 3 (B), it is preferable to carry out in the fixed time slot | zone when the state of the chemical | medical solution 18 is stabilized. Here, the state of the drug aqueous solution 18 being stable is a state in which there is no significant change in the state of the drug aqueous solution 18 within the measurement time. The certain period of time during which the state of the aqueous drug solution 18 is stabilized varies depending on the manufacturing conditions of the MNA 29 (the type of the drug 16, the shape of the needle-shaped recess 14, the temperature at the time of drying, etc.). Can go and decide.

  Returning to FIG. 1, the measuring apparatus 10 vertically transmits the parallel light PL to the first surface 12 a of the mold 12 and transmits a transmitted light pattern indicating the transmitted light intensity distribution of the transmitted light of the parallel light PL emitted from the second surface 12 b. By acquiring and analyzing the image, the volume of the aqueous drug solution 18 for each needle-like recess 14 is measured. As will be described in detail later, the refractive index of the parallel light PL incident on the wall surface of the needle-shaped recess 14 in the aqueous drug solution 18 and the parallel light incident on the wall surface of the needle-shaped recess 14 outside the aqueous solution 18 (on the liquid surface 18a). Since the refractive index of PL changes, the transmitted light pattern image reflects the shape of the liquid surface and the height of the liquid surface of the pharmaceutical aqueous solution 18 in the needle-like recess 14. For this reason, by analyzing the transmitted light pattern image, it is possible to measure the volume of the pharmaceutical aqueous solution 18 for each needle-like recess 14. In addition, the liquid level of the chemical aqueous solution 18 is the height of the liquid level 18a based on the second surface 12b.

  FIG. 4 is an explanatory diagram for explaining the acquisition of the transmitted light pattern image 35 by the measurement apparatus 10. Here, FIG. 4A is a perspective view of the mold 12 set on the aforementioned stage, and FIG. 4B is a cross-sectional view of the mold 12 shown in FIG. FIG. 6 is a front view of a transmitted light pattern image 35.

  As shown in FIGS. 1 and 4A, the surface light source 21 is disposed above the mold 12. The surface light source 21 emits parallel light PL orthogonal to (including substantially orthogonal to) the first surface 12a toward the first surface 12a of the mold 12 after being filled with the chemical aqueous solution 18. The parallel light PL has a center wavelength of a wavelength λ described later.

  The interference filter 22 (see FIG. 1) is disposed between the surface light source 21 and the first surface 12a of the mold 12. The interference filter 22 passes the parallel light PL having a wavelength λ that is a specific wavelength region of the parallel light PL incident from the surface light source 21. Thereby, the parallel light PL having the wavelength λ is incident on the first surface 12 a of the mold 12. In this way, by limiting the wavelength of the parallel light PL incident on the mold 12, the liquid level feature line 42 (see FIG. 8) included in the transmitted light pattern image 35 can be easily detected as will be described in detail later. Can do. In the present embodiment, the wavelength of the parallel light PL incident on the first surface 12a is determined by both the surface light source 21 and the interference filter 22, but the wavelength of the parallel light PL is determined by only one of them. Also good.

  As shown in FIGS. 1 and 4B, the lens 23 constituting the imaging unit 25 is disposed below the mold 12, that is, at a position facing the second surface 12 b of the mold 12. The transmitted light of the transmitted parallel light PL is imaged on the imaging surface of the imaging device 24.

  The image sensor 24 constituting the imaging unit 25 is disposed below the lens 23, that is, on the side opposite to the side of the lens 23 facing the mold 12. The imaging device 24 is a CCD (Charge Coupled Device) type imaging device or a CMOS (Complementary Metal Oxide Semiconductor) type imaging device, and images the transmitted light imaged on the imaging surface by the lens 23.

  At this time, the imaging unit 25 performs imaging by the imaging element 24 in a state where the second surface 12b of the mold 12 is focused in order to capture the transmitted light of the parallel light PL that has passed through the mold 12. In addition, as a method of focusing the imaging unit 25 on the second surface 12b, for example, a mark (which may be an uneven character or a symbol) that is a target of focus adjustment by the imaging unit 25 is formed on the second surface 12b. Various methods such as a method of adjusting the focus of the image pickup unit 25 with this mark as a target, or a method of adjusting the focus of the image pickup unit 25 with the target of dust, scratches and various traces on the second surface 12b are adopted. May be.

  As shown in FIG. 4C, the imaging unit 25 is an image of the transmitted light pattern image 35 corresponding to the transmitted light image of the present invention by an image processing circuit (not shown) based on the imaging signal output from the imaging element 24. Data is generated and this image data is output to the image processing system 26 (see FIG. 1).

  Returning to FIG. 1, the image processing system 26 analyzes the image data of the transmitted light pattern image 35, as will be described in detail later, and the volume of the aqueous drug solution 18 filled in each needle-like recess 14 of the mold 12. Ask for.

[Description of transmitted light pattern image]
As shown in FIG. 4C described above, the transmitted light pattern image 35 is a circular shape formed by the transmitted light that has passed through the needle-shaped recess 14 at a position corresponding to each needle-shaped recess 14 of the mold 12. A bright and dark image 37 (including a substantially circular shape) is included. The bright / dark image 37 corresponds to the image pattern of the present invention, and includes a circular dark image 38 and an annular (ring-shaped) bright image 39 surrounding the outer periphery of the dark image 38. The dark image 38 corresponds to the second image of the present invention, and the bright image 39 corresponds to the first image of the present invention.

  Further, a region other than the bright and dark image 37 in the transmitted light pattern image 35 becomes a gray image 41 that is brighter than the dark image 38 but darker than the bright image 39. Hereinafter, the reason why such a transmitted light pattern image 35 is obtained will be described.

  5A is a cross-sectional view of the mold 12 on which the parallel light PL is incident, and FIG. 5B is a diagram for explaining the optical path (traveling direction) of the transmitted light of the parallel light PL that passes through the mold 12. It is explanatory drawing. 5B, in order to prevent complication of the drawing, the number of needle-like recesses 14 illustrated in FIG. 5A is reduced, and the needle-like recesses 14 are expanded in the horizontal direction in the drawing. ing.

  As shown in FIGS. 5A and 5B, the parallel light PL incident on the non-formation region A, which is a region where the needle-like recesses 14 in the first surface 12a are not formed, is directly applied to the second surface 12b. Go straight ahead. Accordingly, the first transmitted light TL1 of the parallel light PL is emitted from the first region B of the second surface 12b located below the non-formation region A of the first surface 12a in the drawing.

  The parallel light PL incident on the first wall surface portion 14a in the aqueous drug solution 18 among the wall surfaces of the needle-like recess 14 is refracted by the first wall surface portion 14a. Here, the refractive index of the silicon rubber that is the material of the mold 12 is 1.40 to 1.50, which is close to the refractive index (1.35 to 1.50) of the pharmaceutical aqueous solution 18. For this reason, the degree of refraction of the parallel light PL refracted by the first wall surface portion 14a is weakened. Accordingly, the second transmitted light TL2 of the parallel light PL refracted by the first wall surface portion 14a is emitted from the second region C of the second surface 12b located below the needle-shaped recess 14 in the drawing. In addition, the code | symbol C1 in a figure shows the communicating hole area | region corresponding to the communicating hole 31 in the 2nd area | region C. FIG.

  The parallel light PL incident on the first surface 12a side of the wall surface of the needle-shaped recess 14 from the liquid surface 18a of the pharmaceutical aqueous solution 18, that is, on the second wall surface portion 14b located on the liquid surface 18a in the figure, is 2 refracted at the wall surface portion 14b. Here, the refractive index (1.40 to 1.50) of silicon rubber, which is the material of the mold 12, is larger than the refractive index of air (1.003). Thus, since the refractive indexes of air and silicon rubber differ greatly, the parallel light PL incident on the second wall surface portion 14b is refracted more than the parallel light PL incident on the first wall surface portion 14a. Thereby, the third transmitted light TL3 of the parallel light PL refracted by the second wall surface portion 14b is emitted from the partial region B1 (corresponding to a part in the first region of the present invention) which is a part of the first region B. Is done. Since the second wall surface portion 14b is an annular region centered on the center of the needle-shaped recess 14, the partial region B1 is also an annular region centered on the needle-shaped recess 14. Further, the partial region B2 in the drawing is an annular region between the partial region B1 and the second region C.

  FIG. 6A is a cross-sectional view of the needle-like recess 14 of the mold 12. Here, in FIG. 6 (A), the aspect ratio of the needle-like recess 14 is different from that in FIGS. 5 (A) and 5 (B). FIG. 6B is a graph for explaining the intensity distribution (transmitted light intensity distribution) of the transmitted light (each transmitted light TL1 to TL3) of the parallel light PL that passes through the mold 12. Note that the horizontal axis of the graph shown in FIG. 6B is an axial position that indicates an arbitrary axial position that is parallel to the first surface 12a and that passes through the radial center of the needle-like recess 14. The vertical axis of the graph is the transmitted light intensity.

  As shown in FIGS. 6A and 6B, the combined light TL4 of the first transmitted light TL1 and the third transmitted light TL3 is emitted from the partial region B1. Therefore, the transmitted light intensity of the combined light TL4 emitted from the partial region B1 is the transmitted light intensity of the first transmitted light TL1 emitted from the partial region B2, and the transmitted light of the second transmitted light TL2 emitted from the second region C. It becomes higher than strength.

  Further, the transmitted light intensity of the second transmitted light TL2 emitted from the second region C is lower than the transmitted light intensity of the first transmitted light TL1 and the synthesized light TL4 by passing through the aqueous drug solution 18. The reason for this is that the parallel light PL that has entered the drug aqueous solution 18 is scattered by the particles of the drug 16 contained in the drug aqueous solution 18. Further, the transmitted light intensity of the second transmitted light TL2 emitted from the communication hole region C1 is higher than the transmitted light intensity of the other second transmitted light TL2 that transmits the mold 12.

  Thus, the transmitted light intensity distribution of the transmitted light that has passed through the mold 12 has the highest transmitted light intensity of the combined light TL4 emitted from the partial region B1, and the transmitted light of the first transmitted light TL1 emitted from the partial region B2. The intensity is the second highest, and the transmitted light intensity of the second transmitted light TL2 emitted from the second region C is the lowest.

  In the transmitted light intensity distribution shown in FIG. 6B, the position of the boundary between the partial area B1 and the partial area B2, that is, the position of the boundary between the combined light TL4 and the first transmitted light TL1, The position of the boundary with the wall surface part 14b is shown. Since the refraction angle of the parallel light PL refracted by the second wall surface portion 14b and the thickness of the mold 12 are constant, if the position of the boundary between the liquid surface 18a and the second wall surface portion 14b changes, the synthesized light TL4 and the first light beam The position of the boundary with the transmitted light TL1 also changes. Hereinafter, it demonstrates concretely using FIG. 7 (A)-(C).

  FIG. 7A is a cross-sectional view of the needle-like recess 14 and the needle-like recess 14X having different capacities of the aqueous drug solution 18. FIG. 7B is an enlarged view of a region M in FIG. FIG. 7C is an enlarged view in which the transmitted light intensity at the boundary portion on the left side of the partial regions B1 and B2 shown in FIG. 6B is enlarged, and the transmitted light intensity corresponding to the needle-like recess 14 is shown. (Indicated by a solid line in the figure) and transmitted light intensity (indicated by a dotted line in the figure) corresponding to the needle-like recess 14X are shown. Here, the case where the volume of the aqueous drug solution 18 in the needle-shaped recess 14X is reduced by 3% will be described as an example, with the volume of the drug aqueous solution 18 in the needle-shaped recess 14 as a reference (100%). In the present embodiment, the liquid level 18a in the needle-shaped recess 14X is lower than the liquid level 18a in the needle-shaped recess 14 by Δh (about 4 μm).

  As shown in FIGS. 7A to 7C, in the needle-shaped recess 14X, the position of the boundary between the liquid surface 18a and the second wall surface portion 14b is lower than the position of the boundary in the needle-shaped recess 14 by Δh. As a result, the position of the boundary between the combined light TL4 and the first transmitted light TL1 corresponding to the needle-shaped recess 14X is greater than the position of the boundary between the combined light TL4 and the first transmitted light TL1 corresponding to the needle-shaped recess 14. Two regions C are shifted by Δd. The shift amount Δd varies depending on the thickness of the mold 12 and the refraction angle of the second wall surface portion 14b, but is, for example, the size of four pixels of the image sensor 24 in the present embodiment. Although illustration is omitted, when the liquid level 18a of the needle-like recess 14X is higher than the liquid level 18a of the needle-like recess 14 by Δh, the combined light TL4 and the first light TL4 are combined with the first light TL4 according to the magnitude of Δh. The boundary position of the transmitted light TL1 is shifted in the reverse direction.

  Thus, the position of the boundary between the liquid surface 18a and the second wall surface portion 14b and the position of the boundary between the combined light TL4 and the first transmitted light TL1 have a one-to-one correspondence. Therefore, the position of the boundary between the synthesized light TL4 and the first transmitted light TL1 indicates the position of the liquid surface 18a of the pharmaceutical aqueous solution 18 filled in the needle-like recess 14.

  5B, 6B, and 7C described above are diagrams showing a one-dimensional transmitted light intensity distribution in one direction parallel to the first surface 12a of the mold 12. FIG. In addition, the actual transmitted light intensity distribution of the transmitted light transmitted through the mold 12 is represented in two dimensions.

  FIG. 8 is an enlarged view of a part of the transmitted light pattern image 35 shown in FIG. As shown in FIG. 8, a bright image 39 of the bright and dark image 37 is formed by the combined light TL4 emitted from the partial area B1. Further, the dark image 38 of the light / dark image 37 is formed by the first transmitted light TL1 emitted from the partial region B2 and the second transmitted light TL2 emitted from the second region C. Further, the gray image 41 is formed by the first transmitted light TL1 emitted from the first region B other than the partial region B1 and the partial region B2. Accordingly, the transmitted light of the parallel light PL that has passed through the mold 12 is imaged by the imaging unit 25, whereby a transmitted light pattern image 35 including the bright and dark image 37 is obtained at a position corresponding to each needle-like recess 14.

  As shown in FIG. 6B, the transmitted light intensity of the first transmitted light TL1 emitted from the partial region B2 is higher than the transmitted light intensity of the second transmitted light TL2 emitted from the second region C. Get higher. Further, the transmitted light intensity of the second transmitted light TL2 emitted from the communication hole region C1 is higher than the transmitted light intensity of the other second transmitted light TL2. As a result, the central portion and the peripheral portion of the dark image 38 are brighter than the other portions of the dark image 38.

  Thus, in the transmitted light pattern image 35, the bright image 39 is formed by the combined light TL4, and the dark image 38 is formed by the first transmitted light TL1 and the like. For this reason, the position of the boundary between the dark image 38 and the bright image 39 for each of the bright and dark images 37 of the transmitted light pattern image 35 indicates the position of the boundary between the liquid surface 18a and the second wall surface portion 14b for each needle-like recess 14. A liquid surface characteristic line 42 is obtained.

  9A and 9B are a front view of the transmitted light pattern image 35 and a cross-sectional view of the mold 12 when the liquid surface 18a in the needle-like recess 14 is parallel to the first surface 12a. . 9C and 9D are a front view of the transmitted light pattern image 35 and a cross-sectional view of the mold 12 when the liquid surface 18a in the needle-like recess 14 is inclined with respect to the first surface 12a. It is.

  As shown in FIGS. 9A and 9B, when the liquid surface 18a in the needle-like recess 14 is parallel to the first surface 12a, the transmitted light pattern image corresponding to the needle-like recess 14 is obtained. A liquid surface characteristic line 42 having a perfect circular shape is detected from the bright / dark image 37 in 35. On the other hand, as shown in FIGS. 9C and 9D, when the liquid surface 18a in the needle-like recess 14 is inclined with respect to the first surface 12a, the transmitted light corresponding to the needle-like recess 14 is obtained. An elliptical liquid surface characteristic line 42 is detected from the light / dark image 37 in the pattern image 35.

  Although illustration is omitted, the area of the dark image 38 surrounded by the liquid surface characteristic line 42 increases as the height of the liquid surface 18a in the needle-shaped recess 14 increases, and conversely, As the height of the liquid surface 18a decreases, the area of the dark image 38 surrounded by the liquid surface characteristic line 42 decreases. Therefore, by analyzing the transmitted light pattern image 35 and detecting the liquid surface characteristic line 42 for each needle-shaped recess 14, the position of the boundary between the liquid surface 18 a and the second wall surface portion 14 b for each needle-shaped recess 14, that is, The shape and height of the liquid surface 18a for each needle-like recess 14 can be detected.

  In the present embodiment, as described above, the wavelength of the parallel light PL incident on the first surface 12a of the mold 12 is limited using the interference filter 22 or the like. Since the refraction angle of the parallel light PL refracted by the second wall surface portion 14b varies depending on the wavelength of the parallel light PL, the emission position of the third transmitted light TL3 emitted from the second surface 12b varies depending on the wavelength. Therefore, when the wavelength of the parallel light PL incident on the first surface 12a is not limited, the boundary of the bright image 39 becomes unclear due to the deviation of the emission position for each wavelength of the third transmitted light TL3, and the liquid surface characteristics The detection of the line 42 may be difficult. On the other hand, in this embodiment, since the wavelength of the parallel light PL incident on the first surface 12a is limited, the liquid level feature line 42 included in the transmitted light pattern image 35 can be easily detected.

  FIG. 10 is a block diagram showing an electrical configuration of the image processing system 26. As the image processing system 26, for example, a personal computer (including a monitor) can be used. As shown in FIG. 10, the image processing system 26 roughly includes a control unit 46, a storage unit 47, an operation input unit 48, and a display unit 49.

  The control unit 46 includes various arithmetic units and processing units including, for example, a CPU (Central Processing Unit), and various programs and information read from the storage unit 47 based on control signals from the operation input unit 48. By executing the above, the entire measurement apparatus 10 including the image processing system 26 is controlled in an integrated manner. As will be described in detail later, the control unit 46 analyzes the image data of the transmitted light pattern image 35 input from the imaging unit 25 and calculates the volume of the aqueous drug solution 18 for each needle-shaped recess 14.

  The storage unit 47 stores various types of information including the measurement program 51, prior measurement data 52, and needle-like recess shape data 53. The measurement program 51 corresponds to the program of the present invention, and causes the control unit 46 (computer of the image processing system 26) to function as means for measuring the volume of the aqueous drug solution 18 for each needle-like recess 14.

  The preliminary measurement data 52 will be described in detail later, but the radii of the liquid surface characteristic lines 42 of the two types of liquid surfaces 18a that are parallel to the first surface 12a and have different liquid surface heights (hereinafter referred to as liquid surface characteristic line radii). , And data obtained by measuring the liquid level height of the two types of liquid levels 18a in advance (see FIGS. 12 and 13). The acicular recess shape data 53 is obtained by measuring in advance the shape (including dimensions) of the acicular recess 14 formed in the mold 12. The prior measurement data 52 and the needle-like recess shape data 53 are stored in the storage unit 47 for each type of the mold 12 when there are a plurality of types of the mold 12.

  The operation input unit 48 is used for a start operation for measuring the volume of the aqueous drug solution 18 and a start operation for measuring the preliminary measurement data 52. The display unit 49 is, for example, a liquid crystal display, and displays a calculation result of the volume of the pharmaceutical aqueous solution 18 by the control unit 46.

[Configuration of control unit]
The control unit 46 functions as an acquisition unit 59, a liquid surface characteristic line detection unit 60, and a capacity calculation unit 61 by executing the measurement program 51 read from the storage unit 47.

  The acquisition unit 59 is, for example, an interface that is wired or wirelessly connected to the imaging unit 25 (including connection via a communication network such as the Internet). The acquisition unit 59 acquires the image data of the transmitted light pattern image 35 from the imaging unit 25 and outputs the image data to the liquid level feature line detection unit 60. The acquisition unit 59 can also acquire image data of the transmitted light pattern image 35 recorded in advance on a recording medium such as a memory card. In this case, the loading unit into which the memory card is loaded is the acquisition unit 59. It becomes.

  The liquid surface characteristic line detection unit 60 analyzes the image data of the transmitted light pattern image 35 input from the acquisition unit 59 and detects the liquid surface characteristic lines 42 from the bright and dark images 37 for each needle-shaped concave portion 14. For example, in the transmitted light pattern image 35, the brightness value of the white bright image 39 is the highest, whereas the brightness value of the black dark image 38 is the lowest, and the brightness value of the gray image is higher than the brightness value of the bright image 39. Is lower but higher than the luminance value of the dark image 38. Accordingly, the liquid surface feature line detection unit 60 detects the bright value 39 and the dark image 38 from the transmitted light pattern image 35 by detecting and comparing the luminance values of all the pixels of the image data of the transmitted light pattern image 35. .

  Next, the liquid surface feature line detection unit 60 detects the boundary between the bright image 39 and the dark image 38 based on the detection results of the bright image 39 and the dark image 38, thereby causing the liquid surface feature line 42 for each needle-like recess 14. Is detected. Then, the liquid level feature line detection unit 60 outputs the image data of the transmitted light pattern image 35 and the detection result of the liquid level feature line 42 to the capacity calculation unit 61. In addition, the detection method of the liquid level characteristic line 42 is not specifically limited, You may detect by the well-known image analysis method.

  As will be described in detail later, the volume calculation unit 61 calculates the volume of the aqueous drug solution 18 for each needle-like recess 14 of the mold 12 based on the detection result of the liquid surface characteristic line detection unit 60. Here, in addition to the detection result of the liquid surface characteristic line detection unit 60, the previously measured data 52 and the needle-like concave portion shape data 53 are used for the calculation of the volume of the aqueous drug solution 18. For this reason, prior measurement data 52 and needle-like recess shape data 53 are stored in the storage unit 47 before the volume calculation unit 61 calculates the volume of the pharmaceutical aqueous solution 18. As the needle-like recess shape data 53, data obtained by actually measuring the shape of the needle-like recess 14 by a known method may be used, or data measured by the manufacturer of the mold 12 may be used.

<Measurement and storage of pre-measurement data>
Next, the prior measurement data 52 will be described. As shown in FIGS. 11A and 11B, the preliminary measurement data 52 includes the first liquid surface 18a _H and the second liquid surface 18a _L which are parallel to the first surface 12a and have different liquid surface heights. The liquid surface characteristic line radius and the liquid surface height were measured. Here, FIG. 11A is a cross-sectional view of the mold 12 _H in which the first liquid surface 18 a _H is formed in each needle-like recess 14 by filling with the chemical aqueous solution 18. Further, FIG. 11 (B) is a cross-sectional view of a mold 12 _L of the second liquid level 18a _L in each needle-like recesses 14 by the filling of the drug solution 18 is formed. In the present embodiment, the liquid level height of the first liquid level 18a _H is higher than that of the second liquid level 18a _L.

When measuring the liquid surface characteristic line radii of each of the first liquid surface 18a _H and the second liquid surface 18a _L , first, molds 12 _H and 12 _L are set in the measuring device 10 respectively, and the imaging unit 25, the transmitted light that has passed through the molds 12 _H and 12 _L is imaged.

FIG. 11 (C) is a front view of the transmitted light pattern image 35 _H to the light transmitted through the mold 12 _H imaging unit 25 has generated by imaging shown in Figure 11 (A). FIG. 11D is a front view of a transmitted light pattern image 35 _L generated by the imaging unit 25 imaging the transmitted light of the mold 12 _L shown in FIG. Based on the image data of the transmitted light pattern images 35 _H and 35 _L shown in FIG. 11C and FIG. 11D, the liquids on the first liquid surface 18a _H and the second liquid surface 18a _L , respectively, as described later. A surface feature line radius is measured.

12A is an explanatory diagram for explaining the measurement of the liquid surface characteristic line radius of the first liquid surface 18a _H , and FIG. 12B is the liquid surface characteristic line radius of the second liquid surface 18a _L. It is explanatory drawing for demonstrating this measurement.

As shown in the upper and middle stages of FIGS. 12A and 12B, in this embodiment, the image data of the transmitted light pattern images 35 _H and 35 _L for the molds 12 _H and 12 _L generated by the imaging unit 25 is used. The liquid level feature line 42 for each of the molds 12 _H and 12 _L is detected by obtaining the above-mentioned obtaining unit 59 and analyzing both image data by the liquid level characteristic line detection unit 60.

Then, FIG. 12 (A), the distance to each of a plurality of points as shown in the lower part, the needle-like recess 14 from the center (including substantially the center) on the mold 12 _H of the liquid level characteristic line 42 of the (B) The indicated liquid surface characteristic line radius _RH is measured, and the average value of the liquid surface characteristic line radii _RH for each of a plurality of points is stored in the storage unit 47 as the preliminary measurement data 52. Further, the center liquid level characteristic line radius R _L indicating the distance from (including substantially the center) to each of a plurality of points on the liquid surface feature line 42 of the mold 12 _L of the needle recess 14 measures, for each of a plurality of points The average value of the liquid surface characteristic line radius _RL is stored in the storage unit 47 as prior measurement data 52. The liquid surface characteristic line radius _RH corresponds to the first radius of the present invention, and the liquid surface characteristic line radius _RL corresponds to the second radius of the present invention. In the present embodiment, the liquid surface characteristic line radii R _H and R _L are measured by a radius detector 65 (see FIG. 10) described later.

  Here, as described above, the transmitted light intensity of the second transmitted light TL2 emitted from the center of the needle-shaped recess 14, that is, the communication hole 31 (communication hole region C1) is from the second region C other than the communication hole region C1. It becomes higher than the transmitted light intensity of the emitted second transmitted light TL2. For this reason, the center of the needle-like recess 14 can be determined on the transmitted light pattern image 35.

The average value of the liquid surface characteristic line radii R _H and R _L described above is, for example, the liquid surface characteristic line radii R up to a plurality of points on all the liquid surface characteristic lines 42 detected for each needle-like recess 14. _It may be the average value of each of _H 1 and _RL , or may be the average value of the liquid surface feature line radii R _H and R _L up to a plurality of points on the representative liquid surface feature line 42, but not all.

FIG. 13 is an explanatory diagram for explaining the detection of the liquid surface height of the first liquid surface 18a _H and the detection of the liquid surface height of the second liquid surface 18a _L. As shown in FIG. 13, the detection of the first liquid level height _{D H} from the second face 12b to the center of the first liquid level 18a _H (including a substantially center), and the second liquid surface 18a from the second surface 12b the second liquid surface detection height D _L to _L center (including substantially the center) is carried out in known laser confocal microscope 63 (see FIG. 10, also referred to as a laser point sensor). Detection results of the first liquid level height D _H and the second liquid level D _L is stored as a pre-measured data 52 in the storage unit 47.

Such liquid surface characteristic line radius R _H, the average value of R _L, pre-measured data 52 composed of a first liquid level height D _H and the second liquid level D _L is measured in advance Is stored in the storage unit 47 and used for the volume of the aqueous drug solution 18 for each needle-like recess 14 by the volume calculation unit 61 described later (see FIG. 10).

<Calculation processing of capacity calculation unit>
Returning to FIG. 10, the capacity calculation unit 61 determines the needle of the mold 12 based on the detection result of the liquid surface characteristic line detection unit 60 and the pre-measurement data 52 and the needle-like recess shape data 53 stored in the storage unit 47. The volume of the aqueous drug solution 18 for each of the concave portions 14 is calculated. The capacity calculation unit 61 includes a radius detection unit 65 that detects the liquid surface characteristic line radius of the liquid surface 18a, a liquid level height detection unit 66 that detects the liquid level of the liquid surface 18a, and the inside of the needle-like recess 14. And a calculation unit 67 for calculating the volume of the chemical aqueous solution 18. Here, in order to prevent the explanation from being complicated, the calculation of the volume of the aqueous drug solution 18 filled in one needle-like recess 14 will be described as an example.

  FIG. 14A is an explanatory diagram for explaining the detection process of the liquid surface characteristic line radius by the radius detection unit 65. FIG. 14B is an explanatory diagram for explaining a liquid level detection process by the liquid level detector 66.

As shown in FIG. 14A, the radius detection unit 65 has a needle-like concave portion based on the detection result of the liquid surface feature line 42 and the image data of the transmitted light pattern image 35 input from the liquid surface feature line detection unit 60. 14 _(in the figure only one point display) center points C _X 1 lap the liquid surface characteristic line 42 from (including substantial center) of detecting the liquid surface feature line radius R _X indicating the distance to. The liquid level characteristic line radius R _X corresponds to the third radius of the present invention. Then, the radius detector 65 outputs the detection result of the liquid surface feature line radius R _X of each point C _X on the liquid surface feature line 42 to the liquid surface height detector 66 and the calculator 67.

As shown in FIG. 14B, the liquid level detector 66 detects the third liquid level D _X from the second surface 12b for each point C _X on the liquid level characteristic line 42. The liquid level detector 66 detects the liquid surface characteristic line radius R _X of each point C _X input from the radius detector 65 and the preliminary measurement data 52 (R _H , R read from the storage unit 47). _{Based on (L 1} , D _H , D _L ), a liquid level calculation process is performed to detect the third liquid level height D _X at each point C _X.

FIG. 15 is an explanatory diagram for explaining the liquid level calculation processing by the liquid level detector 66. Since the shape of the needle-shaped recess 14 is constant, as shown in FIG. 15, a one-to-one relationship is established between the “liquid surface characteristic line radius” and the “liquid surface height”, and this relationship is measured in advance. It is represented by a linear function defined by the data 52 (R _H , R _L , D _H , D _L ). Therefore, the liquid level detector 66, by substituting the detection result of the liquid level characteristic line radius R _X of each point C _X in the following equation (1), the third liquid level of each point C _X it is possible to obtain the D _X. Thereby, the liquid level height of one round of the liquid level characteristic line 42 is detected. Then, the liquid level detector 66 outputs the detection result of the third liquid level D _X at each point C _X on the liquid level characteristic line 42 to the calculator 67.
D _X = [(R _X −R _L ) × (D _H −D _L )] / (R _H −R _L ) + D _L (1)

Returning to FIG. 10, the calculation unit 67 includes the liquid surface characteristic line radius R _X and the third liquid at each point C _X on the liquid surface characteristic line 42 input from the radius detection unit 65 and the liquid level height detection unit 66. detection results of Mendaka of D _X, based on the needle-like recess shape data 53 read from the storage unit 47, calculates the volume of the drug solution 18 to be filled in the needle recess 14. Based on the detection result of the liquid surface characteristic line radius R _X and the liquid surface height D _X at each point C _X , the shape (including inclination) and the liquid surface height of the liquid surface 18a in the needle-like recess 14 are detected. be able to. Further, the shape of the needle-like recess 14 is also known based on the needle-like recess shape data 53. Therefore, the calculation unit 67 determines the volume of the aqueous drug solution 18 filled in the needle-shaped recess 14 based on the shape and liquid level of the liquid surface 18a in the needle-shaped recess 14 and the shape of the needle-shaped recess 14 ( That is, volume) can be calculated.

  Similarly, the radius detector 65, the liquid level detector 66, and the calculator 67 can calculate the volume of the pharmaceutical aqueous solution 18 filled in all the needle-like recesses 14 of the mold 12. The calculation result of the volume of the drug aqueous solution 18 is stored in the storage unit 47 and displayed on the display unit 49 as a measurement result of the volume of the drug aqueous solution 18 for each needle-like recess 14 of the mold 12.

  In addition, the calculation unit 67 calculates the volume of the drug 16 contained in the drug aqueous solution 18 in the needle-shaped recess 14 based on the measurement result of the volume of the drug aqueous solution 18 in the needle-shaped recess 14.

  FIG. 16 is a graph showing the relationship between the volume (liquid amount) of the pharmaceutical aqueous solution 18 filled in the needle-like recess 14 and the elapsed time immediately after filling. As shown in FIG. 16, the volume of the aqueous drug solution 18 in the needle-shaped recess 14 decreases with time due to the evaporation of water contained in the drug aqueous solution 18 as shown in FIG. The capacity of the medicine 16 in 14 does not change. For this reason, the concentration of the drug 16 in the drug aqueous solution 18 increases with time. Accordingly, the change with time of the volume of the drug aqueous solution 18 in the needle-like recess 14 as shown in FIG. 16 is obtained in advance, whereby the change with time of the concentration of the drug 16 in the drug aqueous solution 18 in the needle-like recess 14 is obtained. It is done.

  By storing the change in the concentration of the drug 16 over time in the storage unit 47 in advance, the calculation unit 67 allows the concentration of the drug aqueous solution 18 in the drug aqueous solution 18 in the needle-shaped recess 14 to be measured. The concentration of drug 16 can be determined. Thereby, the calculating part 67 calculates the capacity | capacitance of the chemical | medical agent 16 for every needle-shaped recessed part 14 based on the density | concentration of the chemical | medical agent 16 in the pharmaceutical aqueous solution 18, and the measurement result of the capacity | capacitance of the chemical | medical agent aqueous solution 18 for every needle-shaped recessed part 14. be able to. The calculation result of the capacity of the medicine 16 is also stored in the storage unit 47 as a measurement result of the capacity of the medicine 16 for each needle-like recess 14 of the mold 12 and displayed on the display unit 49.

[Operation of measuring device]
Next, the operation of the measurement apparatus 10 having the above-described configuration, that is, the measurement process (the measurement method of the present invention) of the volume of the pharmaceutical aqueous solution 18 for each needle-like recess 14 of the mold 12 will be described. First, measurement and storage of the pre-measurement data 52 are started before the measurement of the volume of the aqueous drug solution 18 is started.

<Measurement and storage of pre-measurement data>
FIG. 17 is a flowchart showing a flow of processing for measuring and storing the pre-measurement data 52. As shown in FIG. 17, first, the aqueous solution 18 is filled in each needle-shaped recess 14 of the same mold 12 as the mold 12 to be measured, and the first liquid surface 18 a _H is formed in each needle-shaped recess 14. Form (step S1). Thus, completing the preparation of the mold 12 _H above.

Next, after the mold 12 _H is set on a stage (not shown) of the measuring apparatus 10, the measurement input operation of the preliminary measurement data 52 (liquid surface characteristic line radius R _H ) is performed in the operation input unit 48. When the measurement start operation is performed, the parallel light PL toward the first surface 12a of the mold 12 _H is irradiated from the surface light source 21, the transmitted light of the parallel light PL that has been transmitted through the mold 12 _H (first transmitted light TL1 , Second transmitted light TL2, combined light TL4) is imaged by the imaging unit 25. Then, the imaging unit 25 generates image data of the transmitted light pattern image 35 and outputs it to the image processing system 26.

  The acquisition unit 59 of the control unit 46 of the image processing system 26 acquires the image data of the transmitted light pattern image 35 from the imaging unit 25 and outputs the image data of the transmitted light pattern image 35 to the liquid surface feature line detection unit 60. .

  The liquid surface characteristic line detection unit 60 analyzes the image data of the transmitted light pattern image 35 input from the acquisition unit 59 and detects the liquid surface characteristic lines 42 from the bright and dark images 37 for each needle-shaped concave portion 14. (Step S2, corresponding to the preliminary liquid level feature line detection step of the present invention). Then, the liquid level feature line detection unit 60 outputs the image data of the transmitted light pattern image 35 and the detection result of the liquid level feature line 42 to the capacity calculation unit 61.

The radius detection unit 65 of the capacity calculation unit 61 analyzes the image data of the transmitted light pattern image 35 based on the detection result of the liquid level feature line 42 input from the liquid level feature line detection unit 60, and the needle-like recess 14. The liquid surface characteristic line radius _RH from the center of the liquid surface to a plurality of points on the liquid surface characteristic line 42 is detected, and the average value of the liquid surface characteristic line radius _RH is calculated (step S3, the prior radius detection step of the present invention). Equivalent). Wherein the average value of the liquid level characteristic line radius R _H is, as described above, the average value of the liquid level characteristic line radius R _H to a plurality of points on all of the liquid level characteristic line 42 that is detected for each needle-like recesses 14 _Or an average value of the liquid surface characteristic line radii _RH up to a plurality of points on the representative liquid surface characteristic line 42 may be used. The radius detection unit 65 stores the average value of the liquid surface characteristic line radius _{RH in} the storage unit 47 as a part of the preliminary measurement data 52 (step S3).

Then, the mold 12 _H is set in the laser confocal microscope 63, the detection of the first liquid level height _{D H} from the second surface 12b of the mold 12 _H to the center of the first liquid level 18a _H by a laser confocal microscope 63 (Step S4, corresponding to the preliminary liquid level detection step of the present invention). The detection result of the first liquid level height _DH is input from the laser confocal microscope 63 to the storage unit 47, and is stored in the storage unit 47 as a part of the preliminary measurement data 52 (step S4).

After storing the average value of the liquid surface characteristic line radius _RH and the detection result of the first liquid surface height _DH , the drug aqueous solution 18 is filled in each needle-like recess 14 of the same mold 12 as the mold 12 to be measured. Then, the second liquid surface 18a _L is formed in each acicular recess 14 (step S5). Thus, completing the preparation of the mold 12 _L described above.

Hereinafter, similarly from Step S2 described above until the step S4, the detection of the liquid surface characteristic line 42 (step S6), and the detection of the liquid surface characteristic line radius R _L, calculation of the average value of the liquid level characteristic line radius R _L and storage and (step S7, corresponding to the pre-radius detecting step of the present invention), the detection and storage of the second liquid level D _L (step S8, corresponding to the pre-liquid surface height detection step of the present invention) and are executed The

  Thus, the storage of the preliminary measurement data 52 in the storage unit 47 is completed. Note that the measurement and storage of the pre-measurement data 52 need not be performed every time as long as the type of the mold 12 is not changed, and may be periodically executed. In addition, the preliminary measurement data 52 measured by another measurement apparatus 10 may be acquired and stored in the storage unit 47.

<Measurement of drug aqueous solution capacity>
FIG. 18 is a flowchart showing the flow of the process for measuring the volume of the pharmaceutical aqueous solution 18 for each needle-like recess 14. In the storage unit 47, needle-like recess shape data 53 measured by a known method is stored in advance.

  As shown in FIG. 18, after filling each needle-like recess 14 of the mold 12 with the chemical aqueous solution 18, the mold 12 is set on a stage (not shown) of the measuring apparatus 10 (step S <b> 11).

  Next, when the measurement input operation of the volume of the pharmaceutical aqueous solution 18 is performed in the operation input unit 48, the parallel light PL is irradiated from the surface light source 21 toward the first surface 12a of the mold 12, and the parallel light is applied to the first surface 12a. PL is incident (step S12, corresponding to the incident step of the present invention).

  As shown in FIGS. 5 and 6, the parallel light PL that has entered the non-formation region A of the first surface 12a travels straight toward the second surface 12b. As a result, the first transmitted light TL1 of the parallel light PL is emitted from the first region B of the second surface 12b. Further, the parallel light PL that has entered the first wall surface portion 14a of the needle-like recess 14 is refracted by the first wall surface portion 14a. As a result, the second transmitted light TL2 of the parallel light PL is emitted from the second region C of the second surface 12b. Furthermore, the parallel light PL that has entered the second wall surface portion 14b of the needle-like recess 14 is refracted by the second wall surface portion 14b. Thereby, the third transmitted light TL3 of the parallel light PL is emitted from the partial region B1 of the second surface 12b. As a result, the combined light TL4 of the first transmitted light TL1 and the third transmitted light TL3 is emitted from the partial region B1.

  The imaging unit 25 focuses transmitted light (first transmitted light TL1, second transmitted light TL2, and synthesized light TL4) emitted from the second surface 12b of the mold 12 in a state where the second surface 12b of the mold 12 is focused. An image is picked up by the image pickup device 24 and image data of the transmitted light pattern image 35 is generated (step S13, corresponding to the image pickup step of the present invention).

  Next, the imaging unit 25 outputs the generated image data of the transmitted light pattern image 35 to the image processing system 26. Thereby, the acquisition unit 59 of the control unit 46 of the image processing system 26 acquires the image data of the transmitted light pattern image 35 from the imaging unit 25 (step S14, corresponding to the acquisition step of the present invention). The acquisition unit 59 outputs the image data of the transmitted light pattern image 35 acquired from the imaging unit 25 to the liquid level feature line detection unit 60.

  The liquid surface characteristic line detection unit 60 analyzes the image data of the transmitted light pattern image 35 input from the acquisition unit 59 and performs the analysis from the light and dark image 37 for each needle-like concave portion 14 in the same manner as Steps S2 and S6 described above. The liquid level characteristic line 42 is detected (step S15, corresponding to the liquid level characteristic line detection step of the present invention). Then, the liquid surface characteristic line detection unit 60 outputs the detection result of the liquid surface characteristic line 42 for each needle-like recess 14 and the image data of the transmitted light pattern image 35 to the capacity calculation unit 61.

  Next, the calculation of the volume of the pharmaceutical aqueous solution 18 for each needle-like recess 14 by the volume calculation unit 61 is started (corresponding to the volume calculation step of the present invention). Here, in order to prevent the explanation from being complicated, the calculation of the volume of the aqueous drug solution 18 filled in one needle-like recess 14 will be described as an example.

First, the radius detector 65 analyzes the image data of the transmitted light pattern image 35 based on the detection result of the liquid surface feature line 42 input from the liquid surface feature line detector 60, and the center of the needle-like recess 14. The liquid surface characteristic line radius _RX to each point C _X on the liquid surface characteristic line 42 is detected (step S16, corresponding to the third radius detection step of the present invention). Then, the radius detector 65 outputs the detection result of the liquid surface feature line radius R _X of each point C _X on the liquid surface feature line 42 to the liquid surface height detector 66 and the calculator 67.

Next, the liquid surface height detection unit 66 substitutes the detection result of the liquid surface characteristic line radius R _X of each point C _X input from the radius detection unit 65 into the above formula (1), whereby each point C _X calculating a third liquid level D _X in (step S17, corresponding to the third liquid level detecting step of the present invention). Thus, the third liquid level D _X of each point C _X is detected. Then, the liquid level detector 66 outputs the detection result of the third liquid level D _X at each point C _X to the calculator 67.

The computing unit 67 receives the liquid surface characteristic line radius R _X and the third liquid surface height D _X of each point C _X on the liquid surface characteristic line 42 input from the radius detection unit 65 and the liquid level height detection unit 66, respectively. Based on the detection result, the shape (including inclination) and the liquid level of the liquid surface 18a in the needle-like recess 14 are detected. Next, the calculation unit 67 determines the inside of the needle-shaped recess 14 based on the detection result of the shape and the liquid level of the liquid surface 18 a in the needle-shaped recess 14 and the needle-shaped recess shape data 53 read from the storage unit 47. The volume of the pharmaceutical aqueous solution 18 filled in the container is calculated (step S18, corresponding to the calculation step of the present invention). Thereby, the volume of the aqueous drug solution 18 filled in one needle-like recess 14 is calculated.

  In the same manner, the volume of the aqueous drug solution 18 filled in all the needle-like recesses 14 of the mold 12 is calculated. The calculation unit 67 outputs the calculation result of the volume of the aqueous drug solution 18 for each needle-like recess 14 to the storage unit 47 and the display unit 49. As a result, the calculation result of the volume of the pharmaceutical aqueous solution 18 for each needle-like recess 14 is stored in the storage unit 47 and displayed on the display unit 49. Note that the calculation unit 67 may calculate the volume of the drug aqueous solution 18 in the entire mold 12 by integrating the calculation results of the volume of the drug aqueous solution 18 for each needle-like recess 14.

  Further, the calculation unit 67 is based on the measurement result (not shown) of the concentration of the drug 16 in the drug aqueous solution 18 in the needle-shaped recess 14 stored in the storage unit 47 in advance, and the drug solution 18 described above. The concentration of the drug 16 in the drug aqueous solution 18 in the needle-like recess 14 at the time of measuring the volume of the drug is obtained. Next, the calculation unit 67 calculates the volume of the drug 16 for each needle-shaped recess 14 based on the concentration of the drug 16 in the drug aqueous solution 18 and the measurement result of the volume of the drug aqueous solution 18 for each needle-shaped recess 14. The calculation result is output to the storage unit 47 and the display unit 49. Thereby, the calculation result of the capacity of the medicine 16 for each needle-like recess 14 is also stored in the storage unit 47 and displayed on the display unit 49.

  With the above, the measurement processing of the volume of the pharmaceutical aqueous solution 18 for each needle-like recess 14 of the mold 12 by the measuring device 10 is completed.

  The measurement result of the capacity of the drug aqueous solution 18 for each needle-like recess 14 obtained by the measuring device 10 is fed back to a filling device that fills each needle-like recess 14 of the mold 12 with the drug aqueous solution 18. For example, in the filling process of the chemical aqueous solution 18 by the filling device, the chemical aqueous solution 18 is applied to the first surface 12a of the mold 12, and the excess chemical aqueous solution 18 on the first surface 12a is removed by a brush or a scraper. And a removing step of forming a thin film of the drug aqueous solution 18 on the first surface 12a. These application process and removal process are processes that affect the capacity of the aqueous drug solution 18 in each needle-shaped recess 14. Therefore, by controlling the application speed of the application process and the removal speed of the removal process according to the measurement result (volume size and variation) of the drug aqueous solution 18 for each needle-shaped recess 14, The volume of the pharmaceutical aqueous solution 18 can be adjusted appropriately.

[Effect of this embodiment]
As described above, in the measuring apparatus 10 of the present embodiment, each needle is focused on the difference in the refraction angle of the parallel light PL refracted by the first wall surface portion 14a and the second wall surface portion 14b of each needle-like recess 14. Since the volume of the drug aqueous solution 18 in the concave portion 14 is measured, the volume of the drug aqueous solution 18 for each needle-shaped recess 14 of the mold 12 can be measured nondestructively at high speed. Further, the measuring device 10 can perform measurement without changing the measurement method even if the type of the drug 16 contained in the drug aqueous solution 18 changes.

[Others]
In the above embodiment, the first surface 12a of the mold 12 is not subjected to surface treatment, but for example, hydrophilic treatment such as Teflon (registered trademark) treatment may be performed on the first surface 12a. Thereby, generation | occurrence | production of the meniscus can be suppressed on the liquid level 18a of the chemical | medical solution 18 in the needle-shaped recessed part 14, and the liquid level 18a can be planarized. Thereby, the capacity | capacitance of the chemical | medical agent aqueous solution 18 in the needle-shaped recessed part 14 can be measured with high precision.

  In the above-described embodiment, the water contained in the drug aqueous solution 18 evaporates over time after the drug aqueous solution 18 is filled in each needle recess 14 of the mold 12. Capacity is reduced. At this time, for example, by adjusting the humidity around the mold 12 to 100% humidity (including almost 100%) after filling the aqueous chemical solution 18 until at least the measurement by the measuring device 10 is completed, You may make it suppress evaporation of. As a result, the concentration of the drug 16 in the drug aqueous solution 18 becomes substantially constant regardless of the passage of time, so that the volume of the drug 16 can be easily obtained from the measurement result of the volume of the drug aqueous solution 18. Instead of setting the humidity around the mold 12 to 100%, the evaporation of water may be suppressed by covering the first surface 12a of the mold 12 with a transparent lid (film or the like).

  In the above embodiment, one communication hole 31 is formed on the second surface 12 b of the mold 12 for each needle-like recess 14, but a plurality of communication holes 31 are formed for each needle-like recess 14. May be. Further, the diameter of the communication hole 31 may be changed as appropriate.

  In the above embodiment, the mold 12 is made of silicon rubber, but if the material is closer to the refractive index (1.35 to 1.34) of the pharmaceutical aqueous solution 18 than the refractive index of air (1.003), in particular. There is no limitation.

  In the above embodiment, the measurement apparatus 10 including the surface light source 21, the imaging unit 25, and the image processing system 26 has been described as an example. However, the measurement apparatus of the present invention is configured only by the image processing system 26. Also good. That is, the present invention is also applied to a measuring apparatus that acquires image data of the transmitted light pattern image 35 obtained separately via a memory card or a communication network and calculates the volume of the aqueous drug solution 18 based on the acquired data. be able to.

[Program that causes a computer to function as a means for measuring the volume of a pharmaceutical aqueous solution]
As the measurement apparatus described in the above-described embodiment, a program for causing a computer to function (the above-described measurement program 51 or the like) is a CD-ROM (Compact Disc Read Only Memory), a magnetic disk, or other computer-readable medium (a non-tangible object). A temporary information storage medium) and the program can be provided through the information storage medium. Instead of providing the program by storing the program in such an information storage medium, it is also possible to provide the program signal as a download service using a communication network such as the Internet.

  DESCRIPTION OF SYMBOLS 10 ... Measuring apparatus, 12 ... Mold, 12a ... 1st surface, 12b ... 2nd surface, 14 ... Needle-shaped recessed part, 14a ... 1st wall surface part, 14b ... 2nd wall surface part, 16 ... Drug | medical agent, 18 ... Drug aqueous solution, 18a ... Liquid level, 21 ... Surface light source, 25 ... Imaging unit, 26 ... Image processing system, 31 ... Communication hole, 35 ... Transmitted light pattern image, 42 ... Liquid level characteristic line, 51 ... Measurement program, 52 ... Pre-measurement data , 53 ... Needle-shaped recess shape data, 59 ... Acquisition unit, 60 ... Liquid level characteristic line detection unit, 61 ... Capacity calculation unit, 65 ... Radius detection unit, 66 ... Liquid level height detection unit, 67 ... Calculation unit

Claims (10)

In the measurement method for measuring the volume of the aqueous solution of the medicine filled in the needle-shaped recess of the mold having light permeability in which a plurality of needle-shaped recesses that are the inverted type of microneedles are formed,
A transmitted light image obtained by imaging the transmitted light of the parallel light emitted from the second surface opposite to the first surface by vertical incidence of parallel light on the first surface of the mold on the side filled with the aqueous solution. An acquisition step to acquire,
By analyzing the transmitted light image acquired in the acquisition step, the non-formation region of the needle-like recess, the first wall surface portion in the aqueous solution of the needle-like recess, and the solution of the aqueous solution of the needle-like recess From the image pattern in the transmitted light image formed by the transmitted light of the parallel light respectively incident on the second wall surface portion that is closer to the first surface than the surface, the liquid surface and the second wall surface portion A liquid surface characteristic line detecting step for detecting a liquid surface characteristic line indicating the boundary between
Based on the detection result of the liquid surface characteristic line detection step and the known shape of the needle-like recess, a capacity calculation step of calculating the capacity for each needle-like recess,
Measuring method. The transmitted light is incident on the non-formation region, travels straight through the mold, is emitted from the first region of the second surface, and is incident on the first wall surface portion and the first wall surface. Second transmitted light that is refracted by the portion and exits from the second region corresponding to the needle-like recess of the second surface, and the first transmitted light is incident on the second wall surface portion and is transmitted by the second wall surface portion. A third transmitted light that is refracted at a larger refraction angle and exits from a portion of the first region,
The image pattern is emitted from a portion different from the first portion of the first region and the first image formed by the combined light of the first transmitted light and the third transmitted light emitted from a portion of the first region. The first transmitted light and the second image formed by the second transmitted light emitted from the second region,
The measurement method according to claim 1, wherein the liquid level feature line detecting step detects the liquid level characteristic line based on a position of a boundary between the first image and the second image. The first image is an annular image that surrounds the outer periphery of the second image and is brighter than the second image;
The measurement method according to claim 2, wherein in the liquid surface characteristic line detection step, the annular liquid surface characteristic line is detected. A preliminary liquid level feature line detecting step for detecting in advance the liquid level characteristic lines of the first liquid level and the second liquid level which are parallel to the first surface and have different liquid level heights;
The first radius from the center of the needle-like recess of the liquid level feature line of the first liquid level detected in the preliminary liquid level feature line detection step, and the liquid level feature line of the second liquid level A pre-radius detection step for detecting in advance a second radius from the center of the needle-shaped recess;
Prior liquid level height for detecting in advance a first liquid level height from the second surface to the center of the first liquid level and a second liquid level height from the second surface to the center of the second liquid level. Detecting step,
The capacity calculation step includes:
A third radius detecting step for detecting a third radius from the center of the needle-shaped recess to each of the plurality of points of the liquid surface characteristic line based on the detection result of the liquid surface characteristic line detecting step;
Based on the detection result of the third radius detection step and the detection results of each of the preliminary radius detection step and the preliminary liquid level height detection step, the second surface to each of the plurality of points is detected. A third liquid level detection step for detecting the three liquid levels;
A calculation step of calculating the capacity in the needle-shaped recess based on the detection result of the third radius detection step and the third liquid level height detection step and the known shape of the needle-shaped recess;
The measurement method according to claim 1, comprising: Said first radius and R _H, the second radius and R _L, the first liquid level height and D _H, the second liquid level height and D _L, the for each of the plurality of points the When the third radius is R _X , the third liquid level for each of the plurality of points is D _X, and D _H > D _L , the third liquid level detection step is expressed by the following formula (1 ),
D _X = [(R _X −R _L ) × (D _H −D _L )] / (R _H −R _L ) + D _L (1)
The measurement method according to claim 4, wherein a third liquid level height for each of the plurality of points is detected by using. An incident step of perpendicularly incident the parallel light on the first surface;
An imaging step of imaging the transmitted light emitted from the second surface with an imaging unit to generate the transmitted light image;
The measurement method according to claim 1, wherein the acquiring step acquires the transmitted light image from the imaging unit.   The measurement method according to claim 6, wherein in the imaging step, the transmitted light is imaged using the imaging unit focused on the second surface. In the measuring device for measuring the volume of the aqueous solution of the medicine filled in the needle-shaped recess of the mold having light permeability in which a plurality of needle-shaped recesses that are the inverted type of microneedles are formed,
A transmitted light image obtained by imaging the transmitted light of the parallel light emitted from the second surface opposite to the first surface by vertical incidence of parallel light on the first surface of the mold on the side filled with the aqueous solution. An acquisition unit for acquiring
Analyzing the transmitted light image acquired by the acquisition unit, the non-formation region of the needle-like recess, the first wall surface portion in the aqueous solution of the needle-like recess, and the solution of the aqueous solution of the needle-like recess The liquid surface and the second wall surface based on an image pattern in the transmitted light image formed by the transmitted light of the parallel light respectively incident on the second wall surface portion that is closer to the first surface than the surface A liquid surface characteristic line detection unit that detects a liquid surface characteristic line indicating a boundary with the unit for each of the needle-shaped concave portions, and
Based on the detection result of the liquid surface characteristic line detection unit and the known shape of the needle-shaped recess, a capacity calculation unit that calculates the capacity for each needle-shaped recess,
A measuring apparatus comprising: An incident portion for vertically incidence of the parallel light on the first surface;
An imaging unit that images the transmitted light emitted from the second surface and generates the transmitted light image;
The measurement apparatus according to claim 8, wherein the acquisition unit acquires the transmitted light image from the imaging unit. A program that causes a computer to function as a means for measuring the volume of an aqueous solution of a medicine filled in the needle-like recess of a light-transmitting mold in which a plurality of needle-like recesses that are inverted types of microneedles are formed,
Computer
A transmitted light image obtained by imaging the transmitted light of the parallel light emitted from the second surface opposite to the first surface by vertical incidence of parallel light on the first surface of the mold on the side filled with the aqueous solution. An acquisition unit for acquiring
Analyzing the transmitted light image acquired by the acquisition unit, the non-formation region of the needle-like recess, the first wall surface portion in the aqueous solution of the needle-like recess, and the solution of the aqueous solution of the needle-like recess The liquid surface and the second wall surface based on an image pattern in the transmitted light image formed by the transmitted light of the parallel light respectively incident on the second wall surface portion that is closer to the first surface than the surface A liquid surface characteristic line detection unit that detects a liquid surface characteristic line indicating a boundary with the unit for each of the needle-shaped concave portions, and
The program for functioning as a capacity | capacitance calculating part which calculates the said capacity | capacitance for every said needle-shaped recessed part based on the detection result of the said liquid level characteristic line detection part, and the known shape of the said needle-shaped recessed part.