JP5105221B2 - Micro bubble tester - Google Patents

Description

  The present invention relates to a microbubble tester that automatically performs a microbubble test for judging maturity of a lung in a newborn (fetus).

  Fetal lung maturity is estimated by the amount of pulmonary surfactant contained in maternal amniotic fluid or neonatal gastric fluid. Here, the pulmonary surfactant is a substance that controls the surface tension in the alveoli and prevents the alveoli from collapsing. Usually, the lung surfactant begins to be produced around 20 weeks of gestation, and moves from the fetal lung to the amniotic fluid. It becomes a sufficient amount around the gestation 32 to 36 weeks. However, in the case of premature birth, there is a possibility that this lung surfactant amount is insufficient. Insufficient lung surfactant can cause the fetus to develop respiratory distress syndrome (RDS) by gradually collapsing the alveoli. In order to take measures against the respiratory distress syndrome (RDS), it is important to recognize the amount of pulmonary surfactant.

  A microbubble test is performed to recognize this lung surfactant amount. This is to determine the maturity of the fetal lung by foaming the mother's amniotic fluid or the gastric juice of the newborn and counting the number of microbubbles with a diameter within a predetermined range.

  In the conventional microbubble test, for example, bubbles are manually created with a bath stool pipette, and the foamed specimen taken on the cover glass is observed for five visual fields with a microscope, and the number of bubbles having a diameter of 15 μm or less is observed. And the average value in each field of view was calculated (see, for example, Patent Document 1).

Specifically, 40 μl of a sample is taken on a cover glass, and the sample on the cover glass is bubbled with a bath stool pipette. Next, this cover glass is turned upside down and placed on a hole glass provided with a hollow hole, and left to stand for 4 minutes. This is observed with a microscope for 5 fields, 1 mm ² per field. The number of bubbles having a diameter of 15 μm or less that can be confirmed per field of view is counted, and the average value of the number of counts by observation of five fields of view is calculated.
JP 2002-114135 A

  However, in such a manual microbubble test, it is necessary to master foaming work, and there may be a problem with the accuracy of counting microbubbles. was there. Further, the inspection work takes time, and the inspection takes time and cost.

  Therefore, the present application provides a microbubble tester that does not cause individual differences among examiners due to the foaming work of the microbubble test and the counting accuracy, and can reduce the time, labor, and cost of the inspection work. The task is to do.

  In order to solve the above problems, the present invention takes the following means (1) to (7).

  (1) In other words, the microbubble tester of the present invention is a microbubble tester that detects the occurrence of microbubbles in the specimen O by bubbling the specimen O containing biological fluid as a main component. The foaming means 1 for foaming the specimen O by rotating the terminal 11 while being in contact with the specimen O, the lid closing mechanism 23 for closing the foamed specimen O with the fluoroscopic lid 22, and the fluoroscopic lid 22 are provided. It is characterized by comprising bubble recognition means 3 for recognizing the number of bubbles contained in the closed sample O as viewed from the outside.

  (2) Further, in the microbubble tester, the lid closing mechanism 23 brings the fluoroscopic lid 22 into contact with the liquid surface of the specimen O in an oblique contact state S5, and from the oblique contact state S5, the specimen O It is preferable to be in the facing contact state S6 that faces the liquid surface in parallel.

(3) In any of the above microbubble testers,
The foaming means 1 includes a rotating member 11H provided with a contact terminal 11 at the lower end;
An elevating mechanism 12 that moves the rotating member 11H up and down to place the contact terminal 11 in a separated state S1 or a contact state S2 separated from the specimen O;
A rotating mechanism 13 for rotating the rotating member 11H (around the rotation axis L) in the contact state S2,
A scattering prevention cover 14 for preventing scattering of the specimen O by surrounding the circumference of the specimen O in the contact state S2,
A locking mechanism 15 for locking the anti-scattering cover 14 to the rotating member 11H in the separation state S1,
In the separation state S1, the locking mechanism 15 is in the locking state S4, and the scattering prevention cover 14 is lifted by the rotating member 11H that moves up and down,
In the contact state S2, the locking mechanism 15 is in the unlocked state S3, and the scattering prevention cover 14 is placed at a position surrounding the sample O and the contact terminal 11,
In this contact state S2, it is preferable that the rotating member 11H is rotated by the rotating mechanism 13 to foam the sample O, and the placed scattering prevention cover 14 prevents the sample O from scattering.

  With such a configuration, the scattering prevention cover 14 can be easily set or removed from the set position as the rotating member 11H is raised and lowered. Since there is no need to separately set or remove the scattering prevention cover 14, scattering can be prevented with a simple mechanism or simple procedure.

  In addition, since the scattering prevention cover is in the unlocked state S3 after the setting, the specimen O can be reliably prevented from scattering without rotating together with the rotating member 11H.

  Further, since the scattering prevention cover 14 is locked and integrated with the rotating member 11H in the separated state S1, the rotating member and the scattering preventing cover that have contacted the sample O after foaming can be easily removed and discarded together. Can do.

  (4) Further, in the microbubble tester, the locking mechanism 15 includes a locking piece 15a protruding in a uniform shape to the inside of the anti-scattering cover, and a locked piece 15b protruding axially symmetrically around the rotating member 11H. When the rotating member 11H is raised and lowered, the locking piece 15a is locked to the locked piece 15b, and the scattering prevention cover is locked at a uniform position around the rotating member S4. When descending, it is preferable to shift to the unlocked state S3 while maintaining the uniform peripheral position.

  If it is such, the set position of the scattering prevention cover 14 can be maintained at an appropriate position, and contact between the rotating rotating member 11H and the scattering prevention cover 14 can be reliably prevented.

  Specifically, the latching piece and the latching surface of the latching piece (the concentric holes of the perforated disc and the peripheral end surfaces of the washers) are respectively inclined surfaces and are lifted if they are formed in tapered shapes corresponding to each other. Sometimes, the anti-scattering cover 14 can be automatically centered on the rotating member 11H, and the set position of the anti-scattering cover 14 is kept appropriate.

  (5) In any one of the above microbubble testers, the rotating member 11H is coaxially magnetically attached to the shaft end, which is the tip of the rotating motor shaft 13L of the rotating mechanism 13, and is detachably fixed. It is preferable to rotate coaxially with the rotary motor shaft 13L while being fixed to the rotary motor shaft.

  If it is such, the rotating member 11H can be easily attached to and detached from the rotating motor 13M, and the attaching operation of the rotating member 11H at the time of measurement and the removing operation of the rotating member to which the sample O adheres after foaming are easy. Can be done.

  (6) In any one of the above microbubble testers, the rotating member 11H rotates about the rotation axis L, and the rotation axis L is inclined at a predetermined inclination angle θ with respect to the vertical direction. Is preferred. By tilting the rotation axis L, the sample O can be efficiently bubbled as compared to the rotation axis L oriented in the vertical direction.

  (7) In any one of the microbubble testers, it is preferable that the bubble recognition unit 3 recognizes the number of bubbles in a plurality of depth cross sections of the specimen O. Since microbubbles of minute size, particularly amniotic fluid microbubbles, do not deform more flat than necessary, counting mistakes can be prevented by counting the number of bubbles at a plurality of depths, and can be counted reliably.

  Specifically, as a plurality of depth cross sections, the number of bubbles is recognized and counted in three or more cross sections in the liquid of the specimen O obtained by dividing the thickness direction of the spacer 24 covering the side periphery of the specimen O into at least four equal parts. Then, it is preferable to output and display a value obtained by averaging the number of bubbles in each cross section on the screen of the display means 33 (for example, FIG. 14).

  In the microbubble tester, the foaming means 1 includes a rotating member 11H having a contact terminal 11 at the tip, and the contact terminal 11 of the rotating member 11H is moved up and down by an elevating mechanism 12 so as to have an arbitrary contact length. In addition, it is preferable to contact the specimen O with an arbitrary contact pressure, and to rotate around the rotation axis L inclined from the vertical direction or the vertical direction in the contact state S2.

  Further, in the microbubble tester, the rotating member 11H is a rotating brush having brush hairs as a plurality of contact terminals 11, and at least any one of the plurality of contact terminals 11 is spaced apart when the rotating part brush is rotated. It is preferable that the contact terminal 11 expands toward the tip.

  In the microbubble tester, the bubble recognition unit 3 is recognized by the imaging unit 31 that recognizes the imaging of the sample O, the fluoroscopic lid 22 interposed between the sample O and the imaging unit 31, and the imaging unit 31. It is preferable to include an analysis unit 32 that analyzes the number of bubbles having a diameter within a predetermined range included in the captured image.

  In the microbubble tester, the bubble recognition means 3 may be provided with a magnifying lens such as a microscope.

  In the present application, by adopting the above-mentioned means, there is no individual difference between the examiners due to the microbubble test foaming work and the counting accuracy, and the inspection work time, labor and cost are reduced. A possible microbubble tester can be provided.

  Embodiments of the present invention will be described in detail with reference to the drawings. 1 to 15 show a microbubble tester according to a first embodiment of the present invention, and FIGS. 16 to 19 show a microbubble tester according to the second embodiment.

Specifically, FIG. 1 and FIG. 2 are schematic views showing the overall configuration of the microbubble tester according to the first embodiment of the present invention in the separated state, and are a side view and a front view, respectively.
3 and 4 show an overview of the rotating member 11H and the rotating motor shaft 13L and an exploded explanatory view of the rotating mechanism 13 of the first embodiment.

  FIG. 5 thru | or 7 is a side view explanatory drawing when the raising / lowering unit 12Y exists in an upper position or a lower end position about the operating condition of the raising / lowering mechanism 12 of Example 1, respectively. The state of each figure will be described in detail. In FIG. 5, the contact terminal 11 is in the separated state S1, and the locking mechanism 15 is in the locked state S4. In FIG. 6, the contact terminal 11 is in the separation state S1, and the locking mechanism 15 is in the process of moving from the locking state S4 to the locking release state S3. In FIG. 7, the contact terminal 11 is in the contact state S2, and the locking mechanism 15 is in the unlocking state S3.

  8 to 15 are explanatory views showing the lid closing mechanism 23 according to the first embodiment, and FIG. 8 is a perspective overview of the lid holding arm 23H. FIGS. 9 to 11 are explanatory views in side view when the elevating unit 12Y is in the upper end position or the lower end position, respectively, regarding the operating state of the lid closing mechanism 23 of the first embodiment. FIG. 9 shows the state before closing, FIG. 10 shows the oblique contact state during closing (air escape state), FIG. 11 shows the facing contact state after closing, Each is shown in side view. FIGS. 12 and 13 are side view explanatory views of the mounting plate 21 in the state of FIGS. 9 and 11, respectively, and FIG. 14 is an enlarged side view of the sample O in FIG. 13 (state of FIG. 11). It is explanatory drawing. FIG. 15 is an explanatory plan view showing the placement plate 21 and the see-through lid 23 of FIG. 13 (state of FIG. 11).

  FIG. 16 is a perspective explanatory view showing the configuration of the cover presser plate 17 of the microbubble tester of the second embodiment.

  FIGS. 17 to 19 are explanatory views in side view when the elevating unit 12Y is in the upper end position or the lower end position with respect to the operating state of the elevating mechanism 12 of the second embodiment. Specifically, in FIG. 17, the contact terminal 11 is in the separated state S1, and the locking mechanism 15 is in the locked state S4. Further, in FIG. 18, the contact terminal 11 is in the separation state S1, and the locking mechanism 15 is in the process of moving from the locking state S4 to the locking release state S3. In FIG. 19, the contact terminal 11 is in the contact state S2, and the locking mechanism 15 is in the unlocking state S3.

<Overall Configuration of Microbubble Tester of the Present Invention (FIG. 1)>
The microbubble tester of the present invention detects the occurrence of microbubbles in the specimen O by foaming the specimen O containing biological fluid as a main component. Then, as shown in FIG. 1, the foaming means for foaming the specimen O by rotating the contact terminal 11 to the specimen O in contact with the specimen O at the foaming position P1, and the foaming position at the closed position. A lid closing mechanism 23 for closing the bubbled specimen O with the fluoroscopic lid 22, and the fluoroscopic lid 22 is inspected from the outside at the bubble recognition position P2 to recognize the number of bubbles contained in the closed specimen O. It comprises a bubble recognition means 3 and a placement transport means 2 for placing the specimen O and transporting it to each position. Hereafter, each structure in an Example is explained in full detail.

(Sample O)
Specimen O referred to in the present invention refers to one that can recognize the state by observing the foamed state, and in the microbubble tester for pulmonary surfactant that measures the amount of pulmonary surfactant, It is the gastric juice of a newborn. In the examples, maternal amniotic fluid is shown as specimen O of the microbubble tester for lung surfactant.
[Foaming means 1]

  The foaming means 1 has a contact terminal 11 that can come into contact with the specimen O. The contact terminal 11 comes into contact with the specimen O, and the relative position between the contact terminal 11 and the specimen O is changed to raise the specimen O. Means for foaming. Various forms can be adopted for foaming. Specifically, for example, the rotating member 11H having the contact terminal 11 at the tip is provided, and the contact terminal 11 in contact with the specimen O is rotated. Further, the contact terminal 11 of the rotating member 11H is brought into contact with the specimen O with an arbitrary contact length or an arbitrary contact pressure, and is rotated around the rotation axis L inclined from the vertical direction or the vertical direction in either one or both directions. The sample O is caused to foam by rotating it to the right.

  Specifically, the foaming means 1 according to the first embodiment has a rotation mechanism 13 that can rotate the contact terminal 11 provided at the lower tip at the lower end position, and upper and lower end positions at which the contact terminal 11 is separated from or brought into contact with the specimen O. A lifting mechanism 12 that is moved between the upper end position away from above the specimen O or the upper and lower positions between the lower end positions where the contact terminal 11 contacts the specimen O, and the rotating member 11H and the specimen O at the lower end position. The scattering prevention cover 14 which covers the circumference | surroundings, and the latching mechanism 15 which latches the scattering prevention cover 14 and the contact terminal 11 are provided.

(Rotating member 11H)
The rotating member 11 </ b> H is a cylindrical rod that extends around the rotation axis L and is rotated by a rotation motor of the rotation mechanism 13. Specifically, for example, it is composed of a cylindrical shaft having a diameter of 4 mm, and has a plurality of brush bristles as contact terminals 11 at the lower end.

  In the first embodiment, the upper base end surface of the rotating member 11H is screwed and fixed to the short columnar connecting mechanism 16 that is magnetically attached to the rotating motor shaft 13L and rotates coaxially with the connecting screw 16S (FIGS. 3 and 4). ). A plurality of contact terminals 11 are fixed to the outer periphery of the rotating member 11H. The rotating member 11H is in a state where at least a part of the contact terminal 11 at the tip of the stationary rotating member 11H is in contact with the sample O at the lower end position.

(Contact terminal 11)
The contact terminal 11 consists of a thin linear wire brush. Specifically, a wire having a diameter of 0.1 mm is fixed in the axial direction at an equal interval of 0.1 mm along the outer periphery near the tip of the rotating member 11H. The open length of the contact terminal 11 protruding forward from the rotating member 11H is 15 mm.

  In the stationary state where the rotating member 11H is stationary, each of the contact terminals 11 faces a direction parallel to the rotation axis L direction, and at least the interval between the plurality of contact terminals 11 is the base end of the contact terminal 11 The distance from the (fixed end) to the front end (open end) is substantially equal.

  On the other hand, in the rotation state in which the rotating member 11H is rotated, the interval between at least one of the plurality of contact terminals 11 increases from the proximal end (fixed end) to the distal end (open end) of the contact terminals 11.

  In the contact terminal 11 of the embodiment, one end of a plurality of brush bristles arranged in parallel is fixed with a tape and bundled as a brush tape 11T, and this brush tape 11T is wound and fixed to a lower end of a cylindrical rotating member 11H. Formed. The brush tape 11T bulges out by being fixed to the peripheral surface of the rotating member 11H with a step. For this reason, the brush tape 11T has a function of preventing the washer as a locking piece 15a inserted in the rotating member 11H above the brush tape 11T, or a locked piece 15b that is also inserted in the rotating member 11H. The anti-separation function of the anti-scattering cover having a function is achieved (FIG. 3).

(Rotating axis L)
The rotation axis L is inclined forward with respect to the vertical direction by a minute inclination angle θ in the range of 1 to 10 degrees, preferably 2 to 5 degrees in a side view. In addition, it is a vertical direction in front view. As a result, the rotating brush is brought into contact with the normal line of the liquid level on the horizontal plane (that is, with respect to the vertical direction) with a small inclination angle θ. More specifically, the lower side of the contact terminal 11 circulates around the contact surface between the anti-scattering cover 14 and the mounting plate 21, while the higher side circulates along the inner wall of the anti-disaster cover. As a result, the tip of the contact terminal 11 draws an elliptical trajectory having the major axis of the plane-view projection axis of the rotation axis L. Specifically, for example, when the contact terminal 11 is arranged on a circle having an inner diameter of 15 mm and the inclination of the rotation axis L is set to 3 degrees with respect to the vertical direction, the tip of the contact terminal 11 has a major diameter of 15.02 mm and a short length. Draw an elliptical orbit with a diameter of 15 mm. Thus, the specimen O is scraped up when the brush is raised, and the specimen O is sheared when it is lowered, that is, when it returns to the liquid of the specimen O, and the specimen O is efficiently stirred.

(Elevating mechanism 12)
The elevating mechanism 12 elevates and lowers the rotating member 11H between the upper end position above the specimen O or the lower end position where the contact terminal contacts the specimen O, that is, between the upper and lower end positions. Specifically, it includes an elevating pole 12P vertically installed at the bubble position P1, and a box-type elevating unit 12Y inserted through the elevating pole 12P and controlled to move up and down along the elevating pole 12P. (Figs. 1 and 2). A rotating mechanism 13 is detachably fixed to the elevating unit 12Y from the front side of the box-shaped front by a connecting mechanism 16, and a cover pressing plate 7 is pressed downward from the bottom of the box-shaped arm. The lid holding arm 23H is fixed downward from one side of the side close to the box-type lid closing position (right side in the front view in the embodiment) (FIGS. 1 and 2). The rotating mechanism 13, the cover pressing plate 7, and the lid holding arm 23H move up and down together with the lifting unit 12Y (FIGS. 5 to 7).

  As a result, the contact terminal 11 is moved away from and in contact with the specimen O, so that the separated state S1 or the contact state S2. Further, the cover presser plate 7 is brought into contact with the scattering prevention cover 14 that is grounded to be in the separated state S1 or the contact state S2. Further, the see-through lid 22 held on the inclined plate 23Ht of the lid holding arm 23H is brought into and out of contact with the mounting plate 21 on the plate holder 25H to be in the separated state S1 to the contact state S2, and further in the opposed contact from the oblique contact state S5. Let it be state S6.

  By this elevating mechanism 12, the rotating member 11H is set to a contact state S2 in a state where foaming is possible. In the contact state S2, which is a state where foaming is possible, at least a part (a total number of tips in the embodiment) of the plurality of contact terminals 11 serving as the contact terminals 11 is in contact with the specimen O.

  The lower end position (brush set height) of the rotating member 11H, which is a preferable rotational position, is a height at which all the tip portions of the contact terminals 11 in contact with the surface of the glass serving as the mounting plate 21 in a stationary state. . For example, positioning is performed by a sensor arranged on the side of the mounting plate 21. This sensor may be a non-contact visual sensor that determines the presence or absence of a gap between the upper surface of the mounting plate 21 and the contact terminal 11 by visible light from the side surface, and detects the pressure due to the contact between the contact terminal 11 and the mounting plate 21 It may be a pressure sensor. In addition, the contact terminal 11 and the mounting plate 21 are made of a conductor, and various sensors such as a conductive sensor that detects the amount of conduction due to the contact between the contact terminal 11 and the mounting plate 21 can be used.

  When the liquid amount is 130 μl, the lower end position (brush set height) of the rotating member 11H is preferably an error within plus or minus 1 mm.

(Rotating mechanism 13)
The rotation mechanism 13 is a mechanism that rotates the rotation member 11H around the rotation axis L in the contact state S2 in which the contact terminal 11 is in contact with the specimen O. Specifically, the rotary motor 13L and the rotary member 11H are fixed coaxially with the rotary shaft L. More specifically, as shown in FIGS. 3 and 4, the distal end of the motor shaft and the upper distal end (base end) of the rotating member 11H can be removed by magnetic attachment at the fitting structure and the contact portion in the fitting structure. Fixed to. A prismatic or columnar magnet is fixed to the lower end of the rotary motor shaft 13L as the connecting magnetic body 16M. In addition, a rectangular tube or cylindrical connecting hole 16H is provided coaxially at the upper base end of the rotating member 11H, and the connecting magnetic body 16M is inserted into the connecting hole 16H. A metal plate made of a magnetized body is embedded in the hole bottom of the hole 16H. In the embodiment, the metal plate is composed of a dish-shaped head of a connecting screw 16S that connects the columnar connecting mechanism 16 and the rotating member 11H. The dish-shaped head of the connecting screw 16S comes into contact with the distal end surface of the connecting magnetic body 16M, and is magnetically attached and detachably coaxially fixed (FIGS. 3 and 4).

  When the connecting screw 16S is screwed from the upper base end surface of the thin rod-shaped rotating member 11H, the rotating member 11H is previously provided with a perforated plate as the locking piece 15a of the anti-scattering cover 14 and the locked piece 15b. There is a washer. And as shown in FIG. 3, the washer which is the to-be-latched piece 15b latches on the stepped part of the brush tape 11T bulging on the lower end side of the rotating member 11H, and the perforated plate which is the latching piece 15a Then, it is brought into contact with the washer as the latched piece 15b on the downward inclined side surface and locked (FIG. 3).

(Spattering prevention cover 14)
The anti-scattering cover 14 is placed so as to surround the periphery of the rotating member 11H and the sample O at the lower end position in the contact state S2, thereby preventing the sample O from scattering at the time of foaming. .

  Specifically, for example, it is composed of an inverted container-like cover in which a ceiling plate is provided at the upper end of a cylindrical body that can enclose the rotating member 11H and the specimen O. In order to confirm the state of foaming in particular, for example, a light transmissive member having an inner diameter of 15 mm (that is, a transparent member) is used. The anti-scattering cover 14 is brought down to a position where the lower surface comes into contact with the mounting plate 21 by the elevating mechanism 12 when foaming and the entire lower surface comes into contact (FIGS. 6 and 7). In the contact state S2 where the anti-scattering cover 14 is lowered to the above position, the rotating member 11H rotates with the lower edge of the cover in close contact with the mounting plate 21 (FIG. 7).

(Locking mechanism 15)
The locking mechanism 15 locks the scattering prevention cover 14 and the contact terminal 11 in the separated state S1 where the contact terminal 11 is separated from the specimen O. Specifically, the locking mechanism 15 is in the unlocked state S3 in the contact state S2 in which the contact terminal 11 is in contact with the sample O (FIG. 7), and in the separated state S2 in which the contact terminal 11 is separated from the sample O, It will be in the latching state S4 which latched the scattering prevention cover 14 to the rotating member 11H. That is, when moving from the lower end position to the upper end position, the locking mechanism 15 enters the locking state S4, and the scattering prevention cover 14 is lifted (FIG. 5). Moreover, it will be in the latch release state S3 in the vicinity of the lower end position from the position (FIG. 6) where the anti-scattering cover 14 contacts the ground to the lower end position (FIG. 7).

  In the embodiment, the locking mechanism 15 includes a locking piece 15a that protrudes toward the cylinder shaft side of the cylindrical scattering prevention cover, and a locked piece 15b that protrudes to the periphery from the rotation shaft of the rotating member 11H.

  The locking piece 15a can be made of, for example, a perforated disk in which concentric holes are formed in a disk that covers one end of a cylindrical scattering prevention cover 14 in a lid shape. The locked piece 15b can be made of, for example, a washer inserted through the rotating member 11H (FIG. 4).

  In this way, the cylindrical scattering prevention cover 14 is locked so as to surround the rotating member 11H, so that the rotating member H after foaming is removed or when the lifting unit 12Y is lifted or lowered during the closing process. In this case, the specimen O is not scattered or attached to fingers or the like. After use, the rotating member 11H and the scattering prevention cover 14 to which the sample is attached need to be discarded. By preventing the sample O from scattering and adhering, this disposal operation can be performed in a sanitary manner while preventing unnecessary infection. It can be carried out.

  If the locking surfaces of the locking pieces and the locking pieces (the concentric holes of the perforated disk and the peripheral end surfaces of the washers) are inclined surfaces and are formed in tapered shapes corresponding to each other, they are scattered when lifted. The centering of the prevention cover 14 to the rotating member 11H can be automatically performed, and the set position of the scattering prevention cover 14 is kept at an appropriate one. By keeping the set position of the scattering prevention cover 14 at an appropriate position, contact between the rotating rotating member 11H and the scattering prevention cover 14 can be reliably prevented.

  Since the rotation axis L is shaken when the rotating member 11H is rotated, the rotating rotating member 11H and the scattering prevention cover are likely to come into contact with each other if the set position of the scattering prevention cover 14 is shifted. This contact hinders accurate measurement of the degree of foaming by the mechanical foaming operation, or the scattering prevention cover 14 is lifted and cannot function.

(Cover holding plate 17)
The cover pressing plate 17 according to the first embodiment is composed of a lower bent elastic plate whose tip is a leaf spring portion that is an elastic member. As shown in FIGS. 2 and 5, the leaf spring portion is inclined downward. , And is fixed to the elevating unit 12Y via the pressing plate fixing arm 17H. This leaf spring portion is in a state of being separated upward from the scattering prevention cover 14 when the elevating unit 12Y is at the upper end position (FIG. 5).

  When the elevating unit 12Y moves downward from the upper end position to the lower end position, the holding plate fixing arm 17H and the cover holding plate 17 fixed to the elevating unit 12Y are lowered together with the elevating unit 12Y. Since the descending operation continues even after the scattering prevention cover 14 is grounded, the relative position of the scattering prevention cover 14 with respect to the rotating member 11H is shifted upward. As a result, the cover pressing plate 17 comes into contact with the upper surface of the scattering prevention cover (for example, the state shown in FIGS. 6 to 7). In this contact state, the leaf spring portion elastically biases the anti-scattering cover 14 from above and firmly fixes the position of the anti-scattering cover so that the position of the anti-scattering cover does not change.

  The cover pressing plate 17 according to the second embodiment is a flat plate having a central hole and a notch at the end as shown in FIG. This flat plate is an elastic plate, and an elevating pole 12P of the elevating mechanism 12 passes through the central hole, and the upper surface portion closer to the tip than the central hole is hinged and fixed at a relative angle by a presser plate fixing arm 17H that can be moved up and down. At the same time, the base end side is hinged to the fixing portion (see FIG. 17).

  As the elevating unit 12Y according to the second embodiment moves up and down, the holding plate fixing arm 17H fixed to the elevating unit 12Y moves up and down. In the cover pressing plate 17 of the second embodiment, the base end side is fixed to the fixing portion, and the upper surface portion near the tip is hinged to the pressing plate fixing arm 17H. For this reason, as the presser plate fixing arm 17H moves up and down, the distal end side of the cover presser plate 17 moves up and down while the base end side of the cover presser plate 17 is fixed to the fixing portion (FIGS. 17 to 19).

The vicinity of the front end side of the cover pressing plate 17 of the second embodiment is a leaf spring portion as in the first embodiment by having a notch in the center. This leaf spring portion is in a state of being separated upward from the scattering prevention cover 14 when the elevating unit 12Y is in the upper end position (FIGS. 17 and 18). When the lifting unit 12Y is lowered from the upper end position to the lower end position, the holding plate fixing arm 17H fixed to the lifting unit 12Y is lowered together with the lifting unit 12Y and is hinged to the holding plate fixing arm 17H at a position near the tip. The cover pressing plate 17 rotates downward with the base end as a fulcrum and is inclined downward. Since the descending operation continues even after the scattering prevention cover 14 is grounded, the relative position of the scattering prevention cover 14 with respect to the rotating member 11H is shifted upward (FIG. 18). After that, the cover pressing plate 17 comes into contact with the upper surface of the anti-scattering cover (FIG. 19). In the contact state of the cover holding plate 17 with the scattering prevention cover 14, the leaf spring portion elastically biases the scattering prevention cover 14 from above and firmly fixes the position of the scattering prevention cover so that the position of the scattering prevention cover does not change.
[Loading and transporting means 2]

(Mounting plate 21)
The placement plate 21 is a plate on which the specimen O is placed, and for example, a glass plate is used. The mounting plate 21 on which the specimen O is placed is transported to the foam recognition position P2 by the transport means 25 after the specimen O is foamed by the foaming means 1 at the foaming position P1, and the fluoroscopic lid 22 is the fluoroscopic lid 22. Bubble recognition is performed by the bubble recognition means 3 in a state where 22 slide glasses are stacked.

(Spacer 24)
A spacer 24 having a predetermined thickness is disposed on the upper surface of the mounting plate 21 so as to cover the mounting portion where the specimen O is mounted. The spacer 24 is placed in order to prevent the see-through lid 22 from expanding and overflowing outwardly when the see-through lid 22 covers the placement plate 21 and comes into contact with the foamed specimen O. A space having a predetermined height is secured on the upper surface side of the plate 21 (FIGS. 12 and 13). As the spacer 24 of the embodiment, a plastic tape having a predetermined thickness of 0.2 mm is stuck in a four-sided frame shape in plan view surrounding the specimen O placement portion of the placement board 21 (FIG. 15).

  The predetermined thickness for securing the thickness of the placed specimen O by the spacer 24 is preferably about 0.1 mm to 0.5 mm. This is because the specimen O is foamed and spreads in a plane direction when a slide glass as the fluoroscopic lid 22 is put on, and a liquid layer is secured on the mounting plate 21, so that the visual field range for foam recognition is increased. The thickness can be secured widely. Further, the thickness is such that the liquid layer is too thick to reduce the amount of transmitted light and make bubble recognition difficult.

(Cover mechanism 23)
The lid closing mechanism 23 is configured to bring the fluoroscopic lid 22 into contact with the liquid surface of the specimen O in the oblique contact state S5, and to the opposite contact state S6 in which the inclination angle is gradually reduced from the oblique contact state S5. This is achieved by the lid holding arm 23H descending toward the lower mounting plate 21 and closing the lid while holding the fluoroscopic lid 22 on the pair of inclined plates 23Ht provided parallel to the tip. (FIGS. 9 to 11).

  By contacting from the oblique contact state S5, air between the fluoroscopic lid 22 and the specimen O can be released when the upper part of the specimen O is closed (FIG. 10).

  The oblique contact state S5 is a state in contact with the liquid surface of the specimen O while being tilted, and the opposing contact state S6 is a state in which the liquid contact surface of the specimen O is opposed to the liquid surface in parallel.

(Lid holding arm 23H)
Specifically, as shown in FIG. 8, the lid holding arm 23H holds the vicinity of both ends of the fluoroscopic lid 22 with a pair of minutely inclined plates 23Ht, and the outer sides of both ends of the fluoroscopic lid 22 are provided upright. It is assumed that it is surrounded by a plate 23He. The lid holding arm 23 </ b> H is connected and fixed to the lifting unit 12 </ b> Y of the lifting mechanism 12, and the transparent lid 22 is mounted on the mounting plate 24 by moving up and down with the lifting and lowering operation of the lifting mechanism 12.

(Transparent lid 22)
The see-through lid 22 has translucency that allows the imaging light of the translucent bubble recognition means 3 to pass therethrough. By defining the imaging focus of the imaging means 31 on the surface of the fluoroscopic lid 22, the focus is eliminated and the imaging is sharpened. The fluoroscopic lid 22 is interposed between the specimen O and the imaging unit 31 and transmits the imaging light of the bubble recognition unit 3.

  In the embodiment, during the bubble recognition by the bubble recognition means 3, a slide glass having a relatively large thickness is placed on the placement plate 21 as a transparent lid 22 (FIG. 13). This is for obtaining a plane as a focal position at the time of visual inspection by the imaging means 31 such as a microscope. That is, when a thin cover plate is used as the fluoroscopic lid 22, a minute distortion occurs on the plate surface, and when the plane of the fluoroscopic lid 22 is offset as a reference position, an error may occur in bubble recognition. On the other hand, if a plate body (for example, a slide glass) having a sufficient thickness that keeps the plate surface flat and does not cause unnecessary deflection is used, the upper surface or the lower surface of the fluoroscopic lid 22 is set as a reference position for bubble recognition. In this case, when a position ahead by a predetermined distance from the reference position is recognized, it becomes a uniform recognition position that hardly causes an error.

  The fluoroscopic lid 22 has a function of enlarging the liquid level image of the specimen O, which is a visible image, when the specimen O under the fluoroscopic lid 22 is viewed from above the fluoroscopic lid 22 as an image magnification function. It may be. In addition, as a dimming function, there is a function for adjusting the direction of light transmitted from the lower side of the fluoroscopic lid 22 to the upper side through the fluoroscopic lid 22 by a one-way or two-way filter with a large number of ridges and slits running in parallel. (Neither shown).

(Conveying means 25)
The transport means 25 transports the placement plate 21 on which the sample O is placed at least between the foaming position P1 and the foam recognition position P2.

  The bubble position P1 is a position where at least bubbles are generated by the foaming means 1, and is the left side of the front view of FIG. A takeout port 41 is provided at the bubble position P1 to facilitate the maintenance of the bubble means 1 and the handling during the above operation. The bubble recognition position P2 is a position where the bubble recognition unit 3 performs bubble recognition, and is the left side of the front view of FIG. A high space recognition accuracy is ensured by securing an accommodation space for the bulky bubble recognition means 3 and recognizing the bubble at a stationary position shifted from the bubble position P1.

The transport means 25 of the embodiment includes a transport rail 25R that runs in the left-right direction when viewed from the front by a stepping motor, a mounting plate holder 25H that can move on the transport rail 25R, one end of the transport rail 25R when viewed from the front by the stepping motor, and And a transport driving mechanism 25M that moves between multiple ends. The left end of the transport rail 25R in front view is the foaming position P1, and the right end in front view is the foam recognition position P2 (FIG. 2). The transport drive mechanism 25M controls the amount of movement from the foaming position P1 to the left side when viewed from the front by the number of pulses.
[Recognition means]

(Bubble recognition means 3)
The bubble recognizing means 3 recognizes the number of bubbles in a plurality of depth cross sections of the specimen O (for example, cross sections obtained by equally dividing the spacer 24 in the thickness direction as shown by A, B, and C in FIG. 14). The number, trend, and size of bubbles contained in the foamed specimen O are identified by averaging the number of recognized bubbles. By visually recognizing in a plurality of cross-sections as shown in FIG. 14, it is possible to prevent a misrecognition ratio of impurities that do not become foamed and to grasp the microbubble content rate more accurately.

  Specifically, the bubble recognizing unit 3 includes an imaging unit 31 that recognizes imaging of the specimen O viewed from above the liquid surface, a fluoroscopic lid 22 interposed between the specimen O and the imaging unit 31, and the imaging unit 31. And an analysis unit 32 for analyzing the number of bubbles having a diameter within a predetermined range included in the imaging recognized by the above. The bubble recognition means 3 is preferably provided with a magnifying lens (microscope).

(Imaging means 31)
The imaging unit 31 is a unit that recognizes imaging viewed from above the liquid surface of the specimen O. Specifically, an optical imaging means for a visible visible image including a magnifier such as a CCD camera, a microscope, a loupe lens, and a reflecting mirror, and an invisible or non-visible image including a thermal sensor, a sound wave sensor, and an infrared sensor. Both optical imaging means are included.

(Analysis unit 32)
The analysis unit 32 performs image analysis on the number of bubbles having a diameter within a predetermined range included in the imaging recognized by the imaging unit 31. The analyzed image and the distribution for each bubble size as the analysis result are displayed by the display means 33 together with the patient name, patient ID, and diagnosis doctor name on a predetermined display screen as shown in FIG.
[Others]

(Casing 4)
The casing 4 covers each component such as the foaming means 1, the scattering prevention cover 14, the mounting plate 21, the foam recognition means 3, the imaging means 31, and the transport means 25. The casing 4 is provided with an outlet 41 for storing and taking out the specimen O in a size including the bubble position P1 and the closed position.

  Other specific configurations of the respective parts are not limited to the above-described embodiments, and various modifications can be made without departing from the spirit of the present invention.

(Micro bubble test method)
The specimen O is foamed and the number of bubbles is detected by a microbubble test method that has undergone the following steps, and the microbubble test is achieved. This microbubble test method can be carried out by any device or manually, but it is preferably carried out using a microbubble tester including mechanical bubble means such as the above-described microbubble tester of the present invention.

  (1) First, after setting the cover glass as the mounting plate 21 to a foaming position P1 of the apparatus or an appropriate position mechanically guided to the foaming position P1, the spacer 24 on the upper surface of the set mounting plate 21 is used. The specimen O is dropped onto the enclosed central part (see FIGS. 12 and 15). The sample O may be dropped by an automatic dropping means provided in the apparatus or by manual dropping using a pipette or the like. In addition, the order of setting and dropping of the mounting plate 21 may be reversed, and the mounting plate 21 on which the sample O has been dropped is mechanically guided to the foaming position P1 or the foaming position P1 of the apparatus while being dropped. It is good also as what sets to a position. The state after setting and dropping of the specimen O is shown in FIGS.

  (2) Next, the scattering prevention cover 14 is brought into the contact state S <b> 2 with the placement plate 21 by the lowering operation of the lifting mechanism 12 above the placement plate 21 by the descent operation of the lifting mechanism 12. Set (Figure 6). At this time, the relative position of the anti-scattering cover 14 with respect to the rotating member 11H is shifted upward by continuing the descending operation of the elevating mechanism 12 even after a part of the anti-scattering cover 14 comes into contact with the contact state S2. As a result, the locking mechanism 15 changes from the locked state S4 to the unlocked state S3, and the cover pressing plate 17 presses the upper surface of the scattering prevention cover 14 and the scattering prevention cover 14 is fixed in position.

  Alternatively, the scattering prevention cover 14 may be manually placed on the glass serving as the placement plate 21 and set.

  (3) Subsequently, the elevating mechanism 12 is further lowered and set until at least one of the contact terminals 11 is in contact state S2 in contact with the specimen O (FIG. 7).

  (4) Next, the rotating mechanism 13 rotates the rotating brush as the contact terminal 11 while keeping the tip O in contact with the sample O, and bubbles the sample O. In this rotating state, the tip of the contact terminal 11 rotates at a high speed inside and outside the specimen O while the interval increases. In this way, many micro bubbles are generated in the specimen O.

  (5) After foaming, the scattering prevention cover 14 is removed upward from the mounting plate 21 by the raising operation of the elevating mechanism 12. The anti-scattering cover and the rotating member 11H to which the specimen O adheres are removed and discarded integrally by releasing the magnetic connection of the connecting mechanism 16 connected to the rotating motor shaft 13M.

  (6) Next, the transporting means 25 transports the mounting plate 21 from the foaming position P1 where the foaming means 1 is performed to the closing position where the lid closing operation is performed.

(7) Next, the see-through lid 22 tilted and held by the lid holding arm 23 </ b> H is changed from the separated state S <b> 1 separated from the placement plate 21 to the contact state S <b> 2 in contact with the placement plate 21 by the lifting mechanism 12. At this time, the air between the mounting plate 21 and the fluoroscopic lid 22 escapes in one direction and is closed in a state that does not include excess air by setting the counter contact state S6 in order from the oblique contact state S5. Such a closed lid keeps the bubble state secured.
(8) Next, the carrying means 25 conveys the mounting plate 21 from the closing position where the closing operation is performed to the bubble recognition position P2. When the mounting plate 21 is transported to the bubble recognition position P2, the mounting plate 21 is set immediately below the slide glass as the fluoroscopic lid 22 fixed in advance below the microscope, and the sample O on the mounting plate 21 is placed on the specimen O. In this state, a slide glass serving as the fluoroscopic lid 22 is put on.

  (9) Next, focus adjustment is performed with a microscope as an imaging unit, and an image of the sample O after foaming is acquired.

  (10) Next, the image acquired by the imaging unit is analyzed by the analysis unit 32, the number of bubbles having a diameter within a predetermined range included in the image is automatically counted, and the count number and the analysis image are displayed on the display means (FIG. Display on the display unit.

  (11) Next, the mounting plate 21 is transported to the extraction port 41 by the transport driving mechanism 25M, so that the specimen O can be taken out. Thereafter, the foamed sample is taken out from the take-out port 41. At this time, since the specimen is closed, it is difficult for the specimen O to adhere to fingers and the like.

(About how to make bubbles)
The rotating brush as the rotating member 11H is used in a disposable manner. These are set by a microcomputer provided as one component of the rotary motor 13M for controlling the circuit.

  As the rotation means starts rotating by the rotating motor 13M, the tip of the brush spreads by centrifugal force, and the specimen O is bubbled while being sheared and stirred. Here, the rotation axis L of the rotating means is arranged so as to be inclined at an angle of 1 degree to 10 degrees, preferably 2 degrees to 5 degrees with respect to the vertical direction, thereby obtaining an effect of scooping up the specimen O. Foaming efficiency increases.

  In this embodiment, it is not necessary to press the brush when foaming, and foaming is possible if the height of the brush is high enough to touch the specimen O.

  After foaming, a slide glass as the fluoroscopic lid 22 is stacked. In order to maintain the state in which bubbles remain, a spacer 24 of 0.2 mm is provided between the mounting plate 21 and the slide glass which is the fluoroscopic lid 22 which is the fluoroscopic lid 22. Thereby, a planar view image is obtained under a microscope without crushing bubbles.

It is a side view which shows the whole structure in the separation state of the micro bubble tester of Example 1 of this invention. It is a front view which shows the whole structure in the separation state of the micro bubble tester of Example 1. FIG. It is a general-view figure which shows the rotating member 11H and the rotating motor shaft 11M of Example 1. FIG. FIG. 4 is an exploded explanatory view of the rotating member 11H and the rotating motor shaft 11M of the first embodiment shown in FIG. It is an operation state of the raising / lowering mechanism of the micro bubble tester of Example 1, Comprising: It is side view explanatory drawing which shows a separation state and latching state S4. It is operation | movement condition of the raising / lowering mechanism of the micro bubble tester of Example 1, Comprising: It is side view explanatory drawing which shows the process which transfers to a latching state from the separation state and latching state S4. It is operation | movement condition of the raising / lowering mechanism of the micro bubble tester of Example 1, Comprising: It is side view explanatory drawing which shows a contact state and a latch release state. It is a perspective explanatory view showing lid holding arm 23H of the microbubble tester of Example 1. FIG. 6 is a perspective explanatory view showing an operation state of the lid closing mechanism 23 of the microbubble tester according to the first embodiment and showing a state before the lid is closed. FIG. 6 is a side view explanatory view showing an operation state of the lid closing mechanism 23 of the microbubble tester according to the first embodiment and showing an oblique contact state. FIG. 5 is a side view explanatory view showing an operation state of the lid closing mechanism 23 of the microbubble tester according to the first embodiment and showing a facing contact state. It is side view explanatory drawing which shows the mounting board 21 in the state before the lid closure of the microbubble tester of Example 1. FIG. It is side view explanatory drawing which shows the mounting board 21 and the see-through lid 23 in the opposing contact state after the closure of the microbubble tester of Example 1. It is side surface expansion explanatory drawing which shows the state of the sample in the opposing contact state after the lid closing shown in FIG. FIG. 3 is an explanatory plan view showing the mounting plate 21 and the see-through lid 23 in a facing contact state of the microbubble tester according to the first embodiment. It is a perspective explanatory view which shows the cover presser plate 17 of the micro bubble tester of Example 2, and its periphery structure. It is an operation state of the raising / lowering mechanism of the micro bubble tester of Example 2, Comprising: It is side view explanatory drawing which shows a separation state and latching state S4. It is operation | movement condition of the raising / lowering mechanism of the micro bubble tester of Example 2, Comprising: It is side view explanatory drawing which shows the process which moves to a latching state from the separation state and the latching state S4. It is operation | movement condition of the raising / lowering mechanism of the micro bubble tester of Example 2, Comprising: It is side view explanatory drawing which shows a contact state and a latch release state.

Explanation of symbols

1 Foaming means 11 Contact terminal (brush hair)
11H Rotating member 11T Brush tape 12 Elevating mechanism 12P Elevating pole 12Y Elevating unit 13 Rotating mechanism 13L Rotating motor shaft 14 Anti-scatter cover 15 Engaging mechanism 15a Engaging piece (perforated plate)
15b Locked piece (washer)
16 Connection mechanism 16M Connection magnetic body 16H Connection hole 16S Connection screw 17 Cover pressing plate 17H Holding plate fixing arm 2 Mounting conveyance means 21 Mounting plate 22 Transparent lid (slide glass)
23 Closing mechanism 23H Lid holding arm 23Ht Inclined plate 23 Closing mechanism 24 Spacer (plastic tape)
25 Conveying means 25R Conveying rail 25H Plate holder 25M Conveying drive mechanism 3 Foam recognition means 31 Imaging means 32 Analyzing section 4 Casing 41 Extraction port L Rotating axis θ Inclination angle O Sample P1 Foaming position P2 Foam recognition position S1 Separation state S2 Contact State S3 Unlocking state S4 Locking state S4
S5 Oblique contact state S6 Opposite contact state

Claims (6)

A microbubble tester for foaming a specimen O containing biological fluid as a main component and detecting the occurrence of microbubbles in the specimen O, wherein the contact terminal 11 to the specimen O is rotated while being in contact with the specimen O. The foaming means 1 for foaming the sample O, the lid closing mechanism 23 for closing the foamed sample O with the fluoroscopic lid 22, and the fluoroscopic lid 22 are inspected from the outside, and the foamed sample O is formed. A bubble recognizing means 3 for recognizing the number of contained bubbles, and the lid closing mechanism 23 brings the fluoroscopic lid 22 into contact with the liquid surface of the sample O in an oblique contact state S5 in an oblique contact state. A microbubble tester in the contact state S6 that faces the liquid surface of the specimen O in parallel from the contact state S5 .   A microbubble tester for foaming a specimen O containing biological fluid as a main component and detecting the occurrence of microbubbles in the specimen O, wherein the contact terminal 11 to the specimen O is rotated while being in contact with the specimen O. The foaming means 1 for foaming the sample O, the lid closing mechanism 23 for closing the foamed sample O with the fluoroscopic lid 22, and the fluoroscopic lid 22 are inspected from the outside, and the foamed sample O is formed. Comprising bubble recognition means 3 for recognizing the number of bubbles contained,
The foaming means 1 includes a rotating member 11H provided with a contact terminal 11 at the lower end;
An elevating mechanism 12 that moves the rotating member 11H up and down to place the contact terminal 11 in a separated state S1 or a contact state S2 separated from the specimen O;
A rotating mechanism 13 for rotating the rotating member 11H in the contact state S2,
A scattering prevention cover 14 for preventing scattering of the specimen O by surrounding the circumference of the specimen O in the contact state S2,
A locking mechanism 15 for locking the anti-scattering cover 14 to the rotating member 11H in the separation state S1,
In the separation state S1, the locking mechanism 15 is in the locking state S4, and the scattering prevention cover 14 is lifted by the rotating member 11H that moves up and down,
In the contact state S2, the locking mechanism 15 is in the unlocked state S3, and the scattering prevention cover 14 is placed at a position surrounding the sample O and the contact terminal 11,
A micro bubble tester in which the rotating member 11H is rotated by the rotating mechanism 13 to cause the sample O to foam in this contact state S2, and the placed anti-scattering cover 14 prevents the sample O from scattering. The locking mechanism 15 includes a locking piece 15a that protrudes in a uniform shape toward the inner side of the anti-scattering cover 14, and a locked piece 15b that projects axially symmetrically around the rotating member 11H. The locking piece 15a is locked to the locked piece 15b, and the anti-scattering cover 14 is in the locking state S4 at the uniform peripheral position of the rotating member 11H, and the rotating peripheral member 11H is lowered and remains in the uniform peripheral position. The microbubble tester according to claim 2 , wherein the microbubble tester shifts to the stop release state S3 . The microbubble according to claim 2 or 3, wherein the rotating member 11H is magnetically attached to the tip of the rotating motor shaft 13L and is detachably fixed, and rotates coaxially with the rotating motor shaft 13L while being fixed to the rotating motor shaft 13L. tester. 5. The microbubble according to claim 2, wherein the rotating member 11 </ b> H rotates about a rotation axis L, and the rotation axis L is inclined at a predetermined inclination angle θ with respect to the vertical direction. tester. Bubbles recognition means 3, microbubbles tester according to any one of a plurality of recognizing the number of bubbles in the depth sectional claims 1, 2, 3, 4 or 5 of the analyte O.

Images