Patent Application
20180335430
The present invention relates to an inspection chip for use in an inspection system that detects a subject captured by immunoreaction, and the inspection system.
A detection plate in which a sensing unit that detects a subject and a reagent holding unit with wells formed therein, for storing a reagent and a specimen, are integrated has been conventionally known (see, for example, Patent Literature 1) as a detection plate that detects a subject captured by immunoreaction in inspection or the like performed based on the principle of surface plasmon-field enhanced fluorescence spectroscopy (SPFS) or the like. The detection plate is used, with being secured to a predetermined stage provided on an inspection system, at the time of inspection.
Patent Literature 1: JP 2013-024607 A
Meanwhile, a high-capacity reagent well (for example, a well that stores a waste liquid, a cleaning liquid, and the like.) in the reagent holding unit included in the detection plate is preferably disposed close to the sensing unit. The reason for this is because a reagent well with a large number of access times is generally high in capacity and thus such a well can be disposed close to the sensing unit, thereby resulting in decreases in the migration length of the stage and the migration length of a pipette in feeding of the reagent to the sensing unit, to result in a decrease in the measuring time in an inspection system.
If the high-capacity well is disposed close to the sensing unit, however, the high-capacity well may be illuminated with reflected light of excitation light, reflected by a metallic thin film in inspection, during emission thereof through a prism, thereby causing stray light to be generated.
When stray light is caused, a problem is that background light is increased during inspection, to thereby make the inspection state unstable, resulting in a reduction in the inspection accuracy of an inspection system.
An object of the present invention is to provide an inspection chip and an inspection system in which a reduction in inspection accuracy caused by stray light can be prevented.
In order to achieve at least one object described above, the inspection chip of the present invention is an inspection chip for use in an inspection system that detects a subject captured by immunoreaction, the inspection chip including:
an optical measurement chip having, on a top surface, a reaction field formation surface on which a reaction field for allowing the immunoreaction to occur is formed, and including a prism having a reflected light emission surface that emits reflected light reflected by the reaction field formation surface; and
a cartridge in which at least one well that stores a liquid for use in the inspection system is formed;
wherein the cartridge is not located in a region where a first space and a second space are overlapped under the assumption that:
The inspection chip of the present invention is also an inspection chip for use in an inspection system that detects a subject captured by immunoreaction, the inspection chip including:
an optical measurement chip having a reaction field formation surface on which a reaction field for allowing the immunoreaction to occur is formed, and emitting reflected light reflected by the reaction field formation surface; and
at least one well that stores a liquid to be used or used in the inspection system;
wherein the well is disposed at a position not overlapped with an optical path of the reflected light.
Furthermore, the inspection system of the present invention is an inspection system that detects a subject captured by immunoreaction, the inspection system including:
a light source that emits excitation light; and
an inspection chip including an optical measurement chip provided with a prism having, on a top surface, a reaction field formation surface on which a reaction field for allowing the immunoreaction to occur is formed, and a cartridge in which at least one well that stores a liquid to be used in the inspection system is formed;
wherein the cartridge is not located in an optical path region of reflected light generated due to reflection of the excitation light by the reaction field formation surface.
According to the present invention, a reduction in the inspection accuracy of an inspection system due to stray light can be prevented.
The inspection chip and the inspection system of the present invention encompass the following.
The inspection chip of the present invention is an inspection chip for use in an inspection system that detects a subject captured by immunoreaction, the inspection chip including:
an optical measurement chip having, on a top surface, a reaction field formation surface on which a reaction field for allowing the immunoreaction to occur is formed, and including a prism having a reflected light emission surface that emits reflected light reflected by the reaction field formation surface; and
a cartridge in which at least one well that stores a liquid for use in the inspection system is formed;
wherein the cartridge is not located in a region where a first space and a second space are overlapped under the assumption that:
Thus, when reflected light of excitation light, reflected by a metallic thin film, is emitted from the prism in inspection, stray light due to illumination of a part of the cartridge, such as the well, with the reflected light can be prevented from being generated.
In addition, in the inspection chip of the present invention,
a plurality of wells with different capacities are formed in the cartridge, and
at least one well smaller in capacity than a well having the maximum capacity among the plurality of wells is formed between the well having the maximum capacity and the optical measurement chip.
Thus, the number of wells can be increased with the cartridge being kept small in size.
In addition, in the inspection chip of the present invention,
a well is located in the vicinity of the optical measurement chip and is partially overlapped with the second space, and
an angle between a bottom wall surface rising from the bottom surface of the well towards a peripheral wall surface of the well, the peripheral wall surface being closer to the optical measurement chip, and the perpendicular line of the bottom surface of the well is an angle equal to or less than an angle between the perpendicular line of the reaction field formation surface and the reflected light emission surface.
Thus, even when a high-capacity well is disposed close to the optical measurement chip, the high-capacity well can be allowed not to be illuminated with the reflected light.
In addition, in the inspection chip of the present invention,
a plurality of wells with different capacities are formed in the cartridge, and
any bottom surface center of other well formed in the cartridge, excluding a well having the maximum capacity among the plurality of wells, is not located in the second space.
Thus, even when there is a well whose bottom surface is deep, the possibility can be reduced where the lower portion of the well is illuminated with the reflected light.
In addition, in the inspection chip of the present invention,
a rib that allows the cartridge to ensure rigidity is formed, and the rib is not located in a region where the first space and the second space are overlapped.
In addition, in the inspection chip of the present invention,
a wall surface of the well having the maximum capacity, the wall surface being located at a position overlapped with the second space and being closer to the optical measurement chip, is formed so as to be depressed in a direction opposite to the direction in which the optical measurement chip is located.
Thus, a high-capacity well can be more certainly prevented from being illuminated with the reflected light.
The inspection chip of the present invention is also an inspection chip for use in an inspection system that detects a subject captured by immunoreaction, the inspection chip including:
an optical measurement chip having a reaction field formation surface on which a reaction field for allowing the immunoreaction to occur is formed, and emitting reflected light reflected by the reaction field formation surface; and
at least one well that stores a liquid to be used or used in the inspection system;
wherein the well is disposed at a position not overlapped with an optical path of the reflected light.
In addition, in the inspection chip of the present invention,
the liquid is either a specimen or a reagent.
In addition, in the inspection chip of the present invention,
detection in the inspection system is performed using any of SPFS, SPR and ATR principles.
Furthermore, the inspection system of the present invention is an inspection system that detects a subject captured by immunoreaction, the inspection system including:
a light source that emits excitation light; and
an inspection chip including an optical measurement chip provided with a prism having, on a top surface, a reaction field formation surface on which a reaction field for allowing the immunoreaction to occur is formed, and a cartridge in which at least one well that stores a liquid to be used in the inspection system is formed;
wherein the cartridge is not located in an optical path region of reflected light generated due to reflection of the excitation light by the reaction field formation surface.
Hereinafter, an inspection chip according to an embodiment of the present invention will be described with reference to the drawings with an inspection chip to be used in an inspection system for SPFS measurement as an example.
As illustrated in
The sensing member 4 includes a flow channel chip 4a and an optical measurement chip 4b. The flow channel chip 4a is a chip disposed above the optical measurement chip 4b, and includes two cylindrical injection/ejection ports 5 through which liquids such as a specimen and a reagent are injected and ejected. Further, a flow channel (not illustrated) that guides a specimen and a reagent to a reaction field 12 is formed between the two injection/ejection ports 5.
Further, an excitation-light incident surface 14 upon which excitation light from a light source not illustrated is incident is formed on one side surface (left side surface in
As illustrated in
As illustrated in
As illustrated in
A large well 24b having the maximum volume among the wells 24 has a substantially L-shaped opening portion 25a and a bottom surface 25b, and the wells 24 other than the large well 24b each have an opening portion 25a and a bottom surface 25b each having a substantially elliptical shape obtained by shaping each of both end portions in the longitudinal direction of a rectangle into an arc.
In addition, each of the wells 24 is disproportionately disposed in one region (left region in
Furthermore, each of the wells 24 is formed so that the opening portion 25a extends in an elongated manner from a region (left region in
The wells 24 include a plurality of wells 24 with different volume. A large well 24b having the maximum volume and with a large number of access times is here disposed in the vicinity of the optical measurement chip 4b in order to shorten the travel distance of a stage (not illustrated) provided in an inspection system (not illustrated) and shorten the measuring time in the inspection system. Furthermore, a small well 24c with small volume is disposed between the large well 24b and the optical measurement chip 4b (see
Next, a treatment where measurement based on the principle of SPFS is performed using the inspection chip 2 in an inspection system will be described with reference to a case where an analyte included in a specimen is detected as a reaction product. First, a specimen dispensed into any of the wells 24 formed in the cartridge 6 in the inspection chip 2 secured to the stage in the inspection system is, if necessary, diluted and mixed with a specimen dilution fluid.
Next, the specimen stored in any of the wells 24 is sucked once by a pipette chip not illustrated, and thereafter the specimen is injected into the flow channel chip 4a with which the upper surface of the optical measurement chip 4b is covered. The specimen injected into the flow channel chip 4a is guided by a flow channel not illustrated, to the metallic thin film 10, and captured by a ligand (antibody) where the analyte in the specimen is solid-phased in the reaction field 12, according to immunoreaction.
Next, a cleaning liquid is injected into the flow channel chip 4a to remove foreign substances from the specimen, thereafter a fluorescent substance is injected into the flow channel chip 4a, and the analyte in the specimen is labelled with the fluorescent substance. Next, a further cleaning liquid is injected into the flow channel chip 4a to remove the label nonspecifically adsorbing to the reaction field 12.
The specimen dilution fluid, the cleaning liquid and the fluorescent substance may be enclosed in any of the wells 24 formed in the cartridge 6. Further, the dilution of the specimen, to be if necessary performed, may also be performed in any of the wells 24 formed in the cartridge 6.
Next, excitation light is emitted towards the reaction field 12 from a light source disposed closer to the excitation-light incident surface 14 located at the lower portion of the prism 8 in the inspection system. The excitation light is incident through the excitation-light incident surface 14, and is reflected by the metallic thin film 10. As illustrated in
When the excitation light is reflected by the metallic thin film 10, the excitation light with which the metallic thin film 10 is irradiated generates surface plasmon light (compression wave) on the metallic thin film 10, and the electric field enhancement effect of the surface plasmon light is achieved. Thus, the fluorescent substance bound to the analyte captured by the ligand in the reaction field 12 formed in the metallic thin film 10 is excited, and this fluorescence is observed, thereby resulting in detection of the analyte. For example, the intensity of the fluorescence is measured using a sensor that senses the amount of light, not illustrated, thereby resulting in detection of the analyte.
On the other hand, the reflected light reflected by the metallic thin film 10 is emitted through the reflected light emission surface 16. The inspection chip 2 is here designed so that the cartridge 6 is not located in the optical path region of the reflected light, and therefore the cartridge 6 is not illuminated with the reflected light emitted through the reflected light emission surface 16 and the reflected light does not serve as noise in fluorescence observation.
According to the inspection chip 2 according to this embodiment, there is not generated any stray light due to illumination of the large well 24b or the like with the reflected light emitted through the reflected light emission surface 16, and therefore a reduction in inspection accuracy due to stray light can be prevented.
In the above embodiment, as illustrated in
In addition, in the above embodiment, any well 24 (for example, large well 24b) located in the vicinity of the optical measurement chip 4b and partially overlapped with the second space Y may be subjected to predetermined processing. For example, as illustrated in
In addition, in the above embodiment, the prism 8 does not necessarily have the cross section shape illustrated in
It has been described above in embodiments of the present invention that the cartridge 6 is not illuminated with the reflected light emitted through the reflected light emission surface 16 and the reflected light does not serve as noise in fluorescence observation. In an actual inspection system, the cartridge 6 is secured to a stage (not illustrated) and used. Therefore, even if the cartridge 6 is not illuminated with the reflected light, the stage can be illuminated with the reflected light and thus the reflected light can serve as noise in fluorescence observation.
Therefore, the stage to which the cartridge 6 is secured is desirably so as not to be illuminated with the reflected light emitted through the reflected light emission surface 16 in the vicinity of the reflected light emission surface 16, but to be illuminated therewith as far as possible. If the stage is illuminated with the reflected light in the vicinity of a reflecting surface, such an illumination location is close to the field of view of a light-receiving system and thus reflected light/scattering light at the location serves as noise in fluorescence observation.
For example, when the cartridge 6 is secured onto the stage at the bottom thereof as in
A configuration as illustrated in
In the above embodiments, each of the wells 24 is disproportionately disposed in one width direction of the well formation portion 6b as illustrated in
Although the description of the above embodiments is made with, as an example, an inspection chip to be used in an inspection system for SPFS measurement, the inspection system is not necessarily one for SPFS measurement, and for example, may be used as, for example, an inspection system for attenuated total reflectance (ATR) measurement and an inspection system for surface plasmon resonance (SPR) measurement.
In the above embodiments, although no critical description is made in
In the above embodiments, the opening portion 25a and the bottom surface 25b of each of the wells 24 may each have a circular or elliptical shape.
Although the description of the above embodiments is made with the metallic thin film 10 as the reaction field formation surface, the member to be used in the reaction field formation surface is not necessarily needed to be metallic.
In addition, in the above embodiments, the excitation-light incident surface 14 and the reflected light emission surface 16 are not necessarily a flat surface.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2015-223370 | Nov 2015 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2016/082941 | 11/7/2016 | WO | 00 |
