Patent Description:
In the fields of medical diagnosis or drug-based therapy, the concentration measurement of analytes of anesthetics or harmful chemicals has recently been useful in medical or environmental fields. Above all, the concentration measurement of biological samples used in the fields of medical diagnosis and therapy is increasingly drawing interest along with an increase in human desire to be free from various diseases. Particularly, with regard to diabetes, the glycated hemoglobin test capable of measuring blood sugar allows a relatively long-term average value of the blood sugar to be detected by one-time measurement, and thus has an increasing interest.

Hemoglobin Alc (HbAlc) is also called glycated hemoglobin, and is present in human red blood cells as a part of hemoglobin. When a concentration of blood sugar (glucose) in the blood rises, a glucose moiety in the blood binds to hemoglobin. This hemoglobin conjugated with glucose is referred to as glycated hemoglobin. Blood sugar levels can be determined by this glycated hemoglobin test, which has an advantage in that it can be conducted by collecting blood regardless of the meal time.

<CIT> discloses a reaction vessel, which includes a casing, a reagent and at least one individual element. The casing includes an opening and a detection zone. The opening may be formed on the edge of the casing and used to introduce a sample included an analyte. The detection zone is used to detect the analyte in the sample. The reagent is interacted with the sample. The individual element provides space and flow channel for mixing the sample and the reagent. The sample and the reagent are mixed in the individual element so as to determine the analyte in the detection zone, and thereby increasing accuracy of analyte detection.

Meanwhile, <CIT> discloses a similar apparatus for reacting a test sample with a first reactant in a first inlet port and sequentially reacting the reacted test sample with a second reactant in a second inlet port to measure the analyte present in the test sample. In this case, the measurement of the analyte has to be conducted periodically and sequentially. Further, a user has to intervene in the measuring process in such a manner that he or she injects the test sample sequentially to react the test sample with other materials. Furthermore, since beads conjugated with the glycated hemoglobin have to be filtered once, the measuring process is complicated and takes a long time. That is, since the conventional measuring process requires the user's direct intervention in various processing steps, the user may feel inconvenient. Also, the user's direct intervention makes the measuring process more complicated, thereby further increasing the measuring time.

<CIT> discloses a reagent vessel which is provided to make at least one reagent move to a measuring cassette by making biological specimens inserted into a measuring cassette and to minimize users' intervention.

Additionally, <CIT> discloses a device for measuring HbA1c which has a separable cartridge with two reservoirs. One has a washing liquid, into the other one where the blood sample in injected by a sample injector. Insertion of the cartridge into the measuring cassette releases both fluids, which are subsequently, through rotation of the device, simultaneously transported to a measurement area. On the way the blood sample is mixed with a neutralizer to adjust pH, fractioned into two parts, which are then analysed for total Hb and HbA1c after being exposed to respective immuno-agents in separate detection areas of the device. Further examples of such devices can be found in <CIT> and <CIT>. Furthermore, <CIT> also discloses a cassette characterized by comprising: a first receiving zone for receiving a first reagent; a second receiving zone for receiving a second reagent; a reaction zone in which the blood sample reacts with the first reagent or the second reagent; and a measurement zone for measuring an amount of total hemoglobin or an amount of glycated hemoglobin in a blood sample, wherein the reaction zone and the measurement zone are formed so as to be divided according to a rotation angle of the cassette. However, in the case of this cassette, there is a possibility that some of the two reagents may be mixed in the process of injecting the first reagent and the second reagent into the first receiving zone and the second receiving zone, respectively. Further, since the manufacturing of the cassette is performed by the process of attaching the upper plate to the structure frame in which the internal structure is formed, the movement of the reagents due to the capillary phenomenon may occur along the minute gap present at the adhesion region between the upper plate and the structure frame, thereby causing an error in the measurement results. Thus, it is preferable that the reagents remain in the receiving zones of the cassette for a minimum amount of time. When a blood sample is injected into the cassette from a cartridge including a blood sampling unit configured to contain the blood sample, the amount of the blood sample to be collected is not constant. Further, if the amount of the collected sample exceeds the measurement limit amount, there is a problem that an error may be caused in the measurement results. Furthermore, there is also an inconvenience that the reagents must be mixed well by shaking the cartridge sufficiently before fastening the cartridge to the measurement cassette. There is also a limit in which the reagents remain after use. Similar devices are disclosed also in <CIT>, <CIT>, <CIT> and <CIT>. Therefore, there is a demand for a cassette and a cartridge which are easy to use and can provide accurate measurement results.

The present inventors have completed the present invention based on the idea that when a cassette for measuring glycated hemoglobin is manufactured in the separate form and then the cassette rotates, the reagents automatically leak out sequentially in the course of the rotation of the cassette, so that it is easy to use and the reagents are fully discharged without any residual reagents, thereby outputting the accurate measurement results.

Accordingly, it is an object of the present invention to provide a separable cassette which can more effectively measure glycated hemoglobin by inducing each reagent to leak sequentially in accordance with the rotation of the cassette.

In order to achieve the above purpose, the present invention provides a separable cassette as defined in claim <NUM>. Preferred embodiments are reflected in dependent claims.

The present invention provides a separable cassette for measuring glycated hemoglobin, comprising:.

In an embodiment of the present invention, the bead may include one or more selected from the group consisting of an agarose bead, a sepharose bead, a latex bead, and a glass bead.

In an embodiment of the present invention, the glycated hemoglobin binding material may include one or more selected from the group consisting of a boronic acid, concanavalin A, and an antibody.

In an embodiment of the present invention, the blood sampling unit may be in the form of a capillary.

In an embodiment of the present invention, the cassette may further comprise an insertion guide unit for guiding an insertion direction when the cartridge is inserted into the cassette.

In an embodiment of the present invention, the cartridge further comprises a leakage preventing unit which is disposed at one end of the first storage zone and the second storage zone, respectively, to prevent the first reagent and the second reagent from leaking out, and can be removed from the cartridge when the cartridge is inserted into the cassette.

In an embodiment of the present invention, the leakage preventing unit may be a foil cover or a foil tap.

In an embodiment of the present invention, the leakage preventing unit is removed by a removing part which is disposed in the inlet port of the cassette and may comprise a protruding part so that the leakage preventing unit is caught and removed.

In an embodiment of the present invention, the first reagent may leak from the first storage zone when the cassette rotates <NUM>-<NUM>° in a first direction based on its original state.

In an embodiment of the present invention, the second reagent may leak from the second storage zone when the cassette rotates <NUM>-<NUM>° in a second direction based on its original state.

In an embodiment of the present invention, the cassette may further comprise a delivery guide unit for guiding for the blood sample, the first reagent, or the second reagent, to move to the first measurement zone or the second measurement zone.

In an embodiment of the present invention, the cassette may further comprise a sample absorption unit which is located at one end of the second measurement zone to absorb the measured blood sample and sample.

In an embodiment of the present invention, the cassette may further comprise an optical window from which light received through an external optical sensor is reflected.

The separable cassette for measuring glycated hemoglobin according to the present invention is easy to use because the reagents leak out sequentially in the course of its rotation, the reagents are fully discharged without any residual reagents by the rotation, and the reagents do not mix with each other. Therefore, the measurement results are accurate because there is little error in the amount of the reagents used and the amount of blood samples.

Hereinafter, preferred examples according to the present invention will be described in detail with reference to the accompanying drawings. However, the present invention is not limited to the examples described herein and may be embodied in other forms.

As used herein, terms "rotation in a first direction" and "rotation in a second direction" refer to rotation in mutually opposite directions. For example, if the first direction is clockwise, then the second direction automatically means counterclockwise, or vice versa. The term "original state of the cassette" means that the cassette stands upright on a flat ground without rotation or tilt, and may include a state of tilting about -<NUM> to <NUM>° relative to the ground depending on the shape of the cartridge.

In addition, the separable cassette according to the present invention has a form in which the cartridge and the cassette are separated before the measurement of the glycated hemoglobin. In the measurement of glycated hemoglobin, the measurement is performed while the cartridge is inserted into the cassette including the first reagent, the second reagent, and the blood sample.

The present invention provides a separable cassette for measuring glycated hemoglobin <NUM>, comprising:.

The hemolysate may be, for example, a buffer solution containing a surfactant, such as N-<NUM>-Hydroxyethylpiperazine-N'-<NUM>-ethanesulfonic Acid (HEPES; pH <NUM>). The blood sample hemolyzed by the hemolysate may include both a non-glycated hemoglobin and a glycated hemoglobin.

The glycated hemoglobin binding material may be a material capable of specifically binding to the glycated hemoglobin. For example, the glycated hemoglobin binding material may include one or more selected from the group consisting of a boronic acid (BA), concanavalin A (lectin), and an antibody.

The bead may include one or more selected from the group consisting of a polymer polysaccharide support such as agarose, cellulose, or sepharose; a latex bead such as polystyrene, polymethylmethacrylate, or polyvinyltolune; and a glass bead.

It is preferable that the particle diameter of the glycated hemoglobin binding material-bead is selected in consideration with the precipitation time of the glycated hemoglobin binding material-bead conjugated with glycated hemoglobin after reaction, and the reactivity with the glycated hemoglobin.

In summary, the first reagent includes the hemolysate for hemolyzing the blood sample and the glycated hemoglobin binding material-bead which selectively reacts with the glycated hemoglobin. The first reagent hemolyzes the blood sample, and then the amount of total hemoglobin is measured after about <NUM>-<NUM> seconds and the reaction of the first reagent and the glycated hemoglobin is performed for about <NUM>-<NUM> seconds.

The second storage zone <NUM> stores the second reagent. The second reagent may be a reagent including a washing solution which is able to wash off a mixture of the first reagent and the blood sample.

Most of hemoglobin (Hb) present in red blood cells of a blood sample is non-glycated hemoglobin (Ao). Only <NUM>-<NUM>% of the non-glycated hemoglobin reacts with glucose to become glycated hemoglobin (HbA1c). Accordingly, the glycated hemoglobin binding material-beads in the first reagent which has reacted with the blood sample include non-glycated hemoglobin as well as glycated hemoglobin. Therefore, in order to measure only the glycated hemoglobin in the blood sample, it is needed to remove the non-glycated hemoglobin from the glycated hemoglobin binding material-beads. To this end, it is preferable that the second reagent includes a washing solution which is able to wash off the non-glycated hemoglobin from the glycated hemoglobin binding material-beads to enable the measurement of glycated hemoglobin.

In addition, as the cassette <NUM> rotates by a predetermined angle or more, the first reagent or the second reagent leaks from the first storage zone <NUM> or the second storage zone <NUM>, or may move into the first measurement zone <NUM> or the second measurement zone <NUM>.

To this end, for example, the first storage zone <NUM> and the second storage zone <NUM> may be formed such that the first reagent or the second reagent does not leak out until the cassette <NUM> rotates by a predetermined angle or more. According to the separable cassette <NUM> of the present invention, even if the cartridge <NUM> comprising the first storage zone <NUM> and the second storage zone <NUM> is inserted into the cassette <NUM>, the first reagent and the second reagent do not leak out in its original sate. The first reagent or the second reagent may leak out sequentially only when the cassette <NUM> into which the cartridge <NUM> is inserted rotates by a predetermined angle or more. Therefore, a leakage hole, which is a passage through which the reagent leaks out, may be formed on the upper side of the first storage zone <NUM> and the second storage zone <NUM>. Also, the leakage hole may be formed on the opposite side of the upper of each storage zone so that as the cassette <NUM> rotates in the opposite direction, the first reagent and the second reagent may independently leak out.

The blood sample, the first reagent, and the second reagent, which have leaked into the cassette <NUM> according to the rotation of the cassette <NUM> also move independently from the cassette <NUM> to the measurement zone in accordance with the rotation of the cassette <NUM>.

The first measurement zone <NUM> is a region in which the blood sample and the first reagent react and simultaneously measures the amount of total hemoglobin in the blood sample reacted with the first reagent. In the first measurement zone <NUM>, the amount of total hemoglobin in the blood sample can be measured by an optical reflectometry technique. For example, the optical reflectometry technique utilizes the characteristic that hemoglobin specifically absorbs an optical signal of a specific frequency. The concentration of total hemoglobin can be measured by relatively measuring the intensity or tone of light by the characteristic of hemoglobin.

The second measurement zone <NUM> is a region into which after the blood sample are mixed with the first reagent and the amount of total hemoglobin is measured in the first measurement zone <NUM>, the blood sample mixture that has reacted with the first reagent moves in accordance with the rotation of the cassette <NUM>, as well as a region in which the blood sample mixture reacts with the second reagent and the amount of glycated hemoglobin is measured. The measurement principle may be the same as that of the first measurement region <NUM>. Here, the term "reaction" refers to a comprehensive reaction including not only a chemical reaction but also washing, bonding, agitation, etc..

The blood sampling unit <NUM> may be in the form of a capillary.

It is so that the blood sample to be measured is suck by the form of a capillary of the blood sampling unit <NUM>. Particularly, the inside diameter of the tip of the blood sampling unit <NUM> is smaller than that of the remaining portion so that the capillary phenomenon is easily generated.

On the other hand, when the blood sample is injected into the cassette <NUM> from the blood sampling unit <NUM>, if the amount of the blood sample to be sampled is not constant or exceeds the measurement limit amount, it may lead to an error in the result value. If an excessive amount of blood is contained in the blood sampling unit <NUM>, the measuring device may deviate from the measurable range to obtain an excessive value. In the case of, for example, Clover A1c, available from Infopia Co. , a measurable total hemoglobin level is <NUM>-<NUM>/dl, and if excess blood is injected, the device recognizes that the hemoglobin level is out of the measurable range, thereby resulting in displaying a measured value higher than the normal value.

Therefore, the form of the blood sampling unit <NUM> is important. The tip of the blood sampling unit <NUM> includes a gap formed in parallel to the center, the width of the tip is narrowed toward the end of the tip, and the gap formed inside forms a groove close to the curve.

The amount of blood required for the measurement is preferably about <NUM>-<NUM> ul. The blood sampling unit <NUM> according to the present invention may contain about <NUM> ul of blood and its specific form prevents the excessive blood from sticking together to the blood sampling unit <NUM>.

In an embodiment of the present invention, the cassette <NUM> may further comprise an insertion guide unit <NUM> for guiding an insertion direction when the cartridge <NUM> is inserted into the cassette <NUM>.

The first storage zone <NUM> is preferably inserted into the cassette <NUM> so as to be closer to the first measurement zone <NUM> and the second measurement zone <NUM> than the second storage zone <NUM>. The insertion guide unit <NUM> may be a concavo-convex shape formed on the inner surface of the cassette <NUM> so that the cartridge <NUM> can be inserted into the cassette <NUM> only in one direction by the insertion guide unit <NUM> and cannot be inserted upside down.

In an embodiment of the present invention, the cartridge <NUM> further comprises a leakage preventing unit <NUM> which is disposed at one end of the first storage zone <NUM> and the second storage zone <NUM>, respectively, to prevent the first reagent and the second reagent from leaking out, and can be removed from the cartridge <NUM> when the cartridge <NUM> is inserted into the cassette <NUM>.

The leakage preventing unit <NUM> may be formed at one end, preferably the upper side, of the first storage zone <NUM> and the second storage zone <NUM>, respectively, and may seal the first reagent and the second reagent stored in the storage zones from the outside. The leakage preventing unit <NUM> may be caught and removed or damaged by the removing part <NUM> when the cartridge <NUM> is inserted into the cassette <NUM>. The leakage preventing unit <NUM> may be a foil cover or a foil tab and may be a member that is not corroded or damaged from the reagents.

In an embodiment of the present invention, the leakage preventing unit <NUM> is removed by the removing part <NUM> which is disposed in the inlet port of the cassette <NUM> and may have a protruding part so that the leakage preventing unit <NUM> can be caught and removed.

The leakage preventing unit <NUM> is automatically removed by the removing part <NUM> when the cartridge <NUM> is inserted into the cassette <NUM>, and the removing part <NUM> may have a suitable protruding shape so that the leakage preventing unit <NUM> can be caught and removed.

In an embodiment of the present invention, the first reagent may leak from the first storage zone <NUM> when the cassette <NUM> rotates <NUM>-<NUM>° in the first direction based on its original state.

In an embodiment of the present invention, the second reagent may leak from the second storage zone <NUM> when the cassette <NUM> rotates <NUM>-<NUM>° in the second direction based on its original state.

The rotation in the first direction and the rotation in the second direction mean rotation in mutually opposite directions. Even if the leakage preventing unit <NUM> is removed, the first reagent or the second reagent may not leak until the cassette <NUM> rotates. When the cassette <NUM> rotates <NUM>-<NUM>° in the first direction or the second direction after the leakage preventing unit <NUM> is removed, the first reagent or the second reagent may leak through the leakage holes formed on the upper sides of the storage zones. For example, when the cassette <NUM> rotates <NUM>-<NUM>° in the first direction, only the first reagent may leak, but the second reagent does not leak. Conversely, when the cassette <NUM> rotates <NUM>-<NUM>° in the second direction, only the second reagent may leak, but the first reagent does not leak.

In an embodiment of the present invention, the cassette <NUM> may further comprise a delivery guide unit <NUM> for guiding the blood sample, the first reagent, or the second reagent, to move to the first measurement zone <NUM> or the second measurement zone <NUM>.

The delivery guide unit <NUM> is a concavo-convex shape formed inside the cassette <NUM> and guides so that according to the rotation of the cassette <NUM>, the first reagent leaking from the first storage zone <NUM> may move to the first measurement zone <NUM>, a mixture of the blood sample and the first reagent from the first measurement zone <NUM> may move to the second measurement zone <NUM>, and the second reagent leaking from the second storage zone <NUM> may move to the second measurement zone <NUM>.

In an embodiment of the present invention, the cassette <NUM> may further comprise a sample absorption unit <NUM> which is located at one end of the second measurement zone <NUM> to absorb the measured blood sample and the sample. The sample absorption unit <NUM> absorbs the measured blood sample mixture to prevent the blood sample mixture from leaking out. For example, in order to measure the amount of glycated hemoglobin, the sample absorption unit <NUM> may absorb non-glycated hemoglobin and the remaining materials except for glycated hemoglobin binding material-beads conjugated with glycated hemoglobin, present in the second measurement zone <NUM>. The sample absorption unit <NUM> may be disposed on the side of the second measurement zone <NUM>. In an embodiment of the present invention, the sample absorption unit <NUM> may include, but is not limited to, an absorbent pad.

In an embodiment of the present invention, the cassette <NUM> may further comprise an optical window <NUM> from which light received from an external optical sensor is reflected. The external optical sensor is preferable located at the device for measuring glycated hemoglobin, into which the reaction cassette <NUM> is inserted.

In accordance with an embodiment of the present invention, an exemplary device for measuring glycated hemoglobin <NUM> in which a separable cassette for measuring glycated hemoglobin <NUM> may be used is shown in <FIG>.

Referring to <FIG>, the cassette <NUM> in which the cartridge <NUM> of the present invention is incorporated is inserted into a device for measuring glycated hemoglobin <NUM>. At this time, the device for measuring glycated hemoglobin <NUM> may rotate the cassette <NUM> clockwise or counterclockwise according to a certain pattern. The rotation of the cassette <NUM> causes the first reagent or the second reagent to leak sequentially into the cassette <NUM>, respectively, to be stirred together with the blood sample, and to move into the first measurement zone <NUM> or the second measurement zone <NUM> so that the measurement can be performed. The device for measuring glycated hemoglobin <NUM> can measure the amount of glycated hemoglobin using an optical reflectometry technique.

For example, when the amount of glycated hemoglobin in a blood sample is measured, a characteristic that hemoglobin specifically absorbs an optical signal of a specific frequency is utilized. At this time, it is preferable that the device for measuring glycated hemoglobin <NUM> measures the amount of glycated hemoglobin using a light-receiving element and a light-emitting element such as a photo diode.

Referring to <FIG>, the device for measuring glycated hemoglobin <NUM> may comprise a cassette <NUM> accommodation part <NUM>, a cassette <NUM> check sensor <NUM>, a measurement sensor <NUM>, a driving unit <NUM>, a signal conversion unit <NUM>, and a controller <NUM>.

The cassette <NUM> accommodation part <NUM> has a space into which the cassette <NUM> is inserted. It is preferable that the cassette <NUM> accommodation part <NUM> has a sufficient space so that the cassette <NUM> may rotate clockwise or counterclockwise without any interruption.

The cassette <NUM> check sensor <NUM> may confirm whether the solution containing the reagents such as the first reagent and the second reagent in the cassette <NUM> is properly present in the first storage zone <NUM> and the second storage zone <NUM>. The cassette <NUM> check sensor <NUM> confirms detection of reagents by an absorption photometry method using an optical sensor that emits an optical signal by a light-emitting element and receives the optical signal that has passed through the cassette <NUM> by a light-receiving element. That is, the cassette <NUM> check sensor <NUM> outputs a light-emitting control signal to the light-emitting element and converts an optical signal received from the light-receiving element into an electrical signal, thereby being able to detect whether the first reagent and second reagent are properly present.

In other words, the light-emitting element emits an optical signal having a specific wavelength. For example, when the amount of glycated hemoglobin is to be measured, the hemoglobin in the blood sample may emit an optical signal having a wavelength of about <NUM>-<NUM> in which the hemoglobin specifically shows absorption. The light-receiving element receives an optical signal which is emitted from the light-emitting element and passes through the cassette <NUM>.

The measurement sensor <NUM> measures the amount of total hemoglobin and the amount of glycated hemoglobin which are contained in the second measurement zone <NUM> of the cassette <NUM>. At this time, by outputting a light-emitting control signal to the light-emitting element and converting an optical signal inputted from the light-receiving element into an electrical signal, the amount of total hemoglobin and the amount of glycated hemoglobin which are contained in the cassette <NUM> can be measured.

The driving unit <NUM> applies an external power to the cassette <NUM>. For example, the driving unit <NUM> may be a motor. The cassette <NUM> may rotate according to a predetermined rule by the external power, and the rotation angle may freely be selected from -<NUM>° to <NUM>°.

The signal conversion unit <NUM> is a general Analog-to-Digital (A/D) converter.

The controller <NUM> controls the entire system, and is preferably embodied as a microprocessor into which a ROM, a RAM, and peripheral devices are integrated. The controller <NUM> can identify the cassette <NUM>, detect the injection of a sample solution, or measure the amount of glycated hemoglobin.

That is, by outputting a light-emitting control signal to the light-emitting element and converting an optical signal inputted from the light-receiving element into an electrical signal through A/D converter, whether the first reagent and the second reagent are properly present in the cassette <NUM> can be detected. In this manner, it is possible to measure the amount of glycated hemoglobin included in the second measurement zone <NUM> of the cassette <NUM>.

A method in which the separable cassette for measuring glycated hemoglobin <NUM> according to an embodiment of the present invention can be used comprises a method for measuring glycated hemoglobin comprising the steps of: identifying the information of the engaged cassette <NUM>; confirming whether a first reagent and a second reagent are present in the cassette <NUM>; rotating the cassette <NUM> in a first direction to leak the first reagent; rotating the cassette <NUM> to its original state to react the first reagent with a blood sample and measuring an amount of total hemoglobin; rotating the cassette <NUM> in the first direction to move the blood sample mixture reacted with the first reagent to a second measurement zone <NUM>; rotating the cassette <NUM> in a second direction to leak the second reagent; rotating the cassette <NUM> in the first direction to move the second reagent to a second measurement zone <NUM> and washing the blood sample mixture to measure an amount of glycated hemoglobin; and calculating an amount of glycated hemoglobin in the blood sample based on the measured amount of total hemoglobin and the measured amount of glycated hemoglobin in the blood sample.

Hereinafter, referring to <FIG>, an embodiment of a method for measuring glycated hemoglobin using the separable cassette for measuring glycated hemoglobin <NUM> according to the present invention will be described in detail.

<FIG> is a flowchart illustrating a method of measuring glycated hemoglobin using the cassette <NUM> according to an embodiment of the present invention. As shown in <FIG>, a device for measuring glycated hemoglobin <NUM> identifies the information of the cassette <NUM> engaged therein (S100).

Then, the device for measuring glycated hemoglobin <NUM> confirms whether the first reagent and the second reagent are present in the cassette <NUM> (S110). This can be confirmed by the cassette <NUM> check sensor <NUM>.

The blood sample collected from the human body may inject directly into the cassette <NUM> from outside or may be injected through the blood sampling unit <NUM> according to an embodiment of the present invention, but is not limited thereto.

Then, the device for measuring glycated hemoglobin <NUM> rotates the cassette <NUM> in a first direction to leak the first reagent from the first storage zone <NUM> (S120).

Thereafter, the cassette <NUM> rotates to its original state, the first reagent is reacted with the blood sample in the first measurement zone <NUM>, and the amount of total hemoglobin is measured (S130). The blood sample and the first reagent react to form a blood sample mixture accordingly. Here, the cassette <NUM> may be shaken clockwise and counterclockwise for a predetermined period of time, for example, <NUM> minute, so that the hemolyzed blood sample can sufficiently react with the glycated hemoglobin binding material-beads. This is to induce a blood sample of the blood sampling unit <NUM> to be hemolyzed out by the first reagent and simultaneously to specifically react with the glycated hemoglobin binding material-beads. When the amount of total hemoglobin in the blood sample is measured, it is preferable to measure the amount of total hemoglobin in the blood sample by the optical reflectometry technique through the optical sensor. Also, the cassette <NUM> may rotate about <NUM>-<NUM>° so that the blood sample mixture can gather closely to the first measurement zone <NUM> during the measurement.

Then, when the device for measuring glycated hemoglobin <NUM> rotates the cassette <NUM> in the first direction, the blood sample is mixed with the first reagent in the first measurement zone <NUM>, the amount of total hemoglobin is measured, and the blood sample mixture which has been reacted with the first reagent moves to the second measurement zone <NUM> (S140). At this time, non-glycated hemoglobin and the remaining materials except for glycated hemoglobin binding material-beads conjugated with glycated hemoglobin, present in the second measurement zone <NUM> can be absorbed into the sample absorption unit <NUM>.

Then, the device for measuring glycated hemoglobin <NUM> rotates the cassette <NUM> in a second direction to leak the second reagent from the second storage zone <NUM> (S150).

Then, the device for measuring glycated hemoglobin <NUM> rotates the cassette <NUM> in a first direction to move the leaked second reagent to the second measurement zone <NUM> and washing the blood sample mixture with the second reagent to measure the amount of glycated hemoglobin (S160). Here, as the second reagent containing the washing solution washes the blood sample mixture, non-glycated hemoglobin (Ao) non-specifically present in the blood sample may be removed and absorbed into the sample absorption unit <NUM> together with the second reagent. As in the case of measuring the amount of total hemoglobin from the blood sample mixture reacted with the first reagent, the amount of glycated hemoglobin in the blood sample may be measured by the optical reflectometry technique through the optical sensor.

Then, the relative amount of glycated hemoglobin in the blood sample is calculated by dividing the measured amount of total hemoglobin into the measured amount of glycated hemoglobin (S170). At this time, the ratio of glycated hemoglobin with total hemoglobin in the blood sample is calculated by the following Equation <NUM>.

<FIG> illustrates (a) an external appearance and (b) an internal appearance of the cassette <NUM> according to an embodiment of the invention. The cassette <NUM> of the present invention may be used to measure the amount of glycated hemoglobin (HbA1c) in the blood. At this time, the cartridge <NUM> can be inserted into the cassette <NUM>, and the cassette <NUM> is engaged in the device for measuring glycated hemoglobin <NUM> to be rotatable clockwise or counterclockwise with respect to a horizontal axis. The cassette <NUM> comprises the removing part <NUM> in the inlet port for the cartridge <NUM> insertion so that the leakage preventing unit of the cartridge <NUM> can be caught and removed when the cartridge <NUM> is inserted into the device. In addition, the cassette <NUM> comprises in the interior the insertion guide unit <NUM> for guiding the cartridge <NUM> to be inserted into the cassette <NUM> only in one direction. The cassette <NUM> further comprises on the bottom of the interior a first measurement zone <NUM> in which the first reagent reacts with the blood sample and the amount of total hemoglobin is measured, and in the middle of the right side a second measurement zone <NUM> in which the second reagent washes the reacted blood sample and the amount of glycated hemoglobin is measured. The cassette <NUM> further comprises on the right side the sample absorption unit <NUM> which absorbs non-glycated hemoglobin and the remaining materials except for glycated hemoglobin binding material-beads conjugated with glycated hemoglobin. The cassette <NUM> further comprises on the exterior an optical window <NUM> from which light received through an external optical sensor is reflected.

<FIG> illustrates (a) a front view, (b) a rear view, and (c) a side view of the cartridge <NUM> according to an embodiment of the invention. The cartridge <NUM> comprises a first storage zone <NUM> which has a first reagent, a second storage zone <NUM> for storing a second reagent, a blood sampling unit <NUM> for collecting, containing and leaking a blood sample, a leakage preventing unit <NUM> for preventing the first reagent and the second reagent from leaking out until the cartridge <NUM> is inserted into the cassette <NUM>. The leakage preventing unit <NUM> is formed on upper side of the cartridge <NUM>, respectively. Since the cartridge <NUM> has a standing rhombus, even if the leakage preventing unit <NUM> is removed, the first reagent and the second reagent may be accumulated at the bottom of the cartridge <NUM> in the rhombus shape. Thus, as long as the cartridge <NUM> is in its original state without rotating, the reagents do not leak from the storage zones. The leakage preventing unit <NUM> may be a foil tab.

<FIG> illustrates the external appearance (a) before and (b) after the cartridge <NUM> is inserted into the cassette <NUM>. An insertion preventing unit is formed in the cassette <NUM> so that the cartridge <NUM> can be inserted only in one direction and the leakage preventing unit <NUM> of the cartridge <NUM> can be removed by the removing part <NUM> of the cartridge <NUM> at the time of insertion.

Hereinafter, a measuring process of glycated hemoglobin according to the rotation of the cassette <NUM> into which the cartridge <NUM> is inserted will be described with reference to <FIG>.

<FIG> shows a ready state of the cassette <NUM> including the first reagent, the second reagent, and the blood sample before rotation. The cartridge <NUM> is inserted into the cassette <NUM>, the first reagent is contained in the first storage region <NUM> of the cartridge <NUM>, and the second reagent is contained in the second storage region <NUM>. The leakage preventing unit <NUM> is caught and removed by removing part <NUM> when the cartridge <NUM> is inserted into the cassette <NUM>, and thus is not present. The first reagent and the second reagent do not leak from the storage zones even though the cassette <NUM> is in its original state without a rotation angle and the leakage preventing unit <NUM> is not present. Before starting the measurement, the cassette <NUM> may be shaken for about <NUM> seconds to allow the reagents in the cassette <NUM> to mix well.

First, as shown in <FIG>, the cassette <NUM> may rotate clockwise by about <NUM>°, whereby the first reagent contained in the first storage zone <NUM> may leak through the leak hole of the first storage zone <NUM> by gravity.

Thereafter, as shown in <FIG>, when the cassette <NUM> rotates counterclockwise by about <NUM> ° to be in its original state, the first reagent moves to the first measurement zone <NUM> by the delivery guide unit <NUM>. At this time, the blood sample, which is collected from the human body and contained in the blood sampling unit <NUM>, leaks out through the end of the blood sampling unit <NUM> to react with the first reagent in the first measuring zone <NUM>. In particular, the cassette <NUM> can be shaken for about <NUM> minute using device for measuring glycated hemoglobin <NUM> so that the reaction of the blood sample with the first reagent occurs more easily. At this time, the amount of total hemoglobin in the blood sample can be measured by an optical reflectometry technique through the optical sensor before the reaction is completely finished in the first measurement zone <NUM>.

As shown in <FIG>, the cassette <NUM> can rotate clockwise by about <NUM>°, whereby the blood sample reacts with the first reagent in the first measurement zone <NUM> to measure total hemoglobin, and then the reacted blood sample mixture moves to the second measurement zone <NUM>. At this time, non-glycated hemoglobin and the remaining materials except for glycated hemoglobin binding material-beads conjugated with glycated hemoglobin, present in the second measurement zone <NUM> can be absorbed into the sample absorption unit <NUM>.

As shown in <FIG>, when the cassette <NUM> rotates counterclockwise again by about <NUM>°, it is in a state rotated counterclockwise by about <NUM>° based on its original state, whereby the second reagent may leak through the leak hole of the second storage zone <NUM> by gravity.

Thereafter, when the cassette <NUM> rotates clockwise again by about <NUM>° as shown in <FIG>, and then rotates clockwise by about <NUM> ° as shown in <FIG>, the second reagent moves along the delivery guide unit <NUM> to the second measurement zone <NUM> in which the blood sample mixture is present. Next, when the second reagent and the blood sample react, i.e., the second reagent washes the blood sample mixture, the amount of the glycated hemoglobin can be measured from the blood sample mixture from which the non-glycated hemoglobin has been removed. At this time, the amount of glycated hemoglobin in the blood sample may be measured by an optical reflectometry technique through the optical sensor. Non-glycated hemoglobin and the remaining materials except for glycated hemoglobin binding material-beads conjugated with glycated hemoglobin, present in the second measurement zone <NUM> can be absorbed into the sample absorption unit <NUM>.

In summary, as shown in <FIG>, the device for measuring glycated hemoglobin <NUM> can automatically rotate the cassette <NUM> clockwise or counterclockwise. That is, the first reagent or the second reagent leaks sequentially from the first storage zone <NUM> or the second storage zone <NUM> according to the rotation of the cassette <NUM> to react with the blood sample. That is, at least one reagent automatically reacts with the blood sample according to the rotation. In addition, <FIG> are one example showing the rotation process of the cassette <NUM> and various other rotations can be embodied. In the case of the embodiments in which each zone of the cassette <NUM> is positioned symmetrically compared to the above-described embodiments, the cassette <NUM> can rotate in a manner opposite to the above-described rotation process.

Claim 1:
A separable cassette (<NUM>) for measuring glycated hemoglobin, comprising: a cartridge (<NUM>) which includes a first storage zone (<NUM>) which has a first reagent,
a second storage zone (<NUM>) for storing a second reagent, and a blood sampling unit (<NUM>) capable of injecting a blood sample into the cassette (<NUM>), and is inserted into the cassette (<NUM>); a first measurement zone (<NUM>) in which the blood sample reacts with the first reagent to measure an amount of total hemoglobin; and a second measurement zone (<NUM>) in which the reacted blood sample reacts with the second reagent to measure an amount of glycated hemoglobin,
wherein the first reagent includes a hemolysate, which is a buffer solution containing a surfactant, and a glycated hemoglobin binding material-bead which selectively reacts with the glycated hemoglobin,
wherein as the cassette (<NUM>) rotates by a first predetermined angle or more in a first direction, the first reagent leaks from the first storage zone (<NUM>) and moves into the first measurement zone (<NUM>) or wherein as the cassette (<NUM>) rotates by a second predetermined angle or more in a second direction opposite to the first direction, that is opposite to the first predetermined angle, the second reagent leaks from the second storage zone (<NUM>) and moves into the second measurement zone (<NUM>).