KR20100118340A - Optical measuring disc, optical measuring device and optical measuring method - Google Patents

Abstract

The measuring optical disk of the present invention includes a sample chamber containing a sample for measurement; A reagent chamber containing a reagent comprising a dye precursor that is discolored when reacting with the sample or a phosphor that is fluorescent when reacting with the sample; A reaction chamber which becomes a mixing space of a sample supplied from the sample chamber and a reagent supplied from the reagent chamber and is read by optical pickup; It includes, an optical measuring device and an optical measuring method using the same.

Description

Optical disk for measuring, optical measuring device and optical measuring method using same {OPTICAL MEASURING DISC, OPTICAL MEASURING DEVICE AND OPTICAL MEASURING METHOD}

The present invention relates to a measuring optical disk, an optical measuring device and an optical measuring method, and a measuring optical disk which can optically measure various information for blood diagnosis, water quality analysis, food ingredient analysis, microbial analysis, and the like, An optical measuring device and an optical measuring method capable of collecting information optically.

For example, in the case of blood glucose measurement in the field of blood diagnostics, as the number of diabetic patients has recently increased significantly, a measuring device capable of measuring blood glucose levels simply and quickly and accurately in order to obtain blood glucose level data for the treatment is required. If a blood glucose meter is provided that the patient himself can use safely and easily, the contribution to blood sugar level control will be very large.

The blood glucose level can be determined by measuring the concentration of glucose in the blood. As the measurement method, conventionally, the method based on the reducibility of glucose, the method by direct reaction of sugar under acidic conditions, and the method by enzyme reaction of glucose, etc. As a clinical medical test, blood collected from a finger, a toe, or other blood is reacted with glucose oxidase, and a color reaction based on glucose concentration in the blood is used. The method of measuring and converting it into a blood glucose level is used.

However, the conventionally used blood glucose meters require manual work by experts in the measurement process, and thus, the practical use of an automated blood glucose measurement apparatus capable of easily measuring blood sugar even by non-experts is required.

There is a need for practical use of an optical measuring device that can be measured by optical methods in various fields such as blood glucose measurement as well as other blood diagnostics, water quality analysis, food ingredient analysis, and microbial analysis.

The present invention has been made in view of this need, and provides an optical disc for measurement of a special structure into which a sample and a reagent can be added, and an optical measuring device and an optical measuring device capable of optically measuring data using such an optical disc and an optical pickup. It is for providing a measuring method.

The technical problem to be achieved by the present invention is not limited to the technical problem mentioned above, and other technical problems not mentioned above may be clearly understood by those skilled in the art from the following description. will be.

The measuring optical disk of the present invention includes a sample chamber containing a sample for measurement; A reagent chamber containing a reagent comprising a dye precursor that is discolored when reacting with the sample or a phosphor that is fluorescent when reacting with the sample; A reaction chamber which becomes a mixing space of a sample supplied from the sample chamber and a reagent supplied from the reagent chamber and is read by optical pickup; It includes.

An optical measuring apparatus of the present invention includes a reagent chamber containing a reagent containing a sample chamber containing a sample for measurement, a dye precursor that discolors when reacting with the sample, or a phosphor that reacts with the sample, and a fluorescent substance that exhibits a fluorescent color; A spindle motor for rotating a measurement optical disk having a reaction chamber formed on a surface thereof, the reaction chamber serving as a mixing space of a sample supplied from the chamber and a reagent supplied from the reagent chamber; An optical pickup for reading a color change of the reaction chamber when the sample and the reagent are mixed and reacted in the reaction chamber as the measurement optical disk rotates; A control unit obtaining measurement data of the sample by analyzing the optical signal of the optical pickup; It includes.

An optical measuring method of the present invention includes a sample chamber containing a sample for measurement, a reagent chamber containing a reagent including a dye precursor which discolors when reacting with the sample or a fluorescent substance which reacts with the sample, and the sample; Rotating the optical disk for measurement formed on the surface of the reaction chamber, the reaction chamber serving as a mixing space of the sample supplied from the chamber and the reagent supplied from the reagent chamber, with a spindle motor; Reading a color change of the reaction chamber by an optical pickup when the sample and the reagent are mixed and reacted in the reaction chamber as the measurement optical disk rotates; Acquiring measurement data of the sample by analyzing the optical signal of the optical pickup; It includes.

According to the present invention, in the optical disc for measuring the reaction solution of the sample and reagents and the optical measuring method for measuring the data using the same structure to provide a general component such as optical pickup and spindle motor As a result, it is possible to realize low cost, and a plurality of reaction chambers corresponding to a plurality of reagents can be provided on one optical disk for simultaneous analysis of various measurement items on a single disk. If the reagent and sample are added and used once, and then replaced with a new optical disk, the measurement process can be repeated indefinitely, which facilitates mass measurement and consumes only the reagents and samples that fill the chamber on the surface of the optical disk. Write down the pain and sample purchase costs One can.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. In this process, the size or shape of the components shown in the drawings may be exaggerated for clarity and convenience of description. In addition, terms that are specifically defined in consideration of the configuration and operation of the present invention may vary depending on the intention or custom of the user or operator. Definitions of these terms should be made based on the contents throughout the specification.

Compared to the present invention, a conventional lab on a chip, which implements a bio-test function by patterning various measurement elements on a semiconductor chip, has a MEMS (multi-century centimeter) chip made of glass, silicon, or plastic. All pretreatment and analysis of samples, such as dilution, mixing, reaction, separation and quantification of samples, are performed continuously using Micro Electro Mechanical Systems (NEMS) or Nano Electro Mechanical Systems (NEMS) technology.

In contrast, the present invention provides a lab on a disc in which a lab-on-a-chip technology is implemented in a CD-shaped optical disc, so that many samples can be analyzed in a short time.

In addition, the lab-on-a-chip uses mechanical force and capillary force by a pump operated by external energy to control the flow of the fluid, but it is difficult to accurately control the flow of fluid over time. .

However, in the lab-on-a-disc of the present invention, the centrifugal force, coriolos force, and capillary force are used, so that the sample pretreatment process is easy according to g-force, and the valve controls the flow of fluid. It is possible to easily and reliably implement a valve structure, a metering structure to control the amount of fluid, and a mixing structure to control fluid flow and reaction.

The optical measuring device of the present invention uses a laser light having a wavelength of 405, 650, 780nm band as in the conventional optical pickup, and by measuring the absorption of the light of the reagent at this wavelength it is possible to chemical or medical diagnosis.

Due to the characteristics of the light wavelength, the 405 nm wavelength light of the Blu-ray Disc (BD) -compatible optical pickup can measure the reaction of the red system reagent and the sample having a complementary color relationship. The 650nm wavelength light of the DVD-compatible optical pickup can measure the absorption of light of a blue or green reagent. 780 nm wavelength light is a case of CD compatible optical pickup.

Therefore, if a reagent solution containing a dye precursor (chromogen) reacting with the sample or a fluorescent fluorophor reacting with the sample is mixed with the sample and color change according to the concentration is detected, a common component is a spindle motor and an optical pickup. Biochemical and immunological tests can be performed using.

In general, a biochemical test using an enzyme reaction is expressed as follows.

Substrate + Enzyme = Modified substrate + by-product

Dye precursor (by-product) + enzyme (enzyme) = color change in a solution mixed with sample and reagent

Dye precursors that can be used in CDs read by 780 nm wavelength light,

TOOS (N-ethyl-N- (2-hydroxy-3-sulfopropyl) -3-methylaniline),

NCP (N-methyl-N- (4-aminophenyl) -3-methoxyaniline) is mentioned.

Dye precursors, which can be used in 650nm wavelength light read DVD,

TMB (3,3 ', 5,5'-tetramethylbenzidine),

ABTS (2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid).

Dye precursors that can be used in BD read by 405nm wavelength light,

p-nitrophenyl phosphate (pNPP),

ABTS (2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid).

On the other hand, the immunoassay using the antigen-antibody reaction can quantify the intensity of the emission wavelength of the fluorescent substance linked to the antigen, and the concentration of the sample can be known through a relationship of concentration to light intensity.

The phosphor which can be used in CD read by 780nm wavelength light is IRDYE800. Phosphors that can be used in DVDs read by 650 nm wavelength light include Alexa Fluor 647, Allophycocyanin (APC), and Cyanine 5. Phosphors that can be used in BD read by 405 nm wavelength light include Alexa Fluor 405 and Cascade Blue.

Since the optical measuring device of the present invention uses existing components as it is, the price is very low, the size is small, and there is an advantage of good compatibility with a PC. Therefore, it is easy to store the diagnosis result on an optical disc medium such as a CD, DVD, BD or the like, or to transmit the diagnosis result online to a hospital or service provider server through a PC. Thus, it can be used as home-healthcare equipment and is particularly advantageous for use in small hospitals.

Measurement optical disk of the present invention is the same size as the existing optical disk, the thickness of the reaction chamber 400, etc. corresponding to the diagnostic channel is also very thin, 0.1 ~ 0.5 mm, so the amount of blood, such as a small amount of samples consumed for human use Of course, it is also suitable as a diagnostic device for small animals.

The optical disk for measurement according to the present invention has a metering structure, which enables accurate reaction of the concentration ratio between the reagent and the sample, and for professionals requiring accurate measurement, a calibration chamber containing a sample solution having a standard concentration Chamber is additionally provided.

The optical measuring device of the present invention is capable of bidirectional rotation of the spindle motor so that the mixing process can be performed relatively quickly, and the focus servo or the objective lens of the optical pickup is lifted up and down toward the optical disk ( Through the sweep operation, the light absorption of the sample reacted with the reagent can be measured. The measured light absorptivity may be stored in the optical measuring device, or the concentration of the sample to be measured may be detected through a concentration graph of the reaction solution compared to the light absorptivity measured by a pre-memory or calibration process.

In the optical disk for measuring, measuring method and measuring apparatus of the present invention, if only the reagent is changed, it is applicable to diagnosis other than blood sugar, and can be applied to various fields such as water analysis, food analysis, microbial analysis as well as blood diagnosis.

Once again, the optical disk for measuring blood glucose, blood diagnosis, water quality analysis, food analysis, microbial analysis, etc. can be optically measured using a special optical disk for measurement. It is a device that measures data without changing hardware of common components, making it easy to use for home and small hospitals.

In addition, various inspection items may be simultaneously analyzed on one measurement optical disc in which a plurality of reaction chambers 400 are formed. The measuring optical disk used for one-time measurement is low in cost due to its simple structure so that it can be reused after cleaning, disposable, or replaced with a new one.

In addition, any active element such as an electromagnetic actuator may be excluded, and various micro fluidic functions may be implemented using only passive elements having a mechanical structure such as the reagent chamber 300, the sample chamber 200, and the reaction chamber 400.

In addition, the amount of sample consumed is small, and thus, the amount of reagent required is also small, thereby reducing the pain caused by sampling by the examinee and realizing low cost. In addition, the materials and structures are suitable for mass production.

In order to diagnose the characteristics of a specific sample, the reagents reacting with the same may be mixed in the reaction chamber 400 to diagnose the characteristics of the sample using eye or optical pickup. Automatic mixing on the surface of the optical disc for measurement, without the need for specialists, can help prevent accidents or dangers.

A method of creating a table for correcting a relationship between concentration and light absorption rate using a calibration chamber in which a solution of a first concentration or a second concentration is stored is also provided. When the measurement is performed using the corrected relational expression, the deviation of each disc and the optical measuring device can be corrected, and the measurement can be performed quickly and accurately.

Next, a reagent is demonstrated.

For example, in the case of blood glucose, the concentration of glucose in the blood is blood sugar, and the blood glucose level must be maintained within a certain range to maintain the homeostasis of the human body. Fasting blood glucose levels are 70-110 mg / dl in normal people and do not exceed 180 mg / dl after eating. If hyperglycemia lasting more than 200 mg / dl for more than 2 hours is determined to be diabetes, and in severe patients, blood sugar goes up to 500 mg / dl. The concentration of blood glucose can be known through the measuring apparatus and measuring method of the present invention. At this time, according to the following reaction formula.

Glucose + Glucose oxidase (enzyme) = Gluconic acid + H ₂ O ₂

Dye precursor (Chromogen) + H ₂ O ₂ = peroxidase (enzyme) + color change

For convenience of explanation, the dye precursor is an ABTS that can be used in light of 650nm wavelength for DVD, and the intensity of the color change in the reaction of the sample and the reagent is read as an optical pickup to detect the concentration of blood glucose in the blood.

1 is a spectrum measuring the concentration of glucose in plasma after separating blood cells from the blood. The horizontal axis is the wavelength of light and the vertical axis is the light absorption amount or light absorption rate.

2 is a graph showing the linearity of blood glucose concentration and light reflection amount. The horizontal axis shows the concentration of blood sugar and the vertical axis shows the light absorption rate. According to this, it can be seen that as the concentration of blood glucose increases, the light absorption rate increases due to the complementary color relationship between the reagent and the laser light (in this case, the amount of light reflection decreases). Reagents containing ABTS as dye precursor for 75 mg / dl, 100 mg / dl, 200 mg / dl, 300 mg / dl, 400 mg / dl as the concentration of blood glucose, R ² = 0.998 for 650 nm wavelength light Has a linearity of. Bovine serum albumin (BSA) and Triton X-100 were used to maintain enzyme activity.

For example, the 650 nm wavelength red light of the DVD-compatible optical pickup is emitted from the optical pickup, and when the ABTS is used as the reagent, when the blood glucose concentration of the sample is low, the degree of reaction with the reagent is weak, so that the color of the detector 490 is gray. Or the achromatic color such as opaque color and the detection unit 490 reflects light as if it is the reflective layer 102, but the amount of light absorption is insignificant, but the reaction degree of the sample and reagent increases as the blood glucose concentration increases ) Is mixed with blue or green color and absorbs 650 nm wavelength light in complementary relationship, so the light absorption increases as shown in FIG. 2 and the reflection is naturally reduced.

When the user collects his blood to measure blood glucose, puts it in the sample chamber 200 of the optical disk for measurement, and mounts it on the spindle motor, the optical measuring device rotates the optical disk for measurement and centrifugs the plasma and blood cells. Here, the metering unit 140 of the microtubule structure in which the centrifugal force, the capillary force, and the Coriolis force acts sends the sample to the reaction chamber 400 by measuring the plasma and the reagent as the desired amount.

When the sample and the reagent are mixed in the reaction chamber 400 and a predetermined time required for the reaction has elapsed, the position of the reaction chamber 400 is detected by using optical pickup, and the objective lens is moved upward and downward (Focus sweep). Obtain the light absorption of the reacted sample. The light absorption rate obtained here is determined by the blood glucose concentration vs. light absorption rate graph, which is obtained through the previous calibration process or when the calibration chamber is not provided, and is pre-stored in the optical measuring device.

The measurement results are transmitted to a PC or monitor to which the optical measuring device is connected, and are known to the user, and the results are stored in a recording layer (not shown) or a HDD of the PC which can be provided in the optical disk for measurement. In addition, if the home healthcare system is connected to the network in the home, the data is sent to the server of the hospital or service provider to store the data. This series of data can then be forwarded to doctors for use in diagnosing patients online / offline.

3 is a plan view showing an embodiment of an optical disk for measurement. 4 is a side cross-sectional view showing a cross section of the optical disk for measurement. 5 through 10 are plan views illustrating various embodiments of the reagent chamber 300, the sample chamber 200, the reaction chamber 400, the first calibration chamber 500a, and the second calibration chamber 500b.

The optical disk for measurement of the present invention includes a sample chamber 200, a reagent chamber 300, and a reaction chamber 400. The sample chamber 200 is a space for receiving a sample for measurement. The reagent chamber 300 may be a space for receiving a reagent including a dye precursor that is discolored when reacting with a sample or a phosphor that is fluorescent when reacting with the sample. The reaction chamber 400 is a space where a sample supplied from the sample chamber 200 and a reagent supplied from the reagent chamber 300 are mixed, and includes a detection unit 490 facing the optical pickup to change the color of the mixed solution. Can be read as an optical signal in an optical pickup.

At this time, the reaction chamber 400 is located on the outer circumferential sides of the sample chamber 200 and the reagent chamber 300 so that the sample and the reagent may be supplied to the reaction chamber 400 by the centrifugal force generated during rotation.

For injection of the sample or reagent, the sample chamber 200 or the reagent chamber 300 has an injection port 110. The injection port 110 is a passage in which one end of the sample chamber 200 or the inner side of the reagent chamber 300 is opened and the sample or the reagent is injected. The sample or reagent injected through the injection hole 110 is stored in the storage 115 corresponding to an empty space having a predetermined thickness. The stop valve 112 is provided at a position where the inlet 110 and the storage 115 are connected to prevent the sample or the reagent from flowing back toward the inlet 110. The fluid blocking force of the stop valve 112 is not based on energy supplied from the outside, but merely a passive element by mechanical force. The stop valve 112 is formed as an empty space having a thickness thinner than that of the storage unit 115, and the fluid flows back toward the injection hole 110 due to the thickness step Δt of the stop valve 112 and the storage unit 115. Is prevented.

At least one of the sample chamber 200, the reagent chamber 300, and the reaction chamber 400 includes an air vent 130 open to the atmosphere to prevent the negative pressure from being generated by the fluid movement.

On the other hand, it is preferable that a calibration chamber is provided to accurately correct the relationship of the light absorption ratio to the concentration for each disc and each measurement device. The first calibration chamber 500a contains a standard solution of a first concentration. The second calibration chamber 500b contains a standard solution of a second concentration higher than the first concentration.

By reading the relatively low concentration standard solution of the first concentration contained in the first calibration chamber 500a by optical pickup, the actual light absorption amount corresponding to the first concentration is measured, and the relatively high concentration of the second calibration chamber 500b is measured. The actual light absorption amount corresponding to the second concentration is measured by reading a standard solution of phosphorus second concentration with an optical pickup.

On the other hand, the relational expression of the light absorption to concentration is already stored in the optical measuring device, and in advance to the optical measuring device using the measurement data actually read in the first calibration chamber 500a and the second calibration chamber 500b by optical pickup. The stored relational expression can be corrected accurately according to the individual deviation of the measurement optical disk.

Meanwhile, referring to FIG. 4, the cross-sectional structure of the optical disk for measurement may be described in detail. According to this, the optical disk for measurement includes a substrate 101, a reflective layer 102, a transmissive layer 104, and an adhesive layer 103 for adhering the reflective layer 102 and the transmissive layer 104 to each other. The substrate 101 is the basis of the optical disk for measurement, and the reflective layer 102 is a layer that reflects the light emitted from the optical pickup as it is. The transmission layer 104 is formed of polycarbonate which is a high strength transparent material and transmits light. The sample chamber 200, the reagent chamber 300, and the reaction chamber 400 are formed by forming a space in the permeable layer 104. The reflective layer 102 is formed by coating a light reflection material on the substrate 101, and the adhesive layer 103 reflects the transmissive layer 104 on which the reagent chamber 300, the sample chamber 200, and the reaction chamber 400 are formed. A layer adhered to 102.

Next, the mixing process of the sample will be described.

11 illustrates a mixing process in an optical measuring device capable of bidirectional rotation of a spindle motor. In general, when a sample is to be examined and diagnosed, a sample to be diagnosed and a reagent capable of reacting with the sample to show a difference in optical properties are required. When the reagent and the sample are mixed, the color change may be measured using the human eye or optical pickup, such as reacting with each other and changing color or fluorescent color.

As a hypothetical embodiment in contrast to the present invention, the sample and the reagent may be artificially mixed from the outside and added to the measurement optical disc, but the sample or the reagent is not preferable because it may be harmful or dangerous to the human body. In order to improve this, the present invention injects the reagent and the sample separately into the optical disk for measurement, and then mixes the reagent and the sample according to the rotation of the optical disk for measurement. That is, after the reagent is injected into the reagent chamber 300 and the sample is injected into the sample chamber 200, the spindle motor is rotated in one direction or periodically in both directions so that the reagent and the sample are supplied to the reaction chamber 400.

As time passes, the reagent or sample initially contained in the sample chamber 200 or the reagent chamber 300 moves to the reaction chamber 400 and gradually starts to mix. After a certain time, the reagent and the sample react completely. The color change of the reaction solution accommodated in the reaction chamber 400 can be confirmed. As such, if only the sample and the reagent are used, the optical measuring device can measure not only the concentration of the mixed solution but also other physical and chemical data corresponding to the optical characteristics of the reagent.

Next, a measuring method of data using an optical disc for measurement and an optical measuring device will be described. First, the structure of the optical disk for measurement will be described.

In order to measure the light transmittance of the specimen (reaction solution) accommodated in the reaction chamber 400 of the rotating optical disk for measurement, it is necessary to know the relative position of the optical pickup and the reaction chamber 400, and the reaction chamber 400 passes the optical pickup. It is necessary to measure the amount of laser light reflected by the reflective layer 102 through the test object by accurately stopping the measuring disk at a moment and moving the optical pickup up and down.

Alternatively, in order to measure while the optical disk for measurement is rotating, the optical chamber should vibrate rapidly at the moment when the reaction chamber 400 passes the optical pickup so that the focus of the optical pickup laser passes through the reaction chamber 400. The rotation speed of the optical disk for measurement should be very low, such as 100 to 200 RPM. The higher the rotational speed of the optical disk for measurement, the greater the frequency of the optical pickup, in which case there is a high risk of damage to the optical pickup due to electrical or mechanical limitations.

In addition, to know the relative position of the optical pickup and the reaction chamber 400, the rotation angle (phase angle) of the spindle motor should be known. For this purpose, the FG signal output from the Hall sensor installed in the spindle motor is used.

The photonic device is usually equipped with a brushless DC (BLDC) type spindle motor which controls the coil input / output current in the drive IC according to the FG signal output from the hall sensor. The Hall sensor outputs a positive or negative voltage depending on the polarity of the magnet of the spindle motor, and the FG signal in the form of a square wave can be obtained by sampling the analog output voltage of the Hall sensor based on the threshold value.

If the magnet installed in the spindle motor is magnetized, for example, with 10 N poles and 10 S poles across the entire circumference of the spindle motor, the magnet becomes a 20 pole motor and the Hall sensor shows a sinusoidal analog output voltage of 10 cycles (clocks) Sampling based on the hold value results in 10 FG signal peaks. Therefore, counting 10 peak values of the FG signal recognizes that the spindle motor is rotated one time.

12 is a plan view of the chamber marker 150 and the identification marker 160.

In one embodiment, the optical disk for measurement has a chamber marker 150 or an identification marker 160. The chamber marker 150 is for detecting the exact position of the reaction chamber 400. The identification marker 160 is provided between the chamber markers 150 when the number of reaction chambers 400 is provided to identify and recognize each reaction chamber 400.

The chamber marker 150 or the identification marker 160 blocks or scatters the light so that the laser light irradiated from the optical pickup does not reach or scatter the reflective layer 102 of the measurement optical disk. The dashed arrow is the trajectory of the laser light according to the rotation of the optical disk for measurement. The width of the chamber marker 150 or the identification marker 160 should be small enough so that the focus servo can be stabilized when the laser light is irradiated along this trajectory, and be distinguished from noise such as scratches and fingerprints. The width of the chamber marker 150 or the identification marker 160 should be wide enough to be able to do so. The illustrated width of chamber marker 150 or identification marker 160 is 1 mm.

Each chamber marker 150 is in line with an imaginary line connecting the starting point of the reaction chamber 400 from the inner circumference center of the measurement optical disk, and several chamber markers corresponding to the respective reaction chamber 400. 150 are disposed on the same radius. This is due to the efficiency of the space utilization of the optical disk for measurement and does not necessarily have to be on the same radius.

13 to 15 illustrate a position detection method of the reaction chamber 400. For example, if a 10-clock FG signal is output for one revolution of the spindle motor, the period of the FG signal is 360 ° / 10 = 36 °.

Chamber markers 150 and identification markers 160 are formed on the outer periphery of the measuring optical disk, and these are squares having a width of 1 mm and a length of 2 mm that prevent light transmission, and are opaque scratches on the measuring optical disk without any additional components. Can be processed. The position of the chamber marker 150 and the identification marker 160 is preferably coincident with the point where the reaction chamber 400 starts.

When the measuring optical disk is rotated, the FG signal output from the drive IC of the spindle motor is counted using the microcomputer of the optical measuring device.

Then, the optical pickup is brought to the position ① in Fig. 13, and then the focus servo is operated. At this time, the portion where the RF signal of the reflected light falls is the position of the chamber marker 150, and when the FG signal is compared with the RF signal, the relative position of the chamber marker 150 can be known (see FIGS. 18 and 20).

The RF signal is a value output in proportion to the amount of light from the PDIC (Photo Diode IC) provided in the optical pickup. For focusing servo, the PDIC is divided into four areas. In this case, the RF value is the sum of the light incident on each area of the PDIC for the four areas. That is, when the RF value is large, the amount of light reflection of the optical disk for measurement is large, and the place where the RF value decreases means that the amount of light reflection is drastically reduced, for example, the chamber marker 150.

Next, the time difference t1 between the point where one cycle of the FG signal starts and the point where the chamber marker 150 starts is counted by a timer built in the microcomputer of the optical measuring device (see FIG. 15).

When the point at which the chamber marker 150 starts in the measurement optical disc is in phase with the point at which the reaction chamber 400 starts, the reaction chamber 400 starts by detecting a point at which the chamber marker 150 starts. Know the point (phase) where it is. If the phase difference between the chamber marker 150 and the reaction chamber 400 is given in advance, the starting point (phase) of the reaction chamber 400 may be corrected by correcting the phase difference with respect to the starting point of the chamber marker 150. ) Can be identified.

Meanwhile, in FIG. 15, the point where the RF signal descends after rising is the point at which the chamber marker 150 ends, and the time width t2-t1 can be known by counting with a timer of the optical measuring device.

The ratio of the size of the chamber marker 150 and the reaction chamber 400 formed on the optical disk for measurement is already input to the optical measuring device and the known value (this value is stored in the track of the optical disk for measurement and the optical pickup reads this information. It can be delivered to the optical measuring device) so that the point (phase) where the reaction chamber 400 ends can be known, and the size width of the reaction chamber 400 can be calculated.

Accordingly, in order to know the position of the reaction chamber 400 on the measurement optical disk, the count number of the FG signal at the point where the chamber marker 150 starts and the rising edge of the FG signal at the point where the chamber marker 150 starts ), The time t1 from the edge of the chamber marker 150 to the edge of the chamber marker, the point t2 at which the chamber marker 150 ends, and the relative sizes of the chamber marker 150 and the reaction chamber 400 are known. Know the location and size of the. To improve accuracy, the FG rising edge and the falling edge may be applied separately.

Since the size and position of the reaction chamber 400 are known, the optical pickup can be controlled so that the laser beam passes through the center of the reaction chamber 400 to measure the light reflection amount or the light absorption amount of the test solution in the reaction chamber 400. have.

The amount of light reflection at the place where the reflective layer 102 is measured is avoided where the reaction chamber 400 is located. Therefore, the light transmittance of the solution under test contained in the reaction chamber 400 reflects the amount of light that has passed through the test solution and then is reflected by the reflective layer 102 and returned to the optical pickup. By dividing by the amount of light reflected by), the light transmittance of the solution under test can be calculated.

16 to 20 illustrate a position of the reaction chamber 400 and a method of identifying each reaction chamber 400 when a plurality of reaction chambers 400 are formed. 16 to 20 illustrate a case in which four reaction chambers 400 are installed at intervals of 90 ° as shown in FIG. 12.

When the optical disk for measurement is rotated and the focusing servo is applied at the arrow ① position in FIG. 17, the RF signal of the optical pickup and the FG signal generated by the spindle motor at that time are as shown in FIG. 16. The FG signal was assumed to be 18 clocks per turn. The case where one reaction chamber 400 is installed in the optical disk for measurement has already been described in the description of FIGS. 13 to 15. However, when a plurality of reaction chambers 400 are provided in the measurement optical disk, it is necessary to distinguish each reaction chamber 400. To this end, an identification marker 160 is installed.

The position of the chamber marker 150 1 corresponding to the reaction chamber 400 1 is the count number of the FG signal at which the starting point of the chamber marker 150 1 is located, and the chamber marker 150 1 from the rising edge of the FG signal. The time count of the reaction chamber 400 is calculated as the length of the reaction chamber 400 with respect to the actual chamber marker 150 length. When the spindle motor rotates once, each start position of the chamber markers 150 1 to 4 may be determined and all time intervals between the chamber markers 150 may be known.

The time interval from the identification marker 160 to the chamber marker 150 and the chamber marker 150 is half of the time interval between each chamber marker 150, and the sequence is the chamber marker 150-4. Since it is the identification marker 160-chamber marker 150 1, it is possible to know which of the four reaction chambers 400 is the reaction chamber 400 based on this time interval.

Next, the control method of the optical pickup will be described.

The optical pickup is moved to the position of the dotted line arrow ② in FIG. The optical measuring device uses a sled transfer stepping motor for optical pickup transfer, and the radial position of the reaction chamber 400 is already stored in the optical measuring device or stored in the optical disk for measurement. The optical pickup can be moved to a location.

Even if the sweep start control signal is transmitted to the objective lens of the optical pickup so that the optical focus passes through the calculated starting point of the reaction chamber 400, the optical focus may not accurately pass through the reaction chamber 400. This is because there is a time delay before actually sweeping in response to the control signal due to the mass inertia of the optical pickup or the objective lens. That is, referring to FIG. 18, the moving speed of the optical pickup in and out of the optical pickup should be increased in proportion to the rotational speed of the measuring optical disk. However, since the optical pickup is an object having a predetermined mass, the optical pickup moves later than the control signal.

Therefore, when the actual movement of the optical pickup starts after passing the starting point of the reaction chamber 400, the reaction chamber 400 is missed and the measurement cannot be performed. Therefore, the delay time td between the control signal and the actual movement of the pickup. The control signal should be sent in advance.

However, because there is a manufacturing variation for each optical pickup and also due to temperature or environment, it is necessary to measure the delay time td of the optical pickup before measuring the quantity of light in order to accurately calculate the delay time.

Since the delay time td is the time difference between the start point of the sweep (rising) control signal of the objective lens of the optical pickup and the moment when the optical focus passes through the reflecting surface and enters the reaction chamber 400, the optical marker is selected from the chamber marker 150. ) Or the optical focus reaches the mirror surface from the moment the optical pickup rise control signal is sent after moving to the pure mirror surface (position ③ in FIG. 17) without the reaction chamber 400, and the peak value of the RF signal is output. The time until the moment can be measured by counting the timer of the microcomputer (see FIG. 19).

By compensating for the delay time td at the time when the rising control signal of the optical pickup is output, the optical focus can be passed at a precisely desired position, so that the light reflection amount or the light absorption amount of the reaction chamber 400 can be accurately measured (FIG. 20).

As described above, the light transmittance of the reaction chamber 400 is obtained by dividing the amount of light that has passed through the reaction chamber 400 and returned to the optical pickup by the light reflectance of the pure mirror surface (position ③ in FIG. 17). The measurement sequence is as follows.

First, the FG signal generated by the rotation of the spindle motor is counted with a timer, and the optical pickup is moved to a radial position (reference position ① in FIG. 17) where the chamber marker 150 is located, and then the focus servo is operated to operate the chamber. The position and width of the marker 150 are measured to calculate the position and width of the reaction chamber 400. Then, the optical pickup is moved to the mirror surface position (reference? In FIG. 17) to measure the delay time (td in FIG. 19) and the light reflection amount of the mirror surface.

In the reaction chamber 400 position (ref. 2 in FIG. 17), the optical pickup is raised to measure the light reflection amount in the reaction chamber 400 and compared with the light reflection amount on the mirror surface to determine the light transmittance of the reaction chamber 400. Calculate

That is, the amount of time delay of the optical pickup is calculated by comparing the generation time of the control signal for raising or lowering the objective lens of the optical pickup and the generation time of the RF signal generated when the objective lens is actually operated according to the control signal. The objective chamber is controlled to read the reaction chamber 400 when the time delay amount is compensated.

22 to 25 illustrate a calibration method. The horizontal axis represents concentration and the vertical axis represents light absorption. That is, when detecting the concentration of the mixed solution corresponding to the amount of light reading the reaction chamber 400 according to the relation of the light absorption rate according to the concentration of the mixed solution of the reagent and the sample input in advance, the first calibration chamber 500a by optical pickup. And the at least one of the second calibration chamber 500b to correct the relation.

22 and 23 illustrate a reason for calibrating by using a standard solution for each optical disk for measurement. The standard solution refers to, for example, a mixed solution of a sample and a reagent contained in the first calibration chamber 500a as a first concentration having a relatively low concentration, or a mixed solution contained in the second calibration chamber 500b at a second concentration. .

That is, since the reflectance varies depending on the amount of material of the reflective layer 102 and the thickness of the reflective layer 102, the optical disk for measurement has a variation in the amount of light reflected by the optical disk for measurement. There is a deviation of the amount of light.

For this reason, when the characteristic graphs regarding the concentration of the reagent and the light absorption rate are linear as shown in FIG. 22, the characteristics of the two discs for measuring A Disc and B Disc are different from those of the actual desired characteristic graphs. offset) and, in more severe cases, the slope will vary.

In addition, even when the characteristic graphs regarding the concentration of the reagent and the light absorption rate are secondary, as shown in FIG. Similarly, the characteristics of the A Disc and the B Disc are different from the actual desired characteristic graphs, and an offset occurs in the vertical axis direction, and in a more severe case, the slope is changed.

Therefore, a calibration process is required for more accurate measurements, such as optical discs for measurement for professionals.

21 illustrates a method of obtaining absorbance in an optical measuring device. In order to measure the reflectance on the mirror surface and the reflectance of the calibration chamber region, the optical pickup is swept from the mirror surface region and the calibration chamber region, and then the reflectance is obtained to calculate the absorbance.

The following equation holds for the absorbance of the calibration chamber.

Absorbance of the calibration chamber = (reflectivity of the mirror side-reflectivity of the calibration chamber) / (reflectance of the mirror surface)

In this manner, the optical pickup is swept from the first calibration chamber 500a containing the low concentration of the first standard solution to obtain the absorbance amount ABS_L of the standard solution of the first concentration. The optical pickup is swept from the second calibration chamber 500b containing the high concentration of the second concentration standard solution to obtain the absorbance amount ABS_H of the standard solution of the second concentration.

Table 1 below is a table for use when the absorbance graph according to the concentration is tested with a reagent having a secondary form.

That is, the absorbance of the standard solution of the first concentration, which is the low concentration, and the absorbance of the standard solution of the second concentration, which are the above-mentioned concentrations, are determined as the reference absorbance amount of the low concentration of the reagent (REF_L) and the absorbance amount of the high concentration (REF_H, respectively). ), And the slope value corresponding to the condition is obtained.

After obtaining a gradient value that satisfies the condition, an intact quadratic equation can be obtained using the absorbance amount of the low concentration standard solution (ABS_L) and the high concentration standard solution (ABS_H).

When examining reagents having a primary absorbance according to concentration, the slope and offset can be determined only by the absorbance of the low concentration standard solution and the high concentration of the standard solution without the table shown in Table 1. So we can get a complete linear function.

24 and 25 are graphs comparing the absorbance of each concentration measured with the reference calibration curve obtained by the above method.

FIG. 24 shows the absorbance according to the concentration in the form of a linear equation, where the solid line is the absorbance actually measured and the dotted line is the absorbance calculated through the reference calibration curve. By comparing the two lines, it can be seen that the absorbance obtained through the actual measurement and the absorbance obtained through the reference calibration curve are almost identical.

FIG. 25 shows the absorbance according to the concentration in the form of a quadratic formula, in which a solid line is actually an absorbed amount measured and a dotted line is an absorbed amount obtained through a reference calibration curve. This also shows that the two lines are almost identical.

Fig. 26 is an exploded perspective view showing the basic structure of the optical measuring device of the present invention. Referring to this, the optical tablet measuring device includes a main frame 10, an upper case 70 coupled to an upper portion of the main frame 10, and a tray for transporting the optical disk D for measurement into the optical measuring device ( 60) and an optical pickup 50 for recording information on the measurement optical disk D or reproducing the recorded information. On the upper surface of the tray 60, a disk seating surface 62 on which the optical disk D for measurement is mounted is formed, and the door 61 is coupled to the front end thereof.

In addition, the tray 60 is provided with a hollow portion 63 so that the optical pickup 50 can access the optical disk D for measurement. In addition, the front panel 15 is coupled to the front end of the main frame 10, and the front panel 15 is formed with an opening 16 to allow the tray 60 to enter and exit.

The measurement optical disk D carried by the tray 60 is seated on the turntable 40 installed on the upper side of the spindle motor 30. The turntable 40 is coupled to the rotary shaft of the spindle motor 30 to rotate with the rotary shaft to rotate the optical disk for measurement (D). The spindle motor 30 is installed in the pickup deck 20 coupled to the main frame 10, and the pickup deck 20 has the optical pickup 50 in the radial direction of the optical disc D for measurement. It is installed to be movable.

Although embodiments according to the present invention have been described above, these are merely exemplary, and it will be understood by those skilled in the art that various modifications and equivalent embodiments of the present invention are possible therefrom. Therefore, the true technical protection scope of the present invention will be defined by the following claims.

1 is a spectrum measuring the concentration of glucose in plasma after separating blood cells from the blood.

2 is a graph showing the linearity of blood glucose concentration and light reflection amount.

3 is a plan view showing an embodiment of an optical disk for measurement.

4 is a side cross-sectional view showing a cross section of the optical disk for measurement.

5 through 10 are plan views illustrating various embodiments of a reagent chamber, a sample chamber, a reaction chamber, a first calibration chamber, and a second calibration chamber.

11 illustrates a mixing process in an optical measuring device capable of bidirectional rotation of a spindle motor.

12 is a plan view illustrating a chamber marker and an identification marker.

13 to 15 illustrate a method for detecting a position of a reaction chamber.

16-20 illustrate the location of reaction chambers and the method of identifying each reaction chamber when a plurality of reaction chambers are formed.

21 illustrates a method of obtaining absorbance in an optical measuring device.

22 to 25 illustrate a calibration method.

24 and 25 are graphs comparing the absorbance of each concentration measured with the reference calibration curve obtained by the above method.

Fig. 26 is an exploded perspective view showing the basic structure of the optical measuring device of the present invention.

<Explanation of symbols for the main parts of the drawings>

101 ... substrate 102 ... reflective layer

103 ... adhesive layer 104 ... transparent layer

110 ... Inlet 112 ... Stop valve

115 storage 130 air vent

140 ... metering portion 150 ... chamber marker

160 ... identification marker 200 ... sample chamber

300 ... reagent chamber

400 ... mixing & detection chamber

490 Detecting portion

500a ... a first calibration chamber

500b ... second calibration chamber

Claims (15)

A sample chamber containing a sample for measurement; A reagent chamber containing a reagent comprising a dye precursor that is discolored when reacting with the sample or a phosphor that is fluorescent when reacting with the sample; A reaction chamber which becomes a mixing space of a sample supplied from the sample chamber and a reagent supplied from the reagent chamber and is read by optical pickup; Optical disk for measurement comprising a. The method of claim 1, The reaction chamber is disposed on the outer circumferential side of the sample chamber and the reagent chamber so that the sample and the reagent are supplied from the sample chamber or the reagent chamber to the reaction chamber by centrifugal force generated during rotation. Optical disc. The method of claim 1, The sample chamber or the reagent chamber, An injection hole which is opened at one end of an inner circumferential side of the sample chamber or the reagent chamber and in which the sample or the reagent is injected; A storage unit for storing the sample or the reagent; It is provided at a position where the inlet and the reservoir is connected to have a thickness step with respect to the reservoir, characterized in that it comprises a stop valve for preventing the sample or the reagent from flowing back toward the inlet Optical disc. The method of claim 1, And at least one of the sample chamber, the reagent chamber and the reaction chamber has an air vent open to the atmosphere. The method of claim 1, And at least one of a first calibration chamber containing a standard solution of a first concentration and a second calibration chamber containing a standard solution of a second concentration. The method of claim 1, Substrate, A reflective layer reflecting light emitted from the optical pickup; A transmission layer that transmits the light and is formed with the sample chamber, the reagent chamber, and the reaction chamber; And an adhesive layer for adhering the reflective layer and the transmissive layer. The method of claim 6, And a chamber marker for changing a light reflection amount of the reflective layer to detect a position of the reaction chamber. The method of claim 7, wherein And an identification marker provided between the chamber markers to identify the plurality of reaction chambers provided with each other. A reagent chamber containing a sample chamber containing a sample for measurement, a dye precursor that discolors when reacting with the sample, or a fluorescent substance that reacts with the sample, and a phosphor that reacts with the sample; a sample supplied from the sample chamber and the reagent; A spindle motor for rotating a measurement optical disk having a reaction chamber formed on a surface thereof, the reaction chamber serving as a mixing space of reagents supplied from the chamber; An optical pickup for reading a color change of the reaction chamber when the sample and the reagent are mixed and reacted in the reaction chamber as the measurement optical disk rotates; A control unit obtaining measurement data of the sample by analyzing the optical signal of the optical pickup; Optical measuring device comprising a. 10. The method of claim 9, The measuring optical disk has a chamber marker for changing the amount of light reflection, The spindle motor has a hall sensor for outputting the FG signal when rotating, The optical pickup includes a photo diode IC (PDIC) that receives the light reflected from the optical disk and outputs an RF signal according to the amount of light. The controller compares the RF signal reading the chamber marker with the FG signal to detect the position of the reaction chamber. The method of claim 10, The measuring optical disk includes an identification marker between the chamber markers to identify the reaction chambers provided in plural from each other, And the control unit compares the RF signal reading the chamber marker with the RF signal reading the identification marker and the FG signal to identify different reaction chambers. A reagent chamber containing a sample chamber containing a sample for measurement, a dye precursor that discolors when reacting with the sample, or a fluorescent substance that reacts with the sample, and a phosphor that reacts with the sample; a sample supplied from the sample chamber and the reagent; Rotating the optical disk for measurement on the surface of the reaction chamber, which becomes a mixing space of reagents supplied from the chamber, with a spindle motor; Reading a color change of the reaction chamber by an optical pickup when the sample and the reagent are mixed and reacted in the reaction chamber as the measurement optical disk rotates; Acquiring measurement data of the sample by analyzing the optical signal of the optical pickup; Optical measurement method comprising a. The method of claim 12, The measuring optical disk includes an identification marker between the chamber marker for changing the amount of light reflection and the chamber marker to identify the plurality of reaction chambers provided with each other. The spindle motor has a hall sensor for outputting the FG signal when rotating, The optical pickup includes a photo diode IC (PDIC) that receives the light reflected from the optical disk and outputs an RF signal according to the amount of light. And comparing the RF signal reading the chamber marker with the RF signal reading the identification marker and the FG signal to detect the position of the reaction chamber and identify different reaction chambers. The method of claim 13, Calculating a delay time of the optical pickup by comparing a generation time of a control signal for raising or lowering an objective lens of the optical pickup and a generation time of an RF signal generated when the objective lens is actually operated according to the control signal, And reading out the reaction chamber by controlling the objective lens at the time point when the delay time is compensated. The method of claim 14, The measuring optical disk further comprises at least one of a first calibration chamber containing a standard solution of a first concentration and a second calibration chamber containing a standard solution of a second concentration, The first calibration chamber and the second calibration chamber are detected by the optical pickup upon detecting the concentration of the mixed solution corresponding to the amount of light from which the reaction chamber is read according to a relation of light absorption rate according to the concentration of the mixed solution previously input. Correcting the relationship by reading at least one of the optical measurement methods.

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