Patent Application
20080131315
This application is based upon and claims the benefit of priority from the prior Japanese Patent Application No. 2006-181240, filed on Jun. 30, 2006; the entire contents of which are incorporated herein by reference.
1. Field of the Invention
This invention relates to a color reaction detecting device and a method for manufacturing the same.
2. Background Art
Biosensors are widely used in medical equipment. A color reaction detecting device is one of the measuring instruments based on biosensors. The color reaction detecting device includes a waveguide layer with a thin film provided thereon, and a certain amount of light is guided inside the waveguide layer to measure the intensity of light, that is, the guided light intensity extracted from the waveguide layer.
The thin film placed on the waveguide layer is brought into contact with a biological tissue such as an arm or finger tip. A prescribed substance released from the biological tissue and intruding into the thin film induces color reaction. The light incident on one end of the waveguide layer is absorbed in this color reaction region. The incident light is reflected on the upper and lower surface of the waveguide layer and propagates to the other end of the waveguide layer, but the light intensity is attenuated each time it is absorbed in the color reaction region. Hence, by measuring the amount of this absorption, the amount of color reaction can be determined to serve for the function of a biosensor capable of measuring the prescribed substance released from the biological tissue.
However, in the measurement, the temperature of the color reaction detecting device varies upon contact with a biological tissue such as a human body. In the operating environment susceptible to this temperature variation, the guided light intensity varies. That is, even if the amount of color reaction is constant, the detected guided light intensity may vary and cause errors in the measurement.
JP 2004-113434A discloses a noninvasive blood sugar measuring instrument for measuring blood glucose concentration from outside a human body with improved accuracy.
According to an aspect of the invention, there is provided a color reaction detecting device including: a support configured to support a sensor chip, the sensor chip including a thin film which causes a color reaction by a substance released from an object under inspection; a light source configured to introduce light into the sensor chip supported by the support; a photodetector configured to sense light emitted from the sensor chip; a temperature sensor configured to measure temperature; and a control unit configured to compute an amount of color reaction in the sensor chip using a result of the sensing by the photodetector and a result of the measurement by the temperature sensor.
According to another aspect of the invention, there is provided a method for manufacturing a color reaction detecting device, the color reaction detecting device including a support for supporting a sensor chip, a light source for introducing light into the sensor chip supported by the support, a photodetector for sensing light emitted from the sensor chip, a temperature sensor for measuring temperature, a data storage unit, and a control unit for computing an amount of color reaction in the sensor chip, the method including: storing, in the data storage unit, data for correcting errors due to temperature variation which occurrs during the sensing by the photodetector.
An embodiment of the invention will now be described with reference to the drawings.
The color reaction detecting device 1 of this embodiment comprises a light source 10, a photodetector 20, a temperature sensor 11, a data storage unit 34, and a control unit 33 connected to them. In measurement, a sensor chip 5 is detachably attached and irradiated with emitted light G1 from the light source 10. The sensor chip 5 is brought into contact with an object under inspection 22 such as a human arm or abdomen. A prescribed medium S released from the object under inspection 22 and diffused into the sensor chip 5 induces color reaction. This color reaction is sensed by the photodetector 20, and arithmetically processed in the control unit 33. Thus the amount of medium S released from the object under inspection 22 can be determined.
Here, when the color reaction detecting device 1 is brought into contact with a human arm or the like in measurement, the temperature of the device increases due to body temperature. This causes variation in the wavelength of the light source 10 and the like, and hence errors occur in the measurement. However, in this embodiment, a temperature sensor 11 is provided so that the temperature of the light source 10 and the like can be measured. The temperature data measured by the temperature sensor 11 is sent to the control unit 33. Upon the variation of temperature, the control unit 33 performs correction computation based on the temperature correction data stored in the data storage unit 34 so that the temperature-dependent wavelength drift and other effects can be canceled. As a result, the color reaction detecting device can achieve high accuracy with reduced measurement errors despite any variation in the temperature of the color reaction detecting device 1.
As shown in
The propagating light G2, which is introduced through the first grating 16 into the waveguide layer 14 and propagates therein, is extracted through the second grating 17 and is incident on the photodetector 20. The intensity of the incident light G3 is measured. The thin film 18 is brought into contact with an object under inspection 22 such as a human arm to be tested. A medium S to be detected is released from the object under inspection 22 and intrudes into the thin film 18. Then color development occurs due to chemical reaction with the material contained in the thin film 18. Upon color development, part of the propagating light G2 that propagates in the waveguide layer 14 is absorbed to cause a loss, and its intensity decreases. Hence, by measuring the intensity of the incident light G3 by the photodetector 20, the amount of medium S released from the object under inspection 22 can be determined.
According to this embodiment, a temperature sensor 11 such as a thermistor is placed near the light source 10 to measure the operating temperature of the light source 10. On the basis of the measurement result, the measurement error associated with the temperature variation can be corrected.
The emitted light G1 is incident on the backside of the substrate 12 at incident angle θ. The substrate 12 is illustratively made of glass (with a refractive index of about 1.5). Hence, in the case of incidence from air, the angle of refraction θ0 is smaller than θ.
Upon arrival at the upper surface of the substrate 12, the emitted light G1 produces refracting light by the first grating 16 formed on the upper surface of the substrate 12. The first and second grating 16, 17 are illustratively made of silicon dioxide (SiO2, with a refractive index of about 1.3). The intensity of refracting light and the angle of refraction can be controlled by varying the pitch d and depth of the grating depending on the wavelength of the emitted light. The first and second grating 16, 17 can be illustratively formed by a microfabrication process using a photoresist.
Furthermore, a waveguide layer 14 covers the first and second grating 16, 17. The waveguide layer 14 is illustratively made of resin having a refractive index of about 1.56, and can be formed by spincoating and curing. A thin film 18 illustratively made of resin having a refractive index of about 1.3 is further provided on the upper surface of the waveguide layer 14. The thin film 18 contains a material that reacts with the medium released from the object under inspection and develops a color. Evanescent waves, which are generated when the propagating light G2 is reflected at the interface with the thin film 18, are absorbed by the developed color. That is, when color development occurs in the thin film 18, optical absorption occurs in the absorption region 24, and the loss of the propagating light G2 increases.
More specifically, the measurement begins by bringing the sensor chip 5 into contact with an object under inspection such as a human arm. Then a medium S is diffused from the object under inspection into the thin film 18 (see
In this embodiment, in determining the amount of medium S in this manner, temperature variation is taken into consideration. That is, the measurement by the temperature sensor 11 (see
After the beginning of measurement, initially (T=T0), the temperature is measured by the temperature sensor 11 (step S10). Here it is also possible to wait for the optical power of the light source 10 to be relatively stabilized before starting the measurement and measuring the temperature. Then the sensor chip 5 is irradiated with the emitted light G1 from the light source 10, and the incident light G3 is detected by the photodetector 20 (step S11). After the measurement of the initial detected intensity P0, the detected light intensity gradually decreases as described above with reference to
For example, if a prescribed period of time (T=T1) has elapsed, or if the temporal variation of the detected light intensity falls below a prescribed value (step S12, yes), then the detected light intensity P1 is taken as the final measurement data, and the temperature is measured by the temperature sensor 11 (step S13).
The data of the detected light intensity from the photodetector 20 and the temperature data from the temperature sensor 11 are sent to the control unit 33 (see
If the temperature varies during measurement, the power and wavelength of the emitted light G1 emitted from the light source 10 may vary. The power variation of the emitted light G1 can be restricted through feedback control of the light source 10 using APC (automatic power control) or other techniques. However, it is not easy to restrict the wavelength variation. As described later in detail, variation in wavelength of the light source 10 causes variation in intensity of light that can be introduced as the propagating light G2 in the sensor chip 5. On the other hand, variation in wavelength causes the variation of the optical path of the propagating light G2 inside the sensor chip 5. This causes variation, for example, in the number of reflections between the waveguide layer 14 and the thin film 18, and hence the loss due to absorption in the absorption region 24 (see
Thus temperature variation during measurement affects the detected intensity in the photodetector 20 in an overlapping manner. In this embodiment, such effects of temperature variation are examined beforehand by measurement or simulation, and temperature correction data based thereon is prepared and stored in the data storage unit 34. The table illustrated in
In the table illustrated in
In the table illustrated in
In the following, the embodiment of the invention is described in more detail with reference to examples.
First, the propagation condition of light introduced into the waveguide layer 14 of the sensor chip 5 is described.
The waveguide layer 14 of the sensor chip 5 has a greater refractive index than the substrate 12 and the thin film 18. Hence, if the shape of the gratings 16, 17, the thickness and refractive index of each component, and the incident angle θ satisfy the following relational expressions, then the propagating light G2 propagates in the waveguide layer 14 while repeating total reflection, passes through the second grating 17 provided at the other end of the substrate 12, and is emitted outside as incident light G3 on the photodetector 20.
θ1=sin−1[(sinθ+λ/d)/n1] (1)
θ1<90 deg (2)
θ1>sin−1(n0/n1) (3)
n1>n0 (4)
n1>n2 (5)
n2>n0 (6)
where
θ: incident angle on the backside of the substrate
θ0: angle of refraction
θ1: guiding angle in the waveguide layer
n0: refractive index of the substrate
n1: refractive index of the waveguide layer
n2: refractive index of the thin film
d: pitch of the grating
λ: wavelength of the emitted light
Next, a description is given more specifically with reference to numerical examples.
First, let n1=1.50, n0=1.46, λ=655 nm, and d=1000 nm. From formulas (1) and (2), θ<57.67 deg. On the other hand, from formulas (1) and (3), θ>53.61 deg. That is, the range of incident angle θ allowing the propagating light G2 to propagate in the waveguide layer 14 while repeating total reflection is 53.61<θ<57.67 (deg). Here “total reflection” means that the incident angle is greater than the critical angle, and includes the case where absorption of evanescent waves occurs in the absorption region 24 of the thin film 18 adjacent to the waveguide layer 14.
The emitted light G1 from the light source 10 has a wavelength distribution In the range determined by the structure of the light source 10. For example, when the light source 10 is a semiconductor light emitting element, the emitted light wavelength is continuously distributed in a wide range of 605 to 705 nm. AS a result, when the wavelength is 605 nm, 58.76<θ<63.51 (deg). When the wavelength is 705 nm, 49.02<θ<52.66 (deg). That is, in the wavelength range of 605 to 705 nm, the propagating light G2 undergoing total reflection exists if 49.02<θ<63.51 (deg).
Next, a method for estimating the variation of the guided light intensity is described.
I(λ)=1000×exp(−((λ−655)/22)2) (7)
The incident angle is illustratively assumed as θ=55.0 deg in the range of 49.02<θ<63.51 (deg). Furthermore, it is assumed that n1=1.50, n0=1.46, and d=1000. For total reflection in the waveguide layer 14, the formulas (1) to (3) need to be satisfied. Because these relational expressions include the emitted light wavelength λ, the incident light on the backside of the substrate 12 is not entirely guided. Here the total reflection condition is satisfied when 641 nm <λ<680 nm.
Next, a description is given of the temperature variation of the guided light intensity where the emitted light G1 from the light source 10 is diffracted by the first grating 16 and introduced into the waveguide layer 14.
The wavelength dependence of the intensity of light emitted from the light source 10 varies with temperature. When the light source 10 is an LED, the wavelength dependence of the emitted light intensity is entirely shifted to the longer wavelength side with the increase of temperature while maintaining substantially the same shape.
I(λ)=1000×exp[−{(λ−(655+0.2×ΔT))/22}2] (8)
For temperature variation ΔT=+20° C., the spectral curve is shifted to the long wavelength side by about +4 nm. For temperature variation ΔT=−20° C., the spectral curve is shifted to the short wavelength side by about −4 nm.
Variation in the intensity of the propagating light G2 in the waveguide layer 14 upon the variation of temperature can be estimated from
Next, a description is given of the temperature variation in the number of reflections of the propagating light G2 that propagates with total reflection in the waveguide layer 14. That is, if the temperature varies, the wavelength of light emitted from the light source 10 varies. Hence the optical path of the propagating light G2 in the waveguide layer 14 also varies. This also causes variation in the number of total reflections undergone by the propagating light G2 in the waveguide layer 14.
The angle of reflection at which the propagating light G2 having a wavelength of 641 to 680 nm undergoes total reflection on the waveguide layer 14 as illustrated in
Number of reflections=L/(t×tanθ1) (9)
where
L: Length of the thin film in the guiding direction
t: Thickness of the waveguide layer
Here, the number of reflections on the thin film 18, which are associated with the absorption of evanescent waves in the absorption region 24, only accounts for about half of this total number.
The average number of reflections of the propagating light G2 is 85.3 at ΔT=0° C., and the average number of reflections decreases to 81.5 at λT =+20° C. On the other hand, the average number of reflections increases to 89 at ΔT=−20° C. In terms of the number of reflections to variation ratio, the number of reflections decreases almost linearly from +5% to −5% for the temperature variation from −20° C. to +20° C.
The temperature variation of the amount of absorption of evanescent waves occurring in the absorption region 24 shown in
Next, an example of the color reaction detecting device of this embodiment is described.
According to this embodiments a temperature sensor 11 is provided near the light source 10, for example, and its detected result is outputted through wiring 35 to the controller board 32. In response to variation in the temperature detected by the temperature sensor 11, the controller board 32 performs computation in consideration of the variation in the wavelength of light emitted from the light source 10 and the variation of the optical path of the guided light in the waveguide layer 14 as described above with reference to
The light source 10 can illustratively be an LED of the SMD (surface mounting device) type. To detect its temperature variation, for example, a temperature sensor 11 such as a thermistor or thermocouple can be pressure welded or bonded to the surface of the SMD.
Manufacturing of a color reaction detecting device of this example illustrated in
Then, for an actual measurement where the temperature at the beginning of measurement is 20.2° C. and the temperature at the end of measurement is 21.8° C., the nearest data in the database of TABLE 1 is data C. Thus data C is selected, and a variation ratio of the guided light intensity of +2% and a variation ratio of the number of reflections of −2% can be retrieved to easily estimate the net signal variation due to color reaction.
Alternatively, the temperature dependence of the spectrum of the emitted light G1 from the light source 10 as described above with reference to
As described above, according to this example, the temperature variation of the guided light intensity after diffraction in the first grating 16 is estimated to correct the variation in the intensity of incident light on the photodetector 20. Thus the amount of color reaction can be determined with high accuracy. Furthermore, through computation of the temperature variation in the total number of reflections, the temperature variation in the amount of absorption of evanescent waves of the propagating light G2 is estimated to correct the variation in the intensity of incident light on the photodetector 20. Thus the amount of color reaction can be determined with higher accuracy.
In the case of manufacturing a plurality of color reaction detecting devices, the data regarding temperature dependence stored in the data storage unit 34 may be common to every device, or the data actually measured for each device may be used. For example, if the light source 10 has a small individual difference in temperature characteristics, the same data regarding temperature dependence can be used. On the other hand, if the light source 10 has a large individual difference in temperature characteristics, preferably, data regarding temperature dependence is measured for each color reaction detecting device and stored in the data storage unit 34.
According to this example, there is no need for the component for restricting the temperature variation of the light source. Hence the device can be downsized and is suitable to portable applications. Furthermore, because there is no need for the time until the temperature is stabilized, measurement can be rapidly performed. Moreover, the measurement accuracy can be ensured because of the temperature correction function.
The embodiment of the invention has been described with reference to the drawings. However, the invention is not limited to the above examples. For example, the shape, size, and material of the light source, temperature sensor, substrate, waveguide layer, grating, thin film, and photodetector constituting the color reaction detecting device that are variously adapted by those skilled in the art are also encompassed within the scope of the invention as long as they do not depart from the spirit of the invention.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2006-181240 | Jun 2006 | JP | national |
