1. Field of the Invention
The present invention relates to a sensor device of a microanalysis system (μ-TAS) for detecting a concentration, a fine pressure distribution, a fine temperature distribution, biological information, genetic information, and so forth of a substance flowing through a flow channel of the system.
2. Related Background Art
Recently, techniques are being developed for microanalysis in chemistry, biochemistry, and the like fields by use of a much smaller system. A typical example is a μ-TAS system which employs a micro flow channel, which enables separation/mixing, reactions, and so forth by a much smaller flow channel.
With development of biotechnology and bio-industry, detection elements like DNA chips are being developed and commercialized for reading bio-genetic information.
With the development of three-dimensional working techniques, chemical analysis systems are attracting attention which are constituted of liquid elements such as a micro flow channel, a pump, and a valve, and a sensor in integration on a substrate made of glass, silicon, or the like to conduct chemical analysis. Such a system is called a miniaturized analysis system, μ-TAS (micro total analysis system), or a lab-on-a-chip. The miniaturized chemical analysis system enables decrease of a dead volume in the system, remarkable decrease of a sample quantity, shortening of analysis time, and saving of power consumption of the total system. Further, cost-down of the system can be expected by the miniaturization. Owing to such advantages, the μ-TAS is promising in application in biotechnology fields such as in medical treatment like home medical care, and a bedside monitor; in biotechnology fields such as DNA analysis, and proteome analysis.
Japanese Patent Application Laid-Open No. H10-337173 discloses a micro-reactor which conducts sequential biochemical experimental operations of mixing solutions causing a reaction of the mixture, analyzing a component, and separating the component by employing combination of several cells.
Such a μ-TAS system or a bib-chip requires a final detection step after the reaction or other operation steps. In the detection step, a light beam is useful as the precise detecting means less affective to the objective substance owing to non-contacting and non-reactive properties of the light.
In an example of the detection procedure, an objective substance is labeled with a fluorophor, an exciting light beam is projected to the objective substance, and the fluorescence is detected. In another example of the detection procedure, a light beam is projected to the objective substance, and light transmittance is measured. In still another example of the detection procedure, the light beam is projected to an objective substance through a prism brought close to the objective substance and the loss of the total reflection light is measured.
In the fluorescence labeling method, a desirable label, namely a label sufficiently sensitive for the detection, is not necessarily applicable owing to compatibility between the objective substance and the labeling substance. Further, in this method, the fluorescence as the signal component is interfered less by the intense exciting light as a noise because of the wavelength difference between the exciting light and the fluorescence advantageously, but the generation efficiency of the fluorescence as the signal component cannot readily be raised, which renders difficult to improve the total SN ratio.
In the light transmission measurement method or the light absorbance measurement method utilizing the transmitted light, when the objective substance is contained in a high concentration in the measurement fluid to exhibit a low transmittance, the signal is weak to result in a lower SN ratio. On the other hand, in this method, when the concentration of the objective substance is lowered to solve the above disadvantage, the original signal becomes weak to lower the SN ratio, also. Furthermore, even though the influence of the light is not remarkable, the light penetrating through the objective fluid may cause heat generation or a photoreaction, so that the intensity of the light should be limited.
In the total reflection loss measurement method, more intense light can be used than in the light transmission measurement method. However, the wavelength of the light for detection of a change or loss and the wavelength of the irradiated light are the same, which requires extremely large dynamic range of the detector, disadvantageously. Therefore, with this measurement method, a slight loss by a slight degree of reaction in the micro flow channel cannot be measured with a high accuracy.
On the other hand, a sensor device employing a photonic crystal, which has a high sensitivity, tends to detect an external disturbance as a noise component.
The external disturbance includes a fluctuation of a concentration, a temperature, and a density. The photonic crystal region itself and the substrate connected thermally to the photonic crystal region change in the temperature in various manners depending on the measurement operation environment. This is different from a high-cost or large-sized constitution which is equipped with a temperature-controlling feedback system, namely a temperature sensor, a heater/cooler element, a control circuit, or a power source. The constitution of small integration or a low cost cannot be equipped with such a temperature control means.
In particular, in a detection device in which a concentration of a biological substance as the objective substance in a solution flowing through a flow channel is measured, the measurement is conducted in a sequence of operation steps: (1) firstly a buffer solution containing no biological substance is allowed to flow through the flow channel, (2) secondly a buffer solution containing a biological substance is allowed to flow through the flow channel, and (3) finally a buffer solution containing no biological substance is allowed to flow through the flow channel to detect the difference from the initial level. In such an operation sequence, fluctuation of the concentration, temperature, or density of the buffer solution directly causes fluctuation of the baseline to produce a noise component. To decrease the temperature fluctuation, a means should be equipped for keeping the temperature constant in the aforementioned measurement region, and further a means should be equipped for keeping constant the temperature of the buffer solution before entering the measurement region. This causes a cost increase and a larger size of the device.
The present invention intends to provide a sensor device which is less affected by external disturbance
The present invention provides a device for detecting a substance contained in a fluid, comprising a first photonic crystal region; a second photonic crystal region; a first flow channel connected to the first photonic crystal region to allow a reference fluid to flow; a second flow channel connected to the second photonic crystal region to allow an objective substance-containing fluid to flow; an optical waveguide connected to the first photonic crystal region and the second photonic crystal region to guide the light; and an optical detector for detecting the light which has transmitted through the first photonic crystal region and the waveguide and has transmitted or been reflected by the second photonic crystal region.
The sensor device of the present invention in which plural photonic crystal regions are optically connected enables decrease of a noise component caused by external disturbance.
The sensor device of the present invention in which plural photonic crystal regions are optically connected is useful in apparatuses employing a micro flow channel, the apparatus including micro-chemical or micro-biochemical analysis apparatuses such as a μ-TAS system and a bio-analysis chip, and portable inspection apparatuses.
The present invention is not limited by the examples described below, but the sequence of the flows and other matters may be modified in various manners within the gist of the present invention.
As many apparently widely different embodiments of the present invention can be made without departing from the spirit and scope thereof, it is to be understood that the invention is not limited to the specific embodiments thereof except as defined in the claims.
Other features and advantages of the present invention will be apparent from the following description taken in conjunction with the accompanying drawings in which like reference characters designate the same or similar parts throughout the figures thereof.
The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.
In the present invention, the “photonic crystal” is a structure having the refractivity changing periodically, including specifically flat materials in the form of flat plates having holes periodically arranged therein, laminates thereof, assemblage of columns, and prisms. In the present invention, in particular, nearly flat plates having two-dimensional arrangement are suitable.
The present invention is explained below specifically by reference to
The sensor device of the present invention comprises first photonic crystal region 205; second photonic crystal region 206; first and second flow channels 208,209 connected respectively to first and second photonic crystal regions 205,206; optical waveguide 102 for introducing light to the first and second photonic crystal regions; and an optical detector (106 in
Suppression of an external disturbance is shown later in Example 1 in the case where the first photonic crystal region and the second photonic crystal region are different from each other in an optical property (e.g., spectral transmittance).
Further, suppression of an external disturbance is shown later in Examples 2 and 3 in the cases where the first photonic crystal region and the second photonic crystal region have has same optical property.
In the present invention, the first photonic crystal and the second photonic crystal are connected in series, and the incident light transmits through the first photonic crystal region and reaches the second photonic crystal region. Even when an external disturbance causes a change in spectral transmittance in the respective photonic crystal regions, the change caused is the same in the respective regions. The present invention utilizes this effect.
The present invention offsets an influence of an external disturbance as mentioned above.
The sensor device of the present invention can be constituted also as shown below. For example, the sensor device comprises two or more photonic crystal regions, an optical waveguide for connecting optically serially the photonic crystal regions, a light source for emitting a light flux to be transmitted through or reflected by the photonic crystal regions to give output light, and an optical detector. From the information derived from the output light, an environmental condition is detected at or around the photonic crystal regions.
The aforementioned plural photonic crystal regions are preferably constituted of a transmission type of first and second photonic crystal regions, and the photonic band edge wavelength at the short wavelength side of the first photonic crystal region and the photonic band edge wavelength at the long wavelength side of the second photonic crystal region are preferably close to each other.
In the aforementioned plural photonic crystal regions, the constituting regions are the same or nearly the same photonic crystal regions, and the respective photonic crystal regions are preferably of a transmission type and are preferably connected optically serially.
The aforementioned plural photonic crystal regions are the same or nearly the same, and the respective photonic crystal regions comprises preferably a transmission type region and a reflection type region, and the photonic crystal regions are preferably connected optically serially.
The environmental conditions at or around the photonic crystal regions to be detected include a temperature, a pressure, a refractivity change, presence of an objective substance, a concentration of an objective substance, and a concentration of a solute in the solution.
The present invention is explained below more specifically by reference to examples.
Two photonic crystals different in a property are optically connected serially, and sensing is conducted by utilizing transmitted light having transmitted through the two photonic crystals. The entire constitution of the sensor device of this Example is explained by reference to
In
The photonic crystal optical element system in combination with a micro flow channel mentioned below will change its spectral transmissivity in accordance with an environmental change caused by contact with an objective fluid or by flow of an objective fluid nearby. This change is detected by a change of the optical spectrum shape, or a change in the light transmittance at a fixed wavelength. When the wavelength is fixed, the wavelength may be taken in plurality: for example, two wavelengths, or three wavelengths. The measurement at many wavelengths corresponds to the aforementioned measurement of optical spectrum shape.
For optical coupling of the incident light and outgoing light with the outside of the element, various optical coupling systems are useful, the useful systems including optical fibers, sphere-tipped optical fibers, GRIN lens optical fibers, wedge-shaped optical fibers, fiber bundles, lens coupling systems including a microscope objective lens, diffraction grating type coupling elements, and so forth.
This Example is explained in more detail by reference to
In this Example, the photonic crystals and the optical waveguide (102-104 in
The material of the substrate for constituting the photonic crystals and the optical waveguides may be an SOI wafer, or a like material such as a silicon nitride film formed by CVD growth on a glass plate, a relatively high-refractivity Teflon® resin formed on low-refractivity mesoporous silica, and so forth. The material may be selected suitably in view of the light wavelength, the production cost, environmental resistance, and so forth.
The substrate supporting the photonic crystal optical element system and the optical waveguide is covered with a micro flow channel element 20. The flow channel element is made of an adsorbent PDMS (polydimethylsiloxane) resin, and adheres to the clean Si surface by self-adsorption. The micro flow channel element 207 has two flow channels 208,209. First flow channel 208 is placed on first photonic crystal 205, and second flow channel 209 is placed on second photonic crystal 206. The fluids are allowed to flow as shown by arrow mark 301.
A sensing process by the sensor element constituted of the aforementioned micro flow channel element and the optical element is described by reference to
The process is described below.
(
(
(
(
(
With such a constitution, when the influence of the external disturbance to the first and second photonic crystals is common, λ1 and λ2 are shifted together by nearly the same wavelength portion to λ1′ and λ2′ with the difference kept unchanged. Naturally, the relation of λ1′>λ2′ is also kept unchanged.
(
As described above, the constitution and the detection method according to the present invention realizes a sensing system which does not detect external disturbance but detects only the difference between the fluids flowing through the first flow channel and the fluid flowing through the second flow channel.
In this Example, two defect-containing photonic crystals having the same properties are optically connected in series, and sensing is conducted the utilizing transmitted light having transmitted through the two photonic crystals. The sensor device of this Example has a constitution similar to that shown in
In this Example, the two same photonic crystals are employed which have respectively a deficiency of a cylindrical hole and a defect-resonator 501. Thereby, the spectral transmittance of the photonic crystal has a sharp transmission peak corresponding to the defect level in the photonic band gap.
A sensing process by the sensor element constituted of the aforementioned micro flow channel element and optical element is described by reference to
The process is described below.
(
(
(
(
(
With such a constitution, when the influence of the external disturbance is common to the first and second photonic crystals, the two spectral transmittances shift together by nearly the same wavelength portion with the defect levels kept superposed.
(
As described above, the constitution and detection method according to the present invention realizes a sensing system which does not detect external disturbance but detects only the difference in the fluids flowing through the first flow channel and the second follow channel.
In this Example, two photonic crystals having the same properties are optically connected in series, and the sensing is conducted the utilizing the light transmitted through a first photonic crystal region and then reflected by the second photonic crystal region.
Optical Waveguide
The sensor device of this Example has a constitution similar to that shown in
A sensing process is explained which is less affected by external disturbance. In the process, the sensing is conducted by a sensor element constituted of the aforementioned micro flow channel and the optical element to achieve the purpose of the present invention of offsetting external disturbance. The explanation is made by reference to
(
(
Total spectral transmittance 805 is a multiplication product of the spectral transmittance and the spectral reflectance, and the transmission is obtained at the two edge portions only. The transmittance is about 25% at the highest. This highest transmittance is obtained at the wavelengths where the both of the transmittance and the reflectance are about 50%. The two wavelengths are respectively within the wavelength range of the first incident light or the second incident light. Therefore, for either of the incident light, an intermediate intensity can be obtained: about 25% of the maximum transmittance. The above state is the initial state of the sensing system of this Example.
(
(
(
With such a constitution, when the influence of the external disturbance to the first and second photonic crystals is common, the two spectral transmissivities shift by nearly the same wavelength portion with the edges at the long wavelength-side and the short wavelength-side of the photonic band gaps kept overlapped.
(
As described above, the constitution and detection method according to the present invention realizes a sensing system which does not detect external disturbance but detects only the difference in the fluids flowing through the first flow channel and the second follow channel.
The embodiment of this Example can be realized either with one incident light flux, or an additional second incident light flux. The use of the two light fluxes is advantageous: when the change caused by the second photonic crystal is a shift toward a short wavelength side, the total transmittance of the first incident light becomes zero, and the total transmittance of the second incident light is decreased; and from the decrease, the change can be detected. Thus the amount of the change toward a positive side as well as a negative side can be detected.
Example 4 of the present invention is explained by reference to
This sensor device is worn on a wrist or arm with a belt 902 to detect necessary information by taking blood or a like method as shown in the step in
As shown in
The constitution of Example 3 is expanded to employ three or more photonic crystal regions 1201 connected suitably to each other as shown in
This application claims priority from Japanese Patent Application No. 2005-051997 filed on Feb. 25, 2005, which is hereby incorporated by reference herein.
Number | Date | Country | Kind |
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2005-051997 | Feb 2005 | JP | national |
Number | Name | Date | Kind |
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6788863 | Parker et al. | Sep 2004 | B2 |
7171095 | Sugita et al. | Jan 2007 | B2 |
20050287696 | Dumais et al. | Dec 2005 | A1 |
Number | Date | Country |
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10-337173 | Dec 1998 | JP |
Number | Date | Country | |
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20060193552 A1 | Aug 2006 | US |