1. Technical Field
The present disclosure relates to a signal detection method, a calibration curve creation method, a quantification method, a signal detection device, a measuring device, and a glucose concentration measuring device.
2. Related Art
Various techniques for analyzing a signal of a predetermined component included in a measurement signal are known. One such technique is an independent component analysis.
For example, JP-A-2007-44104 discloses a technique of analyzing the concentration of a target component included in an observation signal, which is a measurement signal from a body, by performing independent component analysis of the observation signal. JP-A-2007-44104 expresses the observation signal as a linear sum of a basic function with the calculated independent component as the basic function.
In addition, JP-A-2013-36973 discloses a technique of performing independent component analysis of observation data that is a measurement signal from a body, calculating a mixing coefficient for a target component included in the observation data, and acquiring a calibration curve from the mixing coefficient and the content of the target component of original observation data.
A signal relevant to the independent component is preferably a signal of a unique component. Accordingly, since there is no influence of other components, the signal relevant to the independent component is “independent” of the other components. In practice, however, each independent component extracted from mixed components by the independent component analysis may not be completely “independent”. In such a case, even if the independent component analysis is performed to detect the concentration of 1% or less of a trace component in a measurement target, it can be difficult to accurately detect the concentration of the trace component.
The present disclosure proposes a technique capable of accurately detecting a signal relevant to a trace component included in a measurement signal such as a signal from a body.
A signal detection method according to this application example includes acquiring a measurement signal, where the measurement signal includes a first signal and a second signal different from the first signal; and performing an orthogonal operation for adjusting the measurement signal such that the measurement signal is orthogonal to the second signal.
According to a study by the inventors, it has been found that a vector representing the first signal is orthogonal to a vector representing the second signal, and the first and second signals form an orthogonal vector space. Therefore, in the signal detection method according to this application example, an orthogonal operation for acquiring a signal corresponding to the first signal by making the measurement signal orthogonal to the second signal. Therefore, by removing the second signal from the measurement signal, it is possible to detect the first signal with improved accuracy. As a result, it is possible to accurately detect the concentration of the component relevant to the first signal in the sample containing the component relevant to the first signal and the component relevant to the second signal.
In the signal detection method according to the application example, it is preferable that a second feature signal (i.e., second sample feature signal) obtained by performing multivariate analysis processing of a second sample signal is used in the orthogonal operation. The second sample signal is obtained by measuring a sample that contains a component relevant to the second signal and does not contain a component relevant to the first signal.
In the signal detection method according to this application example, the second feature signal that is the feature quantity of the component relevant to the second signal can be extracted by performing multivariate analysis processing of the second sample signal obtained by measuring the sample that contains the component relevant to the second signal and does not contain the component relevant to the first signal. In addition, since the orthogonal operation for making the measurement signal orthogonal to the acquired second feature signal is performed, it is possible to effectively remove the second signal from the measurement signal obtained by measuring the sample containing the component relevant to the first signal and the component relevant to the second signal.
In the signal detection method according to the application example, it is preferable that the multivariate analysis processing is an independent component analysis.
In the signal detection method according to this application example, the independent component analysis process is used as the multivariate analysis processing on the second sample signal. Accordingly, in particular, when the component relevant to the second signal is a high percentage component, it is possible to detect the second feature signals (second sample feature signals) that are strongly orthogonal to each other and that have little error.
In the signal detection method according to the application example, the orthogonal operation may be a projection operation for projecting the measurement signal to a space orthogonal to a space extended by the second feature signal (second sample feature signal).
In the signal detection method according to this application example, the second signal is removed from the measurement signal including the first and second signals by performing a projection operation for projecting the measurement signal to the space orthogonal to the space extended by the second feature signal (second sample feature signal). Therefore, it is possible to detect the first signal with high accuracy.
In the signal detection method according to the application example, with the measurement signal provided as a measurement vector M, the first signal provided as a first vector M0, the second feature signal (second sample feature signal) provided as γ interference unit vectors Pk, the space extended by the second feature signal (second sample feature signal) provided as a matrix P including the interference unit vectors Pk, a pseudo-inverse matrix of the matrix P is expressed as P+, and a unit matrix provided as E, the projection operation is expressed by Equation (1).
{right arrow over (M0)}=(E−P·P+){right arrow over (M)} (1)
In the signal detection method according to this application example, the first signal (the first vector M0) included in the measurement signal expressed as the measurement vector M can be detected with high accuracy by performing the projection operation expressed as Equation (1).
In the signal detection method according to the application example, in the orthogonal operation, an orthogonalization method of Gram-Schmidt using the second feature signal (second sample feature signal) may be applied for the measurement signal.
In the signal detection method according to this application example, the second signal (second sample feature signal) is removed from the measurement signal including the first and second signals by applying the orthogonalization method of Gram-Schmidt using the second feature signal (second sample feature signal) for the measurement signal. Therefore, it is possible to detect the first signal with high accuracy.
In the signal detection method according to the application example, with the measurement signal provided as a measurement vector M, the first signal provided as a first vector M0, the second feature signal (second sample feature signal) provided as γ interference unit vectors Pk, γ intermediate vectors provided as Wk, and transposed vectors of the intermediate vectors Wk provided as WkT, the orthogonalization method of Gram-Schmidt is expressed by Equations (2) and (3) with a first intermediate vector W1 as a first interference unit vector P1.
In the signal detection method according to this application example, the γ intermediate vectors Wk are sequentially orthogonalized by the orthogonalization method of Gram-Schmidt expressed as Equations (2) and (3). Accordingly, the measurement vector M is orthogonal to each of the γ intermediate vectors Wk. As a result, the measurement vector M is orthogonal to all of the second signals. Thus, the first signal (first vector M0) included in the measurement signal expressed as the measurement vector M can be detected with high accuracy.
In the signal detection method according to the application example, a percentage of the first signal in the measurement signal may be equal to or less than 1%.
In the signal detection method according to this application example, the amount of the component relevant to the first signal is small, and the first signal of the trace component in the measurement signal can be detected with high accuracy even when the first signal is included in the measurement signal at the percentage of 1% or less.
A calibration curve creation method according to this application example includes: calculating an inner product value between the first signal, which is obtained by executing the signal detection method according to any one of application examples, and a unit signal of the first signal; and creating a calibration curve showing a relationship between a physical quantity relevant to the first signal and the inner product value.
In the calibration curve creation method according to this application example, the calibration curve is created by calculating the inner product value between the first signal, which is obtained by executing the signal detection method capable of detecting the first signal from the measurement signal with high accuracy, and the unit signal of the first signal. Therefore, it is possible to create a high-accuracy calibration curve.
A quantification method according to this application example includes calculating an inner product value between the first signal, which is obtained by executing the signal detection method according to any one of application examples, and a unit signal of the first signal.
In the quantification method according to this application example, since the inner product value between the first signal, which is obtained by executing the signal detection method capable of detecting the first signal from the measurement signal with high accuracy, and the unit signal of the first signal is taken, it is possible to calculate the magnitude (scalar quantity) of the first signal in the vector space with high accuracy.
In the quantification method according to the application example, the method may further include quantifying a physical quantity with reference to the inner product value and a calibration curve.
In the quantification method according to this application example, since the inner product value between the first signal and the unit signal of the first signal and the calibration curve showing the relationship between the inner product value and the physical quantity relevant to the first signal are referred to, it is possible to correctly quantify the physical quantity of the component relevant to the first signal in the sample containing the component relevant to the first signal and the component relevant to the second signal.
In the quantification method according to the application example, it is preferable that the calibration curve is obtained by the calibration curve creation method according to the application example.
In the quantification method according to this application example, since the calibration curve showing the relationship between the inner product value and the physical quantity relevant to the first signal is used, it is possible to quantify the physical quantity of the component relevant to the first signal contained in the measurement target with high accuracy.
In the quantification method according to the application example, the physical quantity may be glucose concentration in blood.
In the quantification method according to this application example, it is possible to quantify the physical quantity of glucose (component relevant to the first signal) contained in a small amount with respect to water (component relevant to the second signal) contained at a high percentage in blood with high accuracy.
A signal detection device according to this application example includes: an acquisition unit that acquires a measurement signal by measuring a measurement target containing a component relevant to the first signal and a component relevant to the second signal different from the first signal; and an arithmetic processing unit that performs an orthogonal operation for making the measurement signal orthogonal to the second signal.
According to the configuration according to this application example, the acquisition unit acquires a measurement signal by measuring the measurement target containing the component relevant to the first signal and the component relevant to the second signal. In addition, the arithmetic processing unit forms a vector space where the vector representing the second signal is orthogonal to the vector representing the first signal, and performs an orthogonal operation for making the measurement signal orthogonal to the second signal in the vector space. Therefore, it is possible to realize a signal detection device capable of detecting the first signal with high accuracy by removing the second signal from the measurement signal including the first and second signals.
A measuring device according to this application example includes: an acquisition unit that acquires a measurement signal by measuring a measurement target containing a component relevant to the first signal and a component relevant to the second signal different from the first signal; and an arithmetic processing unit that performs an orthogonal operation for making the measurement signal orthogonal to the second signal and quantifies a physical quantity using a result of the orthogonal operation.
According to the configuration according to this application example, the acquisition unit acquires a measurement signal by measuring the measurement target containing the component relevant to the first signal and the component relevant to the second signal. In addition, the arithmetic processing unit forms a vector space where the vector representing the second signal is orthogonal to the vector representing the first signal, performs an orthogonal operation for making the measurement signal orthogonal to the second signal in the vector space, and quantifies the physical quantity using the operation result. Therefore, it is possible to realize a measuring device capable of detecting the first signal by removing the second signal from the measurement signal including the first and second signals and quantifying the physical quantity of the component relevant to the first signal with high accuracy.
A first aspect of the present disclosure is directed to a signal detection method including: acquiring a measurement signal (signal from the body) by measuring a predetermined measurement target, the measurement signal including a second signal (interference signal) that is a signal of a high percentage component and a first signal (target signal) that is a signal of a trace component; and performing an orthogonal operation for making the measurement signal (signal from the body) orthogonal to the second signal (interference signal) in a vector space where vectors representing the signals of the respective components are orthogonal to each other.
According to the first aspect of the present disclosure, it is possible to obtain a signal excluding a high percentage component by performing an orthogonal operation for making the measurement signal (signal from the body) orthogonal to the second signal (interference signal), which is a signal of a high percentage component, in the vector space where the vectors representing the signals of the respective components are orthogonal to each other. Since the signal of the high percentage component is removed, it is possible to detect the first signal (target signal), which is a trace component in the measurement signal (signal from the body), with high accuracy.
A second aspect of the present disclosure is directed to the signal detection method according to the first aspect of the present disclosure, in which a percentage of the first signal (target signal) in the measurement signal (signal from the body) is equal to or less than 1%.
According to the second aspect of the present disclosure, even if the first signal (target signal) is slightly included in the measurement signal (signal from the body) at the percentage of 1% or less, it is possible to achieve the same effect as in the first aspect of the present disclosure.
A third aspect of the present disclosure is directed to the signal detection method according to the first or second aspect of the present disclosure, in which a percentage of the second signal (interference signal) in the measurement signal (signal from the body) is equal to or greater than 3%.
A fourth aspect of the present disclosure is directed to the signal detection method according to any one of the first to third aspects of the present disclosure, in which the orthogonal operation is performed by using a signal obtained by performing independent component analysis of the second sample signal (signal of only an interference component) that is obtained by measuring a predetermined sample that contains a component relevant to the second signal (interference signal) and does not contain a component relevant to the first signal (target signal).
According to the fourth aspect of the present disclosure, it is possible to perform the orthogonal operation using the signal obtained by performing multivariate analysis of the second sample signal (signal of only an interference component) that is obtained by measuring a predetermined sample that contains a component relevant to the second signal (interference signal) and does not contain a component relevant to the first signal (target signal). Therefore, it is possible to effectively remove the component relevant to the second signal (interference signal). As the multivariate analysis, it is possible to use various analysis methods, such as an independent component analysis or a main component analysis. Among these, it is most preferable to use the independent component analysis of the strongest independence as the multivariate analysis since it is possible to detect a signal relevant to the trace component with high accuracy.
Specifically, for example, the performing of the orthogonal operation may be configured to include performing a projection operation for projecting the measurement signal (signal from the body) to a predetermined orthogonal subspace that is orthogonal to the second signal (interference signal), as a fifth aspect of the present disclosure.
The performing of the orthogonal operation may be configured to include making the measurement signal (signal from the body) orthogonal to the second signal (interference signal) using an orthogonalization method of Gram-Schmidt, as a sixth aspect of the present disclosure.
A seventh aspect of the present disclosure is directed to the signal detection method according to any one of the first to sixth aspects of the present disclosure, in which the high percentage component of the measurement target is water, and the acquisition of the measurement signal (signal from the body) includes acquiring the measurement signal (signal from the body) as spectrum data.
According to the seventh aspect of the present disclosure, it is possible to acquire the measurement signal (signal from the body) of the measurement target, of which a high percentage component is water, as spectrum data.
An eighth aspect of the present disclosure is directed to the signal detection method according to the seventh aspect of the present disclosure, in which the acquisition of the spectrum data includes acquiring spectrum data of the measurement target at different temperatures.
According to the eighth aspect of the present disclosure, for example, there is a temperature characteristic in the spectrum data (or the composition ratio of feature quantities) of water. Therefore, it is possible to detect the first signal (target signal) in consideration of the temperature characteristic.
A ninth aspect of the present disclosure is directed to a calibration curve creation method including: executing the signal detection method according to any one of the first to eighth aspects of the present disclosure for a plurality of the measurement targets having different component concentrations relevant to the first signal (target signal); and creating a calibration curve for the component concentration relevant to the first signal (target signal).
According to the ninth aspect of the present disclosure, it is possible to create the calibration curve of the component concentration relevant to the first signal (target signal) included in the measurement target.
A tenth aspect of the present disclosure is directed to a concentration measuring method including: executing the signal detection method according to any one of the first to seventh aspects of the present disclosure for the measurement target whose component concentration relevant to the first signal (target signal) is unknown; and measuring the unknown component concentration using the detected signal and the calibration curve created by executing the calibration curve creation method according to the ninth aspect of the present disclosure.
According to the tenth aspect of the present disclosure, the component concentration relevant to the first signal (target signal) included in the measurement target can be accurately calculated by using the calibration curve created according to the ninth aspect of the present disclosure.
An eleventh aspect of the present disclosure is directed to a signal detection device including: an acquisition unit that acquires a measurement signal (signal from the body) by measuring a predetermined measurement target, the measurement signal including a second signal (interference signal) that is a signal of a high percentage component and a first signal (target signal) that is a signal of a trace component; and an arithmetic processing unit that performs an orthogonal operation for making the measurement signal (signal from the body) orthogonal to the second signal (interference signal) in a vector space where vectors representing the signals of the respective components are orthogonal to each other.
According to the eleventh aspect of the present disclosure, it is possible to realize a signal detection device that exhibits the same effect as in the first aspect of the present disclosure.
The present disclosure will be described with reference to the accompanying drawings, wherein like numbers reference like elements.
Hereinafter, example embodiments will be described with reference to the accompanying diagrams.
A physical quantity to be measured is a vector that is expressed as a linear sum of various physical quantities. That is, two or more physical quantity components are included in a measurement signal, where the measurement signal is a signal from a body obtained by measuring a measurement target. The measurement signal is expressed as a linear sum of the signals of the respective physical quantity components. The measurement signal is expressed as a linear sum of a target signal that is a first signal and an interference signal that is a second signal, and the first signal is orthogonal to the second signal.
According to a study conducted by the inventors, since the first and second signals are originally independent of each other, the first signal may be obtained by adjusting the measurement signal such that the measurement signal is orthogonal to the second signal. Therefore, by making the measurement signal orthogonal to the second signal, a signal corresponding to the first signal can be extracted with high accuracy.
An electrical signal, an audio signal, an electromagnetic wave signal, and the like can be considered as measurement targets of this application. The present disclosure can be applied to a case of measuring a specific signal component included in these signals or to a case of measuring the concentration or mass of a specific component contained in a measurement target, such as a gas or liquid. In the following embodiment, concentration is used as an example of the physical quantity component that is a measurement target. However, in the following embodiment, the physical quantity component is not limited to the concentration, and may be all kinds of variation parameters (concentration, temperature, pressure, and the like).
In addition, it is thought that the measurement signal is expressed as a linear sum of the signals of physical quantity components. Therefore, if the signal of each physical quantity component is expressed as a vector, it is possible to define the vector space where a vector representing a physical quantity component of an interference material (vector representing a second signal) is orthogonal to a vector representing a target physical quantity component (vector representing a first signal). As a result, the measurement signal vector can be defined in this vector space. In addition, the number of dimensions of the vector space is the number of independent physical quantity components included in the measurement signal.
The first signal (first vector M0) is orthogonal to the second signal (vector sum of the first interference vector μ1P1 and the second interference vector μ2P2). Thus, the measurement vector M representing the measurement signal is expressed as a linear sum of the first signal (first vector M0) representing the target physical quantity and the second signal (vector sum of all interference vectors, such as the first interference vector μ1P1 or the second interference vector μ2P2) representing the interference physical quantity, and the first and second signals are orthogonal to each other.
In
In the example shown in
For example, even if the first interference vector μ1P1 and the second interference vector μ2P2 form an oblique coordinate system, the first signal (the first vector M0) may be orthogonal to the space where all interference vectors extend (in the example shown in
In the following embodiment, the trace component is a “target component”, and it is an object of the embodiment to correctly detect a signal relevant to the trace component from the measurement signal (signal from the body). Accordingly, it is an object of the embodiment to detect the first vector M0 of the trace component from the measurement vector M representing a measurement signal (signal from the body). On the other hand, the high percentage component can be said to be a component that inhibits the detection of a signal relevant to the trace component from the measurement signal (signal from the body), the high percentage component is referred to as an “interference component”.
Meanwhile, as a method of signal processing for analyzing how much each component is contained, an independent component analysis is known. When measuring the amount (or may be a percentage or concentration) of a specific component contained in the measurement target using the independent component analysis, a problem may occur. Specifically, when a specific component contained in the measurement target is a trace component whose percentage is extremely small compared with the percentage of other components, the independent component analysis has a problem that it is difficult to correctly determine the content (or may be a percentage or concentration) of the trace component.
The independent component analysis is a technique of estimating the number and amount of contained components based on a statistical method using a random variable. Therefore, when one independent component included in the measurement signal (signal from the body) is a trace component whose percentage is 1% or less, it may be difficult to measure the trace component correctly.
However, in the practical independent component analysis, a trace of one target component cannot be completely independently separated from the interference components (two high percentage components). Therefore, the present inventors have found that a state in which the target component includes a slight error of interference components is typically regarded as “independent”. This is because the independent component analysis is an analysis based on the statistical method using a random variable.
It does not matter that the target component cannot be separated completely independent of the interference components in the independent component analysis since the degree of separation can be expressed as the degree of orthogonality between the first signal that is a target component and the second signal that is an interference component. That is, the target signal obtained directly by the independent component analysis is shifted from the normal of the plane defined by the first interference vector μ1P1 and the second interference vector μ2P2.
Even if the shift of the degree of orthogonality of the target signal (inclination of the target signal with respect to the normal of interference components) is a slight error of approximately 1/100, the influence of the interference components cannot be neglected since the amount of the target component is very small. If the first signal that is a target component is completely orthogonal to the second signal that is an interference component, the amount of the target component can be accurately measured regardless of whether the amount is large or small.
However, since the target signal obtained directly by the independent component analysis is not completely orthogonal to the interference components, the amount of high percentage components that are slightly contained affects the amount of the trace component. On the other hand, as described herein, since a component of the measurement signal orthogonal to the interference components is considered to be the first signal, it is natural that the influence of the interference components can be significantly reduced compared with that in the related art.
After all, for conventional quantification based on independent component analysis, even if there is only a slight error in the content of the extracted high percentage component, the error affects the content of a trace component. This causes a large change for the trace component. Therefore, it can be said that, a method for determining the amount (or may be a percentage or concentration) of a trace component, the quantification based on only independent component analysis is not suitable for detecting a small amount of the trace component.
The high percentage component is a component whose amount (or may be a percentage or concentration) can be determined with high accuracy by the independent component analysis, and the percentage of the high percentage component in the measurement signal is 3% or more, for example.
In order to solve the above problem, in the present embodiment, the signal of the target component that is a trace component is detected using orthogonalization (in the present embodiment, also referred to as “orthogonal operation”) that is a method of signal processing. Specifically, the first signal (first vector M0) of the target component that is a trace component is detected by making the measurement vector M orthogonal to the vector (vector sum of the first interference vector μ1P1 and the second interference vector μ2P2) representing the second signal of the interference component that is a high percentage component.
Since the second signal of the interference component is a signal of a high percentage component that is sufficiently included in the measurement signal (signal from the body), the independent component analysis is effective. Therefore, by preparing a sample of the measurement target and analyzing the measurement signal of the sample, which contains an interference component and does not contain a target component, through the independent component analysis, it is possible to calculate the interference component feature quantity (for example, a first interference unit vector P1 or a second interference unit vector P2 shown in
Next, an example of the configuration of a signal detection device to which the present disclosure is applied will be described.
The signal detection device 1 is a kind of electronic computer system including a processing unit 10, a storage unit 50, an operation unit 70, a display unit 80, and a communication unit 90. The processing unit 10 is realized, for example, by a microprocessor, such as a central processing unit (CPU) or a graphics processor unit (GPU), or an electronic component, such as an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or an integrated circuit (IC) memory. In addition, the processing unit 10 controls input and output of data to and from each functional unit, and calculates the concentration of the target component contained in the measurement target by performing various kinds of arithmetic processing based on a predetermined program or data, an operation input signal from the operation unit 70, measurement results of the absorbance measuring device 6, and the like.
The processing unit 10 includes a measurement signal acquisition section 20 as an acquisition section and an arithmetic processing section 30. The measurement signal acquisition section 20 controls the absorbance measuring device 6 by performing predetermined communication with the absorbance measuring device 6, and acquires the result measured by the absorbance measuring device 6 as a measurement signal. The measurement signal may be an analog signal. In this case, however, it is assumed that the measurement signal is converted into measurement signal data, which is a digital signal, by the measurement signal acquisition section 20. The absorbance measuring device 6 is a device for measuring the absorbance spectrum showing the absorbance for the wavelength of each light beam by emitting various light beams having different wavelengths to the measurement target and receiving the transmitted light that has been transmitted through the measurement target. That is, the measurement signal is expressed as an absorbance spectrum.
There are three measurement targets of the absorbance measuring device 6. These are an interference component sample that is a sample of an interference component that does not contain a target component, a known concentration sample that is a sample containing a target component whose concentration is known or is determined by separate measurement, and a concentration measurement target containing a target component whose concentration is unknown and is to be measured. The measured absorbance spectrum is stored in the storage unit 50, as interference component sample measurement signal data 531, known concentration sample measurement signal data 532, and concentration measurement target measurement signal data 533, by the measurement signal acquisition section 20.
The arithmetic processing section (signal processing section) 30 is a processing section that performs various kinds of digital signal processing on the measurement signal acquired by the measurement signal acquisition section 20, and can be said to be a kind of signal processing section. The arithmetic processing section 30 includes a calibration curve creating section 310 and a concentration measuring section 320.
The calibration curve creating section 310 performs a calibration curve creation process (refer to
The interference component feature quantity extracting section 312 performs an interference component feature quantity extraction process according to an interference component feature quantity extraction program 512 that is a subroutine program of the calibration curve creation program 510. The component analysis section 314 performs component analysis processing (multivariate analysis processing) of interference components of the measurement signal. The first target component signal detecting section 316 performs a target component signal detection process for detecting the signal of the target component from a sample having a known concentration according to a target component signal detection program 514 that is a subroutine program of the calibration curve creation program 510.
The concentration measuring section 320 performs a concentration measurement process according to a concentration measurement program 520. Specifically, the concentration measuring section 320 measures the concentration of the target component contained in the concentration measurement target using the calibration curve created by the calibration curve creating section 310. The concentration measuring section 320 includes a second target component signal detecting section 322. The second target component signal detecting section 322 performs a target component signal detection process for detecting the signal of the target component contained in the concentration measurement target, that is, the first signal (first vector M0) according to a target component signal detection program 522 that is a subroutine program of the concentration measurement program 520.
The measurement signal acquisition section 20 and the arithmetic processing section 30 may also be formed by an electronic circuit that performs signal processing, rather than as a software-based functional section that is realized by executing a program as described above. Although the first target component signal detecting section 316 and the second target component signal detecting section 322 have been described as separate functional sections, the first target component signal detecting section 316 and the second target component signal detecting section 322 may be designed as a common functional section.
The storage unit 50 is realized by a storage medium, such as an IC memory, a hard disk, or an optical disc, and stores various programs or various kinds of data, such as data during the calculation process of the processing unit 10. The connection between the processing unit 10 and the storage unit 50 is not limited to a connection using an internal bus circuit in the device, and may be realized by using a communication line, such as a local area network (LAN) or the Internet. In this case, the storage unit 50 may be realized by using a separate external storage device from the signal detection device 1.
The calibration curve creation program 510 and the concentration measurement program 520 are stored in the storage unit 50. The calibration curve creation program 510 includes, as subroutine programs, the interference component feature quantity extraction program 512 for executing the interference component feature quantity extraction process and the target component signal detection program 514 for creating a calibration curve. The concentration measurement program 520 includes, as a subroutine program, the target component signal detection program 522 for measuring the concentration of the concentration measurement target.
In addition, the storage unit 50 stores the interference component sample measurement signal data 531, the known concentration sample measurement signal data 532, the concentration measurement target measurement signal data 533, an interference component feature quantity data 541, a target component feature quantity data 543, and a calibration curve data 545 that are calculated when performing the interference component feature quantity extraction process, the calibration curve creation process, and the concentration measurement process. In addition to these, the storage unit 50 can appropriately store temporary data that is calculated when performing each process.
The operation unit 70 receives various kinds of operation input performed by the user, and outputs an operation input signal corresponding to the operation input to the processing unit 10. For example, the operation unit 70 can be realized by a button switch, a lever switch, a dial switch, a track pad, a mouse, a keyboard, a touch panel, and the like.
The display unit 80 displays a calculation result of the processing unit 10, a guidance display showing the operation procedure, and the like. For example, the display unit 80 can be realized by a liquid crystal display, a touch panel, or the like.
The communication unit 90 realizes a communication function for data exchange between the signal detection device 1 and an external device by connecting the signal detection device 1 to the external device. The communication mode may be wired or may be wireless. In addition, the communication unit 90 may be connectable to the Internet circuit or to a public communication network.
Signal detection method, calibration curve creation method, and quantification method
Next, a signal detection method, a calibration curve creation method, and a quantification method according to the first embodiment will be described. The signal detection method, the calibration curve creation method, and the quantification method according to the first embodiment include an interference component feature quantity extraction process, a calibration curve creation process, and a concentration measurement process.
First, the interference component feature quantity extraction process according to the first embodiment will be described.
In the first embodiment, a method of acquiring the first signal will be described by way of an example in which the signal detection device 1 calculates the concentration of glucose contained in the aqueous glucose solution having an unknown concentration. The aqueous glucose solution of the measurement target contains glucose as a target component (target physical quantity) at a concentration of 1% or less, and contains water as an interference component (interference physical quantity) at a concentration of 90% or more that is equal to or greater than 3%. Therefore, glucose as a target component is a trace component, and water as an interference component is a high percentage component.
The interference component feature quantity extraction process is a process for extracting the feature quantity of the interference component from the measurement signal (second sample signal) of the interference component sample that contains an interference component relevant to the second signal and does not contain a target component relevant to the first signal. In the present embodiment, the interference component sample is a component other than glucose that is a target component, that is, water that is a high percentage component. The interference component feature quantity extraction process is realized by executing the interference component feature quantity extraction program 512 that is a subroutine program included in the calibration curve creation program 510 shown in
In step S01 shown in
In step S02, measurement signals (second sample signals) of β water components having different temperatures are acquired. Here, an absorbance spectrum is acquired as a measurement signal of water that is an interference component sample. The absorbance spectrum of the interference component sample is acquired from the absorbance measuring device 6 through the measurement signal acquisition section 20, and is stored in the storage unit 50 as the interference component sample measurement signal data 531. This is repeated until the measurement of β interference component samples ends (step S03: NO to step S02).
When the measurement for all (β) interference component samples is completed (step S03: YES), data of the absorbance spectrum of water that is an interference component is obtained from the interference component samples as a result.
Here, as an example, the number of levels (j: 1 to β) of the interference component sample (water) was set to 11 at intervals of 1° C. in the water temperature range of 30° C. to 40° C. That is, 11 samples up to 40° C. at which j=β=11 (for example, j=1 is 30° C., and j=2 is 31° C.) were measured. In addition, 90 measurement points (i: 1 to α) were set at intervals of 5 nm in the wavelength range of 800 nm to 1245 nm. That is, β samples were measured at 90 points up to 1245 nm at which i=α=90 (for example, i=1 has a wavelength of 800 nm, and i=2 has a wavelength of 805 nm).
In S04 shown in
Specifically, for example, an element Qij at the first row of the second sample vector Qj of the j-th level is the absorbance at the wavelength of 800 nm of i=1 at the j-th water temperature. In addition, for example, an element Qαj at the α-th row of the second sample vector Qj is the absorbance at the wavelength of i=α (in this example, a wavelength of 1245 nm at α=90) at the j-th water temperature. Thus, αβ pieces of measurement data are expressed as β column vectors of α rows by one column. The second sample vector Qj formed from the measured spectrum data is stored in the storage unit 50 as a second sample signal (interference component sample measurement signal data 531).
In step S05, the component analysis section 314 performs component analysis processing (multivariate analysis processing) on the second sample signal (second sample vector Qj) acquired in step S04. As a result, an interference component feature quantity shown in step S06 is acquired. The multivariate analysis processing may utilize various analysis processes, such as an independent component analysis process or a main component analysis process. Among these, the independent component analysis process is preferable when detecting the signal of the high percentage component with high accuracy since the orthogonality of obtained interference vectors is strong and the independent component analysis process is excellent in error reduction.
By performing the independent component analysis process on the second sample signal (second sample vector Qj) in step S05, an interference component feature quantity (interference unit vector Pk) that is a second sample feature signal (second feature signal) is obtained (step S06). The interference unit vector Pk (k is an integer of 1 to γ) is a column vector of α rows by one column, and γ is the number of independent components formed from the second sample vector Qj. Here, since the number of independent components is 3, γ=3.
The second sample vector Qj is expressed as a linear sum of the interference unit vector Pk, as shown in Equation (5). In equation (5), μkb is a coefficient. For example, the second sample vector Q1 of the first level when the water temperature is 30° C. (j=1) is expressed as a linear sum of the first interference unit vector P1, the second interference unit vector P2, and the third interference unit vector P3 as shown in Equation (6).
As described above, the interference component feature quantity extraction process shown in
Next, the calibration curve creation process according to the first embodiment will be described.
The calibration curve creation process is a process for creating a calibration curve for measuring the concentration of the target component. Therefore, before performing the concentration measurement process to be described later, it is necessary to create a calibration curve in advance. In addition, before performing the calibration curve creation process, the interference component feature quantity needs to be acquired in advance.
Therefore, first, when the interference component feature quantity is not stored as the interference component feature quantity data 541 in step S11 shown in
In step S13, a reference sample is prepared in which the physical quantity of the target component relevant to the first signal is known. In the example of the present embodiment, a target component is glucose, and the physical quantity of the target component is the glucose concentration in the aqueous solution. Therefore, the reference sample is a known concentration sample having a known glucose concentration. Specifically, a plurality (δ; δ is an integer of 2 or more) of aqueous solutions having known and different concentrations of glucose that is a target component are prepared as known concentration samples (measurement targets). Since the spectrum data (or the composition ratio of feature quantities) of water that is an interference component changes with the temperature, it is preferable to prepare, as known concentration samples, not only the samples having different concentrations but also a plurality of samples obtained by changing the temperature as interference component samples.
Since the target component is a trace component having a concentration of 1% or less, the glucose concentration in any known concentration sample is assumed to be 1% or less. This is because the range of glucose concentration to be measured in the body is approximately 50 mg/dl to 600 mg/dl. The specific gravity of the blood is 1 g/cc that is the same as that of water, 1 dl (1 deciliter) is 100 g, and the glucose concentration is 1000 mg/dl or less. Accordingly, the glucose concentration is assumed to be 1% or less.
In step S14, the measurement signal of each of the δ aqueous glucose solutions having different concentrations, which are known concentration samples, is acquired. Here, similar to the case of the interference component sample, an absorbance spectrum is acquired as a measurement signal of the known concentration sample. The absorbance spectrum of the known concentration sample is acquired from the absorbance measuring device 6 through the measurement signal acquisition section 20, and is stored in the storage unit 50 as the known concentration sample measurement signal data 532. This is repeated until the measurement of 8 known concentration samples ends (step S15: NO to step S14).
When the measurement for all (8) known concentration samples ends (step S15: YES), data of the absorbance spectrum of each aqueous glucose solution that is a known concentration sample is obtained as a result.
Here, the number of levels δ of the aqueous glucose solution was set to 28 at intervals of 25 mg/dl in a range of 25 mg/dl to 700 mg/dl. That is, 28 samples up to 700 mg/dl at which g=δ=28 (for example, g=1 was a concentration of 25 mg/dl, and g=2 was a concentration of 50 mg/dl) were measured. In
In step S16 shown in
In step S17, orthogonal processing (orthogonal operation) for making the measurement signal (that is, the reference vector Rg) of the known concentration sample orthogonal to the signal of water, which is an interference component, is performed. In the first embodiment, a projection operation is used as the orthogonal operation. As shown in
In the first embodiment, the orthogonalization reference vector Sg of the target component is calculated by performing a projection operation for projecting the measurement signal (reference vector Rg) of the known concentration sample to the orthogonal subspace extended by the second sample feature signal (second feature signal, interference unit vector Pk). The orthogonalization reference vector Sg of the target component is calculated by Equation (8).
{right arrow over (Sg)}=(E−P·P+){right arrow over (Rg)} (8)
In Equation (8), E is a unit matrix of α rows by α columns, and is expressed by Equation (9). δij is a delta function.
In Equation (8), P is an interference matrix of α rows by γ columns, and is a space extended by the γ interference unit vectors Pk as expressed by Equation (10).
In Equation (8), P+ is a pseudo-inverse matrix of the interference matrix P, and is calculated by Equation (11).
P+(PTp)−1PT (11)
In Equation (11), P+ is a transposed matrix of the interference matrix P, and is calculated by Equation (12). The transposed matrix P+ is a matrix of γ rows by α columns.
By projecting the reference vector Rg to the orthogonal subspace extended by the second sample feature signal (second feature signal, interference unit vector Pk) by performing the projection operation shown in Equation (8), the orthogonalization reference vector Sg is obtained. The orthogonalization reference vector Sg is obtained for each of the δ (=28) known concentration samples. Since the orthogonalization reference vector Sg is orthogonal to the interference unit vector Pk, interference components are rarely contained.
As shown in Equation (13), the orthogonalization reference vector Sg is expressed as δ column vectors of α rows by one column according to the measurement point i (1≦i≦α) and the number of level g (1≦g≦δ). The acquired orthogonalization reference vector Sg is stored as the known concentration sample measurement signal data 532 in the storage unit 50.
The target component signal detection process (steps S13 to S17) is performed according to the target component signal detection program 514, which is a subroutine program of the calibration curve creation program 510, by the first target component signal detecting section 316 shown in
In step S18 shown in
The target unit vector I is orthogonal to the space where all of the interference unit vectors Pk extend (e.g., in
In step S20 shown in
By performing calculation as in Equation (15) for each level (g is an integer of 1 to δ; in this example, δ=28) corresponding to the concentration of aqueous glucose solution, the inner product value of each level is obtained as shown in Table 1. For example, the inner product value in the case of g=1 in which the concentration of the known concentration sample (aqueous glucose solution) is 25 mg/dl is calculated as in Equation (16).
{right arrow over (S)}·{right arrow over (I)}=S
11
I
1
+S
21
I
2
+ . . . S
α1
I
α (16)
In step S21 shown in
In
As shown in
As a comparative example,
As described in the present embodiment, the method of calculating the orthogonalization reference vector Sg of the target component improves the quantification of the trace component. Specifically, the quantification of the trace component is achieved by performing calculations to adjust the reference vector Rg such that the reference vector Rg is orthogonal to the second feature signal (orthogonal subspace extended by all of the interference unit vectors Pk), calculating the target unit vector I from the orthogonalization reference vector Sg, and calculating an inner product between the reference vector Rg and the target unit vector I.
Next, the concentration measurement process according to the first embodiment will be described.
Steps S31 to S34 shown in
In step S32, a measurement signal of the measurement target sample (aqueous glucose solution having an unknown concentration) is acquired. Similar to the case of the known concentration sample, the absorbance spectrum of the measurement target sample is acquired as a measurement signal. Glucose that is a target component and water that is an interference component are contained in the measurement target sample. Accordingly, the measurement signal includes a signal (first signal) of the target component, and a signal (second signal) of the interference component. The absorbance spectrum of the measurement target sample is acquired from the absorbance measuring device 6 through the measurement signal acquisition section 20, and is stored in the storage unit 50 as the concentration measurement target measurement signal data 533.
In step S33, the second target component signal detecting section 322 acquires the measurement vector M based on the data of the absorbance spectrum acquired from the measurement target sample (aqueous glucose solution having an unknown concentration). As shown in Equation (17), the measurement vector M is expressed as a column vector of α rows by one column according to the measurement point i (1≦i≦α).
In step S34, the second target component signal detecting section 322 performs orthogonal processing (orthogonal operation) for making the measurement signal of the measurement target sample (aqueous glucose solution having an unknown concentration) orthogonal to the signal of water, which is an interference component. Similar to step S17 in the calibration curve creation process of
As shown in
Therefore, the first signal (first vector M0) of the target component is calculated by performing a projection operation for projecting the measurement signal (measurement vector M) of the measurement target sample upon the orthogonal subspace extended by the second signal (interference unit vector Pk). The first signal (first vector M0) of the target component is calculated by Equation (18). In Equation (18), E and P are expressed by Equations (9) and (10) described above, respectively, and P+ is expressed by Equations (11) and (12) described above.
{right arrow over (M0)}=(E−P·P+){right arrow over (M)} (18)
Thus, the first signal (first vector M0) of the target component is acquired from the measurement signal (measurement vector M) of the measurement target sample (step S35). The first vector M0 is orthogonal to the space where all of γ interference unit vectors extend (e.g., in
In step S36, as shown in Equation (19), the concentration measuring section 320 calculates an inner product between the first vector M0 of the target component acquired in step S35 and the target unit vector I stored as the target component feature quantity data 543 in the storage unit 50. Through this inner product calculation, as shown in
In step S37, the concentration measuring section 320 determines the glucose concentration of the measurement target sample by comparing the concentration corresponding to the inner product value m0 acquired in step S36 with the calibration curve data 545 (calibration curve of in
As described above, according to the signal detection device 1, the signal detection method, the calibration curve creation method, and the quantification method of the first embodiment, the first signal (first vector M0) relevant to glucose that is a target component contained in the measurement target can be accurately detected from the measurement signal (measurement vector M) obtained by measuring the measurement target. In addition, it is possible to create a calibration curve correctly using the detection of the target component feature quantity (target unit vector I). Therefore, it is possible to correctly measure the concentration of the target component contained as a trace component in the measurement target.
Next, a second embodiment will be described. In the second embodiment, the configuration of the signal detection device 1 is the same as that in the first embodiment, and the signal detection method, the calibration curve creation method, and the quantification method are almost the same as those in the first embodiment except that an orthogonalization method of Gram-Schmidt is used as an orthogonal operation in the calibration curve creation process and the concentration measurement process. Here, the method of orthogonal operation according to the second embodiment will be described focusing on the differences from the first embodiment.
In the calibration curve creation process of the second embodiment, in the orthogonal processing of step S17 shown in
In the second embodiment, an intermediate vector Wk is formed by sequentially orthogonalizing the interference component feature quantity (interference unit vector Pk shown in
{right arrow over (W1)}={right arrow over (P1)} (20)
Then, a second intermediate vector W2 corresponding to the second interference unit vector P2 is made to be orthogonal to the first intermediate vector W1, and a third intermediate vector W3 corresponding to the third interference unit vector P3 is made to be orthogonal to the first intermediate vector W1 and the second intermediate vector W2. In this manner, sequential orthogonalization is performed. Therefore, the respective intermediate vectors Wk are orthogonal to each other. An intermediate vector Wt (t=2 to γ) corresponding to the interference unit vector Pt is expressed by Equation (21).
Assuming that the number of independent components is three (γ=3), from Equation (21), the second intermediate vector W2 is expressed by Equation (22), and the third intermediate vector W3 is expressed by Equation (23).
In the orthogonalization method of Gram-Schmidt, the orthogonalization reference vector Sg obtained in step S17 shown in
Thereafter, as in the first embodiment, by performing the component analysis processing (multivariate analysis processing) on the orthogonalization reference vector Sg in step S18 shown in
In step S20 shown in
Next, in the concentration measurement process of the second embodiment, in the orthogonal processing of step S34 shown in
The intermediate vector Wk is calculated from Equations (20) to (23) described above. The first vector M0 obtained by the orthogonalization method of Gram-Schmidt in step S34 is expressed by Equation (25). The first vector M0 is orthogonal to each intermediate vector Wk. In addition, even if the respective interference unit vectors Pk are not orthogonal to each other, the first vector M0 is orthogonal to the space where all of the γ interference unit vectors Pk extend.
As an example, the first vector M0 when the number of interference unit vectors Pk is three (7=3) is described in Equation (26).
Thereafter, as in the first embodiment, by performing steps S35 to S38 shown in
As described above, also in the second embodiment, the first signal (first vector M0) relevant to glucose that is a target component contained in the measurement target can be accurately detected from the measurement signal (measurement vector M) obtained by measuring the measurement target. In addition, it is possible to create a calibration curve correctly using the detection of the target component feature quantity (target unit vector I). Therefore, it is possible to correctly measure the concentration of the target component contained as a trace component in the measurement target.
Next, a third embodiment will be described. In the third embodiment, the configuration of the signal detection device, the signal detection method, the calibration curve creation method, and the quantification method are the same as those in the first embodiment or the second embodiment, but the applications are different.
That is, in the third embodiment, the human body fluid is used as a measurement target, and the concentration of a specific trace component in the body fluid is measured. As the body fluid, it is possible to use blood, lymph, tissue fluid, sweat, and urine, for example. As a target component (trace component) whose concentration is to be measured, glucose, cholesterol, or triglyceride can be used when the body fluid is blood, and uric acid or sugar can be used when the body fluid is urine.
Also in the third embodiment, an interference component contained in the measurement target can be water. Accordingly, the interference component sample is water. In addition, the known concentration samples need to be a plurality of samples containing target components whose concentrations are to be measured and which have different concentrations. Therefore, for example, body fluids collected at various times, places, and conditions in daily life are used as known concentration samples.
Since water that is a high percentage component contained in the body fluid has a characteristic that spectrum data (or the composition ratio of feature quantities) changes with temperature, it is preferable to further prepare a plurality of known concentration samples by changing the temperature of the sampled body fluids. For example, if the body fluid that is a measurement target is blood and the target component is blood sugar, blood before and after a meal, blood before and after an exercise, or blood before and after going to bed can be collected, and the blood sugar level can be measured using a separate measuring device to prepare a known concentration sample.
In the third embodiment, the body fluid that has been actually collected is used as a known concentration sample. However, it is also possible to create a sample by simulating the body fluid and use the sample.
The embodiments described above are for illustrative purposes, and modifications and applications may be arbitrarily made within the scope of the present disclosure. As modification examples, the following examples can be considered.
In the embodiments described above, the signal detection device 1 is configured to have the signal detection device, the calibration curve creation device, and the measuring device. However, the present disclosure is not limited to the embodiments described above. For example, if the interference component feature quantity extraction process and the calibration curve creation process are performed separately, the operation of the signal detection device and the calibration curve creation device can be separated from the signal detection device 1 of the embodiments described above. Therefore, it is possible to provide a measuring device specialized for the concentration measurement process.
As shown in
The measurement signal acquisition section 20 executes steps S32 and S33 of
According to the configuration of the measuring device 2 shown in the modification example 1, when a measurement target and a target component and an interference component contained in the measurement target can be specified, it is possible to provide a device capable of measuring the concentration of the target component contained in the measurement target at a lower cost.
Application of the present disclosure should not be limited to the embodiments described above. For example, the present disclosure can also be applied to an embodiment for measuring the concentration or amount of impurities that are trace components that may be contained in the ingredients of drug, an embodiment for detecting a frequency signal with low amplitude that may be included in the radio wave, an embodiment for detecting the magneto-cardiogram of a person that is a trace component under the environment in which there is a magnetic interference component, such as geomagnetism, an embodiment for detecting a small abnormal amplitude signal embedded in the pulse wave signal of blood, and the like. In addition, when detecting a defective pixel using a test device for a display, the present disclosure can also be applied to a method of detecting the signal of a defective pixel from the display (interference component) of the entire screen. In addition, the present disclosure can also be applied to an algorithm for detecting the fingerprint of a specific person among many fingerprints.
In the embodiments described above, as an example of the orthogonal operation in the orthogonal processing of steps S17 and S34 of
In the embodiments described above, the independent component analysis has been used for the component analysis process of steps S05 and S18. However, the component analysis process is not limited to the independent component analysis as long as it is a multivariate analysis. For example, principal component analysis or the Fourier transform may be applied. As described in detail in the first embodiment, since a target component is orthogonal to all interference components, each of the interference vectors does not need to be orthogonal to each other. However, since the interference vectors acquired in the independent component analysis are strongly orthogonal to each other, the independent component analysis can be used to reduce error.
The entire disclosure of Japanese Patent Application Nos. 2014-206460 filed on Oct. 7, 2014; 2014-210486 filed Oct. 15, 2014; and 2015-098825 filed May 14, 2015 are incorporated by reference herein.
Number | Date | Country | Kind |
---|---|---|---|
2014-206460 | Oct 2014 | JP | national |
2014-210486 | Oct 2014 | JP | national |
2015-098825 | May 2015 | JP | national |