Fluid detection system

Abstract

A fluid detection system and method. The fluid detection method includes, executed by a processor, acquiring a Raman spectrum corresponding to a measurement time using a Raman measuring device, acquiring a terahertz spectrum corresponding to the measurement time using a terahertz measuring device, removing background spectra from the Raman spectrum to generate a corrected Raman spectrum, and determining the analyte type of the fluid to be tested based on the corrected Raman and terahertz spectra using a detection model.

Description

Technical Field

[0001] This invention relates to a fluid detection system and method. Prior Technology

[0002] Currently, detection in the fluid and biopharmaceutical industries still mainly relies on offline analytical methods. These methods not only require intensive human resources but also have high technical barriers to entry. Existing Raman measurement techniques also lack the ability to accurately analyze the composition of analytes, especially mixtures, without contact measurement.

[0003] Furthermore, when analyzing a analyte with a single measuring instrument, the instrument's sensitivity and resolution may be limited, and it may also be less reactive to certain materials. These factors restrict its effectiveness in certain application scenarios. Summary of the Invention

[0004] In view of the above, the present invention provides a fluid detection system and method for solving the above problems.

[0005] A fluid detection system according to an embodiment of the present invention includes: at least one fluid-carrying device and a non-transitory computer-readable medium. The fluid-carrying device is used to carry the fluid to be measured. The non-transitory computer-readable medium includes at least one computer-executable program, which, when executed by a processor, performs multiple steps, including: acquiring Raman and terahertz spectra corresponding to the same measurement time; removing background spectra from the Raman spectra to generate a calibrated Raman spectrum; and using a detection model to determine the analyte type of the fluid to be measured based on the calibrated Raman and terahertz spectra.

[0006] A fluid detection method according to an embodiment of the present invention includes, executed by a processor, acquiring a Raman spectrum corresponding to a measurement time using a Raman measuring device; acquiring a terahertz spectrum corresponding to the measurement time using a terahertz measuring device; removing background spectra from the Raman spectrum to generate a corrected Raman spectrum; and obtaining the analyte type of the fluid to be tested based on the corrected Raman and terahertz spectra using a detection model.

[0007] In summary, the fluid detection system and method according to one or more embodiments of the present invention provide a non-contact, dual-spectral analysis technique that can be used for online, timely, and continuous detection. Furthermore, in the dual-spectral analysis technique, Raman spectroscopy and terahertz spectroscopy can be used complementaryly to obtain more accurate detection results for the analyte fluid. Moreover, by removing the background spectrum from the Raman spectrum, the influence of the background spectrum on subsequent analysis of the analyte fluid can be avoided.

[0008] The foregoing description of the disclosure and the following description of the embodiments are intended to demonstrate and explain the spirit and principles of the present invention, and to provide a further explanation of the scope of the patent application of the present invention. Simple Explanation of the Diagram

[0009] Figure 1 is a block diagram of a fluid detection system according to an embodiment of the present invention. Figure 2 is an exploded view of a fluid-carrying device according to an embodiment of the present invention. Figure 3 is an exploded view of a fluid-carrying device according to another embodiment of the present invention. Figure 4 is a side view of a fluid-carrying device according to another embodiment of the present invention. Figure 5 is a schematic diagram illustrating multiple fluid-carrying devices connected in series according to an embodiment of the present invention. Figure 6 is a flowchart illustrating a fluid detection method according to an embodiment of the present invention. Figure 7 shows example curves of Raman spectrum, background spectrum and corrected Raman spectrum. Implementation

[0010] The following detailed description of the features and advantages of the present invention is sufficient to enable anyone skilled in the art to understand the technical content of the present invention and implement it accordingly. Based on the disclosure, patent claims, and drawings in this specification, anyone skilled in the art can easily understand the relevant objectives and advantages of the present invention. The following embodiments further illustrate the points of the present invention, but are not intended to limit the scope of the present invention in any way.

[0011] Please refer to Figure 1, which is a block diagram illustrating a fluid detection system according to an embodiment of the present invention. As shown in Figure 1, the fluid detection system 1 includes at least one fluid carrier 11 and a non-transitory computer-readable medium 12. Figure 1 shows one fluid carrier 11, but the fluid detection system 1 may also include multiple fluid carriers 11.

[0012] The fluid carrier 11 can be a light-transmitting fluid carrier. The fluid carrier 11 is used to hold the fluid to be tested and to be irradiated by the Raman measuring device A1 and the terahertz measuring device A2, and is exemplary represented by two dashed lines in Figure 1. The fluid to be tested can be live cell fluid and / or a liquid containing multiple mixtures; the present invention does not limit the fluid to be tested.

[0013] Non-transitory computer-readable media 12 is communicatively or electrically connected to processor A0. Non-transitory computer-readable media 12 contains at least one computer-executable program, which, when executed by processor A0, performs multiple steps. These multiple steps include steps from the fluid detection method described below, for generating analytical results of the fluid under test based on measurement results from Raman measuring device A1 and terahertz measuring device A2. Furthermore, processor A0, used to execute the computer-executable program of non-transitory computer-readable media 12, can be communicatively connected to Raman measuring device A1 and terahertz measuring device A2, and when the computer-executable program is executed by processor A0, the performed steps may include controlling Raman measuring device A1 and terahertz measuring device A2 to simultaneously transmit measurement signals, and these measurement signals may be transmitted toward the fluid carrying device 11. Non-transitory computer-readable media 12 may be a hard drive, optical disc, USB flash drive, magnetic tape, flash memory, read-only memory, a database accessible via a network, etc. The processor A0 is, for example, a central processing unit, a graphics processor, a microcontroller, a programmable logic controller, or other processor with signal processing capabilities.

[0014] Please refer to Figure 2, which is an exploded view of a fluid carrying device according to an embodiment of the present invention. As shown in Figure 2, the fluid carrying device 21 may include a silicon substrate 211, a lower cover 212 of the flow channel, and an upper cover 213 of the flow channel.

[0015] A flow channel cover 212 is disposed on a silicon substrate 211. The flow channel cover 212 includes an inlet groove 212a, an outlet groove 212b, and a fluid containment area 212c communicating with the inlet groove 212a and the outlet groove 212b. The fluid containment area 212c is used to contain the test fluid. When the test fluid contained in the fluid containment area 212c is a live cell fluid, the fluid containment area 212c can be regarded as a culture area for live cell differentiation. The inlet groove 212a and the outlet groove 212b each include a circular hole and a straight cut extending from the circular hole toward the fluid containment area 212c, and the cut communicates with the fluid containment area 212c.

[0016] A flow channel upper cover 213 is disposed on a flow channel lower cover 212. The flow channel upper cover 213 includes a flow channel inlet 213a and a flow channel outlet 213b, wherein the flow channel inlet 213a is connected to an inlet groove 212a, and the flow channel outlet 213b is connected to an outlet groove 212b. Both the flow channel inlet 213a and the flow channel outlet 213b can be implemented as a guide pipe. The flow channel inlet 213a is directly opposite to the inlet groove 212a, and the flow channel outlet 213b is directly opposite to the inlet / outlet groove 212b. Preferably, the orifice diameter of the flow channel inlet 213a is the same as the orifice diameter of the circular hole in the inlet groove 212a, and preferably, the orifice diameter of the flow channel outlet 213b is the same as the orifice diameter of the circular hole in the outlet groove 212b.

[0017] In one embodiment, the lower channel cover 212 and the upper channel cover 213 are preferably made of a material that allows the measurement signal emitted by the Raman measurement device A1 to pass through. Further, the lower channel cover 212 and the upper channel cover 213 may both be made of polydimethylsiloxane (PDMS), glass, or quartz.

[0018] Please refer to Figure 3, which is an exploded view of a fluid-carrying device according to another embodiment of the present invention. As shown in Figure 3, the fluid-carrying device 31 may include a silicon substrate 311, a biocompatible adhesive 312, a lower cover 313 of the flow channel, and an upper cover 314 of the flow channel.

[0019] The lower cover 313 of the flow channel includes an inlet groove 313a, an outlet groove 313b, and a fluid receiving area 313c communicating with the inlet groove 313a and the outlet groove 313b. The fluid receiving area 313c is used to receive the fluid to be measured. The upper cover 314 of the flow channel is disposed on the lower cover 313 of the flow channel. The upper cover 314 of the flow channel includes a flow channel inlet 314a and a flow channel outlet 314b, wherein the flow channel inlet 314a is communicating with the inlet groove 313a, and the flow channel outlet 314b is communicating with the outlet groove 313b.

[0020] The silicon substrate 311, the lower channel cover 313, and the upper channel cover 314 can be the same as the silicon substrate 211, the lower channel cover 212, and the upper channel cover 213 shown in Figure 2, respectively, so the details will not be repeated here.

[0021] A biocompatible adhesive 312 is disposed between the lower cover 313 of the flow channel and the silicon substrate 311. The biocompatible adhesive 312 includes pores 312a. The pores 312a communicate with the fluid containment area 313c, and the size of the pores 312a can be the same as the size of the fluid containment area 313c. Furthermore, the pores 312a and the fluid containment area 313c can have the same outline and size. Therefore, the fluid to be tested can pass through the silicon substrate 311 and the upper cover 314 of the flow channel and remain in the space formed by the pores 312a and the fluid containment area 313c.

[0022] Please refer to Figure 4, which is a side view of a fluid carrier device according to another embodiment of the present invention. As shown in Figure 4, the fluid carrier device 41 includes a silicon prism 400 and a carrier portion 410. The carrier portion 410 is disposed on the silicon prism 400. The carrier portion 410 can be implemented as the fluid carrier device 21 shown in Figure 2 or the fluid carrier device 21 shown in Figure 3. The Raman measurement device A1 may include a lens A11, and the carrier portion 410 may be disposed below the Raman measurement device A1. The lens A11 is used to transmit measurement signals to the carrier portion 410 and receive reflected signals from the carrier portion 410.

[0023] The silicon prism 400 can be disposed below the silicon substrate of the carrying portion, that is, on the side of the silicon substrate opposite to the flow channel cover. As shown in Figure 4, the terahertz measurement device A2 may include a terahertz transmitter A21 and a terahertz receiver A22. The fluid carrying device 41 may be disposed between the terahertz transmitter A21 and the terahertz receiver A22. The terahertz transmitter A21 transmits a measurement signal to the silicon prism 400, and the terahertz receiver A22 receives the reflected signal from the silicon prism 400. Furthermore, the silicon prism 400 can cause total reflection of the measurement signal transmitted by the terahertz transmitter A21.

[0024] In the fluid carrying device of one or more of the above embodiments, the surface of the silicon substrate facing the flow channel cover may include multiple periodic patterns.

[0025] Please refer to Figure 5, which is a schematic diagram illustrating multiple fluid-carrying devices connected in series according to an embodiment of the present invention. As shown in Figure 5, the aforementioned at least one fluid-carrying device may include a first fluid-carrying device 51, a second fluid-carrying device 52, and a third fluid-carrying device 53. Each of the first fluid-carrying device 51, the second fluid-carrying device 52, and the third fluid-carrying device 53 can be implemented as the fluid-carrying device shown in any of Figures 2 to 4. It should be noted that Figure 5 exemplarily shows three fluid-carrying devices connected in series; however, the number of fluid-carrying devices connected in series may also be two or more, and the present invention is not limited thereto.

[0026] The first fluid carrier device 51 includes a fluid receiving area 51a, the second fluid carrier device 52 includes a fluid receiving area 52a, and the third fluid carrier device 53 includes a fluid receiving area 53a. The fluid receiving areas 51a, 52a, and 53a can be used to carry the same or different fluids to be tested.

[0027] One of the flow channel inlet and flow channel outlet of each of the first fluid carrier device 51, the second fluid carrier device 52 and the third fluid carrier device 53 is connected to the other of the flow channel inlet and flow channel outlet of the adjacent one of the first fluid carrier device 51, the second fluid carrier device 52 and the third fluid carrier device 53.

[0028] Specifically, the outlet of the first fluid carrier device 51 is connected to the inlet of the second fluid carrier device 52, and the outlet of the second fluid carrier device 52 is connected to the inlet of the third fluid carrier device 53.

[0029] The outlet of the first fluid carrier device 51 and the inlet of the second fluid carrier device 52 can be connected by a first connecting pipe 54, and the outlet of the second fluid carrier device 52 and the inlet of the third fluid carrier device 53 can be connected by a second connecting pipe 55.

[0030] The inlet of the flow channel of the first fluid carrier 51 and the outlet of the flow channel of the third fluid carrier 53 may be provided with soft plugs 56 to prevent the fluid to be tested from flowing out of the inlet of the first fluid carrier 51 and the outlet of the third fluid carrier 53. In one embodiment, the inlet and outlet of the flow channel of each of the first fluid carrier 51, the second fluid carrier 52 and the third fluid carrier 53 may be provided with soft plugs 56 to prevent the fluid to be tested from flowing to another one of the first fluid carrier 51, the second fluid carrier 52 and the third fluid carrier 53.

[0031] Furthermore, the first fluid carrying device 51 may further include a first connector 51b and a second connector 51c. The first connector 51b and the second connector 51c are connected to the fluid receiving area 51a of the first fluid carrying device 51. One of the first connector 51b and the second connector 51c can be used to allow the fluid to be measured to flow into the fluid receiving area 51a, and the other of the first connector 51b and the second connector 51c can be used to allow the fluid to be measured to flow out of the fluid receiving area 51a.

[0032] In the embodiment shown in Figure 5, the fluid to be measured can flow into the first fluid carrying device 51 from either the first connector 51b or the second connector 51c, and then flow into the second fluid carrying device 52 and the third fluid carrying device 53 through the first connecting pipe 54 and the second connecting pipe 55. Accordingly, multiple fluid carrying devices can be used to measure the same or different fluids to be measured, thereby improving measurement efficiency.

[0033] Please refer to Figure 6, which is a flowchart illustrating a fluid detection method according to an embodiment of the present invention. The fluid detection method is executed by a processor, which executes a computer-executable program stored in the aforementioned non-transitory computer-readable medium to implement the fluid detection method. As shown in Figure 6, the fluid detection method includes: step S111: obtaining a Raman spectrum corresponding to the measurement time from a Raman measuring device; step S113: obtaining a terahertz spectrum corresponding to the measurement time from a terahertz measuring device; step S115: removing the background spectrum from the Raman spectrum to generate a calibrated Raman spectrum; and step S117: obtaining the analyte type of the fluid to be measured based on the calibrated Raman spectrum and the terahertz spectrum using a detection model. The present invention does not limit the execution order of steps S111 and S113. S113 may be executed before S111, or may be executed simultaneously with S111 and S111.

[0034] In step S111, the processor obtains the Raman spectrum generated by the Raman measuring device irradiating the fluid-carrying device as described above. In step S113, the processor obtains the terahertz spectrum generated by the terahertz measuring device irradiating the same fluid-carrying device. The processor may obtain the Raman spectrum from the Raman measuring device and the terahertz spectrum from the terahertz measuring device simultaneously or separately, provided that the Raman and terahertz measuring devices irradiate the same fluid-carrying device simultaneously, thus generating Raman and terahertz spectra corresponding to the same measurement time. In one embodiment, the processor may extract a portion corresponding to the same measurement time from the Raman and terahertz spectra based on the timestamps and measurement time lengths of the respective Raman and terahertz spectra for use in the following steps.

[0035] In step S115, the processor removes the background spectrum from the Raman spectrum to generate a corrected Raman spectrum. This avoids the influence of the background spectrum on subsequent analysis of the fluid being analyzed.

[0036] In step S117, the processor will input the Raman and terahertz spectra into the detection model to obtain the analyte type of the output detection model. The analyte type can indicate the composition of the fluid being tested. The detection model may include at least one of a linear discriminant model, a logistic regression kernel model, and a subspace K-nearest neighbor model.

[0037] In summary, the fluid detection system and method according to one or more embodiments of the present invention can provide non-contact, dual-spectral analysis technology, which can be used for online, timely, and continuous detection. Furthermore, in the dual-spectral analysis technology, Raman spectroscopy and terahertz spectroscopy can be used complementaryly to obtain more accurate detection results for the fluid being tested.

[0038] In a detailed embodiment of step S115, the processor can perform an asymmetrically reweighted penalized least square (arPLS) algorithm on the Raman spectrum to obtain the corrected Raman spectrum. The processor can perform the asymmetrically reweighted penalized least square algorithm using the following formula (1), where For the original Raman spectrum, For background spectrum, For the difference matrix, The diagonal matrix of the weight vector. The smoothing coefficient is used to determine the background spectrum. A smaller smoothing coefficient results in a background spectrum that is closer to the Raman spectrum signal; conversely, a larger smoothing coefficient results in a smoother background spectrum. Formula (1)

[0039] Furthermore, the processor can use the following formula (2) for iterative calculation to converge the background spectrum to a preset value as the optimal solution, where The above diagonal matrix weight vector, This represents the current number of calculations (i.e., the number of iterations). The convergence ratio of the objective is denoted as . The convergence ratio of the objective can be set at . arrive The scope of the iterations is not limited by this invention. Furthermore, the processor can set an upper limit on the number of iterations. Formula (2)

[0040] Please refer to Figure 7, which shows example curves of Raman spectrum, background spectrum, and corrected Raman spectrum. As shown in Figure 7, the processor obtains Raman spectrum C1 from the Raman measurement device, determines the background spectrum C2 corresponding to Raman spectrum C1, and removes the background spectrum C2 from Raman spectrum C1 to generate corrected Raman spectrum C3.

[0041] In one embodiment, the fluid detection method may further include a processor training a detection model as described in step S117 of FIG6 using multiple training Raman spectra and multiple training terahertz spectra corresponding to the analyte type. Specifically, each analyte type may have corresponding multiple training Raman spectra and multiple training terahertz spectra. The processor may use the training Raman spectra and training terahertz spectra to train at least one of a linear discriminant model, a logistic regression kernel model, and a subspace K-nearest neighbor model to generate a detection model, wherein the training Raman spectra may be spectra with background spectra removed.

[0042] Furthermore, in the step of training the detection model using training Raman spectra and training terahertz spectra corresponding to the type of analyte, the processor can train multiple candidate models using these training Raman and terahertz spectra, and select the candidate model with the highest accuracy as the detection model. In other words, the processor can train various different candidate models using training Raman and training terahertz spectra, verify the trained candidate models using a validation dataset, and select the candidate model with the highest accuracy as the detection model described in step S117 of Figure 6.

[0043] Furthermore, in the step of training the detection model using training Raman spectra and training terahertz spectra corresponding to the analyte type, the processor can further utilize the training Raman spectra to generate a first sub-model, utilize the training terahertz spectra to generate a second sub-model, and fuse the first and second sub-models into a detection model. Accordingly, the detection model can be used to determine the analyte type based on Raman and terahertz spectra. The first and second sub-models can each be at least one of a training linear discriminant model, a logistic regression kernel model, and a subspace K-nearest neighbor model.

[0044] In one embodiment, steps S111, S113, S115, and S117 can be executed by a processor, while the training of the detection model can be executed by another processor, and the trained detection model is stored in the non-transitory computer-readable medium shown in Figure 1 by the other processor. In yet another embodiment, steps S111, S113, S115, and S117, as well as the training of the detection model, can be one or more computer-executable programs on a non-transitory computer-readable medium, executed by the same processor, and the trained detection model is stored in the non-transitory computer-readable medium shown in Figure 1 by the same processor.

[0045] In summary, the fluid detection system and method according to one or more embodiments of the present invention provide a non-contact, dual-spectral analysis technique that can be used for online, timely, and continuous detection. Furthermore, in the dual-spectral analysis technique, Raman spectroscopy and terahertz spectroscopy can be used complementaryly to obtain more accurate detection results for the analyte fluid. Moreover, by removing the background spectrum from the Raman spectrum, the influence of the background spectrum on subsequent analysis of the analyte fluid can be avoided. In addition, by connecting multiple fluid carrier devices in series, multiple fluid carrier devices can be used to measure the same or different analytes, thereby improving measurement efficiency.

[0046] While the present invention has been disclosed above with reference to the foregoing embodiments, it is not intended to limit the invention. Any modifications and refinements made without departing from the spirit and scope of the invention are within the scope of patent protection of the present invention. For details regarding the scope of protection defined in the present invention, please refer to the appended claims.

[0047] 1: Fluid detection system 11,21,31,41: Fluid-carrying devices 12: Non-transitory computer-readable media 211, 311: Silicon substrate 212, 313: Lower cover of the flow channel 212a, 313a: Inlet slot 212b, 313b: Outlet channel 212c, 313c, 51a, 52a, 53a: Fluid containment areas 213, 314: Flow channel cover 213a, 314a flow channel inlet 213b, 314b flow channel outlet 312: Biocompatible adhesive 312a: Hole 410: Passenger section 400: Silicon Prism 51: First fluid-carrying device 51b: First connector 51c: Second connector 52: Second fluid-carrying device 53: Third fluid-carrying device 54: First connecting tube 55: Second connecting pipe 56: Soft plug A1: Raman measurement device A11: Lens A2: Terahertz measuring device A21: Terahertz transmitter A22: Terahertz Receiver S111, S113, S115, S117: Steps C1: Raman spectrum C2: Background spectrum C3: Corrected Raman spectrum

Claims

1. A fluid detection system, comprising: At least one fluid carrier for carrying a test fluid; and a non-transitory computer-readable medium containing at least one computer-executable program, which, when executed by a processor, performs multiple steps, including: acquiring a Raman spectrum and a terahertz spectrum corresponding to the same measurement time; removing a background spectrum from the Raman spectrum to generate a corrected Raman spectrum; and using a detection model to determine an analyte type of the test fluid based on the corrected Raman spectrum and the terahertz spectrum, wherein the at least one fluid carrier comprises: a silicon substrate; a flow channel lower cover disposed on the silicon substrate, the flow channel lower cover including an inlet groove, an outlet groove, and a fluid receiving area communicating with the inlet groove and the outlet groove, the fluid receiving area being used to receive the test fluid; a flow channel upper cover disposed on the flow channel lower cover, the flow channel upper cover including a flow channel inlet and a flow channel outlet, wherein the flow channel inlet communicating with the inlet groove and the flow channel outlet communicating with the outlet groove; and a lifetime A biocompatible adhesive is disposed between the flow channel cover and the silicon substrate. The biocompatible adhesive includes a pore communicating with the fluid containment area. The size of the pore is the same as the size of the fluid containment area. The at least one fluid carrier device includes multiple fluid carrier devices. One of the flow channel inlet and the flow channel outlet of each of the fluid carrier devices is connected to the other of the flow channel inlet and the flow channel outlet of an adjacent fluid carrier device. The steps further include: training with multiple training Raman spectra and multiple training terahertz spectra corresponding to the analyte type to obtain the detection model. The training with the training Raman spectra and the training terahertz spectra corresponding to the analyte type to obtain the detection model includes: training with the training Raman spectra to generate a first sub-model, training with the training terahertz spectra to generate a second sub-model, and fusing the first sub-model and the second sub-model into the detection model.

2. The fluid detection system of claim 1, wherein removing the background spectrum from the Raman spectrum to generate the corrected Raman spectrum comprises: performing an asymmetric weighted penalized least squares algorithm on the Raman spectrum to obtain the corrected Raman spectrum.

3. The fluid detection system of claim 1, wherein training the detection model with training Raman spectra and training terahertz spectra corresponding to the type of analyte comprises: training multiple candidate models using the training Raman spectra and training terahertz spectra, and selecting the candidate model with the highest accuracy as the detection model.

4. The fluid detection system as claimed in claim 1, wherein the detection model comprises at least one of a linear discriminant model, a logistic regression kernel model, and a subspace K-nearest neighbor model.

5. The fluid detection system as claimed in claim 1, wherein the flow channel cover comprises a polydimethylsiloxane material.

6. The fluid detection system as claimed in claim 1, wherein the at least one fluid carrying device further comprises: a silicon prism disposed below the silicon substrate.

7. The fluid detection system as claimed in claim 1, wherein the surface of the silicon substrate facing the flow channel cover includes a plurality of periodic patterns.

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