A method and apparatus for measuring microfluidic flow rate

Abstract

The present application belongs to the field of measurement technology, and provides a method and device for measuring microfluid flow rate, wherein microspheres are dispersed in a liquid to be measured to form a dispersion liquid, the dispersion liquid is introduced into a microchannel, an optical tweezer is used to create an optical trap and capture a single microsphere, after the microsphere is captured, the liquid to be measured is formed into a microfluid in the microchannel to flush the captured microsphere, a quadrant detector is used to record the motion track of the captured microsphere in the microfluid, the characteristic frequency f of the motion is obtained through analysis, the diameter d of the microsphere and the Strouhal number Sr are combined, and the flow rate v is calculated according to the formula v=(fxd) / Sr; the method combines the optical tweezer technology with the principle of the Karman vortex flowmeter, and applies the combination to the measurement of the microfluid flow rate, the displacement of the captured particle does not need to be measured, the interference of the Brownian motion can be effectively eliminated, the method is simple, reliable and feasible, and the result is accurate.

Description

Technical Field

[0001] This invention belongs to the field of measurement technology, and in particular relates to a method and apparatus for measuring microfluidic flow velocity. Background Technology

[0002] Microfluidics technology has shown great potential for widespread application in many fields, including chemical reactions, analytical biology, and clinical diagnostics. Its advantages, such as rapid reaction times, localized thermal management, and reduced sample and reagent volumes, are considered crucial factors in the miniaturization of standard analytical techniques.

[0003] With the development of microfluidic devices, such as lab-on-a-chip devices and micro-total analytical systems (MTAS), quantitative measurement of microfluidic flow is crucial for understanding the physical characteristics of transport processes in micro-spaces. Currently, some macroscale velocimetry techniques, such as particle image velocimetry (PIV) or particle tracking velocimetry (PTV), have been applied to microscale velocity measurement. However, these techniques place high parameter requirements on equipment such as cameras, require the measurement of microscopic displacements, and therefore the related calculation methods are quite complex. Furthermore, the measurement of microscopic displacements is affected by the Brownian motion of suspended particles, which can easily lead to significant measurement errors. Summary of the Invention

[0004] In view of the problems existing in the prior art, the purpose of this invention is to provide a method and apparatus for measuring microfluidic flow velocity. The method involves dispersing microspheres in a liquid to be tested to form a dispersion, which is then introduced into a microchannel. Simultaneously, optical tweezers are used to create an optical trap and capture individual microspheres. After capture, the liquid to be tested forms a microfluidic flow within the microchannel to wash over the captured microspheres. A quadrant detector is then used to record the trajectory of the captured microspheres in the microfluidic flow, and the characteristic frequency f of this motion is analyzed. Combined with the diameter d of the microspheres and the Strouhal number Sr, the flow velocity v is calculated using the formula v = (f × d) ÷ Sr. This invention combines optical tweezers technology with the principle of a Karman vortex flowmeter and applies it to microfluidic flow velocity measurement. It eliminates the need to measure the displacement of the captured particles and effectively eliminates interference from Brownian motion. The method is simple, reliable, practical, and yields highly accurate results.

[0005] To achieve this objective, the present invention adopts the following technical solution:

[0006] In a first aspect, the present invention provides a method for measuring microfluidic flow velocity, comprising the following steps:

[0007] Microspheres and the liquid to be tested are mixed to form a dispersion; the dispersion is then passed into a microchannel that is transparent to laser light.

[0008] The laser is used to form optical tweezers and to construct an optical trap in the microchannel to capture one of the microspheres;

[0009] The liquid to be tested is continuously flowed in the microchannel to form a microfluidic, and the captured microspheres are vibrated by the scouring of the microfluidic.

[0010] The trajectory of the captured microspheres in the optical trap is recorded using a quadrant detector to obtain the characteristic frequency of the motion;

[0011] The flow velocity v of the microfluidic is calculated according to the following formula: v = (f × d) ÷ Sr, where f is the characteristic frequency in Hz; d is the diameter of the microsphere in μm; Sr is the Strouhal number; and the unit of flow velocity v is μm / s.

[0012] The method described in this invention uses optical tweezers to create an optical trap and capture a single microsphere. After capture, a microfluidic stream is formed within a microchannel. Then, a quadrant detector is used to record the trajectory of the captured microsphere in the microfluidic stream, and the characteristic frequency f of this motion is obtained by analysis. Combined with the diameter d of the microsphere and the Strouhal number Sr, the flow velocity v is calculated according to the formula v=(f×d)÷Sr. This invention combines optical tweezers technology with the principle of Karman vortex flowmeter and applies it to the measurement of microfluidic flow velocity. It eliminates the need to measure the displacement of the captured particles and effectively eliminates the interference of Brownian motion. The method is simple, reliable, feasible, and yields highly accurate results.

[0013] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. The technical objectives and beneficial effects of the present invention can be better achieved and realized through the following technical solutions.

[0014] As a preferred technical solution of the present invention, the Strouhal number Sr is obtained by fitting calculation. The fitting calculation method includes: continuously flowing the liquid to be tested in the microchannel to form a microfluidic, controlling the microfluidic to a fixed flow rate, denoted as v', obtaining the characteristic frequency of the motion of the microsphere in the optical trap, denoted as f', forming fitting data points (f', v'), and fitting the fitting data points according to Formula 1 to obtain the Strouhal number Sr.

[0015] In this invention, the diameter d of the captured microspheres can be measured by optical microscopy.

[0016] As a preferred technical solution of the present invention, the fitting calculation uses at least three fitting data points formed by different fixed flow velocities.

[0017] As a preferred technical solution of the present invention, the R-value of the fitting process 2 >0.9, preferably ≥0.95.

[0018] As a preferred technical solution of the present invention, the liquid to be tested includes media such as water and / or oil.

[0019] As a preferred embodiment of the present invention, the microspheres comprise silica microparticles.

[0020] As a preferred embodiment of the present invention, the concentration of microspheres in the dispersion is 1000 microspheres / mL to 10000 microspheres / mL.

[0021] In this invention, the concentration of the microspheres in the dispersion medium (referring to the liquid to be tested) should be appropriate, so that individual particles can be found relatively easily, while avoiding interference caused by the interaction of many particles.

[0022] As a preferred embodiment of the present invention, the particle size of the microspheres ranges from 0.5 μm to 10 μm.

[0023] In this invention, the particle size of the microspheres affects the maximum flow rate of the microfluidic fluid that they can withstand when captured by the optical trap, that is, the flow rate of the microfluidic fluid when the captured particles escape from the optical trap due to the scouring of the microfluidic fluid. Thus, it can be understood that the maximum flow rate that can be measured by the method in this invention is less than the flow rate of the microfluidic fluid when the microspheres escape from the optical trap.

[0024] As a preferred technical solution of the present invention, the signal of the captured microsphere detected by the quadrant detector includes a voltage signal, and the voltage signal is subjected to Fourier transform processing to obtain the characteristic frequency.

[0025] As a preferred embodiment of the present invention, the response frequency of the quadrant detector is greater than 10 kHz.

[0026] In a second aspect, the present invention provides an apparatus for measuring microfluidic flow velocity, the apparatus being used to implement the method described in the first aspect, the apparatus comprising a laser, an objective lens, a microchannel, a condenser lens, and a quadrant detector arranged sequentially along the direction of the laser optical path; the objective lens being used to enable the laser to form optical tweezers and construct a photon trap, the condenser lens being used to cause interference between the light that has been captured to obtain a microsphere and the remaining light to form an interference pattern, and the quadrant detector receiving the interference pattern to generate a signal.

[0027] As a preferred embodiment of the present invention, a first reflecting mirror is disposed between the laser and the objective lens;

[0028] As a preferred embodiment of the present invention, a second reflecting mirror is provided between the condenser lens and the quadrant detector;

[0029] As a preferred technical solution of the present invention, the device includes a sample pool, in which the microchannel is provided, and the microchannel forms an inlet and an outlet on the sample pool.

[0030] As a preferred embodiment of the present invention, the device includes a syringe containing a dispersion or a test liquid and connected to the inlet of the sample cell for providing the dispersion or the test liquid to form a microfluidic.

[0031] Compared with existing technical solutions, the present invention has at least the following beneficial effects:

[0032] The present invention provides a method for measuring microfluidics that utilizes optical tweezers to create an optical trap to grasp a single microsphere within the microfluidic fluid. Simultaneously, a quadrant detector records the trajectory of the microsphere, analyzes the characteristic frequency of this motion, and calculates the fluid velocity using the principle of a vortex flowmeter. This method applies the karman vortex flowmeter principle to the microscopic realm, resulting in a convenient and rapid microfluidic velocity testing method. Compared to methods such as particle image velocimetry (PIV) or particle tracking velocimetry (PTV), this method eliminates interference from Brownian motion, improving the accuracy and reliability of the results. Attached Figure Description

[0033] Figure 1 This is a schematic diagram of the device for measuring microfluidic flow velocity in Example 1.

[0034] Figure 2 This is a photomicrograph of a 2 μm diameter silica microsphere captured by optical tweezers in Example 1.

[0035] Figure 3 , Figure 4 as well as Figure 5 These are the characteristic frequencies of the vibration of the captured microspheres obtained when the average flow velocity of the microfluidic was set to 30 μm / s, 150 μm / s, and 300 μm / s, respectively, in Example 1.

[0036] Figure 6 To be Figure 3 , Figure 4 and Figure 5 The result is obtained by linearly fitting the characteristic frequency with the flow velocity. Detailed Implementation

[0037] To make the technical solution, objectives, and advantages of the present invention clearer, the present invention will be further described in detail below through specific embodiments. It should be understood that the specific embodiments described herein are for illustration and explanation only and are not intended to limit the present invention.

[0038] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0039] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "set," "install," "connect," "link," and "connect" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. In the fields of electricity, communication, and optics, they can refer to a wired connection or a wireless connection; "connection" can refer to the connection of the internal spaces of two enclosed spaces through a switch-like control. For those skilled in the art, the specific meaning of the above terms in this invention can be understood according to the specific circumstances.

[0040] In the description of this invention, due to space limitations and to avoid redundancy, this invention does not exhaustively list all point values ​​within the following numerical range, but it is not limited to the listed values ​​either; other unlisted values ​​within the following numerical range are also applicable.

[0041] In one or more embodiments, the present invention provides a method for measuring microfluidic flow velocity, comprising the following steps:

[0042] Microspheres and the liquid to be tested are mixed to form a dispersion; the dispersion is then passed into a microchannel that is transparent to laser light.

[0043] The laser is used to form optical tweezers and to construct an optical trap in the microchannel to capture one of the microspheres;

[0044] The liquid to be tested is continuously flowed in the microchannel to form a microfluidic, and the captured microspheres are vibrated by the scouring of the microfluidic.

[0045] The trajectory of the captured microspheres in the optical trap is recorded using a quadrant detector to obtain the characteristic frequency of the motion;

[0046] The flow velocity v of the microfluidic is calculated according to the following formula: v = (f × d) ÷ Sr, where f is the characteristic frequency in Hz; d is the diameter of the microsphere in μm; Sr is the Strouhal number; and the unit of flow velocity v is μm / s.

[0047] In some implementations, the Strouhal number Sr is obtained through fitting calculation, and the fitting calculation method includes:

[0048] The liquid to be tested is continuously flowed in the microchannel to form a microfluidic. The microfluidic is controlled at a fixed flow rate, denoted as v'. The characteristic frequency of the motion of the microsphere in the optical trap is obtained, denoted as f'. The fitting data points (f', v') are formed. The fitting data points are fitted according to Formula 1 to obtain the Strouhal number Sr.

[0049] In some implementations, the diameter d of the captured microspheres can be measured using an optical microscope.

[0050] In some implementations, the fitting calculation uses at least three fitting data points formed by different fixed flow rates.

[0051] In some embodiments, the R of the fitting process 2 >0.9, preferably ≥0.95.

[0052] In some embodiments, the liquid to be tested includes media such as water and / or oil.

[0053] In some embodiments, the microspheres comprise silica microparticles.

[0054] In some embodiments, the concentration of microspheres in the dispersion is from 1,000 to 10,000 microspheres / mL. For example, it can be 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000 microspheres / mL, etc., preferably 5,000 to 7,000 microspheres / mL.

[0055] In some embodiments, the particle size of the microspheres ranges from 0.5 μm to 10 μm. For example, it can be 0.5 μm, 0.6 μm, 0.7 μm, 0.8 μm, 0.9 μm, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, or 10 μm, etc.

[0056] In some embodiments, the signal of the captured microsphere detected by the quadrant detector includes a voltage signal, which is then subjected to a Fourier transform to obtain a characteristic frequency.

[0057] In some implementations, the response frequency of the quadrant detector is greater than 10 kHz.

[0058] In one or more embodiments, the present invention provides an apparatus for measuring microfluidic flow velocity, the apparatus being used to implement the method provided in the above embodiments, the apparatus comprising a laser, an objective lens, a microchannel, a condenser lens, and a quadrant detector arranged sequentially along the direction of a laser optical path; the objective lens being used to enable the laser to form optical tweezers and construct a photon trap, the condenser lens being used to cause interference between the light that has been captured to obtain a microsphere and the remaining light to form an interference pattern, and the quadrant detector receiving the interference pattern to generate a signal.

[0059] In some embodiments, a first reflecting mirror is disposed between the laser and the objective lens;

[0060] In some embodiments, a second reflecting mirror is disposed between the condenser lens and the quadrant detector;

[0061] In some embodiments, the device includes a sample cell in which the microchannels are provided, and the microchannels form an inlet and an outlet on the sample cell.

[0062] In some embodiments, the device includes a syringe containing a dispersion or a test liquid and connected to an inlet of a sample cell for providing the dispersion or the test liquid to form a microfluidic.

[0063] Example 1

[0064] This embodiment provides a method for measuring microfluidic flow velocity. The method is implemented using a device for measuring microfluidic flow velocity, specifically:

[0065] like Figure 1 As shown, the device includes a laser 1, a first reflecting mirror 2, an objective lens 3, a sample cell 4, a condenser lens 5, a second reflecting mirror 6, and a quadrant detector 7 arranged sequentially along the optical path, and also includes a syringe 8. The sample cell 4 contains microchannels, and these microchannels form an inlet and an outlet on the sample cell 4. The syringe 8 is used to hold the dispersion or the liquid to be tested and is connected to the inlet of the sample cell 4, used to provide the dispersion or form a microfluidic and control the flow rate of the microfluidic. Further, the laser wavelength of the laser 1 is 1064 nm; the objective lens 3 is an Olympus with parameters 100X and 0.8NA; the sample cell 4 is a single-channel glass slide (ibidi 80167); and the syringe 8 is a KDS100 (KDS Scientific).

[0066] The process of the method for measuring microfluidic flow velocity includes:

[0067] S1. Dilute the silica microsphere dispersion (SBWNU-100) purchased from Suzhou Nanomicro Life Technology Co., Ltd. with deionized water (the liquid to be tested) to prepare a dispersion with a concentration of approximately 6000 particles / mL; use syringe 8 to draw the prepared dispersion and inject it into sample cell 4, that is, fill the single-channel glass slide with the dispersion.

[0068] S2. Place the glass slide on the sample stage. The laser emitted by laser 1 passes through the first reflecting mirror 2 and enters the objective lens 3. The objective lens 3 focuses the laser to form optical tweezers, thereby constructing an optical trap to stably capture microspheres in the dispersion in the sample cell 4. Individual silica microspheres are captured using these optical tweezers; the microspheres are then tested using an optical microscope. Figure 2 The diameter d of the captured microspheres is 2 μm. At the same time, the syringe is refilled with the test liquid deionized water and connected to one end of the single-channel glass slide (i.e., the liquid inlet on the sample cell 4). The average flow rate (fixed flow rate v') of the microfluidic formed in the microchannel is controlled by the syringe 8 to be 30 μm / s, 150 μm / s and 300 μm / s respectively. That is, the test is conducted at three different fixed flow rates v'. During this process, care should be taken not to generate air bubbles in the microchannel.

[0069] S3. When the laser passes through the sample plane, interference occurs between the light passing through the captured microsphere and the remaining light. The interference pattern on the focal plane behind the condenser lens 5 depends on the distance from the captured microsphere to the center of the optical trap. After reflection by the mirror 6, the quadrant detector 7 receives the interference pattern and generates a voltage signal proportional to the position of the microsphere. The quadrant detector 7 records the motion trajectory of the silica microsphere in the optical trap under different fixed flow velocities v' of the microfluidic fluid. Fourier transform of this trajectory yields characteristic frequencies f' of 3.3Hz, 15.9Hz, and 29.1Hz for the motion under different fixed flow velocities, respectively. Figure 3 , Figure 4 as well as Figure 5 As shown, this forms three different fitted data points (v', f').

[0070] S4. Fit the three data points using the formula v=(f×d)÷Sr (which can be equivalently transformed into f=(Sr÷d)×v). That is, use v' as the independent variable and f' as the dependent variable to perform a linear fit according to y=kx. After obtaining k, use k=Sr÷d to obtain Sr=0.198. Figure 6 R-squared (goodness-of-fit) of linear fitting 2 The value of 0.99 indicates that the model matches the observation results.

[0071] S5. Subsequently, the characteristic frequency f at time t is obtained through real-time testing. Combined with the known d and Sr, the flow velocity v of the microfluidic at time t can be obtained by substituting it into the formula v=(f×d)÷Sr.

[0072] Currently, existing technologies mainly employ micro-particle image velocimetry (Micro-PIV) to measure fluid velocities within microchannels and microfluidic devices (e.g., references 10.1088 / 0957-0233 / 17 / 8 / 017 or CN103675333A). The apparatus for this method includes a microscope, a digital camera (CCD), and an illumination source. In Micro-PIV measurements, the flow field containing tracer particles is illuminated by a volumetric light source. The plane under test is focused and observed through a microscope objective. The particle distribution on the plane under test is recorded at two consecutive time points (t1 and t2) using a digital camera. The position variable Δs of each tracer particle within this time interval is obtained through correlation techniques, and thus the velocity v = Δs / (t2-t1) at each point on the plane under test is obtained. In comparison, the method described in this invention does not require the introduction of a large number of tracer particles (the introduction of a large number of tracer particles may affect the performance or flow behavior of lab-on-a-chip equipment), does not require high-speed cameras and complex digital image processing techniques, and can move the captured microspheres to a designated location for measurement as needed. It also has higher spatial resolution and faster measurement speed, and has obvious characteristics and advantages.

[0073] In summary, the method of this invention uses optical tweezers to create an optical trap and capture a single microsphere. After capture, a microfluidic stream is formed within the microchannel. Then, a quadrant detector is used to record the trajectory of the captured microsphere in the microfluidic stream, and the characteristic frequency f of this motion is obtained by analysis. Combined with the diameter d of the microsphere and the Strouhal number Sr, the flow velocity v is calculated according to the formula v=(f×d)÷Sr. This invention combines optical tweezers technology with the principle of Karman vortex flowmeter and applies it to the measurement of microfluidic flow velocity. It eliminates the need to measure the displacement of the captured particles and effectively eliminates the interference of Brownian motion. The method is simple, reliable, feasible, and yields highly accurate results.

[0074] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0075] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not describe the various possible combinations separately.

[0076] Furthermore, various different embodiments of the present invention can be combined in any way, as long as they do not violate the spirit of the present invention, they should also be regarded as the content disclosed by the present invention.

Claims

1. A method for measuring microfluidic flow velocity, characterized in that, Includes the following steps: Microspheres and the liquid to be tested are mixed to form a dispersion; the dispersion is then passed into a microchannel that is transparent to laser light. The laser is used to form optical tweezers and to construct an optical trap in the microchannel to capture one of the microspheres; The liquid to be tested is continuously flowed in the microchannel to form a microfluidic, and the captured microspheres are vibrated by the scouring of the microfluidic. The trajectory of the captured microspheres in the optical trap is recorded using a quadrant detector to obtain the characteristic frequency of the motion; The flow velocity v of the microfluidic is calculated according to the following formula: v = (f × d) ÷ Sr, where f is the characteristic frequency in Hz; d is the diameter of the microsphere in μm; Sr is the Strouhal number; and the unit of flow velocity v is μm / s. The Strouhal number Sr is obtained through fitting calculation, and the fitting calculation method includes: The liquid to be tested is continuously flowed in the microchannel to form a microfluidic. The microfluidic is controlled to a fixed flow rate, denoted as v'. The characteristic frequency of the motion of the microsphere in the optical trap is obtained, denoted as f'. The fitting data points (f', v') are formed. The fitting data points are fitted according to Formula 1 to obtain the Strouhal number Sr. The fitting calculation uses at least three fitting data points formed by different fixed flow velocities; the R-value of the fitting process... 2 >0.

9.

2. The method for measuring microfluidic flow velocity according to claim 1, characterized in that, The liquid to be tested includes water and / or oil.

3. The method for measuring microfluidic flow velocity according to claim 1, characterized in that, The microspheres comprise silica particles.

4. The method for measuring microfluidic velocity according to claim 1, characterized in that, The concentration of microspheres in the dispersion is 1000 microspheres / mL to 10000 microspheres / mL.

5. The method for measuring microfluidic velocity according to claim 1, characterized in that, The particle size of the microspheres ranges from 0.5 μm to 10 μm.

6. The method for measuring microfluidic velocity according to claim 1, characterized in that, The signals detected by the quadrant detector of the captured microspheres include voltage signals. The voltage signals are subjected to Fourier transform processing to obtain characteristic frequencies. And / or, the response frequency of the quadrant detector is greater than 10 kHz.

7. A device for measuring microfluidic flow velocity, characterized in that, The device is used to implement the method according to any one of claims 1-6, the device comprising a laser, an objective lens, a microchannel, a condenser lens, and a quadrant detector arranged sequentially along the direction of the laser optical path; the objective lens is used to enable the laser to form optical tweezers and construct a photon trap, the condenser lens is used to cause interference between the light that has been captured to obtain the microsphere and the remaining light to form an interference pattern, and the quadrant detector receives the interference pattern to generate a signal.

8. The apparatus for measuring microfluidic flow velocity according to claim 7, characterized in that, A first reflecting mirror is disposed between the laser and the objective lens; And / or, a second reflecting mirror is provided between the condenser lens and the quadrant detector; And / or, the device includes a sample cell in which the microchannel is provided, and the microchannel forms an inlet and an outlet on the sample cell; And / or, the device includes a syringe containing a dispersion or a test liquid and connected to an inlet of a sample cell for providing the dispersion or the test fluid to form a microfluidic.

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