Microfluidic technology refers to the technique of controlling the flow, mass transfer, and heat transfer of a fluid with a volume of picoliter to nanoliter in a low-dimensional channel structure with at least one dimension of micron or even nanometer scale. It is widely used in biochemical analysis, immunity, minimally invasive surgery, and environmental monitoring. This paper proposes a microfluidic device based on a segmented temperature sensor. This device can be used for segmental temperature measurement and controlling the temperature of the solution in the microchannel of a glass microfluidic chip. The device is based on a transparent indium tin oxide film glass as a heating element. It adopts a temperature control platform of a proportional-integral-derivative control algorithm. The system uses a charged coupled device camera, a fluorescence microscope, and an image acquisition card to form a noncontact fluorescent indicator temperature measuring device. The device measures the temperature distribution of the microfluid space with time and controls the microfluidics. Moreover, the device has the advantages of simple structure, low cost, and convenient operation.
Temperature is an essential parameter in biochemical research, such as bioorganic synthesis, polymerase chain reaction, and gene mutation detection. With the increasing application of microfluidic chip systems in the biochemical analysis [
Like the FIR and FL methods, cholesteric liquid crystals (TLC) are applied to quantify temperature at ±0.1°C accuracy. It provides high accuracy results from drastic hue change within a range of 1°C–2°C. However, instead of high accuracy, the high viscosity and large bead size after necessary encapsulation have restricted the use of TLC in microfluidic devices. In this manuscript, we present a microfluidic device control system that is based on a segmented temperature sensor [ In this paper, a microfluidic device for microfluidic temperature measurement and temperature control in a microfluidic chip system with a simple structure, low cost, and good performance is proposed. The temperature measurement uses fluorescent dye as an indicator to realize the space of microfluid temperature. The device has a simple structure, small volume, small heat capacity, fast temperature rise and fall, accurate temperature control, and a stable dynamic process.
The rest of the paper is organized as follows: In Section
Microfluidics is the science of the system. It uses a few tens to hundreds of micrometers of tubing to process or manipulate tiny amounts (10–9 to 10–18 liters, 1 cubic millimeter to 1 cubic micrometer) of fluid and pass it through. The technology of mass and heat transfer can be widely used in many fields such as biochemical analysis, immunoassay, minimally invasive surgery, and environmental monitoring. The initial microfluidic technology was used for microfluidic device analysis. Microfluidics provides many valuable functions for analysis: high precision and high sensitivity separation and detection using very few samples and reagents, low cost, short analysis time, and small footprint of analytical equipment. Microfluidics takes advantage of its most apparent features—small size and the use of less obvious microchannel fluids, such as laminar flow. It essentially provides the ability to control molecules in space and time [
The fluid in the microfluidic system needs to flow in a certain way in the microchannel of a specific size and structure to achieve heat transfer, mass transfer, and momentum transfer. Therefore, the microchannel is the core of the microfluidic system. Channels with larger dimensions (features larger than 100 m), simple structures, and functions can be prepared with capillaries. In contrast, channels with small dimensions and complex structures need to be prepared using specific materials and specific processes [
The microchannel consists of the main channel, an auxiliary channel (side stream channel), and an output VI. When multiphase fluids need to be input in the main channel, different fluids need to be introduced from different population channels and different outlet channels, and then different fluids processed by the main channel need to be exported. The inlet and outlet sections can be designed as a “T” type, a “Y” type mocking, or a fan-shaped structure. The main channel is the main space for separation, mixing, and the reaction of fluids [
(a) Flat straight path; (b) two-dimensional curved main channel; (c) two-dimensional broken line main channel.
The microchannel structure can be prepared from different materials such as silicon, glass, and high molecular polymers. Monocrystalline silicon wafers are the basic materials of the integrated circuit (IC) industry and are widely used in semiconductor devices and ICs. The process of preparing microchannels on a single crystal silicon wafer is generally fully compatible with microfabrication techniques [
The processing of microchannels on silicon and glass materials mainly uses photolithography and etching techniques to precisely control the shape, size, and position of the microchannels and simultaneously forms patterns on the entire chip surface that is suitable for mass production. With the advancement of the lithography process, the precision of lithography is continuously improved, and the size of the prepared graphic features is continuously reduced. Nanoscale lithography can be used to prepare microchannels with feature sizes less than 500 nm, enabling control and application of nanoscale fluids. However, the lithography process is complicated, requires expensive exposure and etching equipment, and has high cost and low output. At the same time, photolithography and etching are challenging to prepare microchannels of three-dimensional structure. The processing methods of polymer materials are quite different, usually done by soft lithography. The graphic master can be prepared by printing, ordinary lithography, or electron beam. The pattern transfer and copying can be realized by embossing [
Micro-nanoscale fluids are typical laminar flows. Wen Reynolds (Re) number is greater than or equal to 100. If there is a certain obstacle in the sidewall or the pipeline, an asymmetric structure will be formed, which will cause eddy currents and eddies in the flow field. When 100 > Re ≥ 10, it is challenging to form eddy currents in the microchannels of the planar structure, but influential eddy currents can still be generated in the microchannels of the three-dimensional asymmetric structure. For the case where the Re is extremely low, that is Re < 10, an asymmetric groove with a certain angle to the flow direction must be designed on the wall surface of the microchannel to create an anisotropic resistance to the fluid, causing local rotation of the fluid. Stretching can form a chaotic state and vortex. The most effective way to create eddy currents in a laminar flow with a low Re value is to prepare active agitating components at local locations in the fluid and then use external electric fields, magnetic fields, ultrasound, or pressure to control these components to form eddy currents.
Micro-nanofluids can be divided into single-phase flow (such as single liquid flow and single gas flow), two-phase flow, and multiphase flow (such as gas-liquid two-phase flow and liquid-liquid multiphase flow) according to their composition. Multiphase flow can be subdivided into a single component (multiphase, SCMP) and multicomponent (multiphase, MCMP) and can also be divided into mutual soluble multiphase flow and nonintermetallic dissolution phase flow.
At the macroscopic scale, it is difficult to maintain a distinct interface between mutually soluble liquid fluids. However, under laminar flow conditions with low Re, fluids can only be mixed by interfacial diffusion. Therefore, even if the fluids are miscible, there is a clear interface in the middle when they contact each other. However, as the mutual contact time is extended, the interface is broadened and gradually blurred due to the diffusion in the longitudinal direction (along the fluid flow direction) and the lateral direction (perpendicular to the fluid flow direction).
The interface of the immiscible fluid asks for the immiscible two-phase microfluid, and a clear interface can be maintained between the two phases for a long time, i.e., a so-called “pinning” interface is formed. However, the shape of the interface is affected by many factors such as fluid viscosity, interfacial tension, flow velocity, channel feature size, and channel inner wall state, forming stratified flow, wavy laminar flow, inclined interface laminar flow, droplet flow, plug flow, and ring shape. Interfacial control of miscible multiphase microfluidics is one of the key technologies in microfluidic technology. Under macroscopic conditions, the water-soluble and the organic phases are separated by gravity. However, for microfluidics, the interfacial tension between liquid-solid, liquid-gas, and liquid-liquid phases play a dominant role. The method of controlling fluid on a macroscopic scale is no longer applied again. Changing the microchannel structure, such as introducing the guiding structure m1 or using a microchannel with a specific shape cross section, can effectively change the interface morphology between the multiphase immiscible microfluidics. Surface chemical modification of the wall surface of the microchannel by PVP, PEO, PHEMA, ODS, etc., can make the interface morphology more stable and easy to control.
Among the functional units required for microfluidic systems, microfluidic drive and control operating units are particularly important. Under the microsystem conditions, the influence of surface tension becomes very obvious. The conventional driving method of fluid volume flow is often not effective in micropipes in the engineering sense. Common microfluidic drive technologies include mechanical micropump technology and nonmechanical micropump technology based on electricity, light, magnetism, and high-efficiency hybrid control of microfluidics.
Mechanical displacement micropump is the output part of mechanical kinetic energy, it converts mechanical energy into driven fluid. In this type of pump, the flow and pressure are easy to match with the microinfusion, and more emphasis is placed on flow matching. In general, the miniaturization and integration of the pump are not emphasized. A nonmechanical micropump is a continuous dynamic flow by converting or applying other forms of energy (electricity, light, magnetism, heat, etc.) to the driven fluid to have kinetic energy. Since it is generally a valveless structure, it is often called a continuous dynamic flow. Electric (direct) drive (fluid) pumps designed according to electrohydraulic principles are an essential category. In recent years, magnetic flow control technology has been developed to drive and control fluids by adding a magnetically magnetic nanoparticle medium to a fluid. The newly emerging novel light-driven pump technology uses a light control method to control the fluid transport of a microsystem. It is a continuous flow pump technology with development potential. In addition, drive pump technology based on surface tension, gravity, and centrifugal force has also made rapid progress.
In this paper, the microfluidic device based on the segmented temperature sensor adopts the parallel porous electric drive pump technology.
A long time ago, the direct use of direct current or low-frequency alternating current to drive fluids was the conventional way. However, now it has become a reality in the shape of an electrohydraulic power pump (EHD). The study began in the 1960s with an ion drag pump (IDP). IDP is an infusion pump that utilizes the migration movement of charged ions in a fluid under the action of an electric field. With the advancement of microfabrication technology, micro-IDPs etched on single crystal silicon have emerged. The micropump mainly has two etchings on the single-crystal silicon. The mesh channel is connected by electrodes (distance 350 ttm). Injecting the ionic fluid in the initial mesh causes the ions in the fluid to move under the action of the electric field to drive the fluid movement. The EHD can now be used on the chip to achieve fast mixing of fluids. The EKP developed according to the EHD principle mainly includes an electroosmotic flow- (EOF-) based electroosmotic pump (EOP) and an electrophoretic separation- (EPF-) based electrophoresis pump (EPP). Figure
Schematic diagram of EPP and EOP on a glass-based chip.
The parallel multichannel electroosmotic pump is a micropump based on the principle of electroosmosis, consisting of hundreds of parallel small-diameter microchannels or even nanochannels. It provides flow and pressure compatible with the microchip network structure for general analytical applications, i.e., 0.05 l td/min flow and LQ arm backpressure. The small size makes it easy to achieve a multicomposite of a single pump. When the channel is a nanochannel, the pump is a nanochannel electroosmotic pump with the same function as p-EOP. The nanochannel electroosmotic pump has a high delivery pressure, and the pressure is in the l-10 arm, and the flow rate is slightly upgraded. Essentially, since electrophoretic migration in nanochannels is difficult to participate in fluid delivery, this type of pump is a true electroosmotic pump and has the same principle as a capillary channel electroosmotic pump. The ideal electroosmotic pump should be battery-powered. How to effectively reduce the driving voltage is very important.
Compared with the primary electroosmotic pump, the three-stage electroosmotic pump provides an important idea that it is expected to develop a chip-based or miniaturized multistage electroosmotic pump as a microfluidic component, which has been successfully developed by researchers. A 10-stage electroosmotic pump is used for membranes; another effective method is to use a microchannel membrane as the medium for the electroosmotic pump. EKP is very important in microfluidic analysis systems because of the capillary effect, which is often the most efficient way to push fluids in micron-scale pipes (500 tan); it is easy to make as there are no moving parts and can be designed in very small spaces. It is within the volume and is compatible with the chip. EKP delivers buffer solutions and polar organic solvents that can be transported for most analytical chemistries, including liquid chromatography, capillary electrophoresis, and most fluids involved in microfluidic chips. EK has great potential for applications in capillary fluid chromatography, flow injection analysis, sequential flow injection analysis (and microfluid systems such as micro drug delivery). The main disadvantage of EKP is that it can only drive fluid media that can produce electroosmotic flow. Electric drive technology is a very efficient driving method. EKP has revolutionized the technology from conventional electrophoresis to capillary electrophoresis and played an irreplaceable role in the research field of life sciences. However, with the rapid development of micro-nanoscale component technology, limitations are also becoming more and more apparent. As shown in Table
Limitation for electrically driven technique.
Channel size ( | Suitable for electrically driven | Equivalent electric resistance | Alternative | |
---|---|---|---|---|
Conventional electrophoresis | 500–3000 or more | Fit, lower efficiency | Small | Syringe pump, etc. |
Capillary electrophoresis, lab-on-chip, etc. | 50–500 | Fit, high efficiency | Middle | Electrically driven pump |
Single macromolecule analysis | 1–50 | Fit, lower efficiency | Large | Light-driven, etc. |
Nanochannel research | 0.001–1 | Unfit | Huge | — |
The functions that a microfluidic device can perform are dependent on the transmission process in the fluid in the microchannels in the device. For example, a micropump port is a device that uses a different driving method to form an overall directional flow in a specific region of a microchannel. The microseparator utilizes the microparticle characteristics between different fluids. A device that effectively separates multiple particles or fluids, including a micromixer, which allows sufficient material exchange between the various parts of the microfluid to form a layer of mixture. A microreactor is a device that allows fluids that can react with each other to react effectively in the tiny space defined by microchannels or droplets to prepare specific substances. By integrating these devices and assembling them with external energy and signal input and output devices, a fully functional microfluidic system can be prepared for aerospace, medical, and agricultural applications, bioengineering, material processing, chemical industry, and many other fields. The limitation for the electrically driven technique is shown in Table
The measurement part is: the CCD camera is connected to the fluorescence microscope via the interface converter. The laser is fixed on the mirror arm of the fluorescence microscope so that the excitation light and the emitted light are in a confocal manner. The laser spot is 300
The temperature measurement and control system device.
About 20 minutes before the start of the experiment, the ITO glass heating sheet was fixed on the
To measure the temperature with the fluorescence intensity of the dye as the temperature indication, it is first necessary to determine the functional relationship between the temperature value and the dye fluorescence intensity value through experiments. The temperature calibration device is shown in Figure
The temperature calibration device.
The thickness of the ITO film is on the order of ns. Its physicochemical properties are stable. Its hardness is high. It has good adhesion to most substrates, and its resistance to acid, alkali, and organic solvents is strong. Moreover, the transmittance can reach 2 × 10–4 Ω 1 cm and 90% or more, respectively. It is used in the microfluidic chip heating system. It has the advantages of fast temperature rise, good stability, durability, and no optical detection window. In this experiment, commercial ITO film glass is used as the microfluidic system heater, which has many advantages. First, it is cheap and easy to obtain. Second, it is easy to process and can be directly cut into the desired shape for special and complicated graphics. It can be obtained by the etching method. The heater platform and the chip are separated structures, which will not be discarded due to scrapping of the chip; thirdly, the light transmittance of ITO is very good and does not affect the optical detection of the microfluidic system.
The ITO film is used as a heater. Its shape and resistance value have a great influence on the surface temperature distribution. The resistance value can be calculated according to its shape and size. As shown in Figure
Schematic diagram of the ITO layer.
The following formula can express the fluorescence intensity
Under the condition that the excitation light source intensity
To measure temperature by this method, it is first necessary to calibrate the relationship between the intensity of the fluorescent dye and the temperature. In the actual temperature measurement process, the excitation light intensity
Table
The normalized experimental date with the temperature (°C).
Temperature | 20 | 25 | 30 | 35 | 40 | 45 |
---|---|---|---|---|---|---|
Normalized intensity | 1.010 | 0.991 | 0.969 | 0.912 | 0.859 | 0.813 |
Temperature | 50 | 55 | 60 | 65 | 70 | 75 |
Normalized intensity | 0.736 | 0.672 | 0.580 | 0.511 | 0.442 | 0.368 |
Temperature | 80 | 85 | 90 | 95 | ||
Normalized intensity | 0.297 | 0.241 | 0.192 | 0.137 |
Temperature and fluorescence intensity curves.
Furthermore, the fitting formula is obtained by fitting the third-order polynomial (Figure
The device uses a beam splitter to change the optical path and intensity of the excitation light source so that the device can obtain four beams of parallel light of equal intensity and irradiated on the microfluidic chip, thereby measuring the fluorescence intensity by the CCD camera. The concept map of a segmented temperature sensor is shown in Figure
Concept map of segmented temperature sensor.
The microfluidic device based on the segmented temperature sensor designed in this paper can be used for segmental temperature measurement and temperature control of the solution in the microchannel of the glass microfluidic chip. The device uses a transparent indium tin oxide film glass as a heating element. It adopts a temperature control platform of a PID control algorithm. The system uses a CCD camera, a fluorescence microscope, and an image acquisition card to form a noncontact fluorescent indicator temperature measuring device, which realizes the measurement of the temperature distribution of the microfluid space and the temperature measurement with time, and controls the microfluid based on this. The schematic diagram is shown in Figure
The schematic diagram of the control system.
This paper proposes a microfluidic device based on the segmented temperature sensor. This device can be used for segmental temperature measurement and controlling the temperature of the solution in the microchannel of a glass microfluidic chip. The segmented temperature sensor-based microfluidic device control system is highly adaptable, simple in processing, and more flexible. The system uses a charged coupled device camera, a fluorescence microscope, and an image acquisition card to form a noncontact fluorescent indicator temperature measuring device. The device measures the temperature distribution of the microfluidic space with time and controls the microfluid. Moreover, the device has the advantages of simple structure, low cost, and convenient operation.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
The authors declare that they have no conflicts of interest.
The study was supported by “the Sponsored by Qing Lan Project (No. 10 of Official document from Jiangsu Education Department in 2020).”