From “Mona Lisa” to Microfluidics: Kyoto University Advances Research on Structural Color Printing for Fluid Performance Detection and Protein Separation

Sivaniah’s research group at Kyoto University developed a new structural color printing method in 2019 by constructing multiple layers of microfibers and micropores with regular size in polymer films, and named it Organized Microfibrillation (OM, Ordinary Microfibers). OM can print exquisite patterns such as “Mona Lisa” on a size smaller than sesame seeds (Figure 1), and the resolution can reach 14,000 dpi, which is more than 10 times that of ordinary printers. The relevant results of this study were published in the main issue of Nature in June 2019, and have received extensive attention from the scientific research industry, and Nutshell has also been tracked and reported [1,2].

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Figure 1. Structural color printing towards microfluidic devices | Courtesy of the team

Three years later, Dr. Qin Detao of the team further developed a microfluidic preparation technology based on the OM method, which can prepare microfluidic channels with structural colors in a polymer film with a thickness of only 1 micron. The paper will be published in 2022. It was published in Nature Communications on May 19 [3].

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Printing microfluidics with structured microfiber technology

The original intention of the research and development of OM technology is to use polymer materials to construct periodic multilayer structures to reflect specific wavelengths of light to form constructive interference and structural color. The microscopic study of the OM structure found that with the adjustment of experimental parameters, there are pores with a size of tens to hundreds of nanometers between the microfibers. The OM microfluidic technology uses these pores to precisely control the fluid, as shown in the figure 2a.

Microfluidics is a technology for precise manipulation of fluids at the microscopic scale. It can complete separation, purification, detection, reaction and other operations through the high integration of tiny pipelines at the chip size, also known as a lab-on-a-chip. Using OM technology to develop microfluidics, three core problems need to be solved: (1) How to obtain available OM microfluidics? (2) What is special about the OM microfluidic channel? (3) What are the application values ​​of OM microfluidics?

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Figure 2. Microfluidics printed by Ordinary Microfiber Technology (OM). a, Conceptual schematic diagram of OM microfluidics; bd, n-hexadecane (b), pure water (c), aqueous solution with auxiliary wetting agent (d) contact angle on polystyrene OM films; e, OM microfluidics SEM observation of the channel; f, Confocal microscope to observe the flow of liquid in the OM channel | Courtesy of the team

First of all, in order to realize the OM microfluidic technology, it is necessary to verify whether the liquid can enter the micropores and whether the internal flow of the material is smooth. The ability of the liquid to enter the micropore is mainly affected by the wettability of the liquid to the material. Generally, the stronger the wettability of the liquid, the easier it is to enter the micropore. Wettability is characterized by the contact angle of the liquid with the material, the smaller the contact angle, the stronger the wettability. Common polymer materials such as polystyrene and polymethyl methacrylate are used to prepare OM microfluidic channels, and the contact angles of common alcohols or oil liquids such as ethanol and n-hexadecane are lower than 30°. (Fig. 2b), the wettability is very strong; while the contact angle of pure water is greater than 90° (Fig. 2c), the wettability is weak; if an additive to assist wetting is added to the water, the contact angle can be reduced to 40° ( Figure 2d), which can greatly broaden the selection of liquids.

The preparation of OM microfluidics includes three steps: film casting, photolithography, and development . The photolithography step adopts microLED lithography equipment, which can print microfluidic channels with high precision, with an accuracy of up to 5 microns (Fig. 2e). By adding fluorescent molecules to a liquid with strong wettability to the OM film, the confocal microscope can observe that the liquid enters the OM channel under capillary action and flows according to the set pattern (Fig. 2f). This indicates that the micropores are connected in the film plane, indicating that the technology of OM microfluidics is feasible.

Structural color properties of OM microfluidics

Among the structural parameters that determine the hydrodynamic performance of microfluidics, pore size is one of the most critical factors, yet it is difficult to discern the size from micrometers to nanometers with the naked eye. OM microfluidics takes a different approach, and its outstanding feature is the multi-layer stack of microporous channels, which produces visible structural colors in the out-of-plane direction of the film.

Since the interlayer spacing of the multi-layer structure is affected by the thickness of the non-porous dense layer and the thickness of the microporous layer, and the thickness of the dense layer is basically unchanged, the interlayer spacing is proportional to the thickness of the microporous layer, that is, positively related to the micropore diameter. Pore ​​size ultimately determines the color spectrum value, so that the size of the pore size can be identified by color, and the fluid performance characteristics determined by the pore size can be further evaluated.

At the same time, the pore size of sub-micron micropores is smaller than the printing width of micron-scale channels, so the fluid performance is not affected by the printing width, but only determined by the pore size of the micropores. As can be seen in Figure 3.b, the fluid diffusion rate under the same structural color Consistent.

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Figure 3. Structural color properties of OM microfluidics. a The diffusion parameter (dL2/dt) of the capillary flow in the OM channel is positively correlated with the peak position of the Bragg reflection peak of the structural color; b, c Changing the channel printing width does not affect the fluid diffusion rate (dL2/dt) under the same structural color | Team Photo courtesy

Briefly, in OM microfluidics, the fluid properties are closely related to the structural color, independent of the apparent size of the channel printing . In this way, the performance of the fluid is directly reflected in the structural color. The redder the color of the OM channel, the larger the interlayer spacing of the internal structure and the larger the corresponding micropore diameter, the smaller the fluid resistance in the channel, and the smaller the fluid resistance. The faster the diffusion rate.

This characteristic can be directly used to detect many properties of the fluid, such as the viscosity of the fluid by analyzing the diffusion rate of the fluid in the OM microchannel. In addition, different media in the micropores will change the refractive index of the OM structure, and the structural color of the OM microfluidics can also be used to detect the refractive index of different liquids.

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Figure 4. Detection performance of OM microfluidics. a, It is experimentally observed that the diffusion parameter of liquid in the OM channel is inversely proportional to the viscosity of the liquid (the abscissa is the reciprocal of viscosity μ); b, the Bragg reflection peak of the structural color of the OM channel responds to the refractive index of the fluid | Photo courtesy of the team

OM Microfluidic Screening of Aqueous Fluid Biomolecules

The core advantage of OM microfluidics is that the size of the micropores can be precisely regulated according to different purposes, and the micropores of different sizes can be combined together. The structural color can directly reflect the combined result. In the figure below, the central main channel is redder than the side channel, indicating that the micropore diameter of the main channel is larger. In the important development field of biomedicine, this feature of OM microfluidics can develop a series of related applications, such as molecular weight sieving of biomolecules.

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Figure 5. Separation channel prepared by OM-regulated micropore size. The channel structure color (a,b) is consistent with the pore size observation of the cross section by scanning electron microscope (ce) | Courtesy of the team

The OM microfluidic combined channels with different pore sizes can separate biomolecules such as polysaccharides and proteins in the mixed solution. Many recent studies have revealed a pathological association between the new coronavirus (covid-19, SARS-CoV-2) and the exacerbation of diabetes [4], among which insulin is related to diabetes, and the new coronavirus nucleocapsid protein (Nucleocapsid protein) It is related to antigen detection, so the first step of this experiment is to achieve the separation of these two proteins.

Figure 6 shows the results of protein separation. The insulin protein (red fluorescence) with a small molecular weight diffuses faster in the OM channel than the nucleocapsid protein (green fluorescence) of the new coronavirus with a large molecular weight, while the nucleocapsid protein of the new coronavirus is in micro The main channel with larger pores has a significantly faster diffusion rate than the side channel. As shown in the figure, there is only red fluorescence in the side channel, indicating that proteins can be separated in the side channel.

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Figure 6. OM microfluidic sieving function. a The mixture enters the OM channel from the side, red is the main channel with larger pore size, and yellow is the side channel with smaller pore size; b Insulin (5.8 kDa, red fluorescence), SARS-CoV-2 nucleocapsid protein (55 kDa, green fluorescence) | Photo courtesy of the team

Microfluidic Technology and Prospect

Microfluidics can realize the miniaturization of analytical equipment, and has the advantages of high sensitivity, low energy consumption, less reagent requirements, and portability, and has attracted attention in many fields. However, the process flow of high-precision preparation is complex and requires specific materials or equipment, which limits its large-scale development.

The advantage of OM microfluidics is that the process is simple, and the use of common engineering polymer materials can prepare flexible, transparent and other styles . Qin Detao, the first author of the paper, believes that the regular microfiber method provides new technologies and ideas for the preparation of microfluidics. OM microfluidics has taken an important first step in the work of screening biomolecules. In the future, this technology It is expected to provide a more convenient microfluidic test platform for more bioengineering research and drug testing research and development.

references

[1] Masateru M. Ito, Andrew H. Gibbons, Detao Qin, Daisuke Yamamoto, Handong Jiang, Daisuke Yamaguchi, Koichiro Tanaka, and Easan Sivaniah. Structural colour using organized microfibrillation in glassy polymer films. Nature, 2019, 570, 363- 367.

[2] I am a scientist iScientist. How can I draw the Mona Lisa smaller than a sesame without paint? https://ift.tt/wrK5iN0

[3] Detao Qin, Andrew H. Gibbons, Masateru M. Ito, Sangamithirai Subramanian Parimalam, Handong Jiang, H. Enis Karahan, Behnam Ghalei, Daisuke Yamaguchi, Ganesh N. Pandian, and Easan Sivaniah, Structural Colour Enhanced Microfluidics. Nature Commnications , 2022, 13, 2281.

[4] JA Müller, R. Groß, C. Conzelmann, et al., SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nature Metabolism, 2021, 3, 149-165.

Author: Qin Detao (special researcher at Kyoto University)

Editor: Jin Xiaoming

Typesetting: Yin Ningliu

Title image: The polymer transparent film on the finger. The microfluidic channel with structural color is printed by OM (Organized Microfiber) technology, which is composed of multiple layers of micropores. The fluid flows along the gap, and the fluorescent probe molecules are like detection submarines entering the channel between the microfibers. cruise.

Source of the title map: Provided by the Pureosity team of Kyoto University

Paper information

Published the journal Nature Communications

Posted on May 19, 2022

Thesis titleStructural colour enhanced microfluidics

(DOI: https://ift.tt/gzAKM4N)

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[Extended reading] How to draw “Mona Lisa” smaller than sesame without paint?

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