Microfluidic devices are processed on a scale of the order of nanometers or millimeters, mainly in the form of planar surfaces, using micro-machining technology in resin, glass and silicon. In recent years, microfluidic devices have been used in a very wide range of applications. These applications have been increasing noticeable in the fields of life science, chemistry and analysis. Here we present many of the applications of commonly used microfluidic devices. Different materials are suitable for different applications, with glass and resin being the materials of choice, but further development of glass microfluidic channels is expected through the expansion of new applications and the development of glass machining technology.
Microfluidic devices are also sometimes referred to as μTAS (micro total analysis systems), lab-on-a-chip, or flow cells, but are generally referred to as microfluidic devices. They are processed on a scale of the order of nanometers or millimeters, mainly in the form of planar surfaces, using micro-machining technology in resin, glass and silicon. Microfluidic channels are made in a complicated structure on a flat surface in order to provide various functions inside. In recent years, software developments have enabled highly accurate prediction of complex channel structures, flow, diffusion and capillary action.
AGC has long been involved in mass production using glass micro-machining in the optics field. Microfluidic devices have glass micro-machining in common, and are particularly relevant to the field of optics. Specifically, optical evaluation such as observation by imaging, fluorescence, Raman measurement and spectroscopy are indispensable tools, and we offer a wide range of optical components for use in analytical systems. Here we focus mainly on microfluidic devices and examples of the processing handled by AGC. Click here to see our optical component products.
Various types of glass machining are available on request. Both isotropic and anisotropic etching shapes are supported. Please contact us if you would like to consider a prototype for mass production, or if you need high aspect ratio and deep glass micro-machining.
High performance processing using glass materials and micro-machining technology
High transmission and reliability of glass materials
Mass production track record in glass processing technology
High-aspect ratio and deep glass processing through unique processing method
Direct glass bonding technology
Various kinds of coating treatment available
Applications of Microfluidic Devices
In recent years, microfluidic devices have been used in a very wide range of applications. They are used frequently in the fields of life science, chemistry and analysis, in particular. Different materials are suitable for different applications, and glass is used for some of them, but here we present a wide range of applications of commonly used microfluidic devices.
Cell sorters, flow cytometry, cell counters
Diagnostic chips (Immunoassays, PCR, and CTC)
Synthesis of nano and micro particles
Cell sorters, flow cytometry, cell counters
These chips are used to analyze, separate, and measure cells by flowing them through a channel structure. A flow cytometer is a device that tests cells by arranging them in a row and using a laser beam to measure the scattered light and fluorescence. It is widely used in institutions that handle cells. Conventionally, a quartz optical flow cell, in which a rectangular linear flow path is formed on bulk quartz, has been used. Recently, microfluidic devices are used to control the flow of cells inside a single-chip channel, allowing them to be arranged in a row, analyzed, and separated.
Cell sorting technology is also used in the detection of rare cells. This is CTC (circulating tumor cell) separation technology. CTCs are rare cells, with only a few per milliliter of blood, but they are very effective in helping to detect cancer. Methods of separating them using microfluidic channels are currently being developed.
Immunoassays are a general method of biomarker detection that exploits the capability of antibodies to bind specifically to certain antigens. Familiar examples include immunochromatography, which tests for viral antigens such as influenza and coronavirus, and antibody testing, which checks for the presence of antibodies.
ELISA (enzyme linked immunosorbent assay) is a quantitative immunoassay evaluation method, in which an antibody to which an enzyme binds as a labeling substance is combined in solution with the target antibodes which are bounded at the bottom of a microwell, etc. The use of microfluidic channels enables highly sensitive analysis on a single chip.
PCR (polymerase chain reaction) is a method of amplifying DNA. It can amplify even minute amounts of DNA and is widely used in research and medicine. In recent years, viral DNA or RNA has been amplified by PCR to detect viruses. The PCR method utilizes the fact that double-stranded DNA splits into single-stranded DNA when heated in an aqueous solution, and that complementary DNA strands recombine to form double-stranded DNA when cooled. Repeating this process results in amplification. It requires mixing and adjustment of the reaction solution during the cycle, temperature control such as heating and cooling, and inspection of the repetition frequency and reaction products, and can be simplified as a single-chip process using microfluidic channels.
DNA double helices are composed of four bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Determining the sequence of these bases is called DNA sequencing. The basic principle is to first amplify the target DNA using PCR to produce DNA fragments of various lengths. These DNA fragments are then arranged by length and their base sequence determined by detecting a fluorescent dye attached to the terminal bases. While this method can only analyze one DNA sequence at a time, which is time-consuming, a method called next-generation sequencing uses a microfluidic device to determine multiple DNA sequences at once simultaneously.
Microphysiological Systems (MPS)
Microphysiological Systems (MPS) are also called biomimetic chips or organs-on-chips. They create a structure on a channel and evaluate the response by absorbing cells. In addition to the three-dimensional structure of organs and the exchange of liquid at their interface, however, the chips can create an environment closer to the actual human body by simulating physical stimuli such as pulling and pushing. The number of types of organ being developed is increasing, mainly in the field of drug discovery, and this is expected to accelerate the speed of development and reduce the risk of toxicity by predicting the response from organs without conducting human experiments.
Synthesis of nano and micro particles
By merging solutions from two microfluidic channels, nano- and micro-size particles (droplets) are synthesized. For example, when water and oil are merged, liquid droplets or oil droplets are produced, and the use of channels can produce more uniform droplet sizes compared with conventional emulsification methods. It is even possible to perform an analysis inside a closed droplet by introducing RNA or DNA to be analyzed into an individual droplet, which has been attracting a great deal of attention in recent years in the field of digital PCR and single-cell analysis.
In addition, the use of microfluidic channels enables chemical reactions to occur that cannot be achieved in bulk systems. For example, it can make diffusion very rapid, and can even control the sequence of reactions in order to achieve a higher synthetic yield in a mixed system. μTAS, which is based mainly on such chemical reactions, is also called a microreactor.
Being able to analyze extremely small quantities makes it possible to do things like monitoring chemical quantities. This is used for testing water quality and so on. It is also used in analytical equipment such as optical spectrometers and chromatographs.
Materials Used in Microfluidic Devices
As a material, PDMS is getting more frequently used because it is easy to process in a laboratory. PDMS is often used because it allows prototyping by conventional photolithography processing, and because it is stretchable, allowing mechanical forces such as pressure to be applied to channels. Polycarbonate (PC), polystyrene (PS), PMMA, COC, COP, and polymer materials are also used with mass production in mind, such as emboss molding and injection molding.
Quartz and borosilicate glass are used as glass. The advantages of glass are its high transmittance, high processing accuracy, and processing methods that offer superior mass productivity. Because it is chemically stable, it can be used with a variety of reagents and organic solvents. In the case of resin, there is a risk of drugs penetrating through the inner wall of a channel or being dissolved by organic solvents, but in the case of glass, this is rarely a concern.
With its low autofluorescence and the lack of deterioration or damage due to lasers, glass is also often used in high-end fluorescence analysis. Silicon (Si) is another material with excellent durability and processability, but it is unsuitable for optical evaluation due to its lack of transparency. LTCC (low-temperature co-fired ceramic) is a ceramic substrate formed by sheet lamination, and is an intriguing material because of its high physical and chemical durability, and because it allows for easy formation of channel structures and internal wiring.
Microfluidic channels are designed to be disposable in some cases or to be reusable after cleaning and sterilization. The glass chips can be used repeatedly because they do not deteriorate even in sterilization processes such as UV irradiation and autoclaving. Their reuse has advantages in terms of cost, but it is also effective when you want to maintain accuracy due to manufacturing variations.
AGC has a long track record in glass processing technology and can handle everything from prototyping to mass production. In particular, we have developed technologies for high-aspect, ultra-deep channel processing, and direct bonding without the use of adhesives. Please feel free to contact us for a consultation on any areas where it has been difficult to succeed with conventional dry and wet etching processing.
Other inorganic materials
Borosilicate glass Quartz
PDMS, PC, PS, PMMA, COC, COP, etc.
Transmittance decreases depending on material and wavelength
Photodegradation occurs depending on material and wavelength
Easily damaged by drug penetration or strong organic solvents
Not suitable for high temperature processing
Occurs depending on material
Can be reused for cleaning or sterilization as necessary
Basically assumed to be disposable
Examples of Microfluidic Device Processing
Channels are formed by processing the glass directly. The examples shown here are typical structures commonly used for microfluidic channels. In practice, the shape is designed to suit the application, and furthermore, multiple channel structures are used in combination.
Linear channels: This is the basic structure for observation while transporting liquids, cells or microparticles. The length, depth, width and cross-sectional shape of the channel can be customized.
Channels with chambers: This structure has a chamber in each channel. It can be used to observe cells, control chemical reactions, collect particles, etc.
Droplet generator: Aqueous and oily solutions are merged from two channels, and droplets are formed by the effect of surface tension.
Micro-machined channels: Micro-machining is done inside channels to control liquid-to-liquid diffusion and the chemical reaction at the interface.
Y-mixers: The reaction proceeds as the two liquids mix inside the channel. The reaction time can be changed by the channel length.
Spiral cell sorter: A liquid is introduced from the central inlet and a centrifugal force is used to separate and collect microparticles or cells.
SEM images of micro-machinied area: Various types of glass machining are available on request. Both isotropic and anisotropic etching are supported. Please contact us if you would like to consider a prototype for mass production, or if you need high aspect ratio and deep glass micro-machining.
Channels can be bonded using a resin adhesive, but if there are problems with resin elution or deterioration due to the solvent used or the processing of the microfluidic device, we can also discuss optical bonding of glass. Optical bonding is usually done by heating to about 900 degrees Celsius, but please also consult with us about bonding processes at low temperatures.
Products Related to Microfluidic Devices
Microfluidic Device Contract Machining
Various types of glass machining are available on request. Both isotropic and anisotropic etching are supported. Please contact us if you would like to consider a prototype for mass production, or if you need high aspect ratio and deep glass micro-machining. Optical evaluation such as observation, fluorescence, Raman measurement and spectroscopy are important applications for microfluidic devices. Please also consult with us about processing in combination with optical components (optical thin films, optical micro-machining, etc.)
Water Repellent Coat Cytop™
Cytop™ has an amorphous structure which makes it extremely transparent. It dissolves in a special fluorinated solvent and can therefore be applied as a thin film coating. In addition to transparency, it simultaneously has properties such as electrical insulation, water and oil repellency, chemical resistance, low refractive index, refractive index similarity to water, and non-fluorescence.
Laboratory products「IWAKI」Vessels for spheroid culture EZSPHERE®
AGC TECHNO GLASS (AGC group) provides researchers with various plastic products for cell culture that have undergone raw material procurement, production, and inspection under strict quality control at its own factory in Japan. We also manufacture and sell unique cell culture products such as EZSPHERE®, a microwell processing product that can produce large amounts of uniformly sized spheroids.