On-Chip Gel-Valve Using Photoprocessable Thermoresponsive Gel
© Ito et al.; licensee Springer 2014
Received: 22 January 2014
Accepted: 24 May 2014
Published: 30 August 2014
Microfluidic chips are powerful tools for biochemical experiments. High speed and precise flow control can be achieved by using microvalves on a chip. Several types of microvalves that can be integrated into a microfluidic chip have been reported. Among them, gel microvalves have certain advantages over other valves because of their soft structure, which will contribute to prevent mechanical damage the cells passing though the valve. Here we use Bioresist, a photoprocessable thermoresponsive gel, as a key component of the microvalve. Since Bioresist is photopatternable, we can create any arbitrary 2D shape from the thermoresponsive gel using photolithography. Moreover, Bioresist has the unique feature of a phase transition around 30°C, and swells and shrinks repeatedly with temperature change. By integrating the patterned thermoresponsive gel with a microheater, we developed a gel actuator and designed a gel-valve. The gel-valve has the advantages of a simple actuation mechanism: high leakage pressure, high speed actuation and low power consumption. The valve is biocompatible and easily integrated into a chip by using conventional photolithography. Using this valve, we achieved on-chip flow control, and applied it to cell sorting on a chip.
Demand for single cell analysis has increased with progress in cell biology and micro- and nanofabrication technologies –. For the purpose of single cell analysis, single cell manipulation capabilities, such as positioning, immobilization, and sorting of target cells, are needed. Microfluidic chips are powerful tools that make it possible to perform these tasks with high throughput, low cost, and high repeatability –. Since these cell manipulations are carried out along with flow control, microvalves are key components. For high speed and precise flow control, microvalves should be closely connected to the microfluidic channels on a chip –. For this purpose, there have been several types of microvalve reported that can be integrated with microfluidic chips, including electrostatic microvalves –, pneumatic microvalves –, magnetic microvalves –, and thermoresponsive gel microvalves –.
Gel microvalves have certain advantages over other types because they have a soft structure, which can prevent mechanical damage to cells passing through the valve. Here we use a photoprocessable thermoresponsive gel (Bioresist, Nissan Chemical Industries Ltd.), as a key component of a gel microvalve. Since Bioresist can be patterned using photolithography, we can create any arbitrary 2D shape from the thermoresponsive gel. Moreover, Bioresist has the unique feature of a phase transition around 30°C, and swells and shrinks repeatedly with temperature change. By integrating the patterned thermoresponsive gel with a microheater, we developed a gel actuator and designed a gel-valve. The gel-valve is controlled by a microheater, and therefore, its structure is quite simple. The gel-valve has the advantages of a simple actuation mechanism: high leakage pressure, high-speed actuation and low power consumption. The valve is biocompatible and easily integrated into a chip using conventional photolithography. In this study, we focused on the evaluations of the gel-valve using Bioresist as an on-chip microfluidic component. We evaluated the resolution of patterning and expansion rate of Bioresist. After fabrication of microvalves, we evaluated the frequency characteristics and pressure resistance of the microvalves. Finally, we demonstrated on-chip cell sorting as an application of the microvalves by sorting cells using the proposed gel-valves.
The remainder of this paper is organized as follows. After an introduction of microvalves for on-chip flow control, we propose the gel-valve in section 2. In section 3, we explain the experimental system and results. We discuss advantages of the proposed gel-valve in section 4, followed by concluding remarks in section 5.
Related works of microfluidic valves
Many studies of on-chip microvalves have been previously reported. Electrostatic microvalves can be fabricated by silicon-based micro electro mechanical system (MEMS) processes and easily integrated into microfluidic chips –. For single cell applications, however, they have possibility of mechanical damage to cells passing through the valve because they have a solid and complex mechanical structure associated with the microfluidic channel. Pneumatic microvalves can be fabricated from soft materials such as polydimethylsiloxane (PDMS) and can reduce mechanical damage to cells –. However, each microvalve requires independent gas pressure control. This makes the whole system complex, and it is difficult to integrate many pneumatic microvalves into one chip. Magnetic microvalves can also be fabricated from soft materials. They are actuated by permanent magnets or electromagnets –. It is difficult to integrate many magnetic microvalves into one chip because the magnetic fields interfere with each other. Gel microvalves based on the thermoresponsive gels mixed with a solution in microfluidic channels are also reported such as poly(ethylene oxide)x-poly(propylene oxide)y-poly(ethylene oxide)x and Poly-(N-isopropylacrylamide) (PNIPAAm) –. For example, by using the combination of the gel mixed solution and microelectrodes on the substrate of the microchannel, we can expect high-speed response of gel microvalves within several tens milliseconds ,,. These thermo-responsive gels are biocompatible material. The soft structure of such valves protects cells from mechanical damage . Moreover, these valves can be actuated by local heating of the channel by microheaters or laser irradiation. The actuation mechanism is quite simple and can be easily integrated into a chip. However, conventional gel microvalves require mixing of thermoresponsive polymer into the culture medium.
In this paper, we propose a novel gel-valve using Bioresist. The gel-valve mainly consists of patterned gel and a microheater. Patterned gel is simply fabricated by photolithography of Bioresist, and the microheater is made using the lift off process. Such a simple fabrication process makes it possible to integrate many gel-valves into a chip. Furthermore, it has been already confirmed that Bioresist is biocompatible . Gel-valves should therefore be suitable for cell manipulation on a chip.
Gel-valve using Bioresist
Gel-valve fabrication process
Microheaters are patterned on the glass substrate using the lift-off process.
Microchannels are fabricated using SU-8 (Nippon Kayaku Co. Ltd.).
Bioresist is patterned by photolithography as a gel-valve.
The molded PDMS cover is bonded with the glass layer, and the electrodes are attached.
Evaluation of Bioresist patterning resolution
Evaluation of temperature dependent expansion of Bioresist
Application: microvalve and cell sorter
In this study, we focused on the evaluations of the gel-valve using Bioresist as an on-chip microfluidic component and demonstrated on-chip flow control using gel-valves. The proposed gel-valve is advantageous for integration as a microfluidic component in a chip, since the structure is quite simple. The gel-valves can be integrated using standard photolithography, which is suitable for mass production. Moreover, it can be driven with low power consumption. For example, we can actuate the gel-valve with 39.3 mW (38.2 mA and 1.03 V) for open/close control. The gel-valve can be driven by a small battery, and we can easily set up a small system.
We proposed a gel-valve that can be highly integrated into a microfluidic chip. The gel-valve can be fabricated with 20 μm resolution by standard photolithography and lift off processes. We can actuate the gel-valve at 5 Hz with 38.2 mA. Furthermore, we demonstrated cell sorting by using two gel-valves fabricated near the branch of a microchannel on a chip. The target cell was successfully sorted. Since the proposed gel-valve can be actuated simply by local heating with a microheater with a power consumption of 39.3 mW, we can easily apply the valve in microfluidic chips.
This work is supported by a Grant–in–Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (23106002), the Japan Society for the Promotion of Science, and Nissan Chemical Industries, LTD.
- Wacogne B, Pieralli C, Roux C, Gharbi T: Measuring the mechanical behaviour of human oocytes with a very simple SU-8 micro-tool. Biomed Microdevices 2008, 10: 411–419. 10.1007/s10544-007-9150-7View ArticleGoogle Scholar
- Zare RN, Kim S: Microfluidic platforms for single-cell analysis. Annu Rev Biomed Eng 2010, 12: 187–201. 10.1146/annurev-bioeng-070909-105238View ArticleGoogle Scholar
- Lindström S, Andersson-Svahn H: Miniaturization of biological assays – overview on microwell devices for single-cell analyses. Biochim Biophys Acta 2011, 1810: 308–316. 10.1016/j.bbagen.2010.04.009View ArticleGoogle Scholar
- Hagiwara M, Kawahara T, Yamanishi Y, Masuda T, Feng L, Arai F: On-chip magnetically actuated robot with ultrasonic vibration for single cell manipulations. Lab Chip 2011, 11: 2049–2054. 10.1039/c1lc20164fView ArticleGoogle Scholar
- Sakuma S, Arai F: Cellular force measurement using a nanometric-probe-integrated microfluidic chip with a displacement reduction mechanism. J Robot Mechatronics 2013, 25: 277–284.Google Scholar
- Wheeler AR, Throndset WR, Whelan RJ, Leach AM, Zare RN, Liao YH, Farrell K, Manger ID, Daridon A: Microfluidic device for single-cell analysis. Anal Chem 2003, 75: 3581–3586. 10.1021/ac0340758View ArticleGoogle Scholar
- Li PC, Harrison DJ: Transport, manipulation, and reaction of biological cells on-chip using electrokinetic effects. Anal Chem 1997, 69: 1564–1568. 10.1021/ac9606564View ArticleGoogle Scholar
- Yamada M, Seki M: Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. Lab Chip 2005, 5: 1233–1239. 10.1039/b509386dView ArticleGoogle Scholar
- Han J, Yeom J, Mensing G, Flachsbart B, Shannon MA: Characteristics of electrostatic gas micro-pump with integrated polyimide passive valves. J Micromechanics Microengineering 2012, 22: 095007. 10.1088/0960-1317/22/9/095007View ArticleGoogle Scholar
- Yıldırım E, Arıkan MS, Külah H: A normally closed electrostatic parylene microvalve for micro total analysis systems. Sensors Actuators A Phys 2012, 181: 81–86. 10.1016/j.sna.2012.05.008View ArticleGoogle Scholar
- Anjewierden D, Liddiard GA, Gale BK: An electrostatic microvalve for pneumatic control of microfluidic systems. J Micromechanics Microengineering 2012, 22: 025019. 10.1088/0960-1317/22/2/025019View ArticleGoogle Scholar
- Hosokawa K, Maeda R: A pneumatically-actuated three-way microvalve fabricated with polydimethylsiloxane using the membrane transfer technique. J Micromechanics Microengineering 2000, 10: 415–420. 10.1088/0960-1317/10/3/317View ArticleGoogle Scholar
- Go JS, Shoji S: A disposable, dead volume-free and leak-free in-plane PDMS microvalve. Sensors Actuators A Phys 2004, 114: 438–444. 10.1016/j.sna.2003.12.028View ArticleGoogle Scholar
- Thuillier G, Malek CK: Development of a low cost hybrid Si/PDMS multi-layered pneumatic microvalve. Microsyst Technol 2005, 12: 180–185. 10.1007/s00542-005-0007-9View ArticleGoogle Scholar
- Bosch D, Heunhofer B, Muck G, Seldel H, Thumser U, Welser W: A silicon microvalve with combined electromagnetic /electrostatic actuation. Sensors Actuators A Phys 1993, 38: 684–692. 10.1016/0924-4247(93)80116-XView ArticleGoogle Scholar
- Meckes A, Behrens J, Kayser O, Benecke W, Becker TH, Müller G: Microfluidic system for the integration and cyclic operation of gas sensors. Sensors Actuators A Phys 1999, 76: 478–483. 10.1016/S0924-4247(99)00060-6View ArticleGoogle Scholar
- Bae B, Kim N, Kee H, Kim SH, Lee Y, Lee S, Park K: Feasibility test of an electromagnetically driven valve actuator for glaucoma treatment. J Microelectromechanical Syst 2002, 11: 344–354. 10.1109/JMEMS.2002.800921View ArticleGoogle Scholar
- Fu C, Rummler Z, Schomburg W: Magnetically driven micro ball valves fabricated by multilayer adhesive film bonding. J Micromechanics Microengineering 2003, 13: 96–102. 10.1088/0960-1317/13/4/316View ArticleGoogle Scholar
- Stoeber B, Yang Z, Liepmann D, Muller SJ: Flow control in microdevices using thermally responsive triblock copolymers. J Microelectromech Syst 2005, 14: 207–213. 10.1109/JMEMS.2004.839330View ArticleGoogle Scholar
- Yamanishi Y, Teramoto J, Magariyama Y, Ishihama A, Fukuda T, Fumihito A: On-chip cell immobilization and monitoring system using thermosensitive gel controlled by suspended polymeric microbridge. IEEE Trans Nanobioscience 2009, 8: 312–317. 10.1109/TNB.2009.2035273View ArticleGoogle Scholar
- Arai F, Ichikawa A, Fukuda T, Katsuragi T: Isolation and extraction of target microbes using thermal sol–gel transformation. Analyst 2003, 128: 547. 10.1039/b212919aView ArticleGoogle Scholar
- Ichikawa A, Arai F, Yoshikawa K, Uchida T, Fukuda T: In situ formation of a gel microbead for indirect laser micromanipulation of microorganisms. Appl Phys Lett 2005, 87: 191108. 10.1063/1.2126800View ArticleGoogle Scholar
- Arai F, Ng C, Maruyama H, Ichikawa A, El-Shimy H, Fukuda T: On chip single-cell separation and immobilization using optical tweezers and thermosensitive hydrogel. Lab Chip 2005, 5: 1399–1403. 10.1039/b502546jView ArticleGoogle Scholar
- Arakawa T, Shirasaki Y, Aoki T, Funatsu T, Shoji S: Three-dimensional sheath flow sorting microsystem using thermosensitive hydrogel. Sensors Actuators A Phys 2007, 135: 99–105. 10.1016/j.sna.2006.06.074View ArticleGoogle Scholar
- Shirasaki Y, Tanaka J, Makazu H, Tashiro K, Shoji S, Tsukita S, Funatsu T: On-chip cell sorting system using laser-induced heating of a thermoreversible gelation polymer to control flow. Anal Chem 2006, 78: 695–701. 10.1021/ac0511041View ArticleGoogle Scholar
- Yokoyama Y, Umezaki M, Kishimura T, Tamiya E, Takamura Y: Micro-and nano-fabrication of stimulus-responsive polymer using nanoimprint lithography. J Photopolymer Sci Technol 2011, 24: 63–70. 10.2494/photopolymer.24.63View ArticleGoogle Scholar
- Tanaka T, Sato E, Hirokawa Y: Critical kinetics of volume phase transition of gels. Phys Rev Lett 1985, 55: 2455–2458. 10.1103/PhysRevLett.55.2455View ArticleGoogle Scholar
- Zhang J, Peppas NA: Synthesis and characterization of pH- and temperature-sensitive poly (methacrylic acid)/poly (N -isopropylacrylamide) interpenetrating polymeric networks. Macromolecules 2000, 33: 102–107. 10.1021/ma991398qView ArticleGoogle Scholar
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