Abstract
It has long been thought that an optical sensor, such as a light waveguide implemented total analysis system (TAS), is one of the essential functional components needed to realize a “ubiquitous human healthcare system”. In accordance with this, we have proposed the fundamental structure for a light waveguide capable of illuminating a cell or particle running along a microfluidic channel and detecting fluorescence even from the extremely weak power of such a minute particle. We successfully trial-manufactured an optical TAS chip with a microfluidic channel containing a 15 × 20-μm cross-section, and a higher aspect ratio (6-μm wide, 10-μm high) core of a light waveguide. To obtain extremely weak forward- and side-direction emitted fluorescence within the chip, we utilized the L- or T-shaped microfluidic channels used in previous studies. As we could predict the fluorescent substances would have very low efficiency, we created a high-power light source using a semiconductor laser (488-nm-wavelength), and a high-performance fluorescence detecting optical system, consisting mainly of a dichroic mirror and interference filters. With this system, we were able to obtain fluorescent responses emitted from substances attached to a particle, adjusting gains in value of the maximum photoelectron multiplier tube modules. Response signal waveforms indicated higher signal-to-noise ratio in forward-direction emitted fluorescence and side-direction emitted. These two detected fluorescences and the side-scattered source light were fully synchronized. Furthermore, a series of experiments revealed that the forward-direction and side-direction emitted fluorescence components had approximately the same order of magnitude. Typical pulse magnitude detected in both directions ranged from 1 pW to several hundreds of pW.
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References
Gregor NF (2002) Device and method for investigating analysis in liquid suspension or solution, International Application Published under the Patent Cooperation Treaty (PCT). PCT/GB02/05567
Mapps T, Vannahme C, Schelb M, Lemmer U, Mohr J (2009) Design for optimized coupling of organic semiconductor laser light into polymer waveguides for high integrated biophotonic sensors. Microphotonic Eng 86:1499–1501
Mitasaki T, Senda M (2006) Write-once recording for multilayered optical waveguide-type holographic cards. Opt Soc Am 23(3):659–663
Ohkubo T, Hashimoto M, Hirota T, Itao K, Niwa T, Maeda H, Mitsuoka Y, Nakajimka K (2000) Mechanical characteristics of an optical flying-head assembly with visible light-wave guide flexure. J Inf Storage Process Syst 2:323–330
Ohkubo T, Terada N, Yoshida Y. (2011) Minute particle detection using a light-wave-guide incorporated optical TAS (total analysis system). In: Microsystem technologies, vol 17. Springer, New York, pp 849–856
Ohkubo T, Terada N, Yoshida Y (2013) In-plane detection of scattered light from a minute particle using a resin-based light waveguide incorporated with a microfluidic channel. In: Microsystem technologies, vol 19. Springer, New York, pp 1319–1328
Ohkubo T, Terada N, Yoshida Y (2014) Illumination and scattered light detection using a light source consisting of sub-micrometer defect arrays formed on a extremely flat light waveguide core. In: Microsystem technologies, vol 20. Springer, New York, pp 1413–1423
Okagbare PI, Emoey LM, Datta P, Goettert J, Soper SA (2010) Fabrication of cyclic olefin copolymer waveguide embedded in a multi-channel poly (methyl methacrylate) fluidic chip for evanescence excitation. Lab Chip 10:66–73
Senda M, Aoki Y (2008) Identification data reproduction in multilayered optical waveguide-type holographic memory cards. Appl Opt 47(21):3973–3979
Sheridan AK, Stewart G, Ur-Reyman H, Suyal N, Uttamchandani DG (2009) In-plane integration of polymer microfluidic channels with optical waveguides—a preliminary investigation. IEEE Sens J 9(12):1627–1632
Takahashi N, Aki A, Ukai T, Nakajima Y, Maekawa T, Hanajiri T (2009) Electrophoretic mobility and resultant zeta potential of an individual cell analyzed by electrophoretic counter method. In: Int. Symp. semiconductor device research symposium. Washington, pp WP4–03
Vazquez RM, Osellame R, Nolli D, Dongre C, Hvd Vlekkert, Ramponi R, Pollnau M, Cellulo G (2009) Integration of femtosecond laser written optical waveguides in a lab-on-chip. Lab Chip 9:91–96
Yagi S, Imai T, Ueno M, Ohtani Y, Endo M, Kurokawa Y, Yoshikawa H, Watanabe T, Fukuda M (2008) Pit distribution design for computer-generated waveguide holography. Jpn J Appl Phys 46(2):942–946
Yamada H, Yoshida Y, Terada N, Hagiwara S, Komatsu T, Terasawa A (2009) Laser fabrication of a micro-fluidic device for a blood cell counter. In: Proceedings of autumn annual meeting, Japan society for precision engineering, vol G64, pp 543–544
Acknowledgments
This research has been supported in part by a Grant-in-Aid for Scientific Research [category of general research field (C)], sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan (April 2014). It has also been partially supported since April 2011 by a Grant for the Program of the Strategic Research Foundation at Private Universities S1101017, organized by the Ministry of Education, Culture, Sports, Science and Technology, Japan.
The authors would like to thank Dr. Makoto Hikita and Dr. Saburo Imamura, NTT Advanced Technology Corporation, for their useful and valuable technical advice on designing a resin-based light waveguide structure with a high-aspect-ratio core and fabricating a 10-μm microfluidic channel, and for their suggestions concerning a method for precisely observing a transparent light waveguide core structure under a high-magnification optical microscope.
We would also like to thank Dr. Hidetaka Maeda, Sigma Koki Corporation, for his valuable advice and proposal concerning introducing laser power into the minute light waveguide core of the optical TAS chip used.
Finally, we would like to thank Dr. Tomofumi Ukai, Assistant Professor, Toyo University, for his valuable advice on introducing a resin particle dispersed sample into a microfluidic channel, and the treatment of fluorescence substance attached particles.
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Ohkubo, T., Terada, N. & Yoshida, Y. Fluorescence detection of minute particles using a resin-based optical total analysis system with a high-aspect-ratio light waveguide core. Microsyst Technol 21, 2611–2622 (2015). https://doi.org/10.1007/s00542-015-2505-8
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DOI: https://doi.org/10.1007/s00542-015-2505-8