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Patternable particle microarray utilizing controllable particle delivery

Patternable particle microarray utilizing controllable particle delivery In this study, we demonstrate an on-demand delivering and sequential arraying of single microparticles utilizing multiple pneumatic pressure-driven elastomer valves and a deterministic particle arraying mechanism. Two types of separate microfluidic devices are combined: (i) a particle transfer device and (ii) a particle arraying device, to construct a desired particle pattern. The elastomer valve integrated in the transfer device acts as a removable particle trap that enables the trapping and on-demand releasing of a particle depending on the application of the pneumatic pressure. The arraying device is composed of highly packed particle trapping sites to deterministically array incoming particles that are released and transferred from a transfer device. Repeating the “trapping-transfer-and-array” sequence can construct an array of different types of particles in a certain pattern. One-dimensional linear and two-dimensional planar microparticle-based patterns were demonstrated using bare and red-fluorescent microparticles. Keywords: Microfluidics, Microparticle, Pneumatic microvalve, Controllable particle delivery, Patterning Introduction Generally, different types of functionalized particles are Recently, particle-incorporated microfluidic platforms arrayed randomly to perform analyses; thus, the encod- have emerged as effective tools to conduct various anal - ing and decoding of individual particles must be per- yses in biological and chemical research fields [1–5]. formed for their identification and readout of the results When compared with flat substrates or supports, micro - after their reactions (i.e., mix-and-match). Although particles can serve as a mobile substrate and provide several strategies for particle encoding exist [12–14], multiple functionalities including huge analytical surface a high-resolution imaging system is typically required and the capability of effective mixing, sorting, and trans - to identify individual particles based on their encod- porting of molecules of interest [6]. For most cases in ing method. Meanwhile, a position-based signal readout these platforms, particles are trapped in an array format method facilitates an easy readout of the results such as within microchannel networks with embedded physical the wellplate-based enzyme-linked immunosorbent assay barrier structures (e.g., weirs or micropillars) or external (ELISA). Thus, the advantages of particle-based analysis active forces (e.g., electric forces). Depending on the tar- and position-based easy readout can be combined in an get applications, surfaces of particles can be functional- integrated system. ized (e.g., DNA or antibody conjugation). To construct Several studies have been carried out to generate spe- the particle array, the particles (i.e., array elements) are cific particle patterns using microfluidic platforms. A introduced from an off-chip environment and subse - 1-D microfluidic bead array was constructed by depos - quently arrayed within microfluidic devices [7–11]. iting particles one by one using vacuum tweezers [15, 16]. This approach can form a desired particle pattern in predefined channels, but is a cumbersome process. As an alternative approach, an additional microbead *Correspondence: joonwon@postech.ac.kr loading channel was integrated to deposit the func- Sanghyun Lee and Hojin Kim contributed equally to this work 1 tionalized microparticles into predetermined positions Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang, [17, 18]. This requires additional components and has Gyeongbuk 37673, South Korea limitation to enable a single particle level patterning. Full list of author information is available at the end of the article © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 2 of 6 Without using physical trap structures, dynamic parti- Braille numbers) using bare and red-fluorescent poly - cle patterning was demonstrated using standing surface styrene particles. acoustic waves (SSAWs) [19, 20]. However, complicated device fabrication and system setup are required. Materials and methods In this regard, we present a method to construct Device design and operation a particle array in a desired pattern (i.e., patternable To demonstrate on-demand single particle delivery and particle array) instead of a random pattern, to enable the sequential arraying of particles, two types of micro- a position-based easy readout using different types of fluidic devices are integrated: (i) a particle transfer device particles with a single-particle-level resolution. Our and (ii) a particle arraying device (Fig.  1a). The outlet of strategy combines two types of separate microflu - the transfer device and the inlet of the arraying device are idic devices that offer different functions: (i) a particle connected using a tube for particle transfer. The particle transfer device and (ii) a particle arraying device. Pneu- transfer device is composed of pneumatic pressure inlets, matic microvalve-based removable trap techniques and particle inlets, wastes, and an outlet. A pneumatic chan- deterministic particle arraying techniques are used in nel is used to operate the elastomeric pneumatic microv- the transfer and arraying devices, respectively. A trans- alve. The particle arraying device is composed of an inlet, fer device can selectively transfer the particles of inter- a particle arraying site, and an outlet. est; these can be patterned in the arraying device in a In the transfer device, particles are introduced through desired pattern. Many studies have demonstrated parti- the particle inlet and abundant particles are washed out cle manipulation (e.g., trapping, releasing, and pairing) toward waste. The particle transfer function can be ena - using pneumatic pressure-driven elastomer microv- bled by operating the elastomeric pneumatic microvalve alve structures [21–25]. Depending on the state of the that acts as a removable particle trap depending on the valve (i.e., either “on” or “off ”), particles can be either applied pneumatic pressure [25]. When a positive pneu- trapped or released. An arraying device can capture the matic pressure is applied through the pneumatic channel, introduced particles deterministically (i.e., from the a thin membrane (i.e., channel wall) is deflected and as a transfer device) based on flow fractionation [10, 26]. result, a narrowed branch pocket that can trap a single As a proof-of-concept of our method, we demonstrated particle is formed (Fig. 1c). The pillar structure can guide particle patterns of one-dimensional (1D) linear (e.g., the particles to migrate close to the channel wall; this “dot-dash” line) and two-dimensional (2D) planar (e.g., facilitates particle trapping [27]. Once a single particle Fig. 1 Device design and operation mechanism. a Schematic illustration of the particle transfer device and particle arraying device. b Sequential particle arraying mechanism. Incoming particles are sequentially arrayed at each vacant trap site based on flow fractionation. c Single particle trapping by pneumatic microvalve operation. Channel wall is deflected by applied pneumatic pressure and it can trap a single particle. d Once a single particle is trapped, subsequent particles bypass the trap and migrate toward the waste. e Trapped single particle can be released by removal of the applied pneumatic pressure Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 3 of 6 is trapped, subsequent particles will migrate toward the supply system to operate the elastomeric valve and infuse waste without any additional trapping (Fig.  1d). The particles and (ii) a negative pressure supply system to trapped particles can be released and transferred to facilitate particle transfer and arraying. A positive pres- the arraying device in an on-demand manner when the sure application system (connected with the pneumatic/ applied pneumatic pressure is removed (Fig. 1e). particle inlet of the transfer device) consists of a pressure The target particle can be transferred from the trans - pump (i.e., positive pressure generation), solenoid valves, fer device to the arraying device through the tube con- a pressure regulator, and a pressure monitor. A negative nection. Based on the flow fractionation at each vacant pressure application system (connected with the outlet trap sites (i.e., flow is distributed into main flow Q and of the arraying device) consists of a pressure pump (i.e., trapping flow Q ), the transferred particle is trapped negative pressure generation), pressure regulator, and deterministically at each vacant trap site (sequentially pressure monitor. Microscopic images were acquired from upstream to downstream) of the particle arraying using an inverted microscope (IX 73, Olympus) with device (Fig. 1b) [26]. By repeating the “trapping-transfer- a charge-coupled device (CCD) camera (DP80, Olym- and-array” sequence, we can construct the particle array pus). For fluorescence detection, a SOLA light engine in a controllable manner (i.e., patternable particle array). (SM 365, lumencor) and filter cube (U-FGWA, Olym - We can select specific particles to be transferred using pus) were used as the light source and fluorescence filter, different types of particle suspensions at different parti - respectively. cle inlets. The numbers of particle inlets and pneumatic pressure inlets can be varied based on the types of parti- Results and discussion cles that are arrayed. 1D linear patterning of particles On-demand single particle release and delivery was dem- Device fabrication onstrated with elastomeric microvalve operation. The Both microfluidic devices were fabricated using polydi - valve deflection state (i.e., ON or OFF) can be controlled methylsiloxane (PDMS) (Sylgard 184, Dow Corning Inc.) using the applied pneumatic pressure and solenoid valve by standard soft lithography [28]. Negative tone photore- operation (Fig.  2a). When the valve state is “ON” (i.e., sist (KMPR 1025, MicroChem, Inc.) was used to prepare the wall of the valve is deflected under the application of the master molds. It was deposited onto two four-inch pneumatic pressure), a single particle can be trapped at silicon wafers with the same thickness (32  µm) by spin the narrow channel created by valve deflection (Fig.  2b). coating and soft baking (100  °C for 15  min). Ultraviolet The average diameter of the particle used in this test was (UV) exposure through a photomask and post-exposure approximately 25  μm. Particle suspensions were intro- baking (100 °C for 3 min) and development (SU-8 devel- duced into the particle transfer chip under a pneumatic oper, MicroChem, Inc.) were proceeded to define the pressure of 5  kPa. To trap a single particle, we applied a patterns. pneumatic pressure of 200  kPa to deflect the wall of the Two different PDMS prepolymer mixtures (i.e., differ - microvalve. After particle trapping, subsequent particles ent PDMS monomer base to crosslinker ratio) were used passed the valve and migrated toward the waste chan- to prepare PDMS replicas using the master molds: (i) 12:1 nel owing to a sudden increase in hydraulic resistance of w/w ratio mixture for the particle transfer device and (ii) the channel through the microvalve. When the applied a 10:1 w/w ratio mixture for the particle arraying device. pneumatic pressure was removed by triggering a solenoid Regardless of the PDMS mixture ratio, PDMS replicas valve (switching time of 100 ms) in an on-demand man- were prepared by the same procedure. The PDMS mix - ner, the trapped single particle was selectively released ture was poured onto the master mold and degassed; this and migrated to the outlet of the transfer device (Fig. 2c). was then thermally cured at 100 °C for 20 min. The cured This particle was subsequently transferred to the parti - PDMS replica was peeled off from the master mold and cle arraying device under an applied vacuum pressure of holes were punched using a disposable biopsy punch. The − 15 kPa at the outlet of the arraying device. holes were rinsed with isopropanol. The PDMS replica 1D linear particle patterning was demonstrated and glass substrate were irreversibly bonded by contact using two types of particles: (i) bare polystyrene beads after air plasma treatment (CUTE-MP, FemtoScience). (mean diameter ≈ 25  μm; SD: ± 0.21  μm, Sigma- The prepared devices were stored at room temperature Aldrich), (ii) red-fluorescent polystyrene beads (mean for 24 h for a reliable device operation. diameter ≈ 25  μm; SD: ± 0.20  μm, excitation/emis- sion = 530/607  nm, microParticles). Concentrations of Experimental setup particle suspensions were set to 10,000  particles/mL for For system operation, separate custom-built pneumatic both particle types. By repeating the “trapping-trans- pressure supply systems are used: (i) positive pressure fer-and-array” sequence (i.e., one time red-fluorescent Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 4 of 6 Fig. 2 On-demand particle transfer utilizing pneumatic valve operation. a Depending on the applied pneumatic pressure, the valve wall is either deflected (“ON” state) or not (“OFF” state). These two states are switchable by controlling the integrated solenoid valve. b Particle trapping. Single particle is trapped at the narrow channel created by valve deflection. c Particle releasing. Removing the pneumatic pressure allows the trapped particle to be released and transferred in an on-demand manner particle and two times bare particles) using individual in the particle arraying device are described in Additional solenoid valve triggering, we can construct a line pattern, file 1: S1. as shown in Fig.  3a. The fluorescence image reveals that the particle line pattern is constructed as a “dot-dash” Conclusion line (Fig. 3b). In this study, we demonstrated a patternable particle microarray by trapping, releasing, transferring, and sequentially arraying two types of particles. A parti- 2D planar patterning of particles cle transfer device and a particle arraying device were The multiple row patterning of 1D particle lines can yield combined to construct desired particle patterns. In 2D planar particle patterns. Selective and on-demand the particle trapping device, the integration of a pneu- particle transfer and sequential arraying of particles were matic pressure-driven elastomer microvalve enabled used similar to the 1D linear particle patterning method single-particle trapping and selective, on-demand described above. Inspired by Braille patterns (Fig.  4a), releasing of particles of interest. The released parti - which are used by the visually impaired, we constructed cle was transferred to the arraying device and subse- 2D particle patterns to display Braille numbers using con- quently trapped at vacant sites sequentially from the trollable transfer and arraying of bare and red-fluorescent upstream direction. 1D linear (e.g., “dot-dash” line) particles (Fig.  4b). Fluorescence detection revealed that and 2D planar (e.g., Braille numbers) particle patterns several Braille number patterns (1, 2, 3, 4, and 5) were were constructed in a controllable manner by repeat- displayed by the proper combination of particles (Fig. 4c). ing the “trapping-transfer-and-array” sequence. Even Schematic of generating Braille-inspired particle patterns though we demonstrated particle patterns using two Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 5 of 6 Fig. 3 1D linear pattern using two types of particles by repeating the “trapping-transfer-and-array” sequence. a Bright-field microscopic image of arrayed particles. Bare (indicated with black arrows) and red-fluorescent particles (indicated with red arrows) are deterministically trapped in an arraying device. b Fluorescent image revealing the linear pattern of the “dot-dash” line Fig. 4 2D planar pattern using two types of particles. a Braille representation of numbers from 0 to 9. b Bright-field microscopic image of arrayed particles composed of the combination of bare and red-fluorescent particles. c Fluorescent image revealing the planar pattern that displays the Braille numbers 1, 2, 3, 4, and 5 types of particles (i.e., bare and red-fluorescent parti - protein-conjugated particles) can facilitate a pattern- cles), more complex particle patterns can be achieved based easy-readout multiplex immunoassay platform. with different types (e.g., > three types) of particles by operating additional particle inlets. The programmable operation of multiple pneumatic valves can facilitate the construction of desired particle patterns composed Additional file of different types of particles. We believe that the par - ticle patterning technique presented herein has poten- Additional file 1. Additional information is available about schematics of generating Braille-inspired patterns. tial for various applications such as microarrays, drug screening, and cellular studies. Furthermore, proper integration of functionalized particles (e.g., DNA or Acknowledgements Not applicable. Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 6 of 6 Authors’ contributions 11. Teshima T, Ishihara H, Iwai K, Adachi A, Takeuchi S (2010) A dynamic SL and HK performed the experiments, analyzed the data and wrote the microarray device for paired bead-based analysis. Lab Chip 10:2443–2448 manuscript. WL carried out device fabrication. JK supervised the research and 12. Burger R, Reith P, Kijanka G, Akujobi V, Abgrall P, Ducrée J (2012) Array- reviewed the manuscript. All authors read and approved the final manuscript. based capture, distribution, counting and multiplexed assaying of beads on a centrifugal microfluidic platform. Lab on a Chip 12:1289–1295 Funding 13. Lee H, Kim J, Kim H, Kim J, Kwon S (2010) Colour-barcoded magnetic This research was supported by Basic Science Research Program through the microparticles for multiplexed bioassays. Nat Mater 9:745 National Research Foundation of Korea (NRF) funded by the Ministry of Sci- 14. Appleyard DC, Chapin SC, Srinivas RL, Doyle PS (2011) Bar-coded hydro- ence and ICT (No. NRF-2017R1A2B4003328). gel microparticles for protein detection: synthesis, assay and scanning. Nat Protoc 6:1761 Availability of data and materials 15. Zhang H, Yang X, Wang K, Tan W, Li H, Zuo X, Wen J (2008) On-chip The datasets supporting the conclusions of this article are included within the oligonucleotide ligation assay using one-dimensional microfluidic beads article and its additional file. array for the detection of low-abundant DNA point mutations. Biosens Bioelectron 23:945–951 Competing interests 16. Zhou L et al (2006) Quantitative intracellular molecular profiling using a The authors declare that they have no competing interests. one-dimensional flow system. Anal Chem 78:6246–6251 17. Zhang H, Fu X, Liu L, Zhu Z, Yang K (2012) Microfluidic bead-based Author details enzymatic primer extension for single-nucleotide discrimination using Department of Mechanical Engineering, Pohang University of Science quantum dots as labels. Anal Biochem 426:30–39 and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeong- 18. Zhang H, Liu L, Fu X, Zhu Z (2013) Microfluidic beads-based immunosen- buk 37673, South Korea. BioMEMS Lab, RadianQbio, 53 Gasan digital 2-ro, sor for sensitive detection of cancer biomarker proteins using multi- Geumcheon-gu, Seoul 08588, South Korea. enzyme-nanoparticle amplification and quantum dotslabels. Biosens Bioelectron 42:23–30 Received: 20 May 2019 Accepted: 18 July 2019 19. Shi J, Ahmed D, Mao X, Lin S-CS, Lawit A, Huang TJ (2009) Acoustic twee- zers: patterning cells and microparticles using standing surface acoustic waves (SSAW ). Lab on a Chip 9:2890–2895 20. Ding X, Shi J, Lin S-CS, Yazdi S, Kiraly B, Huang TJ (2012) Tunable pattern- ing of microparticles and cells using standing surface acoustic waves. Lab Chip 12:2491–2497 References 21. Tonooka T, Teshima T, Takeuchi S (2013) Clustering triple microbeads 1. Birtwell S, Morgan H (2009) Microparticle encoding technologies for in a dynamic microarray for timing-controllable bead-based reactions. high-throughput multiplexed suspension assays. Integr Biol 1:345–362 Microfluidics Nanofluidics 14:1039–1048 2. Liu L, Wu S, Jing F, Zhou H, Jia C, Li G, Cong H, Jin Q, Zhao J (2016) 22. Ma C et al (2011) A clinical microchip for evaluation of single immune Bead-based microarray immunoassay for lung cancer biomarkers using cells reveals high functional heterogeneity in phenotypically similar T quantum dots as labels. Biosens Bioelectron 80:300–306 cells. Nat Med 17:738 3. Kim H, Lee S, Lee W, Kim J (2017) High-density microfluidic particle-clus- 23. Kim HS, Devarenne TP, Han A (2015) A high-throughput microfluidic ter-array device for parallel and dynamic study of interaction between single-cell screening platform capable of selective cell extraction. Lab engineered particles. Adv Mater 29:1701351 Chip 15:2467–2475 4. Han SW, Jang E, Koh W-G (2015) Microfluidic-based multiplex immunoas- 24. Kim H, Kim J (2014) A microfluidic-based dynamic microarray system with say system integrated with an array of QD-encoded microbeads. Sens single-layer pneumatic valves for immobilization and selective retrieval of Actuators B Chem 209:242–251 single microbeads. Microfluidics Nanofluidics 16:623–633 5. Hung L-Y, Huang T-B, Tsai Y-C, Yeh C-S, Lei H-Y, Lee G-B (2013) A micro- 25. Kim H, Lee S, Kim J (2012) Hydrodynamic trap-and-release of single fluidic immunomagnetic bead-based system for the rapid detection of particles using dual-function elastomeric valves: design, fabrication, and influenza infections: from purified virus particles to clinical specimens. characterization. Microfluidics Nanofluidics 13:835–844 Biomed Microdevice 15:539–551 26. Sochol RD, Dueck ME, Li S, Lee LP, Lin L (2012) Hydrodynamic reset- 6. Derveaux S, Stubbe B, Braeckmans K, Roelant C, Sato K, Demeester J, De tability for a microfluidic particulate-based arraying system. Lab Chip Smedt S (2008) Synergism between particle-based multiplexing and 12:5051–5056 microfluidics technologies may bring diagnostics closer to the patient. 27. Iwai K, Tan W-H, Ishihara H, Takeuchi S (2011) A resettable dynamic micro- Anal Bioanal Chem 391:2453 array device. Biomed Microdev 13:1089–1094 7. Carlo DD, Wu LY, Lee LP (2006) Dynamic single cell culture array. Lab Chip 28. Xia Y, Whitesides GM (1998) Soft lithography. Angewandte Chem Int Edn 6:1445–1449 37:550–575 8. Jung Y, Hyun J-C, Choi J, Atajanov A, Yang S (2017) Manipulation of cells’ position across a microfluidic channel using a series of continuously vary- ing herringbone structures. Micro Nano Syst Lett 5:6 Publisher’s Note 9. Tan W-H, Takeuchi S (2007) A trap-and-release integrated microflu- Springer Nature remains neutral with regard to jurisdictional claims in pub- idic system for dynamic microarray applications. Proc Natl Acad Sci lished maps and institutional affiliations. 104:1146–1151 10. Chung K, Rivet CA, Kemp ML, Lu H (2011) Imaging single-cell signaling dynamics with a deterministic high-density single-cell trap array. 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Patternable particle microarray utilizing controllable particle delivery

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Springer Journals
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Copyright © 2019 by The Author(s)
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Engineering; Circuits and Systems; Electrical Engineering; Mechanical Engineering; Nanotechnology; Applied and Technical Physics
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Abstract

In this study, we demonstrate an on-demand delivering and sequential arraying of single microparticles utilizing multiple pneumatic pressure-driven elastomer valves and a deterministic particle arraying mechanism. Two types of separate microfluidic devices are combined: (i) a particle transfer device and (ii) a particle arraying device, to construct a desired particle pattern. The elastomer valve integrated in the transfer device acts as a removable particle trap that enables the trapping and on-demand releasing of a particle depending on the application of the pneumatic pressure. The arraying device is composed of highly packed particle trapping sites to deterministically array incoming particles that are released and transferred from a transfer device. Repeating the “trapping-transfer-and-array” sequence can construct an array of different types of particles in a certain pattern. One-dimensional linear and two-dimensional planar microparticle-based patterns were demonstrated using bare and red-fluorescent microparticles. Keywords: Microfluidics, Microparticle, Pneumatic microvalve, Controllable particle delivery, Patterning Introduction Generally, different types of functionalized particles are Recently, particle-incorporated microfluidic platforms arrayed randomly to perform analyses; thus, the encod- have emerged as effective tools to conduct various anal - ing and decoding of individual particles must be per- yses in biological and chemical research fields [1–5]. formed for their identification and readout of the results When compared with flat substrates or supports, micro - after their reactions (i.e., mix-and-match). Although particles can serve as a mobile substrate and provide several strategies for particle encoding exist [12–14], multiple functionalities including huge analytical surface a high-resolution imaging system is typically required and the capability of effective mixing, sorting, and trans - to identify individual particles based on their encod- porting of molecules of interest [6]. For most cases in ing method. Meanwhile, a position-based signal readout these platforms, particles are trapped in an array format method facilitates an easy readout of the results such as within microchannel networks with embedded physical the wellplate-based enzyme-linked immunosorbent assay barrier structures (e.g., weirs or micropillars) or external (ELISA). Thus, the advantages of particle-based analysis active forces (e.g., electric forces). Depending on the tar- and position-based easy readout can be combined in an get applications, surfaces of particles can be functional- integrated system. ized (e.g., DNA or antibody conjugation). To construct Several studies have been carried out to generate spe- the particle array, the particles (i.e., array elements) are cific particle patterns using microfluidic platforms. A introduced from an off-chip environment and subse - 1-D microfluidic bead array was constructed by depos - quently arrayed within microfluidic devices [7–11]. iting particles one by one using vacuum tweezers [15, 16]. This approach can form a desired particle pattern in predefined channels, but is a cumbersome process. As an alternative approach, an additional microbead *Correspondence: joonwon@postech.ac.kr loading channel was integrated to deposit the func- Sanghyun Lee and Hojin Kim contributed equally to this work 1 tionalized microparticles into predetermined positions Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang, [17, 18]. This requires additional components and has Gyeongbuk 37673, South Korea limitation to enable a single particle level patterning. Full list of author information is available at the end of the article © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 2 of 6 Without using physical trap structures, dynamic parti- Braille numbers) using bare and red-fluorescent poly - cle patterning was demonstrated using standing surface styrene particles. acoustic waves (SSAWs) [19, 20]. However, complicated device fabrication and system setup are required. Materials and methods In this regard, we present a method to construct Device design and operation a particle array in a desired pattern (i.e., patternable To demonstrate on-demand single particle delivery and particle array) instead of a random pattern, to enable the sequential arraying of particles, two types of micro- a position-based easy readout using different types of fluidic devices are integrated: (i) a particle transfer device particles with a single-particle-level resolution. Our and (ii) a particle arraying device (Fig.  1a). The outlet of strategy combines two types of separate microflu - the transfer device and the inlet of the arraying device are idic devices that offer different functions: (i) a particle connected using a tube for particle transfer. The particle transfer device and (ii) a particle arraying device. Pneu- transfer device is composed of pneumatic pressure inlets, matic microvalve-based removable trap techniques and particle inlets, wastes, and an outlet. A pneumatic chan- deterministic particle arraying techniques are used in nel is used to operate the elastomeric pneumatic microv- the transfer and arraying devices, respectively. A trans- alve. The particle arraying device is composed of an inlet, fer device can selectively transfer the particles of inter- a particle arraying site, and an outlet. est; these can be patterned in the arraying device in a In the transfer device, particles are introduced through desired pattern. Many studies have demonstrated parti- the particle inlet and abundant particles are washed out cle manipulation (e.g., trapping, releasing, and pairing) toward waste. The particle transfer function can be ena - using pneumatic pressure-driven elastomer microv- bled by operating the elastomeric pneumatic microvalve alve structures [21–25]. Depending on the state of the that acts as a removable particle trap depending on the valve (i.e., either “on” or “off ”), particles can be either applied pneumatic pressure [25]. When a positive pneu- trapped or released. An arraying device can capture the matic pressure is applied through the pneumatic channel, introduced particles deterministically (i.e., from the a thin membrane (i.e., channel wall) is deflected and as a transfer device) based on flow fractionation [10, 26]. result, a narrowed branch pocket that can trap a single As a proof-of-concept of our method, we demonstrated particle is formed (Fig. 1c). The pillar structure can guide particle patterns of one-dimensional (1D) linear (e.g., the particles to migrate close to the channel wall; this “dot-dash” line) and two-dimensional (2D) planar (e.g., facilitates particle trapping [27]. Once a single particle Fig. 1 Device design and operation mechanism. a Schematic illustration of the particle transfer device and particle arraying device. b Sequential particle arraying mechanism. Incoming particles are sequentially arrayed at each vacant trap site based on flow fractionation. c Single particle trapping by pneumatic microvalve operation. Channel wall is deflected by applied pneumatic pressure and it can trap a single particle. d Once a single particle is trapped, subsequent particles bypass the trap and migrate toward the waste. e Trapped single particle can be released by removal of the applied pneumatic pressure Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 3 of 6 is trapped, subsequent particles will migrate toward the supply system to operate the elastomeric valve and infuse waste without any additional trapping (Fig.  1d). The particles and (ii) a negative pressure supply system to trapped particles can be released and transferred to facilitate particle transfer and arraying. A positive pres- the arraying device in an on-demand manner when the sure application system (connected with the pneumatic/ applied pneumatic pressure is removed (Fig. 1e). particle inlet of the transfer device) consists of a pressure The target particle can be transferred from the trans - pump (i.e., positive pressure generation), solenoid valves, fer device to the arraying device through the tube con- a pressure regulator, and a pressure monitor. A negative nection. Based on the flow fractionation at each vacant pressure application system (connected with the outlet trap sites (i.e., flow is distributed into main flow Q and of the arraying device) consists of a pressure pump (i.e., trapping flow Q ), the transferred particle is trapped negative pressure generation), pressure regulator, and deterministically at each vacant trap site (sequentially pressure monitor. Microscopic images were acquired from upstream to downstream) of the particle arraying using an inverted microscope (IX 73, Olympus) with device (Fig. 1b) [26]. By repeating the “trapping-transfer- a charge-coupled device (CCD) camera (DP80, Olym- and-array” sequence, we can construct the particle array pus). For fluorescence detection, a SOLA light engine in a controllable manner (i.e., patternable particle array). (SM 365, lumencor) and filter cube (U-FGWA, Olym - We can select specific particles to be transferred using pus) were used as the light source and fluorescence filter, different types of particle suspensions at different parti - respectively. cle inlets. The numbers of particle inlets and pneumatic pressure inlets can be varied based on the types of parti- Results and discussion cles that are arrayed. 1D linear patterning of particles On-demand single particle release and delivery was dem- Device fabrication onstrated with elastomeric microvalve operation. The Both microfluidic devices were fabricated using polydi - valve deflection state (i.e., ON or OFF) can be controlled methylsiloxane (PDMS) (Sylgard 184, Dow Corning Inc.) using the applied pneumatic pressure and solenoid valve by standard soft lithography [28]. Negative tone photore- operation (Fig.  2a). When the valve state is “ON” (i.e., sist (KMPR 1025, MicroChem, Inc.) was used to prepare the wall of the valve is deflected under the application of the master molds. It was deposited onto two four-inch pneumatic pressure), a single particle can be trapped at silicon wafers with the same thickness (32  µm) by spin the narrow channel created by valve deflection (Fig.  2b). coating and soft baking (100  °C for 15  min). Ultraviolet The average diameter of the particle used in this test was (UV) exposure through a photomask and post-exposure approximately 25  μm. Particle suspensions were intro- baking (100 °C for 3 min) and development (SU-8 devel- duced into the particle transfer chip under a pneumatic oper, MicroChem, Inc.) were proceeded to define the pressure of 5  kPa. To trap a single particle, we applied a patterns. pneumatic pressure of 200  kPa to deflect the wall of the Two different PDMS prepolymer mixtures (i.e., differ - microvalve. After particle trapping, subsequent particles ent PDMS monomer base to crosslinker ratio) were used passed the valve and migrated toward the waste chan- to prepare PDMS replicas using the master molds: (i) 12:1 nel owing to a sudden increase in hydraulic resistance of w/w ratio mixture for the particle transfer device and (ii) the channel through the microvalve. When the applied a 10:1 w/w ratio mixture for the particle arraying device. pneumatic pressure was removed by triggering a solenoid Regardless of the PDMS mixture ratio, PDMS replicas valve (switching time of 100 ms) in an on-demand man- were prepared by the same procedure. The PDMS mix - ner, the trapped single particle was selectively released ture was poured onto the master mold and degassed; this and migrated to the outlet of the transfer device (Fig. 2c). was then thermally cured at 100 °C for 20 min. The cured This particle was subsequently transferred to the parti - PDMS replica was peeled off from the master mold and cle arraying device under an applied vacuum pressure of holes were punched using a disposable biopsy punch. The − 15 kPa at the outlet of the arraying device. holes were rinsed with isopropanol. The PDMS replica 1D linear particle patterning was demonstrated and glass substrate were irreversibly bonded by contact using two types of particles: (i) bare polystyrene beads after air plasma treatment (CUTE-MP, FemtoScience). (mean diameter ≈ 25  μm; SD: ± 0.21  μm, Sigma- The prepared devices were stored at room temperature Aldrich), (ii) red-fluorescent polystyrene beads (mean for 24 h for a reliable device operation. diameter ≈ 25  μm; SD: ± 0.20  μm, excitation/emis- sion = 530/607  nm, microParticles). Concentrations of Experimental setup particle suspensions were set to 10,000  particles/mL for For system operation, separate custom-built pneumatic both particle types. By repeating the “trapping-trans- pressure supply systems are used: (i) positive pressure fer-and-array” sequence (i.e., one time red-fluorescent Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 4 of 6 Fig. 2 On-demand particle transfer utilizing pneumatic valve operation. a Depending on the applied pneumatic pressure, the valve wall is either deflected (“ON” state) or not (“OFF” state). These two states are switchable by controlling the integrated solenoid valve. b Particle trapping. Single particle is trapped at the narrow channel created by valve deflection. c Particle releasing. Removing the pneumatic pressure allows the trapped particle to be released and transferred in an on-demand manner particle and two times bare particles) using individual in the particle arraying device are described in Additional solenoid valve triggering, we can construct a line pattern, file 1: S1. as shown in Fig.  3a. The fluorescence image reveals that the particle line pattern is constructed as a “dot-dash” Conclusion line (Fig. 3b). In this study, we demonstrated a patternable particle microarray by trapping, releasing, transferring, and sequentially arraying two types of particles. A parti- 2D planar patterning of particles cle transfer device and a particle arraying device were The multiple row patterning of 1D particle lines can yield combined to construct desired particle patterns. In 2D planar particle patterns. Selective and on-demand the particle trapping device, the integration of a pneu- particle transfer and sequential arraying of particles were matic pressure-driven elastomer microvalve enabled used similar to the 1D linear particle patterning method single-particle trapping and selective, on-demand described above. Inspired by Braille patterns (Fig.  4a), releasing of particles of interest. The released parti - which are used by the visually impaired, we constructed cle was transferred to the arraying device and subse- 2D particle patterns to display Braille numbers using con- quently trapped at vacant sites sequentially from the trollable transfer and arraying of bare and red-fluorescent upstream direction. 1D linear (e.g., “dot-dash” line) particles (Fig.  4b). Fluorescence detection revealed that and 2D planar (e.g., Braille numbers) particle patterns several Braille number patterns (1, 2, 3, 4, and 5) were were constructed in a controllable manner by repeat- displayed by the proper combination of particles (Fig. 4c). ing the “trapping-transfer-and-array” sequence. Even Schematic of generating Braille-inspired particle patterns though we demonstrated particle patterns using two Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 5 of 6 Fig. 3 1D linear pattern using two types of particles by repeating the “trapping-transfer-and-array” sequence. a Bright-field microscopic image of arrayed particles. Bare (indicated with black arrows) and red-fluorescent particles (indicated with red arrows) are deterministically trapped in an arraying device. b Fluorescent image revealing the linear pattern of the “dot-dash” line Fig. 4 2D planar pattern using two types of particles. a Braille representation of numbers from 0 to 9. b Bright-field microscopic image of arrayed particles composed of the combination of bare and red-fluorescent particles. c Fluorescent image revealing the planar pattern that displays the Braille numbers 1, 2, 3, 4, and 5 types of particles (i.e., bare and red-fluorescent parti - protein-conjugated particles) can facilitate a pattern- cles), more complex particle patterns can be achieved based easy-readout multiplex immunoassay platform. with different types (e.g., > three types) of particles by operating additional particle inlets. The programmable operation of multiple pneumatic valves can facilitate the construction of desired particle patterns composed Additional file of different types of particles. We believe that the par - ticle patterning technique presented herein has poten- Additional file 1. Additional information is available about schematics of generating Braille-inspired patterns. tial for various applications such as microarrays, drug screening, and cellular studies. Furthermore, proper integration of functionalized particles (e.g., DNA or Acknowledgements Not applicable. Lee et al. Micro and Nano Syst Lett (2019) 7:10 Page 6 of 6 Authors’ contributions 11. Teshima T, Ishihara H, Iwai K, Adachi A, Takeuchi S (2010) A dynamic SL and HK performed the experiments, analyzed the data and wrote the microarray device for paired bead-based analysis. Lab Chip 10:2443–2448 manuscript. WL carried out device fabrication. JK supervised the research and 12. Burger R, Reith P, Kijanka G, Akujobi V, Abgrall P, Ducrée J (2012) Array- reviewed the manuscript. All authors read and approved the final manuscript. based capture, distribution, counting and multiplexed assaying of beads on a centrifugal microfluidic platform. Lab on a Chip 12:1289–1295 Funding 13. Lee H, Kim J, Kim H, Kim J, Kwon S (2010) Colour-barcoded magnetic This research was supported by Basic Science Research Program through the microparticles for multiplexed bioassays. Nat Mater 9:745 National Research Foundation of Korea (NRF) funded by the Ministry of Sci- 14. Appleyard DC, Chapin SC, Srinivas RL, Doyle PS (2011) Bar-coded hydro- ence and ICT (No. NRF-2017R1A2B4003328). gel microparticles for protein detection: synthesis, assay and scanning. Nat Protoc 6:1761 Availability of data and materials 15. Zhang H, Yang X, Wang K, Tan W, Li H, Zuo X, Wen J (2008) On-chip The datasets supporting the conclusions of this article are included within the oligonucleotide ligation assay using one-dimensional microfluidic beads article and its additional file. array for the detection of low-abundant DNA point mutations. Biosens Bioelectron 23:945–951 Competing interests 16. Zhou L et al (2006) Quantitative intracellular molecular profiling using a The authors declare that they have no competing interests. one-dimensional flow system. Anal Chem 78:6246–6251 17. Zhang H, Fu X, Liu L, Zhu Z, Yang K (2012) Microfluidic bead-based Author details enzymatic primer extension for single-nucleotide discrimination using Department of Mechanical Engineering, Pohang University of Science quantum dots as labels. Anal Biochem 426:30–39 and Technology (POSTECH), 77 Cheongam-Ro, Nam-Gu, Pohang, Gyeong- 18. Zhang H, Liu L, Fu X, Zhu Z (2013) Microfluidic beads-based immunosen- buk 37673, South Korea. BioMEMS Lab, RadianQbio, 53 Gasan digital 2-ro, sor for sensitive detection of cancer biomarker proteins using multi- Geumcheon-gu, Seoul 08588, South Korea. enzyme-nanoparticle amplification and quantum dotslabels. Biosens Bioelectron 42:23–30 Received: 20 May 2019 Accepted: 18 July 2019 19. Shi J, Ahmed D, Mao X, Lin S-CS, Lawit A, Huang TJ (2009) Acoustic twee- zers: patterning cells and microparticles using standing surface acoustic waves (SSAW ). Lab on a Chip 9:2890–2895 20. Ding X, Shi J, Lin S-CS, Yazdi S, Kiraly B, Huang TJ (2012) Tunable pattern- ing of microparticles and cells using standing surface acoustic waves. Lab Chip 12:2491–2497 References 21. Tonooka T, Teshima T, Takeuchi S (2013) Clustering triple microbeads 1. Birtwell S, Morgan H (2009) Microparticle encoding technologies for in a dynamic microarray for timing-controllable bead-based reactions. high-throughput multiplexed suspension assays. Integr Biol 1:345–362 Microfluidics Nanofluidics 14:1039–1048 2. Liu L, Wu S, Jing F, Zhou H, Jia C, Li G, Cong H, Jin Q, Zhao J (2016) 22. Ma C et al (2011) A clinical microchip for evaluation of single immune Bead-based microarray immunoassay for lung cancer biomarkers using cells reveals high functional heterogeneity in phenotypically similar T quantum dots as labels. Biosens Bioelectron 80:300–306 cells. Nat Med 17:738 3. Kim H, Lee S, Lee W, Kim J (2017) High-density microfluidic particle-clus- 23. Kim HS, Devarenne TP, Han A (2015) A high-throughput microfluidic ter-array device for parallel and dynamic study of interaction between single-cell screening platform capable of selective cell extraction. Lab engineered particles. Adv Mater 29:1701351 Chip 15:2467–2475 4. Han SW, Jang E, Koh W-G (2015) Microfluidic-based multiplex immunoas- 24. Kim H, Kim J (2014) A microfluidic-based dynamic microarray system with say system integrated with an array of QD-encoded microbeads. Sens single-layer pneumatic valves for immobilization and selective retrieval of Actuators B Chem 209:242–251 single microbeads. Microfluidics Nanofluidics 16:623–633 5. Hung L-Y, Huang T-B, Tsai Y-C, Yeh C-S, Lei H-Y, Lee G-B (2013) A micro- 25. Kim H, Lee S, Kim J (2012) Hydrodynamic trap-and-release of single fluidic immunomagnetic bead-based system for the rapid detection of particles using dual-function elastomeric valves: design, fabrication, and influenza infections: from purified virus particles to clinical specimens. characterization. Microfluidics Nanofluidics 13:835–844 Biomed Microdevice 15:539–551 26. Sochol RD, Dueck ME, Li S, Lee LP, Lin L (2012) Hydrodynamic reset- 6. Derveaux S, Stubbe B, Braeckmans K, Roelant C, Sato K, Demeester J, De tability for a microfluidic particulate-based arraying system. Lab Chip Smedt S (2008) Synergism between particle-based multiplexing and 12:5051–5056 microfluidics technologies may bring diagnostics closer to the patient. 27. Iwai K, Tan W-H, Ishihara H, Takeuchi S (2011) A resettable dynamic micro- Anal Bioanal Chem 391:2453 array device. Biomed Microdev 13:1089–1094 7. Carlo DD, Wu LY, Lee LP (2006) Dynamic single cell culture array. Lab Chip 28. Xia Y, Whitesides GM (1998) Soft lithography. Angewandte Chem Int Edn 6:1445–1449 37:550–575 8. Jung Y, Hyun J-C, Choi J, Atajanov A, Yang S (2017) Manipulation of cells’ position across a microfluidic channel using a series of continuously vary- ing herringbone structures. Micro Nano Syst Lett 5:6 Publisher’s Note 9. Tan W-H, Takeuchi S (2007) A trap-and-release integrated microflu- Springer Nature remains neutral with regard to jurisdictional claims in pub- idic system for dynamic microarray applications. Proc Natl Acad Sci lished maps and institutional affiliations. 104:1146–1151 10. Chung K, Rivet CA, Kemp ML, Lu H (2011) Imaging single-cell signaling dynamics with a deterministic high-density single-cell trap array. Anal Chem 83:7044–7052

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Micro and Nano Systems Letters – Springer Journals

Published: Jul 23, 2019

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