Microfabrication Process for High-density Micro Pipette Array and ...
Microfabrication Process for High-density Micro Pipette Array and Matching Multi-Well Plate with Mixers Kee Suk Ryu*, Zhifang Fan, Chang Liu University of Illinois, 208 North Wright Street, Urbana, IL 61801 (* Email: [email protected]) Summary In this paper, we present an efficient and robust microfabrication process for realizing high-density micropipette arrays, as a fluid interface to integrated lab-on-achip. The developed fabrication process is simple and high yield over existing methods [1,2]. We have also developed micro multi-well plate that spatially matches the micropipette array. Magnetic micro-stir-bar mixers are integrated with each well reactor. The resultant high-density micro-well/micro-pipette instrument can function as a high throughput platform for combinatorial chemistry analysis. Keywords: Lab-on-a-chip, micropipette 1. Introduction Combinatorial chemical analysis for applications such as drug discovery may involve parallel chemical analysis involving hundreds to tens of thousands of candidate organic chemical compounds. Automated platforms for combinatorial analysis would invariably utilize two-dimensional pipette arrays and matching multi-well plates. A Figure 1: Schematic diagram of a high-density micro micromachined high-density micro pipette array with matching micro well plate. Each pipette/multi-well platform would allow well contains at least one active mixer. higher density of pipette/well over existing standard formats and potentially increase the speed of combinatorial analysis. A schematic diagram is shown in Figure 1. 2. Micropipette Array Fabrication A new process for realizing the micropipette array has been proposed and developed (Fig. 2). Starting with a silicon wafer, we first perform anisotropic etching (such as deep reactive ion etching) from one or both sides of the silicon wafer. Silicon dioxide is then grown thermally. The oxide film is highly conformal and can grow uniformly even if the sizes of the anisotropically-etched openings are small. The silicon oxide on the front side is selectively removed by using mechanical polishing with the cavities temporarily filled with wax (to prevent polishing damages to the interior). Subsequently, we selectively remove silicon from the front side to a desired depth,
revealing silicon oxide tubes with the shell thickness of approximately 1.2 µm. This process is simple and offers high yield (Fig. 3 and 4). Each step of the process flow features high material selectivity and hence robustness in terms of process control. Furthermore, only one layer of thin film growth is needed. One existing method [3] uses LPCVD silicon nitride in conjunction with thermally grown silicon oxide. It involves significantly more materials and process steps. This new method would provide much reduced time and costs. 3. Multi-Well Plate with Mixers Matching micro-well plate can be fabricated by using reactive ion etching method to pattern through-wafer holes in silicon. The volume of a well with height of h (in mm) and diameter of d (in mm) is ( πD 2 h / 4 ) µl. (The dimensions of well are dependant on the sensitivity of assay and accordingly the minimal amount of required fluids). Alternatively, the well plate may be formed by plastic machining. Due to the small volume of the wells, diffusion-based mixing may need to be augmented by active mixing. We developed a process to form micro wells with dedicated mixers (Fig. 5, 6) by bonding a multi-well plate with another substrate containing an array of magnetic micro stir-bar mixer, demonstrated earlier [4]. The mixers are micro magnetic stir bars operated by using a global, external magnetic field. No individual powering is needed.
Figure 2: Schematic diagram of major microfabrication process steps for realizing a micropipette array made in silicon substrate. High selectively is realized in each step.
Figure 3: SEM micrograph of an array of micropipettes. Distance between pipette openings is 60 µm in this picture.
4. Conclusions In this paper, a novel method to fabricate micropipette array has been presented. The method is simple and requires fewer steps in processing compared to existing methods. The silicon dioxide, which forms the pipette array, is not reactive to most
Figure 4: Close-up of one micropipette. The shell of the vertical tube is made of thermally grown silicon dioxide. It can be strengthened further by conformal deposition of materials, if necessary.
Figure 5: SEM micrograph (top view) of an array of prototype micro wells each with a magnetic micro stir-bar mixer at the bottom.
candidate chemicals, thus eliminating the needs to select materials based on their specific use. Acknowledgements
This work is supported by the Defense University Research initiative in Nanotechnology program (NAVY CL 2468 ANTIC), the Nano Science and Engineering Center (NSEC), and initiative of NSF under NSF award number EEC-118025. References
Figure 6: Enlarged SEM perspective view of micro wells with an integrated magnetic micro stir-bar mixer. The well is 400 µm deep and 500 µm in diameter.
1. Papautsky, I.; Brazzle, J.; Swerdlow, H.; Weiss, R.; Frazier, A.B., Micromachined pipette arrays, Biomedical Engineering, IEEE Transactions on, Volume: 47 Issue: 6, pp 812 –819, 2000 2. K.S.Chun, G. Haschigushi, H.Toshiyoshi, H. Fujita, B. Le Pioufle, Y. Kikuchi, J. Ishikawa, Y. Murakami, E.Tamiya, DNA injection into plant cell conglomerates by micromachines hollow microcapillary arrays, Transducers’99, Sendai, (Japan), pp 44-47, 1999 3. Ryoichi Ohigashi, Katsunori Tsuchiya, Yoshio Mita, and Hiroyuki Fujita, Micro capillaries array head for direct drawing of fine patterns, 14th IEEE International Conference on Micro Electro Mechanical Systems, pp 389-392, 2001 4. L-H Lu, K. Ryu, C. Liu, A novel Microstirrer and arrays for microfluid mixing, Fifth International Conference on Miniaturized Chemical and Biochemical Analysis Systems, pp 28-30, 2001
revealing silicon oxide tubes with the shell thickness of approximately 1.2 µm. This process is simple and offers high yield (Fig. 3 and 4). Each step of the process flow features high material selectivity and hence robustness in terms of process control. Furthermore, only one layer of thin film growth is needed. One existing method [3] uses LPCVD silicon nitride in conjunction with thermally grown silicon oxide. It involves significantly more materials and process steps. This new method would provide much reduced time and costs. 3. Multi-Well Plate with Mixers Matching micro-well plate can be fabricated by using reactive ion etching method to pattern through-wafer holes in silicon. The volume of a well with height of h (in mm) and diameter of d (in mm) is ( πD 2 h / 4 ) µl. (The dimensions of well are dependant on the sensitivity of assay and accordingly the minimal amount of required fluids). Alternatively, the well plate may be formed by plastic machining. Due to the small volume of the wells, diffusion-based mixing may need to be augmented by active mixing. We developed a process to form micro wells with dedicated mixers (Fig. 5, 6) by bonding a multi-well plate with another substrate containing an array of magnetic micro stir-bar mixer, demonstrated earlier [4]. The mixers are micro magnetic stir bars operated by using a global, external magnetic field. No individual powering is needed.
Figure 2: Schematic diagram of major microfabrication process steps for realizing a micropipette array made in silicon substrate. High selectively is realized in each step.
Figure 3: SEM micrograph of an array of micropipettes. Distance between pipette openings is 60 µm in this picture.
4. Conclusions In this paper, a novel method to fabricate micropipette array has been presented. The method is simple and requires fewer steps in processing compared to existing methods. The silicon dioxide, which forms the pipette array, is not reactive to most
Figure 4: Close-up of one micropipette. The shell of the vertical tube is made of thermally grown silicon dioxide. It can be strengthened further by conformal deposition of materials, if necessary.
Figure 5: SEM micrograph (top view) of an array of prototype micro wells each with a magnetic micro stir-bar mixer at the bottom.
candidate chemicals, thus eliminating the needs to select materials based on their specific use. Acknowledgements
This work is supported by the Defense University Research initiative in Nanotechnology program (NAVY CL 2468 ANTIC), the Nano Science and Engineering Center (NSEC), and initiative of NSF under NSF award number EEC-118025. References
Figure 6: Enlarged SEM perspective view of micro wells with an integrated magnetic micro stir-bar mixer. The well is 400 µm deep and 500 µm in diameter.
1. Papautsky, I.; Brazzle, J.; Swerdlow, H.; Weiss, R.; Frazier, A.B., Micromachined pipette arrays, Biomedical Engineering, IEEE Transactions on, Volume: 47 Issue: 6, pp 812 –819, 2000 2. K.S.Chun, G. Haschigushi, H.Toshiyoshi, H. Fujita, B. Le Pioufle, Y. Kikuchi, J. Ishikawa, Y. Murakami, E.Tamiya, DNA injection into plant cell conglomerates by micromachines hollow microcapillary arrays, Transducers’99, Sendai, (Japan), pp 44-47, 1999 3. Ryoichi Ohigashi, Katsunori Tsuchiya, Yoshio Mita, and Hiroyuki Fujita, Micro capillaries array head for direct drawing of fine patterns, 14th IEEE International Conference on Micro Electro Mechanical Systems, pp 389-392, 2001 4. L-H Lu, K. Ryu, C. Liu, A novel Microstirrer and arrays for microfluid mixing, Fifth International Conference on Miniaturized Chemical and Biochemical Analysis Systems, pp 28-30, 2001
