Automated liquid dispensing pin for DNA microarray applications

This paper describes a new liquid dispensing/aspirating system that is capable of producing micron-size spots/droplets for molecular biology research and analysis. In particular, the application is focused on deoxyribonucleic-acid microarray fabrication with the goals of uniform spot morphology, smaller spot size, higher yield, more efficient use of biological materials, and the capacity to handle high viscosity liquids. The new system is based on active sensing and control and it is part of a fully integrated robotic microarray system for genomic and proteomic applications. The prototype system handles thick liquids such as 100% glycerol as well as aqueous solutions and generates uniform spots in a contactless manner with controllable spot size ranging from 80 microns to 200 microns. Note to Practitioners-Microarraying is a powerful tool that enables the expression profiling of a vast quantity genetic/proteomic materials in parallel. Current printing technology includes photolithography, impact pins, inkjet, etc. Although these designs have been successful in printing spot size down to 100 microns, a new approach is needed to handle the order of magnitude increase in density while reducing cost. The SmartPin described in this paper is a sensor-based motion-controlled print head created for printing the next-generation microarrays. It is capable of depositing any aqueous samples (e.g., deoxyribonucleic acid, protein, etc.) and has the flexibility and cost advantage of the printing approach and yet possesses high performance and telepresence accessibility. The system utilizes an optical-fiber-based sensor probe for both sensing and sample delivery. Sensing is then integrated with computer control so that it can generate the microarray with fully controllable spot density and size. By maintaining a uniform gap distance between the pin tip and the target slide, performance and reliability are enhanced. The current work is at the prototype development state and will need further refinement for commercialization.

[1]  Edwin Hou,et al.  Optimal Input Shaper Design For High-Speed Robotic Workcells , 2003 .

[2]  Puttiphong Jaroonsrisphan.  Web Based Distance Experiments For Real Time Control , 2002 .

[3]  Xuemei Sun,et al.  Analysis and control of monolithic piezoelectric nano-actuator , 2001, IEEE Trans. Control. Syst. Technol..

[4]  Timothy N. Chang,et al.  Vibration control on linear robots with digital servocompensator , 2000, Proceedings of the 2000 American Control Conference. ACC (IEEE Cat. No.00CH36334).

[5]  S. Quake,et al.  Microfabricated fountain pens for high-density DNA arrays. , 2003, Genome research.

[6]  M. Morley,et al.  Making and reading microarrays , 1999, Nature Genetics.

[7]  D. L. Cunningham,et al.  ACAPELLA-1K, a capillary-based submicroliter automated fluid handling system for genome analysis. , 2000, Genome research.

[8]  Richard Bruce,et al.  Ultra-High-Throughput Microarray Generation and Liquid Dispensing Using Multiple Disposable Piezoelectric Ejectors , 2004, Journal of biomolecular screening.

[9]  Timothy N. Chang,et al.  Vibration control of linear robots using a piezoelectric actuator , 2003 .

[10]  Reggie J. Caudill,et al.  Contactless magnetic leadscrew: vibration control and resonance compensation , 2000, Proceedings of the 2000 American Control Conference. ACC (IEEE Cat. No.00CH36334).

[11]  Chang-Jin Kim,et al.  Silicon Microarray Pin With Selective Hydrophobic Coating , 2004 .

[12]  P. Spellman,et al.  Ceramic capillaries for use in microarray fabrication. , 2001, Genome research.

[13]  Timothy N. Chang,et al.  Control of hysteresis in a monolithic nanoactuator , 2001, Proceedings of the 2001 American Control Conference. (Cat. No.01CH37148).

[14]  Kimberly A. Smith,et al.  POSaM: a fast, flexible, open-source, inkjet oligonucleotide synthesizer and microarrayer , 2004, Genome Biology.

[15]  F Dangond.  Chips around the world: proceedings from the Nature Genetics microarray meeting. , 2000, Physiological genomics.

[16]  Ernest Otto Doebelin,et al.  Measurement Systems Application and Design , 1966 .

[17]  Dimitra N. Stratis-Cullum,et al.  Investigation of microfabrication of biological sample arrays using piezoelectric and bubble-jet printing technologies , 2004 .

[18]  William M. Reichert,et al.  The optimization of quill-pin printed protein and DNA microarrays , 2002, Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology.

[19]  Xuemei Sun,et al.  Integrating Nanotechnology into Undergraduate Experience: A Web-based Approach* , 2002 .