Project

Micro-Systems & Control Laboratory, NTHU

Programmable Bio-sorting Microsystem Chip using Enhanced DEP Array

Objectives:

To separate, sort out, purify and detect target biological particles/molecules like DNA, proteins, viruses, and cells from very low-concentration sample solutions has been important in bio-medical applications and molecular/cellular biotechnology research. Recent advances in Micro Electro Mechanical System (MEMS), Nano, and Fluorescent labeling technologies have demonstrated quite a lot of impressive possibilities regarding the manipulation and detection of a single molecule in a tens-nanometers scale as well as a sequence of bio-chemical processes at the monolithic chip level. Even with such technological advances and impressive technological demonstrations, the high effective and adaptive separation, sorting, and purification for target bio-molecules in a very low-concentration sample solution via a monolithic chip are still a challenge for practical applications. Our group develops adaptive biochips with the features of the high effective and adaptive separation, sorting, and purification of target bio-molecules for low-concentration bio-sample solution.

Technical Approach:

Adaptive biochip integrating dielectrophoresis (DEP) traps and a programmable multi-sorting DEP array for the multi-sorting applications of bio-molecules such as proteins and DNA is developed. The prototype illustration is shown in Fig. 1. We also use movable beads as the mobile probes to capture the target protein molecules. These beads are chemically modified and immobilized with conjugate proteins. An array of micro-pyramid DEP traps with a good levitation control on the height of the beads is located at the upstream to enhance the hybridization function of the mobile probes. A programmable multi-sorting DEP array located at the downstream sorts out the hybridized beads, which are fluorescently labeled, based on the fluorescent detection signals. The magnitude and direction of the DEP force applied to the beads with and without labeling fluorescence in the multi-sorting DEP array are controlled via the distribution of time-variant non-uniform electric fields. The voltage on the individual electrode of the multi-sorting DEP array is pre-programmed and controlled by a LabVIEW controller with fluorescence detection feedback signals. Our work reported at Journal of MicroElectroMechanical Systems 16 (4), pp. 816-825, 2007 successfully demonstrates the research concept. The design of this biochip integrating with the hybridization enhancement via micro-pyramid DEP traps and the adaptive multi-sorting DEP array for the mobile probes has never been proposed or implemented before based on our knowledge.

 

 

Fig. 1 The illustration of our biochip integrating dielectrophoresis (DEP) traps and a programmable multi-sorting DEP array for the multi-sorting applications of bio-molecules such as proteins and DNA.

         

Fig. 2 SEM pictures of micro-pyramid DEP traps with metal deposition and wires.

Fig. 3 The trapping /releasing pictures for the probe bead via micro-pyramid DEP trap

 

 

Fig. 4 the adaptive multi-guiding/sorting performance of the 55 multi-sorting DEP array.

 

References:

1.      Ting-chen Shih, Kuang-han Chu and Cheng-Hsien Liu, “A programmable biochip for the applications of trapping and adaptive multi-sorting using dielectrophoresis array,” Journal of MicroElectroMechanical Systems 16 (4), pp. 816-825, 2007.

  1. Wen-Yu Chang and Cheng-Hsien Liu, “An Integrated Dielectrophoresis Biochip for Single Cell Manipulation,” Proceedings of 10th International Conference on Miniaturized Chemical and Biochemical Analysis Systems, 2006. (MicroTAS 2006)

3.      Pang-Chih Liu  and Cheng-Hsien Liu, “ A Dielectrophoresis Cell Manipulation Chip Integrated with AC Electrkinetic Pump for Single Cell Electroporation,” Proceedings of 10th International Conference on Miniaturized Chemical and Biochemical Analysis Systems, 2006. (MicroTAS 2006)

4.      Bang-Chih Liu, Tsan-I Chen and Cheng-Hsien Liu, “A Cell Separation Chip Using Micro-structures Filter and Multi-Frequencies Dielectrophoresis,” Proceedings 13th International Conference on Solid State Sensors and Actuators, pp. 1733-1736, 2005. (IEEE Transducers05)

5.      Kuang-han Chu and Cheng-Hsien Liu, “Manipulation of bio-particles by electrokinetics,” Proceeding of ASME IMECE Bio-engineering session, 2004

  1. Tsan I Chen and Cheng-Hsien Liu, “A dielectrophoretic cell separation device with size filtering,”  Proceedings of 9th International Conference on Miniaturized Chemical and Biochemical Analysis Systems, pp. 108-110, 2004. (MicroTAS2004)

Contact Information :

·         Kuang-Han (Hank) Chu   khchu@mit.edu (Ph.D. study at MIT now)

·         Ting-Chen Shih

·         Tsan-I Chen

·         Cheng-Hsien Liu   liuch@pme.nthu.edu.tw

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