B I O M E D I C A L   A P P L I C A T I O N

 

 Cell chip & Lab-on-a-chip using MEMS technology

Micro Systems Lab. in AJOU UNIVERSITY


Fig. 1. The schematic sketch of the immunsensing biochip design

Fig. 2. The photograph of the fabricated biochip and inter-connection structure.
(1) air bladder, (2) air vent, (3) waste chamber,
(4) hydrophobic pattern, (5) sample inlet port,
(6) buffer solution reservoir, (8) the fluid barrier pole

 

 (a)

(b)

(c)

Fig. 3. The operation process of the biochip.
(a) buffer solution loading, (b) sample reaction, (c) washing with buffer solution

 

Smart Bioelectrocatalytic Immunosensing Lab-on-a-chip for Portable Diagnostic Application
S. W. Park, J. H. Lee, J. H. Lee, H. C. Yoon and S. S. Yang
ABSTRACT
The development of lab-on-a-chip (LOC) using immunoassay has evolved to applications in clinical diagnostics.  The highly-sensitive and reliable imunosensing biochips integrated with biospecific electrodes are in a stage of expansion by merging bioanalytical science and MEMS technology.  Combining two technologies provides some synergy effects such as speed, ease of use, relatively-low cost per sample, which are adequate for potable clinical systems.  
For the immunosensing LOC system, researchers follow two main approaches consisting of the development of efficient signal detecting strategies and the microfluidic-based chip designs proper for sensing strategies.  In order to have a meaningful physical signal associated with the biological detection and immunoassay, various methods such as electrochemical, piezoelectric, or optical techniques are employed. Among them the electrochemical method is the most suitable for miniaturized device because of simple instrumentation and easy signal quantification.  The electrochemical method, however, has complicated antibody labelling steps or need expensive labeled secondary antibodies to reduce labeling steps.  Another focus of the bioelectrocatalytic immunosensing LOC is the development of reliable microfluidic manipulation techniques.  Various researchers have explored active control devices including active micropumps and microvalves.   However, the active microfluidic control is not acceptable in the portable diagnostic systems due to high cost, difficulty in integration, complexity in fabrication and the need for external power supply.  The immunosening mechanism applied to this biochip is the electrochemical signaling from antigen-antibody interaction with bioelecrocatalyzed enzymatic signal amplification. The proposed signaling strategy is based on the back-filling method and uses the enzyme-labeled antibody of immunosensing surface with biocatalytic enzyme which does not require the complicated process such as antibody labeling steps or any labeled secondary antibody.  The electrochemical immunosensing biochip has been designed, fabricated and successfully confirmed. Except for the washing process operated by pushing the air bladder, the whole process is performed autonomously. From the experimental results we confirmed that the enzymetic back-filling immunoassay method is a simple and effectively method for the miniaturized diagnostic systems. From the calibration tests for anti-DNP, we achieve a wide dynamic detection range of the immunosensing. In the near future, we will improve the performance by adapting a better structure and develop a portable monitoring system proper to the disposable biochip.



 

Fig. 4. The captured video clips showing
the sequential sample washing process

Fig. 5. Cyclic voltammetric traces and calibration curves for the DNP/anti-DNP affinity biosensors as a function of target protein concentration

 

  Related Papers

  1. S. H. Lim, S. W. Park, J. H. Lee, H. K. Choi, S. S. Yang, and H. C. Yoon, "Disposable Smart Immunosensing Biochip Using a Novel Electrochemical Signaling Method," 1st IEEE International Conference on Nano/Micro Engineered and Molecular Systems (IEEE NEMS 2006),  Zhuhai, China, pp. 148, 2006. 01.
  2. 임석희, 박신욱, 이준황, 윤현철, 양상식, “밸브가 필요없는 원터치 타입의 전기화학 면역 바이오칩,” 제8회 한국 MEMS 학술대회 논문집, pp. 84-87, 2006. 04.
  3. Sin Wook Park, Jun Hwang Lee, Hyun C. Yoon and Sang Sik Yang , Fabrication of a smart microchip for electrochemical immunosensing,  2006년 한국바이오칩학회 창립학술대회, 고려대학교,서울,  2006. 06. 23
  4. S. W. Park, S. H Lim, J. H. Lee, H. C. Yoon and S. S. Yang, A Smart Immunoassayfor Portable Clinical Diagnostic System, Singapore, Asia-Pacific Conference of Transducers and Micro-Nano Technology 2006, (2006.06.25-28)
  5. Cao, C., Kim, J.P., Kim, B.W., Chae, H.Y., Yoon, H.C., Yang, S.S., Sim, S.J., A strategy for sensitivity and specificity enhancements in prostate specific antigen-α1-antichymotrypsin detection based on surface plasmon resonance, Biosensors & Bioelectronics, 21, 2106-2113 (2006)
  6. Sin Wook Park, Jun Hwang Lee, Hyun C. Yoon , Sang Sik Yang, "A Smart bioelectrocatalytic Immunosensing Lab-on-a-chip for Portable Diagnostic Application", Biochip Journal, Vol.1, No.1, 35-42, 2007.3
  7. 박신욱, 강태호, 양상식 “휴대용 POC 시스템을 위한 원터치형 면역 센싱 랩온어칩” Trans. KIEE. Vol 56, No. 8, 1424-1429, 2007. 8.
  8. Sin Wook Park, Jun Hwang Lee, Hyun C. Yoon, Byung Woo Kim, Sang Jun Sim, Heeyeop Chae and Sang Sik Yang, "Fabrication and testing of a PDMS multi-stacked Hand-operated LOC for use in portable immunosensing systems", Biomedical Microdevices, Vol. 10, No. 6, pp. 859-868, 2008. 12.
  9. Sin Wook Park, Jun Hwang Lee, Kang-il Kim, Hyun C. Yoon and Sang Sik Yang, "An electrochemical immunosensing lab-on-a-chip integrated with latch mechanism for hand operation", Journal of Micromechanics and Microengineering, , Vol. 19, No. 2, 025024, 2009. 2.

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