On Chip Detection of Tau Protein Using Microtubule Based Bioassay

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26790030
• Research Institution: The University of Tokyo
• Principal Investigator: TARHAN Mehmet・C 東京大学, 生産技術研究所, 研究員 (50582839)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: Protein detection / On-chip detection / Tau protein / Microtubules / Kinesin

Outline of Annual Research Achievements

On-chip detection successfully demonstrated differences between MTs exposed to different concentrations of tau protein. Higher tau concentration resulted in a denser attachment on MTs causing higher decrease in the average velocity compared to lower concentration showing smaller decrease with respect to the no-tau control experiments. Also, effect of different tau isoforms were detected: (i) Tau with higher MT-binding repeats (MTBR) caused slower bead motion compared to tau with lower MTBR, (ii) Tau with shorter projection domain (PD) caused slower bead motion compared to tau with longer PD.
A novel technique for mutated tau detection was introduced. As mutated tau has limited attachment to MTs, detection is extremely difficult. Thus, an additional pre-incubation step was added to mix healthy and mutated tau proteins for 8 hours. Mutated tau can affect the healthy tau and decrease the healthy tau concentration in the solution that will later be used in the detection method. The results showed that having the same healthy tau concentration with varying mutated tau levels in the pre-incubation step caused different average velocity levels parallel to the mutated tau concentration.
This study demonstrates the previously proposed tau detection method in an on-chip format. Moreover, additional pre-incubation step can solve issues on detecting mutated tau while amplifying the sensitivity towards physiological levels. After necessary optimizations, clinical samples (e.g. cerebrospinal fluid) should be used to test the performance for demonstrating the diagnostic capabilities.

Research Products

• [Journal Article] On-chip microtubule gliding assay for parallel measurement of tau protein species (2016)
  • Author(s): S. P. Subramaniyan, M. C. Tarhan, S. L. Karsten, H. Fujita, H. Shintaku, H. Kotera and R. Yokokawa
  • Journal Title: Lab On Chip Volume: next volume Pages: n.a.
  • DOI: DOI: 10.1039/C5LC01486G
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Nano systems and devices for applications in biology and nanotechnology (2016)
  • Author(s): G. Perret, P. Ginet, M. C. Tarhan, A. Baccouche, T. Lacornerie, M. Kumemura, L. Jalabert, F. Cleri, E. F. Lartigau, B. J. Kim, S. L. Karsten, H. Fujita, Y. Rondelez, T. Fujii and D. Collard
  • Journal Title: Solid-State Electronics Volume: 115 Pages: 66-73
  • DOI: doi:10.1016/j.sse.2015.08.019
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Point-of-Care (POC) Devices by Means of Advanced MEMS (2015)
  • Author(s): S. L. Karsten, M. C. Tarhan, L. C. Kudo, D. Collard and H. Fujita
  • Journal Title: Talanta Volume: 145 Pages: 55-59
  • DOI: doi:10.1016/j.talanta.2015.04.032
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] DNA mechanical characterization inside biological buffer by the Double-Actuator Silicon Nano Tweezers (2016)
  • Author(s): Gregoire Perret, M. C. Tarhan, Nicolas Lafitte, Laurent Jalabert, M. Kumemura, T. Lacornerie, E. Lartigau, F. Cleri, H. Fujita and D. Collard
  • Organizer: Asia- Pacific Conference on Transducers and Micro-Nano Technology
  • Place of Presentation: Kanazawa bunka hall, Kanazawa, Japan
  • Year and Date: 2016-06-26 – 2016-06-29
  • Int'l Joint Research
• [Presentation] Manipulating Different Biological Samples by Silicon Nanotweezers (2016)
  • Author(s): M. C. Tarhan, G. Perret, N. Lafitte, M. Kumemura, L. Jalabert, Y. Takayama, S. L. Karsten, H. Fujita and D. Collard
  • Organizer: International Conference on Microtechnologies in Medicine and Biology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2016-04-20 – 2016-04-22
  • Int'l Joint Research
• [Presentation] 3D Humidity Imager in Micro Environment Based on DNA Conductivity and Rigidity Measured by Silicon Nano Tweezers (2016)
  • Author(s): G. Perret, N. Lafitte, M. C. Tarhan, L. Jalabert, M. Kumemura, T. Lacornerie, E. Lartigau, F. Cleri, H. Fujita and D. Collard
  • Organizer: IEEE International Conference on Micro Electro Mechanical Systems
  • Place of Presentation: Shanghai, China
  • Year and Date: 2016-01-24 – 2016-01-28
  • Int'l Joint Research
• [Presentation] SNTs Combined to a Microfluidic Device for Monitoring the Mechanical Effects of Metal Cations on DNA (2015)
  • Author(s): Y. Tauran, M.C. Tarhan, N. Lafitte, L. Jalabert, B.J. Kim, H. Fujita, A.W. Coleman and D. Collard
  • Organizer: International Conference on Miniaturized Systems for Chemistry and Life Sciences
  • Place of Presentation: Gyeongju, Korea
  • Year and Date: 2015-10-25 – 2015-10-29
  • Int'l Joint Research