Microcantilever operated in liquid environment for in-vitro biomolecular detection

Kilho Eom's picture

We have recently reported the piezoelectric thick film microcantilever, which enables the in-situ real-time detection of the protein related to disease (e.g. C reactive protein) in liquid environment. This work was published at APL (click here).

"In-situ real-time monitoring of biomolecular interactions based on resonating microcantilevers immersed in a viscous fluid"

We report the precise (noise-free) in-situ real-time monitoring of a specific protein antigen-antibody interaction by using a resonating microcantilever immersed in a viscous fluid. In this work, we utilized a resonating piezoelectric thick film microcantilever, which exhibits the high quality factor (e.g. Q = 15) in a viscous liquid at a viscosity comparable to that of human blood serum. This implies a great potential of our resonating microcantilever to in-situ biosensor applications. It is shown that our microcantilever enables us to monitor the C reactive protein (CRP) antigen-antibody interactions in real-time, providing an insight into the protein binding kinetics.


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Rui Huang's picture

vibrations in liquid environment

Interesting work. I am sure many imechanicians who have wroked on fluid-structure interactions would find this an interesting application in biomolecular research. I have not really worked much in this area myself, but would like to share some experience about vibrations in a liquid environment.

Since early 1980s, many liquid-phase sensors/detectors (mostly for chemical applications; see Ref. 1) have been studied using piezoelectric quartz-crystal resonators. In most cases, the resonator vibrates in a thickness-shear mode and generates a shear wave in the liquid. Due to viscous damping of the liquid, the shear wave decays very fast over a short distance, which leads to a shift in the frequency of the resonator and a drop in its quality factor.

Since mid-1990s, some experiments have shown that the frequency shift for a thickness-shear mode resonator in liquid actually depends on the boundary condition and oscillates with the thickness of a finite liquid layer (Refs. 2 and 3). Theoretical models have been put forward, including a piece of my own work (Ref. 4), which explains the oscillation as a result of the propagation of compressional wave in the liquid and its reflection at the liquid surface or interface. It is found that a compressional wave can propagate a much longer distance in a liquid than the shear wave, despite the viscous damping. This poses a challenge for the shear-mode resonators as liquid-phase sensors because thickness-shear mode vibrations are almost always coupled with a flexural mode that generates a compressional wave in the liquid.

For the microcantilever resonator, I believe it operates in a flexural mode and thus the effect of the compressional wave in the liquid must be carefully examined. For example, does the resonator frequency or Q-factor depend on the size of the liquid cell?

Another question I have is: Is Q = 15 really a high quality factor? Recently we reported a quality factor of 7000 for a torsional-mode resonator in water (Ref. 5). Of course, the Q would be lower for a higher viscosity liquid.

Finally, I was curious about what piezoelectric material was used in this study, but could not find the information in the paper.

 

Some references:

  1. Kanazawa and Gordon, Anal. Chim. Acta. 175, 99-105 (1985).
  2. Schneider and Martin, Anal. Chem. 67, 3324-3335 (1995).
  3. Lin and Ward, Anal. Chem. 67, 685-693 (1995).
  4. P.C.Y. Lee and R. Huang, Effects of a liquid layer on thickness-shear vibrations of rectangular AT-cut quartz plates. IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control 49, 604-611 (2002).
  5. T. Knowles, M.K. Kang, R. Huang, Trapped torsional vibrations in elastic plates. Applied Physics Letters 87, 201911 (2005).

Kilho Eom's picture

RE: cantilever operated in liquid for biomolecular detection

Thank you for your interests to my current work. As you mentioned, microcantilever is operated in the flexural mode in liquid. The resonance behavior of a cantilever in liquid is well described in the reference by Kirstein (S. Kirstein, M. Mertesdorf, M. Schonhoff, J Appl Phys, 84, p1782, 1998), which I used in the paper. For the effect of compressional wave, I still need to check how it affects the resonance of a cantilever. The resonance of a cantilever in liquid might be also dependent on the liquid cell size, but in this paper we did not consider.

For quality factor, obvious Q=15 in liquid is not quite high. But, most of micron-scale cantilever exhibits the low quality factor in liquid environment, so that it is very difficult to detect the biomolecule in liquid based on the resonant frequency shift due to biomoelcular interactions (e.g. protein antigen-antibody interaction, DNA hybridization). For instance, Craighead group have recently reported the micron-scale oscillator which exhibit the high-frequency dynamical range (e.g. 20 ~ 100 MHz) as well as high Q factor (e.g. Q ~ 10^6) in normal air [for details, See paper by Verbridge et al., Nano Lett, 6, p2109, 2006]. However, their oscillator exhibit the very poor Q factor (e.g. Q ~ 5) in liquid environment, so that their oscillator may not be used as an in-situ biosensor yet. Until recently, as far as I know, most micron-scale cantilever resonator possesses the low Q factor in liquid so that it has not been well used as an in-situ biosensor. Hence, I believe that the challenge resides in the development of micron-scale (or nano-scale) oscillator that bears the high Q factor even in liquid environment for in-situ biosensor applications.

For PZT materials, we could not give the detailed information in the paper because of length. For our PZT resonating cantilever, we used PZW-PZT thick film, which is well described in the following references: T.Y. Kwon, et al., J Cryst Growth, 295, p172, 2006T.Y. Kwon et al, Appl Phys A, in press. Also, the fabrication method of microcantilever is well described in the following paper: J.H. Park et al, Adv Funct Mater, 15, p2021.

I think that NEMS/MEMS resonators may be interesting to people in mechanics and/or applied physics, because of their various applications. The following references might be interesting.

S.B. Shim, M. Imboden, P. Mohanty, "Synchronized oscillation in coupled nanomechanical resonators," Science, 316, p95 (2007)

M. Li, H.X. Tang, M.L. Roukes, "Ultra-sensitive NEMS-based cantilevers for sensing, scanned probe, and very high-frequency applications," Nature Nanotechnol., 2, p114 (2007)

J.S. Bunch, A.M. van der Zande, S.S. Verbridge, I.W. Frank, D.M. Tanenbaum, J.M. Parpia, H.G. Craighead, P.L. McEuen, "Electromechanical resonators from graphene sheets," Science, 315, p490 (2007)


Rui Huang's picture

very well received

Kilho:

Thanks for your response. I appreciate it, especially the list of references that seem to be interesting and relevant.

Curiously I wonder what is the current understanding of the low quality factors in micron-scale oscillators and what one can do to improve the quality factor in liquid. I think the related mechanics is quite interesting, probably requiring studies on both solid and fluid mechanics. 

RH