Development of an integrated microchip for cancer
prescreening using Caenorhabditis elegans
Wei-Long Chen
1, Chang-Shi Chen
2, and Han-Sheng Chuang
1, 3,**(
[email protected]
)
1
Department of Biomedical Engineering
National Cheng Kung University, Tainan 701, Taiwan
2Biochemistry and Molecular Biology
National Cheng Kung University, Tainan 701, Taiwan
3Medical Device Innovation Center
National Cheng Kung University, Tainan 701, Taiwan
Abstract – Caenorhabditis (C.) elegans is a multicellular model animal, which shares a high genetic similarity and molecular pathways with human being. C.elegans features small size, transparency, short life cycle, ease of cultivation, and fully-sequenced genome. Prior studies has shown that C.elegans can regulate its locomotion in response to the surrounding environment depending on the worm’s olfactory.[1] As a result, C. elegans can be treated as a potential biosensor in detection of diseases.[2] Accordingly, an integrated microchip for cancer prescreening was developed. This microchip comprising three layers was made of polymethylmethacrylate(PMMA) and engraved by a CNC mill machine (Roland, RPS-400). The middle sliding layer inculded one chamber (1 mm in height) with one outlet was used for worm transferring. The bottom control layer consisted of one culture chamber and five testing chamber, the testing chamber included one gaitprint analysis chamber (0.1 mm in height), one kinetic power analysis chamber (0.1 mm in height and 2 mm in diameter), and the others are for cancer prescreening. Two image algorithms, gaitprint analysis and kinetic power, were developed to decipher the information embedded in the locomotion. In the former, the Empirical Mode Decomposition (EMD) was used to decompose the worm’s kymogram into 12 features. By comparing the features between an unknown worm and a predefined database, a gaitprint was obtained. In the latter, the knetic power was derived from a velocity vector map of particle image velocimetry (PIV).[3] Since worms were isolated in a droplet, the force exerted from them would be calculated from the fluid movement. For the cancer prescreening, Caco-2 and Hela cells were used. The culture media of both cancer cells were extracted and readjusted their pH to 8. The same culture medium with no cancer cells was used as a control for subsequent comparisons. Small drops of all the media were pipetted to three microchips, respectively. Five wild-type (N2) worms were simultaneously cultured and measured on the microchip. The result showed that worms incubated with the cancer cell culture medium became more active than the control group. Finally, the worms cultured with urine from cancer patient will lead to different results of gaitprint and kinetic power, in the future. Keywords: Caenorhabditis elegans, Gaitprint analysis, Kinetic power analysis, Cancer prescreening, Microchip.
References:
1. Piggott, B. J., Liu, J., Feng, Z., Wescott, S. A., and Xu, X. Z. S., “The Neural circuits and synaptic mechanisms underlying motor initiation in C. elegans.” Cell, Vol. 147, no. 4, pp. 922-933, 2011.
2. Hirotsu, T., Sonoda, H., Uozumi, T., Shinden, Y., Mimori, K., Maehara, Y., Ueda, N., Hamakawa, M., “A highly accurate inclusive cancer screening test using Caenorhabditis elegans scent detection.” PLoS One, Vol. 10, no. 3, pp. e0118699, 2015.
3. Kuo, W.J., Sie, Y.S. and Chuang, H.S., “Characterizations of kinetic power and propulsion of the nematode
Caenorhabditis elegans based on a micro-particle image velocimetry system.” Biomicrofluidics, Vol.8, no. 2,
