A molecular-imprint nanosensor for ultrasensitive detection of proteins

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Molecular imprinting is a technique for preparing polymer scaffolds that function as synthetic receptors1,2,3. Imprinted polymers that can selectively bind organic compounds have proven useful in sensor development2,3,4,5,6,7. Although creating synthetic molecular-imprinting polymers that recognize proteins remains challenging8,9,10,11, nanodevices and nanomaterials show promise in this area12,13,14. Here, we show that arrays of carbon-nanotube tips with an imprinted non-conducting polymer coating can recognize proteins with subpicogram per litre sensitivity using electrochemical impedance spectroscopy. We have developed molecular-imprinting sensors specific for human ferritin and human papillomavirus derived E7 protein. The molecular-imprinting-based nanosensor can also discriminate between Ca2+-induced conformational changes in calmodulin. This ultrasensitive, label-free electrochemical detection of proteins offers an alternative to biosensors based on biomolecule recognition.

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Figure 1: Fabrication of an MI protein nanosensor.
Figure 2: Detection of hFtn using an MI nanosensor.
Figure 3: Detection mechanism of the MI nanosensor.
Figure 4: Detection of calcium-dependent calmodulin conformational changes and HPV-derived oncoproteins.


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The authors acknowledge financial support from The Seaver Institute (T.C.C and M.J.N.). L.R. was supported by the China Scholarship Council (no. 2008677005). We thank O. Gursky and S. Jayaraman (Boston University School of Medicine, Department of Physiology and Biophysics) for use of their Aviv spectropolarimeter.

Author information

D.C. contributed to the original MI nanosensor concept, overall experimental design, data analysis, manuscript preparation and directing of the measurements. L.R. was responsible for the EIS recordings and contributed to sensor fabrication. H.Z. fabricated the nanotube arrays. C.X. was responsible for protein preparation and purification. Y.Y. contributed to development of the PPn nanocoating. H.W. and Y.L. helped with the high-resolution TEM image. M.F.R. was responsible for the circular dichroism measurements. L.Z. and J.H.C. were responsible for computational analysis of the interaction between the E7 protein and PPn. M.J.N. provided technical support for nanotube fabrication and assisted in manuscript editing. Z.R. contributed expertise regarding nanotube fabrication, experimental design for TEM evaluation of hFtn entrapment, and editing of the manuscript. T.C.C. contributed to the design of experiments for demonstrating nanosensor selectivity and was responsible for writing and editing the revised manuscript.

Correspondence to Dong Cai.

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Cai, D., Ren, L., Zhao, H. et al. A molecular-imprint nanosensor for ultrasensitive detection of proteins. Nature Nanotech 5, 597–601 (2010) doi:10.1038/nnano.2010.114

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