Programming bulk enzyme heterojunctions for biosensor development with tetrahedral DNA framework
Open Access
- 11 February 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-10
- https://doi.org/10.1038/s41467-020-14664-8
Abstract
Protein-protein interactions are spatially regulated in living cells to realize high reaction efficiency, as seen in naturally existing electron-transfer chains. Nevertheless, arrangement of chemical/biochemical components at the artificial device interfaces does not possess the same level of control. Here we report a tetrahedral DNA framework-enabled bulk enzyme heterojunction (BEH) strategy to program the multi-enzyme catalytic cascade at the interface of electrochemical biosensors. The construction of interpenetrating network of BEH at the millimeter-scale electrode interface brings enzyme pairs within the critical coupling length (CCL) of ~10 nm, which in turn greatly improve the overall catalytic cascade efficiency by ~10-fold. We demonstrate the BEH generality with a range of enzyme pairs for electrochemically detecting clinically relevant molecular targets. As a proof of concept, a BEH-based sarcosine sensor enables single-step detection of the metabolic biomarker of sarcosine with ultrasensitivity, which hold the potential for precision diagnosis of early-stage prostate cancer.Keywords
Funding Information
- Ministry of Science and Technology of the People’s Republic of China (2016YFA0201200)
- National Natural Science Foundation of China (21991134, 21834007, 21722502, 21505045, 21705048)
This publication has 49 references indexed in Scilit:
- Interenzyme Substrate Diffusion for an Enzyme Cascade Organized on Spatially Addressable DNA NanostructuresJournal of the American Chemical Society, 2012
- Exclusive recognition of sarcosine in water and urine by a cavitand-functionalized silicon surfaceProceedings of the National Academy of Sciences of the United States of America, 2012
- Challenges and opportunities for structural DNA nanotechnologyNature Nanotechnology, 2011
- Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targetsNature Chemistry, 2011
- Efforts to resolve the contradictions in early diagnosis of prostate cancer: a comparison of different algorithms of sarcosine in urineProstate Cancer and Prostatic Diseases, 2011
- Re: Florian Jentzmik, Carsten Stephan, Kurt Miller, et al. Sarcosine in Urine after Digital Rectal Examination Fails as a Marker in Prostate Cancer Detection and Identification of Aggressive Tumours. Eur Urol 2010;58:12–8European Urology, 2010
- Metabolomic profiles delineate potential role for sarcosine in prostate cancer progressionNature, 2009
- Preparation of electrode-immobilized, redox-modified oligonucleotides for electrochemical DNA and aptamer-based sensingNature Protocols, 2007
- Long-Range Heterogeneous Electron Transfer Between Ferrocene and Gold Mediated By n-Alkane and N-Alkyl-Carboxamide BridgesThe Journal of Physical Chemistry B, 2000
- Polymer Photovoltaic Cells: Enhanced Efficiencies via a Network of Internal Donor-Acceptor HeterojunctionsScience, 1995