Electrochemical Biosensors for Whole Blood Analysis: Recent Progress, Challenges, and Future Perspectives.

Whole blood, as one of the most significant biological fluids, provides critical information for health management and disease monitoring. Over the past 10 years, advances in nanotechnology, microfluidics, and biomarker research have spurred the development of powerful miniaturized diagnostic systems for whole blood testing toward the goal of disease monitoring and treatment. Among the techniques employed for whole-blood diagnostics, electrochemical biosensors, as known to be rapid, sensitive, capable of miniaturization, reagentless and washing free, become a class of emerging technology to achieve the target detection specifically and directly in complex media, e.g., whole blood or even in the living body. Here we are aiming to provide a comprehensive review to summarize advances over the past decade in the development of electrochemical sensors for whole blood analysis. Further, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms.

Precise Preparation of Supramolecular Spherical Nucleic Acids for Nucleolin-Targeted Gene Delivery.

Molecular spherical nucleic acids (m-SNAs) are a second generation of spherical nucleic acids (SNAs), which are of significance in potential application of targeted delivery of nucleic acids or gene regulation due to their defined molecular structures. Nevertheless, m-SNAs typically involve a single DNA sequence which greatly limits its functions as either targeting purpose or gene regulation. In response, we proposed here a third generation, supramolecular spherical nucleic acids (Supra-SNAs) with two different sequences to achieve both above-mentioned functions. Specifically, we constructed a series of supramolecular self-assembly structures by coupling a cell membrane receptor (i.e., nucleolin)-recognizing aptamer (AS1411)-modified adamantine as targeting probe and human epithelial growth factor receptor 2 (HER2) antisense-functionalized ß-cyclodextrin to specifically inhibit the overexpression of HER2 proteins for gene regulations. In comparison to the m-SNA precursors, such Supra-SNA structures exhibited enhanced levels of resistance to nuclease degradation, cellular uptake, gene regulation capabilities and tumor retention capacity. We demonstrated that Supra-SNAs exhibited optimal cell suppression rates and cell apoptosis via a phosphatidylinositol 3-kinase/protein kinase B signaling pathway. The well-defined molecular structures provide an attractive platform for investigating interrelationship between structure and property at the molecular level.

Incorporation of a Multi-Valent Aptamer into Electrochemical Biosensors to Achieve an Improved Performance for Thrombin Analysis in Blood Serum.

The electrochemical aptamer-based (E-AB) biosensor usually has a long reaction time when detecting thrombin. This work reports the design of an E-AB biosensor with dual recognition sites to quickly detect thrombin. Specifically, two specific recognition sites of thrombin were used to design three aptamer sequences (TBA-15, TBA-29 and TBA-U), followed by fabrication of corresponding sensors. First, we tested these three types of biosensors in tris buffer solution, and found that the response time of the TBA-U sensor to the same concentration of thrombin was about 2 hours, which is shorter than TBA-15 and TBA-29 sensors. Then, we also did the same test in 50 % diluted serum with 500 nM thrombin. The response time of the TBA-U sensor was about 2 hours, which is still faster than the 3 hours of TBA-15 sensor and the 5.5 hours for TBA-29 sensor. In addition, in terms of dynamic range and specificity, TBA-U has good performance.