Target-Triggered Aggregation of Modified E. coli for Diagnosis of Ovarian Cancer.

Bacteria inherently possess the capability of quorum sensing in response to the environment. In this work, we have proposed a strategy to confer bacteria with the ability to recognize targets with quorum-sensing behavior. Meanwhile, we have successfully achieved artificial control over the target-triggered aggregation of Escherichia coli (E. coli) by modifying the bacteria surface in a new way. Furthermore, by making use of green fluorescent protein (GFP) expressed by E. coli as the output signal, the aggregation of modified E. coli can be observed with the naked eye. Therefore, via the detection of the target, MUC1, an ovarian cancer biomarker, a simple and conveniently operated method to diagnose ovarian cancer is developed in this work. Experimental results show that the developed low-background and enzyme-free amplification method enables the highly sensitive detection of MUC1, achieving a remarkable limit of detection (LOD) of 5.47 fM and a linear detection range spanning from 1 pM to 50 nM and 50 nM to 100 nM, respectively. Clinical samples from healthy donors and patients can give distant assay results, showing great potential for clinical applications of this method.

Magnetic Nanoagent Coated with an Activated Macrophage Membrane for Colorimetric Detection of Bacteria.

The construction of cell mimics replicating the surface landscape and biological functions of the cell membrane offers promising prospects for biomedical research and applications. Inspired by the inherent recognition capability of immune cells toward pathogens, we have fabricated activated macrophage membrane-coated magnetic silicon nanoparticles (aM-MSNPs) in this work as an isolation and recognition tool for enhanced bacterial analysis. Specifically, the natural protein receptors on the activated macrophage membrane endow the MSNPs with a broad-spectrum binding capacity to different pathogen species. By further incorporation of a tyramide amplification strategy, direct naked-eye analysis of specific bacteria with a detection limit of 10 CFU/mL can be achieved. Moreover, application to the diagnosis of urinary tract infections has also been validated, and positive samples spiked with bacteria can be clearly distinguished with an accuracy of 100%. This work may enrich cell membrane-based architectures and provide an experimental paradigm for point-of-care testing (POCT) detection of bacteria.

Engineered Escherichia coli as a Controlled-Release Biocarrier for Electrochemical Immunoassay.

Micro/nanocarriers hold great potential in bioanalysis for molecular recognition and signal amplification but are frequently hampered by harsh synthesis conditions and time-consuming labeling processes. Herein, we demonstrate that Escherichia coli (Ec) can be engineered as an efficient biocarrier for electrochemical immunoassay, which can load ultrahigh amounts of redox indicators and simultaneously be decorated with detection antibodies via a facile polydopamine (PDA)-mediated coating approach. Compared with conventional carrier materials, the entire preparation of the Ec biocarrier is simple, highly sustainable, and reproducible. Moreover, immune recognition and electrochemical transduction are performed independently, which eliminates the accumulation of biological interference on the electrode and simplifies electrode fabrication. Using human epidermal growth factor receptor 2 (HER2) as the model target, the proposed immunosensor exhibits excellent analytical performance with a low detection limit of 35 pg/mL. The successful design and deployment of Ec biocarrier may provide new guidance for developing biohybrids in biosensing applications.

An electrochemical biosensor based on electroactive peptide nanoprobes for the sensitive analysis of tumor cells.

Peptides possess many appealing and desirable features, which have attracted increasing attention in the field of electrochemical biosensing. However, peptides hardly produce noticeable electronic signals in response to target binding events. In this work, amphipathic peptides FFFGGGGRGDS with both target recognition and self-assembly capabilities are designed to be co-assembled with the electroactive species ferrocenecarboxylic acid (FcCOOH). Furthermore, the resultant electroactive peptide nanoprobes (ePNPs) are applied for sensitive electrochemical analysis of tumor cells. Specifically, tumor cells are captured by the electrode modified with the corresponding DNA aptamers, and ePNPs can then selectively bind to integrin proteins on the cell surface, thereby accompanied by a remarkable increase of electrochemical signal. Taking the assay of MDA-MB-231 cells, the fabricated biosensor can detect cancer cells with a detection limit of 7 cells mL-1. Moreover, the ePNPs can act as a universal probe for the detection of different cell lines. Given the merits of easy synthesis, convenient operation, and favorable analytical performance, the proposed biosensor exhibits great potential in developing peptide-based electrochemical biosensing for clinical applications.