Zhi-Jun Liu

Bio: Zhi-Jun Liu is an academic researcher from Jiangsu University. The author has contributed to research in topics: DNA walker & Electrochemiluminescence. The author has an hindex of 5, co-authored 11 publications receiving 64 citations.

Simple Tripedal DNA Walker Prepared by Target-Triggered Catalytic Hairpin Assembly for Ultrasensitive Electrochemiluminescence Detection of MicroRNA.

Abstract: In contrast to common DNA walkers, multipedal DNA walkers exhibit larger walking area and faster walking kinetics and provide increased amplification efficiency. Consequently, they have received a considerable amount of attention in biosensing. However, most of them are synthesized by immobilizing multiple DNA walking strands on the surface of Au nanoparticles, which is tedious and time-consuming. Simple preparation of multipedal DNA walkers remains a challenge. Herein, we adopted a simple enzyme-free target-triggered catalytic hairpin assembly (CHA) circuit to synthesize a tripedal DNA walker. By walking on a DNA track-functionalized electrode, a sensitive electrochemiluminescence DNA nanomachine biosensor was constructed for sensing miRNA-21. The DNA walker was powered by toehold-mediated strand displacement; the whole process did not need the assistance of enzymes, thus avoiding tedious procedures and enzyme degradation under unfavorable environmental conditions. Specifically, a superior detection limit of 4 aM and a broad linear range of 10 aM to 1 pM were achieved. This CHA-tripedal DNA walker biosensor was then applied for the detection of miRNA-21 in human serum and showed high selectivity and excellent reproducibility, demonstrating its practical application in bioanalysis. In particular, the Y-shaped tripedal DNA walker comes from the DNA circuit, which makes the approach ideally suited for biosensing of small nucleic acid targets.

Nonenzymatic chemiluminescence detection of circulating tumor cells in blood based on Au@luminol nanoparticles, hybridization chain reaction and magnetic isolation

Abstract: Circulating tumor cell (CTC) analysis has great significance for cancer diagnosis and monitoring. However, selective capture and quantification of CTCs from whole blood remains challenging due to the extremely scare number of CTCs. Here, we developed a simple method for ultrasensitive detection of circulating tumor cells (CTCs) based on enzyme-free chemiluminescence reaction, hybridization chain reaction (HCR) signal amplification and magnetic enrichment and isolation. In this detection system, the CTCs-spectific aptamer AS1411 modified magnetic nanoparticles were employed to identify and isolate CTCs from whole blood samples; Au@luminol nanoparticles-HCR assembly (ALHA) containing multiple MUC1 aptamer (specific to a type of CTCs, MCF-7) acted as both the response signal and specific recognition element for sensing CTCs;. On the basis of the chemiluminescence properties of Au@luminol nanoparticles in K2S2O8 solution, the captured CTCs can be sensitively detected using enzyme-free chemiluminescence technique. Furthermore, due to the amplified effect of HCR, the detection sensitivity could be as low as 3 MCF-7 cells /mL. Sensitive, selective results and simple instrument made this method should be useful for further CTCs-related routine applications.

High luminous efficiency Au@CDs for sensitive and label-free electrochemiluminescent detection of circulating tumor cells in serum

Abstract: In this work, new gold@carbon dots nanoalloys (Au@CDs) were synthesized by directly heating carbon dots (CDs) and HAuCl4 aqueous solution to boiling. The as-synthesized Au@CDs exhibited 12-fold enhancement in the ECL emission compared to the single CDs. The high luminous efficiency Au@CDs was further used to fabricate an ECL cytosensor for the direct detection of circulating tumor cells (CTCs) in serum by ligation of a cell-specific aptamer. Briefly, human mucin1 protein (MUC1) aptamer was immobilized onto the surface of Au@CDs on the electrode for capturing MUC1-positive MCF-7 cells (a type of CTCs). On the basis of the increased steric hindrance, the captured MCF-7 cells can be quantitatively detected. Our strategy was free from complicated separation and labeling treatment, and realized the detection of MCF-7 cells (a type of CTCs) from 100 to 10,000 cells/mL with a detection limit of 34 cells/mL, offering promising applications in ultrasensitive routine clinical analysis and point-of-care testing.

A dual-potential ratiometric electrochemiluminescence biosensor based on Au@CDs nanoflowers, Au@luminol nanoparticles and an enzyme-free DNA nanomachine for ultrasensitive p53 DNA detection

Abstract: Herein, an amplified electrochemiluminescence (ECL) ratiometric biosensor for p53 DNA sequence assay was described based on gold@carbon dots nanoflowers (Au@CDs), gold@luminol nanoparticles (Au@luminol) as luminophors and an enzyme-free DNA walker for signal amplification. The ratiometric strategy endowed the sensor with a prominent accuracy. Taking advantage of DNA-walker signal amplification feature, a high sensitivity for target detection was achieved. Under the optimal conditions, the designed biosensor exhibited a lower limit of 0.34 fM and wide linear range from 1 fM to 10 pM for p53 DNA sequence detection. In particular, compared with traditional Ru(bpy)33+/Ru(bpy)32+ derivatives and semiconductor nanoparticles, Au@luminol and Au@CDs have the advantages of cost-effective, excellent biocompatibility, and easy labeling, which offered new opportunity for building ratiometric ECL biosensor platform.

Aptamer-Based Detection of Circulating Targets for Precision Medicine.

Abstract: The past decade has witnessed ongoing progress in precision medicine to improve human health. As an emerging diagnostic technique, liquid biopsy can provide real-time, comprehensive, dynamic physiological and pathological information in a noninvasive manner, opening a new window for precision medicine. Liquid biopsy depends on the sensitive and reliable detection of circulating targets (e.g., cells, extracellular vesicles, proteins, microRNAs) from body fluids, the performance of which is largely governed by recognition ligands. Aptamers are single-stranded functional oligonucleotides, capable of folding into unique tertiary structures to bind to their targets with superior specificity and affinity. Their mature evolution procedure, facile modification, and affinity regulation, as well as versatile structural design and engineering, make aptamers ideal recognition ligands for liquid biopsy. In this review, we present a broad overview of aptamer-based liquid biopsy techniques for precision medicine. We begin with recent advances in aptamer selection, followed by a summary of state-of-the-art strategies for multivalent aptamer assembly and aptamer interface modification. We will further describe aptamer-based micro-/nanoisolation platforms, aptamer-enabled release methods, and aptamer-assisted signal amplification and detection strategies. Finally, we present our perspectives regarding the opportunities and challenges of aptamer-based liquid biopsy for precision medicine.

Carbon Dots in Bioimaging, Biosensing and Therapeutics: A Comprehensive Review

Abstract: Carbon dots (CDs), comprising crystalline graphitized carbon cores and polymer surface groups, are currently attracting a lot of interest in biological fields owing to their fluorescent properties, high photostability, biocompatibility and low toxicity. In addition, the easy preparation and functionalization of CDs stimulate the development of CDs‐based composite materials with specific functions. Presently, the biological applications of CDs are growing at a remarkable speed, justifying the need for up‐to‐date review articles that capture recent progress in this blossoming field. In this review, breakthroughs in the synthesis, modification, optical properties, toxicology and biocatalytic platforms of CDs are described. Further, recent research related to bioimaging, biosensing, drug delivery, antibacterial, anticancer (photothermal therapy, photodynamic therapy and synergistic therapy) and antiviral therapies involving CDs are discussed in detail. Finally, a perspective on the prospects and challenges of CDs in the fields of biomedicine and biotechnology is provided.

The Recent Development of Hybridization Chain Reaction Strategies in Biosensors.

Abstract: With the continuous development of biosensors, researchers have focused increasing attention on various signal amplification strategies to pursue superior performance for more applications. In comparison with other signal amplification strategies, hybridization chain reaction (HCR) as a powerful signal amplification technique shows its certain charm owing to nonenzymatic and isothermal features. Recently, on the basis of conventional HCR, this technique has been developed and improved rapidly, and a variety of HCR-based biosensors with excellent performance have been reported. Herein, we present a systematic and critical review on the research progress of HCR in biosensors in the last five years, including the newly developed HCR strategies such as multibranched HCR, migration HCR, localized HCR, in situ HCR, netlike HCR, and so on, as well as the combination strategies of HCR with isothermal signal amplification techniques, nanomaterials, and functional DNA molecules. By illustrating some representative works, we also summarize the advantage and challenge of HCR in biosensors, and offer a deep discussion of the latest progress and future development trends of HCR in biosensors.

Clustered Regularly Interspaced Short Palindromic Repeats-Mediated Amplification-Free Detection of Viral DNAs Using Surface-Enhanced Raman Spectroscopy-Active Nanoarray.

Abstract: Nucleic acid biomarkers have been widely used to detect various viral-associated diseases, including the recent pandemic COVID-19. The CRISPR-Cas-based trans-activating phenomenon has shown excellent potential for developing sensitive and selective detection of nucleic acids. However, the nucleic acid amplification steps are typically required when sensitive and selective monitoring of the target nucleic acid is needed. To overcome the aforementioned challenges, we developed a CRISPR-Cas12a-based nucleic acid amplification-free biosensor by a surface-enhanced Raman spectroscopy (SERS)-assisted ultrasensitive detection system. We integrated the activated CRISPR-Cas12a by viral DNA with a Raman-sensitive system composed of ssDNA-immobilized Raman probe-functionalized Au nanoparticles (RAuNPs) on the graphene oxide (GO)/triangle Au nanoflower array. Using this CRISPR-based Raman-sensitive system improved the detection sensitivity of the multiviral DNAs such as hepatitis B virus (HBV), human papillomavirus 16 (HPV-16), and HPV-18 with an extremely low detection limit and vast detection range from 1 aM to 100 pM without the amplification steps. We suggest that this ultrasensitive amplification-free detection system for nucleic acids can be widely applied to the precise and early diagnosis of viral infections, cancers, and several genetic diseases.

CRISPR/Cas-Based In Vitro Diagnostic Platforms for Cancer Biomarker Detection.

Abstract: Timely diagnosis is of great benefit to improve the survival rate of cancer patients. Body fluid cancer biomarker detection is a critical kind of noninvasive method for cancer diagnosis. Nevertheless, traditional methods for cancer biomarker detection always rely on a large-scale instrument and involve sophisticated operation. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-based in vitro diagnosis can simplify the detection procedures and improve sensitivity and specificity, holding great promise as the next-generation molecular diagnostic technology. In this Feature, we introduce the working mechanisms of different kinds of CRISPR/Cas systems for biosensing and CRISPR/Cas-mediated detection strategies for different kinds of cancer biomarkers including nucleic acids, proteins, and extracellular vesicles. In addition, the perspective and challenges of CRISPR/Cas-based strategies for cancer biomarkers are discussed.