Research
  Key Laboratories
  Research Divisions
  Research Interests
  Supporting System
  Achievements
  Research Progress
  Research Programs
  Technology Transfer
    Location: Home > Research > Research Progress

Researchers Reveal Ultrasensitive Dissolution-Enhanced Luminescent Bioassay Based on Inorganic Lanthanide Nanoprobe

Dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA), as one of the most sensitive luminescent bioassay techniques, has been widely adopted in research and a variety of medical institutions. Commercial DELFIA using molecular probes like lanthanide (Ln3+)-chelates as biolabels often suffers from a series of disadvantages, such as low labelling ratio of Ln3+ per biomolecule (up to 10-30), low photostability and high cost of Ln3+-chelates. Compared with Ln3+-chelates, inorganic Ln3+ nanoparticles (NPs) possess many advantages such as higher resistance to photobleaching, less toxicity, more flexible for bioconjugation, and much lower cost.  

However, the parity-forbidden nature of intra-4f transitions within Ln3+ strongly limits the photoluminescence (PL) of Ln3+-NPs and thus deteriorates their sensitivity in bioassays. To overcome these concerns, the technique of Ln3+ nanoprobes can be hybridized with the DELFIA protocol by simply replacing Ln3+-chelates with Ln3+-NPs. Due to the highly concentrated Ln3+ ions in a single NP that leads to a much higher labelling ratio of Ln3+, a myriad of Ln3+ ions are released and transformed into highly luminescent Ln3+-micelles after the dissolution of the NPs by the enhancer solution, which significantly amplifies the PL signal and thus improves the detection sensitivity as compared to that of DELFIA. 

Following this concept, the research groups headed by Prof. CHEN Xueyuan and Prof. HUANG Mingdong at Fujian Institute of Research on the Structure of Matter (FJIRSM) of Chinese Academy of Sciences have recently developed a unique and ultrasensitive bioassay method, i.e. dissolution-enhanced luminescent bioassay (DELBA), based on the dissolution-enhanced PL of inorganic Ln3+-NPs. 

By simply replacing Ln3+-chelates with Ln3+ NPs in conventional DELFIA protocol, the proposed DELBA can effectively enhance the labelling ratio of Ln3+ per biomolecule, which greatly improves the PL signal (106 times) and detection sensitivity. By employing sub-10 nm NaEuF4 NPs along with enhancer solution containing β-NTA, the authors revealed the mechanism of the dissolution-enhanced PL of the NPs. Utilizing the biotinylated NaEuF4 NPs as dissolution-enhanced luminescent nanoprobes, they demonstrated the ultrasensitive and accurate detection of an important tumor marker CEA in human serum samples with a limit of detection (LOD) down to 0.1 pg/mL (0.5 fM), which is the lowest among those ever reported (about three orders of magnitude improvement relative to that of DELFIA).  

The CEA levels derived from DELBA were compared with those independently measured using a commercial DELFIA kit, and a good agreement was found between both methods. Further indicators such as the coefficient of variations (CVs; in the range of 95–105%) and the recoveries (< 8%) of the assays revealed the excellent accuracy and precision of the proposed DELBA. Results of this study have been published as a communication in Angew. Chem. Int. Ed. (Angew. Chem. Int. Ed. 2014, 53, DOI: 10.1002/anie.201405937). 

Previously, Prof. CHEN and HUANG’s groups had made a series of relevant progress on the in vitro biodetection of tumor markers based on Ln3+-doped luminescent nanoprobes (Angew. Chem. Int. Ed. 2014, 53, 1252 and Angew. Chem. Int. Ed. 2013, 52, 6671).  

 

 

 


Schematic representation of a) conventional DELFIA based on Ln3+-chelates and b) the proposed DELBA based on inorganic Ln3+-NPs. (Image by Prof. CHEN Xueyuan's group)

 

 


Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences
Address: 155 Yangqiao Road West,Fuzhou,350002,P.R.China Tel: 0591-83714517 Fax: 0591-83714946 E-mail: fjirsm@fjirsm.ac.cn
Copyright @ 2000-2009 fjirsm. All rights reserved.