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Novel Aptamer-based Techniques for the Chemiluminescent Biosensors

Author: PengZuoZuo
Tutor: LuJianZhong
School: Fudan University
Course: Pharmaceutical Analysis
Keywords: Aptamers Chemiluminescence Biosensor Technology Magnetic microspheres 96-well plates Polystyrene microspheres Rolling circle amplification enlarge DNAzyme
CLC: TP212.3
Type: Master's thesis
Year: 2011
Downloads: 199
Quote: 0
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Abstract


Aptamers are systematic evolution of ligands exponential enrichment (SELEX) technology, from the synthetic oligonucleotide library can be obtained by screening with the target molecule of high affinity and high specificity binding oligonucleotide fragment (single-stranded DNA or RNA). Molecular recognition between the aptamer and target molecule with antibodies are very similar, but a very wide range of target molecule aptamers can specifically bind to cells, proteins, amino acids, drugs and metal ion, it appears for the chemical and biological academia and the biomedical community to provide efficient and rapid identification of a new platform. Aptamer stability, fast reversible denaturation renaturation, the target molecules in a wide range of specificity and high affinity, chemical synthesis is relatively simple, fast, easy to obtain, easy modification and tag, and in the design of the biosensor flexible advantages, in recent years, concern in bioanalytical detection. Has become a hot spot of research in many areas of clinical diagnostics, environmental monitoring, biomedical, pharmaceutical research. Chemiluminescence (CL) analysis is a trace analysis of the substance content is determined according to the optical radiation generated by the chemical reaction. Chemiluminescence analysis without the excitation source, to avoid interference from stray light, the equipment is simple, easy to operate, wide linear range (3-6 orders of magnitude), with high sensitivity, is conducive to the realization of a fully automated detection characteristics The analysis is becoming a valuable tool in the detection. With the expansion of cross-over study with other disciplines and application areas, has been successfully applied in many other areas such as pharmacy, biology, molecular biology, clinical medicine, and environmental studies. In this paper, we use a chemiluminescence method, use of aptamers high resolution to identify the characteristics of the target molecule, the development of three innovative recognition aptamer-based chemiluminescence biosensor. Text composed by the following four parts: The first chapter gives an overview of the preparation, characteristics and advantages of the aptamer, and its application in the detection field, and highlights based aptamer biosensors research progress, including without mark, mark detection technology and signal amplification system in the aptamer biosensor applications, and cited the detection technology in recent years, part of the typical example, and finally a brief introduction to the main contents of the chemiluminescent detection technology as well as the subject. The second chapter describes the use of polystyrene microspheres as enlarged carrier, build a high sensitivity magnetic surface of the microspheres instantaneous derivative chemiluminescence IgE detection technology. First, the IgE antibody is fixed on the carboxylated magnetic microspheres then combined with the antigen IgE, binding the IgE aptamers specific modified polystyrene microspheres, after washing using a specific chemiluminescent reagent TMPG with the surface of the magnetic microspheres capture guanine (G) nucleotide reaction chemiluminescent label-free detection of IgE; subsequent IgE aptamer sequence 5 'end modified G base-rich (GGT) n fragment, and further improve the detection sensitivity. The minimum detectable concentration of up to 4.60 pM, the linear range of 4.88 pM-20 nM (1gI = 0.7573 1gC 2.4529, R2 = .9853) Chapter as the carrier, carboxyl-modified 96-well plates by carboxyl - fixed PDGF-amino reaction BB monoclonal antibody specifically binding to the target protein, PDGF-BB binding aptamer - primer sequences, this sequence contains two functional areas: one for the specific recognition of the target protein of PDGF-BB; another in the 3 ' The terminal contains a triggering rolling circle amplification the zoom (RCA) reaction primers. The primer in the presence of cyclic template and a series of enzymes, after RCA reaction, can be obtained a single strand of DNA containing a plurality of circular DNA template complementary to the repeated sequence unit, which is capable of hybridizing to combine many of the biotin-labeled complementary oligonucleotide The guanylate report probe. Subsequently combined with streptavidin and prime modification of horseradish peroxidase (HRP), was measured after washing of HRP retained on the 96-well plate generated chemiluminescence, quantification of PDGF-BB. RCA amplification system PDGF.BB linear range of 10 fM-1 nM the (1gI = 0.8791gC-0.446, R2 = 0.998), the minimum detectable concentration of up to 10 fM RCA reaction detection sensitivity 1000 times. The fourth chapter is based between the aptamer with the target molecule binding capacity is greater than the interaction between the complementary DNA duplexes, the establishment of a homogeneous detection technology platform adenosine. We will first adenosine aptamer sequence containing heme molecules formed the tetramer structure a special sequence GGG TAG GGC GGG TTG GG hybridization; adenosine added in combination with the aptamer sequence, sequence release tetramer; tetramer sequences with heme molecules form a DNAzyme, the catalytic Luminol and H202 CL, adenosine. Experimental results show that: the method is simple and rapid analysis, interference experiments show that the technology has certain specific recognition ability. Adenosine concentration of the target molecule within the concentration range of 7.81 × 10-6-5.00 × 10-4M having a good linear relationship, the correlation coefficient was R2 = 0.9670, and 7.81 × 10-6 M, the detection limit can be achieved.

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