Rapid Characterization of Oligonucleotides Using ZipChip CE-MS

Oligonucleotides are a special class of therapeutic agents—including RNA, DNA, and their structural analogs—that have shown therapeutic efficacy against a wide range of diseases. The recent COVID-19 pandemic has dramatically accelerated the development of this novel biotechnology, with mRNA vaccines becoming immensely popular. As a result, synthetic oligonucleotides have attracted considerable attention from the biopharmaceutical industry; several candidate drugs have already been approved for market or have entered late-stage clinical trials. Structurally, oligonucleotides are linear molecules—either single-stranded or double-stranded—that contain nucleotide residues linked by phosphodiester bonds. Compared to small-molecule drugs and protein-based therapeutics, these polyanionic molecules exhibit unique chemical and physical properties, presenting distinctive challenges for analytical characterization.

2024-01-23

Oligonucleotide (oligos) is a special class of therapeutic drugs, including RNA 、 DNA and its structural analogs have therapeutic effects on many diseases. The recent COVID-19 pandemic, mRNA The booming demand for vaccines has greatly accelerated the development of this new type of biotechnology. Synthetic oligonucleotides have attracted considerable attention from the biopharmaceutical industry, and several candidate drugs have already been approved for market launch or have entered late-stage clinical trials. Structurally, oligonucleotides are linear molecules—either single-stranded or double-stranded—that contain nucleotide residues linked by phosphodiester bonds. Compared with small-molecule drugs and protein-based therapeutics, these polyanionic molecules exhibit unique chemical and physical properties, posing special challenges for analytical characterization.

Currently, LC-MS It remains the gold standard for characterizing oligonucleotides, in which ion-pairing is employed. (IP) Reverse phase of the reagent LC These methods are particularly widely used. These approaches not only require ion-pair reagents ( ion pairing reagent) Moreover, the analysis also requires a relatively long time to equilibrate the system and the chromatographic column, meaning that the analysis of oligonucleotide samples typically necessitates specialized equipment. LC/MS System. Therefore, it is essential to develop a simple oligonucleotide analysis method by combining orthogonal separation techniques with high-resolution mass spectrometry. ZipChip CE-MS By seamlessly integrating capillary zone electrophoresis with electrospray ionization, samples can be rapidly and efficiently separated without the need for ion-pair reagents, and then directly introduced into mass spectrometry for structural characterization.

ZipChip The device is the front-end inlet of the mass spectrometer. , It can perform capillary zone electrophoresis. (CZE) Separation, leveraging the natural speed advantage of microfluidic technology to enhance performance. CEO Separation efficiency. ZipChip The device can seamlessly connect to multiple commercial mass spectrometers. Thermo Fisher 、 User and SCIEX ). The structural design of the microchip avoids the drawbacks of traditional capillary types. CE-ESI Defects such as dead volume in the interface, sample dilution, and spectral band broadening are eliminated, ensuring that... CEO The speed and sensitivity of the analytical process. Meanwhile, a special coating treatment applied to the surface of the separation channel reduces electroosmotic flow. End of File ) the impact it has, ensuring the reliability and reproducibility of separation.

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