Chromatography and Nanotechnology

Nanotechnology is a relatively new field that has become one of the critical research endeavors of the early 21st century. Factors such as size, surface area, tailorability, solubility, and multifunctionality of nanoparticles allow them to be used in applications that can improve several analytical techniques. This article will discuss the applications of nanotechnology in the field of chromatography.

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The application of nanotechnology to chromatography

Nanotechnology refers to research and technology which operates at the atomic, molecular, and macromolecular scale. Structures can be manipulated and studied at a scale in the range of 1-100nm, leading to tailor-made nanostructures that have new properties their bulk counterparts do not. Multifunctional nanoparticles can be designed by cross-discipline researchers for a variety of uses.

Chromatography is a robust analytical technique that can separate mixtures to analyze their component compounds. Nanotechnological applications to chromatography have mostly concentrated on liquid and gas chromatography methods. Nanoscale materials can provide improvements to chromatography phases and options for miniaturization, to name but two advantageous applications.

Improving chromatography phases with nanomaterials

Improvements in stationary and mobile phases in chromatographic methods lead to better analysis of the compounds present in a target mixture. However, materials traditionally used in stationary phases can have their limitations, especially when it comes to scale and analyte selectivity and retention. By utilizing nanotechnology, improvements to the materials used in the stationary phase of GC and LC can be made.

Research has been focused on the development of novel phases and the modification of currently available stationary phases. This improves the retention of analytes which are hard to analyze due to the inherent limitations of traditional stationary phases which have been in use for decades.

The study of properties of stationary phases at the nanoscale has also informed the construction of better-performing material and the design of nanoscale phase material. Many different nanomaterials have been proposed for this purpose.

Carbon-based and inorganic nanomaterials have been considered for use in LC. The proposed materials range from carbon nanotubes to nanodiamonds and nanostructures based on compounds such as zirconia, titanium dioxide, and silica. These materials can be incorporated into LC systems include covalent immobilization, entrapment, and synthesis of nanomaterials as part of chromatographic support.

Nanomaterials have been used in many different types of LC including reversed and normal phase LC, ion-exchange modes, as well as chiral separations, and hydrophilic interaction liquid chromatography. Analytes including drugs, amino acids, and proteins have been used to evaluate their suitability and potential applications for them. The use of nanomaterials has been considered for planar, capillary, and column-based chromatography.

Nano-liquid chromatography and miniaturization techniques

Miniaturization of chromatographic techniques was first proposed in the 1950s. Proteomics research has driven their recent development, and with the advent of nanotechnology research has gathered pace with various techniques now available for analytical chemists.

Nano-LC is a recently developed technique that provides scientists with a potentially game-changing analytical chemistry technique. It has the potential for use in the pharmaceutical and biomedical industries. Major advantages of this system include improved retention and analysis of analytes, reduced waste (in keeping with a “green chemistry” ethos) and less use of toxic reagents. However, the equipment is still expensive to produce, which limits widespread usage of Nano-LC.

Nano-LC uses much the same equipment as conventional liquid chromatography, but the conventional instrumentation is miniaturized. Equipment including pumps, columns, detection interfaces, and injection loops must all be of dimensions ideal for small volumes and low back-pressure. Parameters must be tightly controlled if chromatographic separation with nano-LC systems is to be successful.

Materials used in these systems must be designed well and their unique properties considered by designers of nano-liquid chromatography equipment. Nanomaterials commonly used in the columns of nano-LC systems tend to be polyimide-fused silica capillaries. Other nanoscale materials used include titanium and stainless-steel based nanocolumns.

Other nanotech-based techniques that both complement and compete with nano-LC are microchip systems and nano-capillary electrophoresis. Miniaturization techniques such as these are constantly being improved by researchers.

PAC: a system which brings together DNA nanotechnology and chromatography

One method for gathering information on the states of a cell population is by analyzing the variation patterns of transcription factors. By using a method of connecting chromatography and DNA-based signal transduction, multiplexed detection of TFs is possible. This method uses multi-channeled isothermal amplification to achieve the desired results.

In a system known as “PAC” (Protection, Amplification, Chromatography) DNA-modified magnetic microbeads can capture TFs. This capturing event is converted into a triggering signal which is then amplified, and DNA reporters are generated. By using liquid chromatography, the DNA reporters are then separated and detected. 5 major and essential TFs can be quantitatively detected by this system.

By using this method, DNA nanotechnology and chromatography can be used together to create a robust analytical method that provides researchers with a cutting-edge method of multiplexed TF measurement for molecular diagnostics of cultured cells, tumors, and blood-based liquid biopsies.

In conclusion

Nanotechnology is providing several solutions for common problems in chromatography and driving the development of better chromatography equipment. By combining the two technologies, analytical chemists working in several fields have a powerful suite of tools at their disposal in the laboratory.


  • Beeram, S.A et al. (2017) Nanomaterials as stationary phases and supports in liquid chromatography Electrophoresis 38(19):2498-2512 [Accessed online 16th January 2021]
  • Laher, M et al. (2013) Assessing the Nanoscale Structure and Mechanical Properties of Polymer Monoliths used for Chromatography Anal. Chem 85(12): 5645-5649[Accessed online 16th January 2021]
  • Yue, C et al. (2020) A signal transduction approach for multiplexed detection of transcription factors by integrating DNA nanotechnology, multi-channel isothermal amplification, and chromatography Journal of Chromatography A 1624:461148 [Accessed online 16th January 2021]
  • Garma, R.C, Collins, C.H. & Bottoli, C.B.G (2013) Nano-liquid Chromatography in Pharmaceutical and Biomedical Research Journal of Chromatographic Science 51(7):694-703 [Accessed online 16th January 2021]

Further Reading

Last Updated: Feb 2, 2021

Reginald Davey

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Reginald Davey

Reg Davey is a freelance copywriter and editor based in Nottingham in the United Kingdom. Writing for AZoNetwork represents the coming together of various interests and fields he has been interested and involved in over the years, including Microbiology, Biomedical Sciences, and Environmental Science.


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