Potential Graphene-Based Low-Cost Diagnostic Systems

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Any type of altered biological state, such as what occurs in the incidence of cancer and infectious diseases, can be detected and monitored by understanding how the specific cells are functioning over the course of the disease. Therefore, the ability to selectively detect, isolate and quantify important biological molecules present in cells, such as the DNA and proteins, not only allows for the physiology to be understood, but also offers the opportunity to provide early diagnosis and accurate monitoring of the response of the individual following treatment1. In an effort to enhance this very useful method of detection, a wide variety of nanomaterials have successfully been developed for biosensor technologies due to their exceptional optical properties as compared to their bulk counterparts.

Of the several different types of nanomaterials used in these applications, carbon-based nanomaterials, such as graphene and its related derivatives, have demonstrated a high affinity towards biomolecules of interest as a result of their planar architecture. Within this material is a benzene ring, whose basal structure of aromatic functional groups displays a strong attraction towards certain biomolecules. While some of the most commonly used carbon-based nanomaterials include carbon nanotubes, fullerenes and nanodiamonds, graphene oxide (GO)1 is one of the most studied biosensingnanomaterials. GO is typically obtained following the oxidation of graphite, multiple layers of graphene which are stacked on top of each other, in a mixture containing both a strong acid and oxidizing agent2.

As a result of its ability to facilitate processes for large-scale and inexpensive thin-film production and its ability to deposit onto a wide variety of substrates with exceptional ease are some of the many benefits associated with the use of GO. While cell-capture methods using GO-based composites are few in number, previous studies have shown a relatively high sensitivity of GO to capture whole blood cells, however significant limitations exist in its approaches resulting in its high throughput screening. In an effort to improve the fundamental physical and chemical structure of the GO nanomaterial when applied as a biosensor, researchers at the Massachusetts Institute of Technology (MIT) and the National Chiao Tung University have engineered unique structure of GO in combination with nanosized single-domain antibodies, which are also referred to as nanobodies, to enhance the functionalization and performance of the device when applied for biosensor purposes3.

To obtain control of the distribution of the oxygen functional groups present on the presynthesized GO substrates, researchers performed a single-step transformation process. This phase transformation of GO involved a thermal annealing process in which arsenic-synthesized GO structures undergo a remarkable phase transformation when exposed to temperatures ranging from 50-80 °C.At this temperature, oxygen atomsdiffuse along the basal plane of the graphene, leading to the formation of distinct graphite and oxygen clustersdue to the formation of bonds that are particular to the compound and the surface of the GO material1. By preserving the total amount of oxygen present on the GO sheets, a gradual variation in the sheet resistance,as well as a visible absorbance, is achieved.

Devices using the GO nanosheets were studied for their ability to carry out cell capture experiments following the transformation processes of the structure. The GO sheets were covalently functionalized with diaminopoly(ethylene glycol) linkers, which were then linked with an NHS-activated dibenzocyclooctyne (DBCO)1. A nanobody fragment of VHH7 was then “clicked” onto the DBCO, accounting for certain advantageous as compared to conventional antibodies as a direct result of their smaller size. As compared to the control used in this experiment, nanobody treated GO sheets exhibited a increased efficiency in their cell capture abilities, which was shown with an increased duration of the preliminary annealing procedures.

Researchers hypothesized that the ability of the treated GO sheets to exhibit this enhanced cell capture technique is a direct result of the improved antibody grafting, which allowed for an improved reactivity and functionalization of the GO structures to occur between the linkers and the nanobodies1. Another contributing factor of this exceptional efficiency is a result of the chemical changes that were induced following the clustering of oxygen on the surface of the GO structures that occurred during the initial step of transformation.

The research performed in this study ignites the potential future of enhanced diagnostic systems usinggrapheneoxidate substrates to capture and target specific cells or molecules within the biological system to be a practical reality. Additionally, this greater understanding of the functionalization of the GO nanosheets can provide open the doors for researchers to look into how to fine-tune these processes for future application of GO-based devices in applications including catalysis, batteries, solar energy conversion, supercapacitators and chemical sensors1.

References

  1. Neelkanth M. Bardhan et al, Enhanced Cell Capture on Functionalized Graphene Oxide Nanosheets through Oxygen Clustering, ACS Nano (2017).
  2. Lee, Jieon, Jungho Kim, Seongchan Kim, and Dal-Hee Min. "Biosensors Based on Graphene Oxide and Its Biomedical Application." Advanced Drug Delivery Reviews 105 (2016): 275-87. Web.

Chandler, David L. "Graphene Sheets Capture Cells Efficiently." Phys.org. 3 Mar. 2017. Web. https://phys.org/news/2017-03-graphene-sheets-capture-cells-efficiently.html.

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Benedette Cuffari

Written by

Benedette Cuffari

After completing her Bachelor of Science in Toxicology with two minors in Spanish and Chemistry in 2016, Benedette continued her studies to complete her Master of Science in Toxicology in May of 2018. During graduate school, Benedette investigated the dermatotoxicity of mechlorethamine and bendamustine, which are two nitrogen mustard alkylating agents that are currently used in anticancer therapy.

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