Date: 27th March 2020
The ability to electrically detect biomolecules, in particular DNA/RNA, is a highly sought after tool for many areas of science and healthcare. From pharmacogenomics and drug discovery, to healthcare diagnostics this technology would further enable personalised medicine, forensics and environmental monitoring along with many other areas. Now scientists have developed an ultra-sensitive biosensor which detects nucleic acids using crumpled graphene and is able to detect cancer markers in patient blood or serum.
Field-effect transistor (FET)-based biosensors allow label-free detection of biomolecules by measuring their intrinsic charges. They can be readily integrated with other electronic components, such as data analysers and signal transducers to create highly sensitive biomolecular sensing platforms. Graphene is a promising component for biosensor transducers because of its high sensitivity to changes in the environment.
A team, led by Rashid Bashir from the University of Illinois, US, had a particular interest in cancer detection and wanted to turn to biosensor technology to create an ultra-sensitive, rapid diagnostic tool.
Current approaches to diagnosing cancer at the genetic level are based largely on techniques using polymerase chain reaction (PCR). This is due to the fact that existing detection systems require relatively large quantities of DNA and therefore require an amplification stage. However, PCR can be prone to interference by inhibitory factors in biological samples and therefore analysis cannot be directly performed from blood or serum samples. If an alternative method of detection could be generated then it may allow for liquid biopsy, which could replace invasive tumor-tissue biopsies in many diagnostic applications.
To explore a solution here the team predicted, using previous work,that the graphene component of a biosensors could be made more sensitive to DNA detection by curving it.
Biosensor design
A graphene FET biosensor was created by using probe DNA anchored via a linker molecule to either a flat or crumpled graphene channel of FET sensors. The target DNA was then allowed to hybridise to the probes, and various electrical and capacitance measurements were taken.
The team discovered that, when compared to a flat structure, the crumpled graphene biosensor was incredibly 10,000 times more sensitive at detecting DNA due to a combination of factors including increased surface area; electron flow differences and the formation of so-called electrical “hot spots” within the material.
The team then tested the crumpled graphene’s ability to sense DNA and cancer-related microRNAs in both a buffer solution and in undiluted human serum. In both cases they saw the significantly better performance over the flat graphene and detection was even made possible without amplification. They could detect in buffer and human serum samples down to concentrations of 600 zM and 20 aM, respectively; corresponding to ∼18 and ∼600 nucleic acid molecules.
The team reported it as the highest sensitivity reported so far using any electronic biosensor for the detection of DNA.
Conclusion and applications:
The team here have created an ultra-sensitive biosensor which can detect nucleic acids in buffer and human serum at very low levels, accurately and rapidly.
This technology has the potential to pave the way for more reliable, efficient and potentially more cost-effective diagnostic tools for many diseases. It is hoped it may also offer the basis for implantable biosensors for the early detection of biomolecules for various human diseases.
The ultimate goal for the team on the diagnosis front is to couple the tech with a handheld device and a cartridge designed to detect target molecules in a few drops of blood. The Bashir group is now testing crumpled graphene in sensors for proteins and small molecules showing the systems flexibility and potential for a wide range of applications.
With this in mind, one of the most exciting applications of graphene biosensors to emerge in recent times is the Genome Sensor™, which combined the technology of a revolutionary graphene biosensor platform with CRISPR-Cas9 nucleotide detecting technology, it what was coined “The world’s first DNA search engine”. The question next to be answered is will this new ‘crumpled’ graphene tech be embraced by others, offering increased sensitivity to other existing graphene based biosensors? And will the technology being developed by the Bashir lab rival current biosensors?
Given the current race in developing COVID-19 diagnostic and antibody detecting kits, this new ‘crumpled’ graphene biosensor, if developed quickly enough into a handheld device, could potentially prove a value tool in the fight against the spread of coronavirus.
For more information please see the press release from University of Illinois
Hwang, M. T., M. Heiranian, Y. Kim, S. You, J. Leem, A. Taqieddin, V. Faramarzi, Y. Jing, I. Park, A. M. van der Zande, S. Nam, N. R. Aluru and R. Bashir (2020). “Ultrasensitive detection of nucleic acids using deformed graphene channel field effect biosensors.” Nature Communications 11(1): 1543.
https://doi.org/10.1038/s41467-020-15330-9
