John Tingay, CTO, Paragraf, explains how a test capable of providing diagnostic information on the spot within minutes could transform healthcare provision for both patients and professionals alike.
At present, existing detection methods limit the ability to provide such a swift and efficient service. But that could be set to change. Graphene, the 2D layer of carbon atoms with extremely high electron mobility, holds the potential to deliver vastly improved diagnostic capability. Although at an early stage of development, graphene could result in faster and more accurate disease detection, transforming health outcomes and use of precious healthcare resources.
Limitation of existing methods
It is worth assessing the pros and cons of the two leading detection technologies – immunoassays and nucleic acid amplification techniques, such as polymerase chain reaction (PCR) - before we look at the potential for graphene-based diagnostics.
Immunoassays work on the principle of an antigen/antibody reaction, detecting whether the body has produced an immune response to the disease (through the production of antibodies). These tests indicate that the patient has been exposed to a disease but cannot tell whether the disease is still active.
PCR tests amplify small segments of target DNA to detect the presence of pathogens (e.g. viruses, bacteria and parasites) through their unique DNA fingerprints. PCR is commonly used to establish the presence of a wide range of pathogens but cannot tell if the pathogen is alive or dead. This provides earlier detection of diseases, as immune responses are typically delayed, but some treatments, such as cancer therapies, may kill the pathogen while it remains in the body.
Consequently, neither is perfect and they perform complementary tasks, one telling you whether the pathogen is present and the other whether the body has generated an immune response to it.
While immunoassays and PCR are tried and trusted approaches, they have limitations for use at the point-of-care. In both cases, sample preparation is usually complex and requires careful process control, lab equipment and a trained operator – all of which takes time and resources. Both techniques are also incompatible and cannot be performed using the same equipment, restricting their use in primary care settings. As a result, common diseases that require both techniques for an accurate diagnosis typically remain undiagnosed at the point of care.
How graphene transforms biosensing
There is a need for faster accurate point-of-care diagnostics that provide results within the space of a normal medical appointment. This is where the inherent characteristics of graphene hold such potential.
Graphene is a 2D aromatic layer of carbon atoms with extremely high electron mobility. Attaching ionic molecules to graphene results in dramatic changes in its conductivity, providing high sensitivity detection. Its biocompatibility also allows a very wide range of biomolecules to be detected, including DNA, antibodies and enzymes. This means that graphene can perform the same functions as immunoassays and PCR, detecting both antibodies and DNA simultaneously in a single test. This ability, combined with high sensitivity and speed, can deliver increased diagnostic accuracy for many diseases where both technologies are required to make an accurate diagnosis.
As graphene detects via electronic rather than optical means, there is no need for complex sample preparation. With graphene, detection occurs the moment the reaction takes place, so results are delivered in real time. Together, these factors – the ability to combine DNA and antibody tests, lower operational resource requirements and speed of response – provide significant benefits over existing technologies, especially at the point of care.
There are other considerations, too. Paragraf, has developed a highly reproducible graphene manufacturing process compatible with established semiconductor processes, which enables multiple test cells to be fabricated on a single chip. Highly repeatable manufacture allows the same size and quality of material to be produced every time, meaning that each measurement is quantitively accurate. This means that artificial intelligence can be used to differentiate between patients of different ages, ethnic origin and sex. Being able to perform multiple tests on-chip means only one small-volume sample is required from the patient. This significantly improves patient experience and Paragraf is engaging with patient public involvement (PPI) experts to help define the optimal patient experience and usability.
Making graphene biosensing a reality
Graphene has the potential to transform the way healthcare services are delivered. A medical practitioner could, for instance, perform a test that analyses several different common diseases in minutes. Tests for infection could be carried out in the home or at the point of care and recuperation could be managed remotely using accurate results to monitor therapeutic response. This capability would result in more timely diagnosis, resulting in more targeted and measured treatments, easing the pressure on secondary healthcare services. More accurate on-the-spot diagnosis would also help reduce over-prescription of antibiotics which is increasing bacterial resistance. Antimicrobial resistance is already making some diseases increasingly difficult and costly to treat, and timely diagnosis can help reduce oversubscription and aid antibiotic stewardship.
