Even before Covid-19, many healthcare systems were working at or near full capacity. The drain on systems caused by the pandemic further restricted access to healthcare services, resulting in delayed diagnosis and treatment of illnesses, and a record number of patients now seeking medical attention.
Emergency services, patient care and the wellbeing of healthcare providers have all been negatively impacted by capacity issues.1 Hospitals are overrun, with critical bed shortages and insufficient resources to deliver the required standards of care. Patients who have experienced delays are more likely to need emergency inpatient attention, creating a vicious cycle where emergency care uses more beds and resources, further delaying the treatment of other patients, whose conditions are left to deteriorate.
Another factor compounding capacity issues is drug resistance, particularly with respect to antibiotics. In the absence of a timely diagnosis, clinicians routinely resort to treating infections with broad-spectrum antibiotics, up to 50% of which are prescribed inappropriately.2 Inappropriate antibiotic use allows bacteria that are not totally eradicated to develop resistance, limiting treatment options and extending treatment times.
Capacity issues are only set to get worse. Based on projected health statistics, the global cancer burden is expected to nearly double by 20403 and antibiotic resistance will overtake cancer prevalence by 2050.4
Faster and more specific diagnosis will help reduce the impact of these additional strains on healthcare services, by ensuring that appropriate treatment is initiated as early as possible. Earlier diagnosis will avoid the use of inappropriate medications and increase the likelihood of successful patient outcomes. It will also reduce instances of avoidable emergency treatment, freeing up beds and hospital staff.
Due to record-breaking waiting lists and growing antimicrobial resistance, accurate and rapid diagnostic tests that hasten care pathways and identify correct treatments are of particular value. Current diagnostic biosensor technology (e.g. immunoassays and molecular tests) normally require complex laboratory instrumentation or sample preparation. This usually means samples are taken to dedicated laboratories, and diagnostic processes can take hours – or even days – to deliver results, postponing timely access to appropriate treatments.
Using graphene in biosensors
Graphene is a single atom thick sheet of carbon, a biocompatible material that has extraordinarily high electrical conductivity. Graphene-based biosensors can be modified to trap molecules such as proteins, enzymes and nucleic acids. When these target molecules bind to graphene, they significantly alter its electrical properties, allowing immediate detection of the target species electronically. Graphene’s unique electrical properties mean that highly sensitive measurements of biomarkers of specific illnesses can be made in real time with minimal sample preparation, unlike traditional diagnostic approaches.5
This facilitates faster diagnosis, allowing healthcare systems to deliver improved care promptly and breaking the vicious cycle of delays.
Speed of results
Due to graphene’s biosensing properties and the lack of need for sample preparation, results from graphene biosensors are available almost immediately. Graphene biosensors can be read by small, handheld devices that can be used at the point of need and connected to the internet. This means the diagnosis of specific conditions can be made immediately at the point of care – including remote/mobile clinics far from conventional hospitals and laboratories, while capturing the data for transfer to electronic patient records.
Increased detection capabilities
The extremely high sensitivity of graphene, combined with its speed and reduced sample preparation, extends the opportunities to use diagnostics for screening and early detection of disease. Moreover, because graphene only requires very small sample volumes for measurements, the patient experience of providing samples is much better. Consequently, graphene can detect disease earlier in its progression, improving patient care and resource utilisation. By increasing treatment efficacy, allowing swift identification of the correct treatment and limiting treatment to what is necessary, graphene biosensors will help tackle the growing resource limitations faced by global healthcare services.
Limited sample preparation
Biological samples such as blood, urine and saliva can be placed directly onto graphene biosensors without the need for reagents or complex sample preparation, such as the use of a centrifuge to isolate sample components. This reduces the risk of contamination caused by sample preparation, which is relatively common, and reduces the cost of performing tests. Likewise, graphene biosensors could allow tests to be conducted and results delivered all within an outpatient setting, which previously wouldn’t have been possible due to the requirement for large, expensive and often off-site machinery.
Fewer pre-analytical errors
Conventional biosensors require complex preparation of samples to remove particles and condition the human samples for optical detection. A graphene biosensor produces electronic readings based on the charge of the target molecules trapped on the surface, eliminating the need for photodetectors, optical filters, dyes and optical stages. This is likely to enhance accuracy, as there is no risk of process-related contamination7. Reduced sample preparation also demands less training and equipment to perform the tests and interpret the readings. Testing could be taken into the community, without the need for specialist staff and results could be available without delays.
Possibility for multiplexing
The number of target biomarkers that can be detected simultaneously using current diagnostic technologies, such as ELISA, is limited at the point of care by the availability of dyes that can be distinguished using affordable optics. Simultaneous detection of more than six target molecules generally requires complex lighting, lenses, optical detectors and even movement mechanisms. These components all add appreciable cost to any system and increase the overall complexity of the instrumentation, rendering them less portable and robust.
Graphene diagnostic devices are not limited in this way, as each diagnostic measurement is an individual electrical measurement performed on a graphene “chip”. As these chips are produced using semiconductor fabrication processes identical to those used to make microprocessors, the number of assays that could be fabricated on a chip far exceeds the limitations of optical detection approaches. This capability offers the ability to run multiple tests simultaneously, on a single sample. Test to rule in or rule out diseases could be performed simultaneously on patients presenting with non-specific symptoms.
A single platform
Multiplexed graphene biosensors will make it possible to perform molecular, enzymatic and immunoassays using a single, handheld instrument that will be robust, compact and affordable. This offers significant advantages compared to existing diagnostic technologies, particularly in primary and low resource care settings, where the cost of purchasing discrete instrumentation for each test type, as well as the ancillary sample preparation equipment, is too costly and space-consuming, and where trained operators are unavailable. Graphene technology places the power of a clinical laboratory at the disposal of even the lowest resource settings.
Furthermore, as the measurement circuits are electronic and can tolerate a wide range of electrical signals (photodetectors are generally limited in dynamic range), new tests can be accepted by the reader device with a simple software update. This allows a single instrument to not only operate pre-existing tests, but to be up-graded as and when new tests emerge. With no moving parts, a single investment in an instrument can provide almost limitless test access.
The future of diagnostics
Diagnostic technology is not new but, thanks to graphene and for the first time, it will be possible for patients to receive a diagnosis of serious illness in a short medical appointment. The ramifications of this will be huge, as access to highly sensitive and rapid diagnostic technologies will allow earlier screening and detection of disease with lower demand on limited healthcare resources.
Early detection of diseases like cancer, typically improves patient outcomes and reduces the cost of treatment. Graphene diagnostics could also prove pivotal in the fight against antimicrobial resistance, by allowing for prompt, targeted treatment for bacterial infections that avoids unnecessary antibiotic exposure.
- NHS. The NHS Long Term Plan. Published online January 7, 2019.
- Milani RV, Wilt JK, Entwisle J, Hand J, Cazabon P, Bohan JG. Reducing inappropriate outpatient antibiotic prescribing: normative comparison using unblinded provider reports. BMJ Open Qual. 2019;8(1):e000351. doi:10.1136/bmjoq-2018-000351
- Ramadan S, Lobo R, Zhang Y, et al. Carbon-Dot-Enhanced Graphene Field-Effect Transistors for Ultrasensitive Detection of Exosomes. ACS Appl Mater Interfaces. 2021;13(7):7854-7864. doi:10.1021/acsami.0c18293
- Interagency Coordination Group on Antimicrobial Resistance. No Time to Wait: Securing the future from drug-resistant infections. Report to the Secretary-General of the United Nations. Published online April 2019.
- Kuila T, Bose S, Khanra P, Mishra AK, Kim NH, Lee JH. Recent advances in graphene-based biosensors. Biosensors and Bioelectronics. 2011;26(12):4637-4648. doi:10.1016/j.bios.2011.05.039
- Damborský P, Švitel J, Katrlík J. Optical biosensors. Estrela P, ed. Essays in Biochemistry. 2016;60(1):91-100. doi:10.1042/EBC20150010
- Peña-Bahamonde J, Nguyen HN, Fanourakis SK, Rodrigues DF. Recent advances in graphene-based biosensor technology with applications in life sciences. Journal of Nanobiotechnology. 2018;16(1):75. doi:10.1186/s12951-018-0400-z
- Bhalla N, Jolly P, Formisano N, Estrela P. Introduction to biosensors. Estrela P, ed. Essays in Biochemistry. 2016;60(1):1-8. doi:10.1042/EBC20150001