Researchers used off-the-shelf components to create a sensor device that is not only low-cost but can quickly detect 32 different pathogens with a sensitivity comparable to the most advanced biosensors used in pathology laboratories. The novel device has applications ranging from monitoring the effectiveness of cancer therapies to predicting the course of viral diseases.
Diagnosing diseases early benefits both patients and doctors. It enables treatments to slow the progression of the disease and reduce the risk of complications, thereby improving long-term health. Taking into account the importance of early diagnosis, a team at the Helmholtz Zentrum Dresden-Rosendorf (HZDR) research laboratory in Germany has used off-the-shelf components to create a cost-effective, palm-sized device that can detect 32 different pathogens simultaneously.
To create the new device, the researchers borrowed basic concepts from the field of electronics, using field-effect transistors (FETs). Field-effect transistors use electric fields to control the flow of electricity in semiconductors. It has three components: source, gate and drain. Applying a voltage to the gate surface changes its potential and controls the current flow between the source and drain. The device "powers on" only when the gate voltage reaches a certain threshold. Different pathogens generate different electrical potentials and thus different currents. For example, cancer cells produce a different electrical current than the flu virus. No significant change in current means that no disease-relevant biomolecules are bound to the sensor (gate) surface, and vice versa.
A major disadvantage of traditional biosensors based on field-effect transistors is that the test surface cannot be reused and the entire transistor needs to be discarded after use, which is costly and not environmentally friendly. To solve this problem, the researchers used a separate electrode connected to the transistor's gate to measure changes in electrical potential.
"This gave us the opportunity to use the transistor multiple times," said Larysa Baraban, corresponding author of the study. "We separated out the gate and called it an 'extended gate' -- an extension of the test system."
To further improve the system, the researchers created an expansion gate with 32 test pads capable of detecting multiple pathogens.
"We certainly hope that this system can perform multiple analyses," Balaban said. "This means that one sample can be tested for different pathogens on each pad at the same time."
The researchers used their device to detect interleukin-6 (IL-6), a protein produced in response to infection and tissue damage. It is a potent marker of immune system activation and is elevated in inflammation, infection, autoimmune disease, cardiovascular disease, and certain cancers.
"Whether it's a simple cold or cancer, IL-6 concentrations change," Balaban said. "Different diseases and different stages of disease produce different clinical manifestations. This is why IL-6 is very suitable as a marker."
They found that adding gold nanoparticles, using an off-the-shelf nanoparticle kit designed for researchers, could concentrate or localize charges and amplify the voltage signal, thereby increasing the device's sensitivity. The sensitivity of the test was significantly higher than when working without nanoparticles.
They found that their device produced results quickly, with sensitivity and limit of detection (LOD) values that were comparable to state-of-the-art field-effect transistor-based biosensors. In fact, the device has a much lower LOD value compared to the standard enzyme-linked immunosorbent assay (ELISA) method commonly used by laboratories to detect antibodies in blood.
The researchers say their biosensing device is low-cost and has a range of potential applications, from monitoring the progress of immunotherapy in cancer patients to predicting the severity and course of viral illnesses such as influenza or COVID-19.
The research was published in the journal Biosensors and Bioelectronics.