A handheld unit could be used to create bespoke diagnostic systems for medical professionals.
One day in the not-too-distant future, medical professionals will be able to test patients for life-threatening diseases in minutes, rather than days.
That is the vision of engineers at National Physical Laboratory (NPL) spin-out Argento Diagnostics, which recently took the wraps off a customisable ’technology platform’ that could be used by its customers to build small, handheld units that could test for a range of diseases.
Argento’s technology provides a quick, full diagnosis from a single sample (such as blood or urine), returning results within minutes. The results can quickly identify medical conditions or injuries, enabling rapid treatment before long-term damage can be done and increasing chances of a quick recovery.
The biomarkers that the Argento Diagnostics system is capable of detecting include proteins in bodily fluids, which can reflect the presence or severity of a particular disease. The company has also shown that its system is capable of detecting specific viruses or hormones as well.
The Argento technology platform appears simple enough – it comprises a test strip and a reader. Once a sample from a patient has been taken, it is placed onto the test strip and then inserted into the reader, which performs a specific analysis of the sample and presents the results on an LCD screen.
Although the procedure itself is straightforward, the innovative chemical and electronic processes used by the system to actually perform the tests on samples are key to its effectiveness, according to Dr Rob Porter, chief scientific officer of Argento Diagnostics.
The microfluidic slide used in the system contains a number of chemicals in a reaction chamber that are used to capture proteins of interest in a sample. These are then channelled through a microfluidic pathway to a sensor, through which the amount of protein present can be determined by the reader.
More specifically, two types of molecules on the microfluidic slide must be tailored to bind to a specific protein or hormone that is to be measured. One of these is a positively charged silver nanoparticle, while the other is a small magnetic bead. Both are coated with a monoclonal (or polyclonal) antibody in order that they can attach themselves to the target analyte or sample under analysis.
Once a sample is placed on the slide, both the positively charged nanoparticle and the magnetic bead attach themselves to the target forming a complex chemical sandwich.
Porter said: ’Proteins have several binding sites onto which antibodies can attach themselves. So, if you can get two antibodies binding to a specific protein, you can bind both a magnetic particle and a silver particle to the protein, because these bind to different areas on the protein, they stick to it on different sides and form a sandwich.’
The complex sandwich containing the nanoparticle, the magnetic bead, and protein or hormone to be targeted can then be moved around the test strip by applying a magnetic field across the sample on the slide.
After a short incubation period – typically around three minutes in the reaction chamber on the strip – electromagnets activated in the test strip pull the complexes formed away from the chamber into a measurement zone while the remaining unbound silver nanoparticles are left behind.
’Since only the silver nanoparticles that enter the measurement zone are bound to the protein that was in the solution, it is then possible for the reader to determine the concentration of the proteins that are in the solution based on the number of nanoparticles that are present,’ said Porter.
To extract the nanoparticles from the complex, the chemical complex brought to the measurement area interacts with a solution of a thiol called ammonia thiocyanate, although Porter says that other thiols could also be used to the same effect.
The thiol effectively wraps itself around the complex, forming a negatively charged aggregated monolayer around the silver nanoparticles. This makes the complex negatively charged while also removing the magnetic particle. Once in the measurement area, the negatively charged coated silver nanoparticles are then drawn towards a positive electrode, which they effectively electroplate.
Next, using a process known as anodic stripping voltammetry (ASV) – a technique invented in the 1920s – the electroplated silver metal nanoparticles are then sequentially stripped off the electrode as millions of silver ions, which generates a current that can be measured.
’The current produced in the process is proportional to the amount of metal ions being stripped off, which in turn is proportional to the expressed amount of biomarker. The beauty of the technique is that since the number of ions in any given nanoparticle can be in the millions, the effect is that the ASV technique effectively “amplifies” the readings,’ said Porter.
Having made such measurements, the device can then analyse the level of biomarker present and, using a computer program, summarise it on an on-screen readout.
Keith Page, chief executive at Argento Diagnostics, is quick to point out that the system must be tailored for use by customers who will want to customise it to identify specific diseases by coating both the nanoparticle of silver and the magnetic bead with antibodies specific to the analyte that is to be detected.
That’s why, he said, the company is in discussions with several parties who are interested in using the technology to build their own bespoke devices that could be used in emergency treatment, veterinary, bio-defence and environmental applications. For confidentiality reasons, Page was unable to disclose who many of these companies are. However, UK Sport is to use the technology to improve training programmes for athletes.
UK Sport expects to use the platform to allow athletes to monitor biomarker proteins that reveal details about the condition of the body before, during and after training sessions. These biomarkers can give a clear indication of their physical health and the effectiveness of a particular training programme.
Dr Scott Drawer, head of research and innovation at UK Sport, said: ’Real-time monitoring will enable training to be customised not only to the individual but also to their current condition.’