The growing role of biosensors

Part 2: Professor Laura Lechuga, biosensor pioneer 

Professor Lechuga, a leading biosensor researcher, explains the challenges involved in developing medical biosensors and why, due to covid, the technology's time has come.  

Professor LechugaLaura Lechuga is a multideciplinarian. She read chemistry at university, did a doctorate in physics while her postdoctoral research was in electrical engineering. She has even worked in a cleanroom, making chips.

Group leader at the NanoBiosensors and Bioanalytical Applications Group at the Catalan Institute of Nanoscience and Nanotechnology (ICN2), Lechuga thus has an ideal background for biosensor research.

Biosensors are used for health, environmental, food control, veterinary and agriculture applications. They are used to test for chemical substances and comprise a biological element and an optical sensor.

Her initial focus was environmental biosensors but she quickly switched to medical devices, partly because of the great interest healthcare generates.

Biosensors

The main two optical sensor technologies used for biosensors are surface plasmon resonance (SPR) and silicon photonics circuits. Biochemistry is used to catch the tiny biomaterials - analytes - being tested for. Analytes can be organic compounds, bacteria, viruses and gases.

Microfluidics is a third element used, to deliver precisely the fluid samples to the sensor. All three components – the sensor, biochemistry and microfluidics – must work in unison for the biosensor to deliver highly reliable, repeatable performance.

Medical diagnostics 

The medical diagnostics market spans traditional lab equipment found in hospitals and central labs; newer bench-top equipment known as point-of-care systems, and home testing and portable devices including wearables used for medical diagnostics and for health and wellbeing. 

Established medical diagnostics companies using SPR-based systems include GE Healthcare’s Cytiva and Nicoya Lifesciences. Meanwhile, several start-ups are coming to market with point-of-care systems based on silicon photonics. These include Genalyte, SiDx, SiPhox and Antelope DX. Genalyte is over 10-years-old and has a product while the other start-ups are all bringing products to market.

These point-of-care systems deliver rapid test results: a wait of 20-30 minutes instead of the current practice of sending off a sample to a centralised lab and waiting hours or even days for the results.

Such point-of-care systems can be used in intensive care, ambulances, doctors’ offices and locations such as rural clinics.

Most doctors would love to have such platforms providing rapid analysis for everything, says Lechuga, who works with doctors in a main public hospital in Spain and across Europe as part of EU projects.

In intensive care, it’s much better if tests can be done there rather than have to send the sample to a lab and wait for the results, she says. The same applies to emergency rooms and ambulances where with just a drop of blood, saliva or urine, near-immediate insights are possible.

Another attraction of biosensor technologies based on SPR and silicon photonics is they enable compact, cheaper systems that can measure multiple health indicators - biomarkers - in parallel, a technique referred to as multiplexing.

But medical diagnostics is a challenging market to enter.

“We have been pushing to go to market with point-of-care equipment for many different applications but the big diagnostic industry that sells to the labs have always been critical, saying this is not going to become a big business," says Lechuga. "But this is not true.”

The same applies to portable equipment and smartphone-coupled biosensors. Once a biosensor works, it is straightforward to connect it to a smartphone or tablet, says Lechuga.

Such a device would serve people with chronic diseases such as diabetics, or celiac sufferers where it could help control what they eat. Also, for anticoagulants, it is hard to control doses and a biosensor device would help here.

SPR and silicon photonics

Optical detection SPR systems use a laser, a prism attached to a gold surface and a detector. Light is shone through the prism and is reflected from the gold layer before being detected. At a certain incident angle, the light causes electron resonance on the gold surface causing the reflected light intensity to dip.

Attaching receptors to the gold surface tailored to the analyte causes the a shift in resonance angle. The angle change can be used to measure the presence of the tested-for material.

In contrast, silicon photonics-designs measure refractive index changes in the light caused by analytes attached to receptors on the surface of the sensor. Two sensor designs are used: a laser with either a Mach-Zehnder interferometer (MZI) or a ring resonator.

The ring resonator is smaller than the MZI, making it ideal for compact, multiplexed designs. SPR and ring-resonator biosensors have comparable sensitivity while the MZI's exceeds both.

An SPR sensor's measurements can be variable requiring the system to be robust and temperature controlled. However, its biochemistry is simpler compared to that of a silicon photonics design. The advantage of silicon photonics is that it can be mass produced to enable low-cost designs, important for a disposable biosensor design.

Lechuga's group is a rarity among research centres in that it researches both optical sensor types.

During her postdoc spell in The Netherlands, Lechuga was at a biosensor lab that used both technologies. When she returned to Spain, she decided to research both. At that time her main focus was silicon photonics but she realised SPR was easier.

“I try to maintain the two," says Lechuga. "I love the two of them so much: it is like having a husband and a lover.”

Overall, Lechuga favours plasmonics. “Anything similar to plasmonics can’t compete," she says. "Plasmonics is probably the most wonderful biosensing technology.”

Lechuga says that whatever work her lab does, it is always benchmarked with plasmonics. From a chemistry and biological point of view, plasmonics is a simpler design.

That said, medical diagnostics start-up SiDx is a proponent of silicon photonics because of its precision manufacturing and scalability. And Aryballe, a start-up that has a biosensor product for odour detection, is switching its design from SPR to silicon photonics. Aryballe says it is switching since its odour product has to be robust and accurate.

Challenges 

Lechuga stresses the challenge of developing the required chemistry to make the biosensor functional.

Lechuga’s research group has spent years developing its chemistry know-how and has mastered how to analyse samples without having to clean and filter them first.

She says many biosensor research groups haven’t invested the time in solving the chemistry because it is hard and time-consuming. But with sufficient resources, it can be solved and once it is, the biosensor can be used in any location and marketplace.

Lechuga cites as an example the glucose sensor that uses proteins for the biochemistry. These proteins must work in all sort of regions, across a range of temperatures and humidities.

Her group is also developing a tuberculosis biosensor and it has taken some 18 months to create the associated chemistry.

Research focus in the coming years 

Lechuga says the pandemic has highlighted the shortfall of centralised testing and the question is what will happen now.

“We should focus to translate all these technologies as soon as possible to the market," says Lechuga. "We should choose the best, most promising technologies and move them the market as soon as possible to have these point-of-care technologies.”

There is also much research to be done to refine biosensors and their multiplexing capabilities.

"The multiplexing capabilities is one of the main problems, as is the integration with microfluidics and how to handle samples," she says. "Many of these issues we still have to solve."

Non-medical applications is another obvious area for research. “We have a very big environmental problem,” she says. "Food is also important, as is agricultural control."

Once the basic biosensor technology is available, the same system can be used for different applications simply by interchanging the sensor cartridge.

”There is room for many companies,” concludes Lechuga.

Further Information:

Nanophotonic Biosensors: Driving Personalised Medicine, click here