The researchers improved the accuracy of family-based continuous glucose monitoring

Until now, family-based continuous glucose monitoring systems for diabetics have had to trade ease of use, low cost, and portability for lower sensitivity and accuracy
compared to similar systems in clinics or hospitals.
Now, a team of researchers has developed a biosensor for such monitors, which includes "zero-dimensional" quantum dots (QDs) and gold nanospheres (AUNS), and no longer has to compromise
on accuracy.

A paper describing biosensor design and its enhanced performance was published in the Nov.
9, 2022 issue of
the journal Nanoresearch.

In recent years, the development of continuous blood glucose monitoring (CGM) technology has brought great benefits
to diabetics.
Unlike pre-meal and bedtime glucose testing, round-the-clock CGM devices detect blood glucose levels in real time, quickly, and accurately, significantly improving diabetes management
.
Glucose trends are easier to track, making diet, exercise and medication changes to diabetes care plans easier to execute throughout the day, alerting when blood sugar levels climb too high or too low, sending information to individuals or parents, partners or caregivers
.

CGMs typically work by implanting miniature biosensors under the skin that measure glucose levels
in the intercellular fluid.
This sensor checks every few minutes and sends information to a monitor
.
The monitor can also be connected to an
insulin pump.

Various glucose detection techniques have been developed, including colorimetry, infrared spectroscopy, fluorescence spectroscopy, and mass spectrometry
.
But for home operations rather than in clinics or hospitals, electrochemical glucose detection is the most widely accepted technique because it is responsive, easy to use, low-cost, and portable
.

Liu Huan, a microelectronics expert at the School of Optics and Electronic Information of Huazhong University of Science and Technology, said: "Its sensitivity is also good, but it is not very good
.
" "This is not the case
compared to other technologies used in healthcare settings.
So we wanted to see if we could improve this sensitivity and therefore its accuracy
.
”

Electrochemical glucose sensors can be divided into enzyme-based sensors and non-enzyme-based sensors
.
Among enzyme-based glucose electrochemical sensors, glucose oxidase (GOx)—an enzyme that accelerates (catalyzes) oxidation-reduction chemical reactions—is widely used to oxidize glucose
on the electrode surface of CGM sensors.
The electrodes absorb electrons from glucose (oxidize them) and in the process generate an electric current
that varies with glucose levels.
GOx is widely used for this purpose
because of its high selectivity to glucose (ability to select glucose over other substances), high stability, and high activity at a wide range of pH levels.

However, when GOx binds directly to the surface of the bare electrode, not only does GOx itself easily fall off (stripping off some of its layers), but its biological activity and stability are also affected
.
In addition, the electron transfer efficiency between GOx and the electrode surface is a key factor
in determining sensor sensitivity.

So far, many attempts have been made to make the GOx enzyme more firmly attached to the electrode, thereby enhancing direct electron transfer
between the electroactive center (electron-active site) and the electrode surface.
A notable attempt is to use nanoscale designed electrodes so that the structure on the electrode provides greater surface area and higher electrocatalytic activity
.
Unfortunately, these nanostructures add to the complexity of
fabricating such electrochemical biosensors.
Their construction also relies on the synthetic polymer Nafion as a scaffold, which creates barriers
to the transfer of charge at the interface between the sensor and the measured fluid.

Therefore, the researchers conducted a study in a completely different direction
.
The team's goal is to improve glucose sensing performance
by using colloidal quantum dots (CQDs) as materials for modifying electrodes.
CQD is a "zero" dimensional semiconductor nanoparticle
.
(They are not actually zero-dimensional, but very tiny in diameter, usually between 2 and 20 nanometers)
。 They are rich in active sites (where chemical reactions occur) and can bind
very stably to biological protein molecules.

Even better, because CQD is very small, it undergoes quantum effects such as quantum tunneling, and charge transfer at the CQD-protein interface can be adjusted
by the application of an external electric field.
CQD is also compatible with a range of different rigid and flexible substrate materials, making them easier to manufacture
.

To enhance this effect, the researchers integrated gold "nanospheres" (auns) into the structure of the sensor's
electrodes.
These are ultra-tiny spherical nanoparticles
with a diameter between 10-200 nanometers.
Due to their unique physical and chemical properties, they are increasingly used in biosensing applications
.
In particular, when used as a component of enzyme electrochemical biosensors, AUNS allows protein enzymes to maintain their biological activity as they adhere to surfaces and reduces the insulating role of the protein coat for direct electron transfer
.
In CGM, this greatly enhances the signal amplitude
of the electrochemical biosensor.

The researchers constructed a proof-of-concept CGM using CQDS and aunss-modified electrodes — in this case, CQDS made from
lead sulfide.
They found that, as expected, the addition of auns significantly improved the current signal
detected by the electrochemical sensor.

Combined, these changes show great potential in detecting glucose in different samples such as blood, sweat, and other body fluids, providing a fast (less than 30 seconds) electrochemical biosensor with a wide detection range and the ultra-high sensitivity
the team is looking for.

The researchers now aim to use their proof-of-concept CGM for commercial-scale production
.