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The diagnosis and monitoring of diabetes entail the use of blood tests, which is an invasive and expensive method of testing. Patients with diabetes exhale excess amounts of acetone during respiration. This surplus acetone production is due to the body metabolizing fats instead of glucose during energy production. Therefore, human breath analysis, particularly acetone monitoring, offers a non-invasive alternative in the field of diabetes testing. This is where semiconducting metal oxide (SMO) sensors come in.
SMOs are a non-invasive testing method for diabetes and offer a low-cost, reliable, portable, and straightforward diagnostic approach.
Acetone Monitoring for Diabetes Diagnosis
The human breath contains hundreds of volatile organic compounds (VOCs) with concentrations ranging from part-per-million (ppm) to part-per-trillion (ppt).
Acetone is a VOC that is exhaled during respiration. It is produced from the oxidation of non-esterified fatty acids, via spontaneous decarboxylation or enzymatic conversion. The acetone produced travels through the bloodstream and is excreted from the body through urine, sweat and/or exhaled breath.
Various research studies have determined that quantification of acetone concentration in human breath correlates strongly with acetone concentration in the blood. There is also a direct correlation between blood glucose levels and volatile organic compounds, particularly acetone.
The endogenous acetone concentration in human breath varies from 0.3 to 0.9 ppm in healthy people, to more than 1.8 ppm in individuals with diabetes. Therefore, acetone can act as a biomarker for diabetes using breath analysis techniques.
Conventional blood glucose tests suffer from inaccuracies due to the patients' fat loss rate, health condition, and diet. Measurement of breath acetone provides a more reliable, painless and accurate diabetes diagnosis, compared to the use of blood glucose measurements.
Nanomaterials for Acetone Measurement
In recent years, there has been an increased implementation of nanomaterials in the field of breath analysis. The nanoscale size of these materials ensures they have numerous essential properties, such as large surface-to-volume ratio and unique chemical, optical and electrical properties.
The large surface area of the nanomaterials provides highly active interfaces for the analytes to interact, increasing sensitivity and lowering the response and recovery times.
The low concentration interaction is achieved through several pre-concentration devices, minimum detectable mass, controllable morphology, and unique physical/chemical properties. This results in a sensor with better sensitivity, specificity, and portability for rapid, real-time acetone measurement.
Different nanomaterials have been exploited for VOC-sensing elements, including nanoparticles, nanotubes and nanomaterial nets. The dynamic range, as well as the selectivity of the nanomaterial-based sensors, can be tailored to accurately detect specific breath VOCs of a given disease, in this case, the detection of acetone for diabetes diagnosis.
Semiconducting Metal Oxide Sensors
SMOs are especially promising for the non-invasive diagnosis and monitoring of diabetes. They offer many advantageous properties, including a simple operating principle (resistivity change upon exposure of acetone to the SMOs surface layers), uncomplicated device fabrication, and miniaturization.
Multiple factors influence the sensitivity of SMO nanosensors. These include the chemical composition, surface modification, microstructure, and testing environment. SMO nanosensors include two mixed components, either as composites or pure metal oxides, and demonstrate increased sensitivity compared to their counterparts.
Furthermore, SMOs possess chemi-resistive properties and show a change in resistance proportional to gas or VCO concentrations. This is a fundamental feature as the acetone concentration in breath is very low, so SMO nanosensors depend on resistance variation to produce a readout.
Read more here about how blood is tested with sensors.
One of the main limitations of traditional nanostructures is the high temperature at which they operate. SMO nanosensors can be made to operate at room temperature by doping metals (noble and transition metals) or conducting polymers. This surface modification acts as a catalyst for the adsorption of ambient oxygen and the acetone biomarker.
3D-Printed SMO Acetone Sensors
The latest research in this field has led to the development of a technique to produce highly sensitive and energy-efficient sensors for acetone measurement.
3D printing is a cost-effective and straightforward production method that can be used to manufacture SMO sensors that can precisely measure the concentration of acetone vapor.
The new technique utilizes composite SMOs and a simplistic two-step fabrication to produce the acetone sensors.
The first stage of the process is the production of ink fabricated by mixing copper and iron microparticles in ethanol and stirring in polyvinyl butyral (PVB) until homogeneous.
In the printing stage, the sensor's unique structure is formed by 'direct ink writing' the metal particles onto the surface of a glass substrate. The result is a layer-by-layer building of meandering copper-iron stripes that create a bridging multi-phase SMO net.
Click here to find out more about sensors equipment.
The glass slide with the 3D-printed object is thermally annealed to produce the oxide nanostructures, and gold-coated to produce the final single sensor device.
The resulting sensor consists of a net of CuO/Cu2O/Cu nanowires and Fe2O3/Fe nanospikes. The net structure captures acetone molecules in its thicket of nanowires, which changes the resistance of the sensor and releases measurable signals.
The unique surface is visible under a high-resolution electron microscope; this reveals how the nanowires and nanospikes increase the size of the sensor surface and makes it highly sensitive to acetone detection for the diagnosis of diabetes.
The Future for SMO Sensors
Automated 3D printing can be performed at room temperature in normal ambient air. The process is ideal for industrial-scale production as several sensors can be created at the same time and within a few minutes.
The sensors are also energy efficient as only a small number of electrical signals pass through the nanowires. This makes mobile, portable testing devices conceivable and can be read directly via smartphones.
References and Further Reading
Saasa, V. et al. (2018) Sensing Technologies for Detection of Acetone in Human Breath for Diabetes Diagnosis and Monitoring. Diagnostics. https://dx.doi.org/10.3390%2Fdiagnostics8010012
Guo, D. et al. (2012) Non-invasive blood glucose monitoring for diabetics by means of breath signal analysis. Sensors and Actuators B: Chemical. https://doi.org/10.1016/j.snb.2012.06.025
Siebert, L. et al. (2020) Facile fabrication of semiconducting oxide nanostructures by direct ink writing of readily available metal microparticles and their application as low power acetone gas sensors. Nano Energy. https://doi.org/10.1016/j.nanoen.2019.104420
Kiel University (2020) 3-D printed sensors could make breath tests for diabetes possible. [Online] Phys Org. Available at: https://phys.org/news/2020-03-d-sensors-diabetes.html (Accessed on 1 May 2020).
Kalidoss, R & Umapathy, S. (2019) An overview on the exponential growth of non-invasive diagnosis of diabetes mellitus from exhaled breath by nanostructured metal oxide Chemi-resistive gas sensors and μ-preconcentrator. Biomedical Microdevices. https://doi.org/10.1007/s10544-019-0448-z
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