Lab-on-a-chip nanogenerator device developed for monitoring blood conductivity

In another example of lab-on-a-chip technology, biomedical engineers at the University of Pittsburgh have developed a nanogenerator device and artificial intelligence (AI) models for measuring the electrical conductivity of blood at low frequencies.

Potentially valuable in point-of-care and remote patient monitoring situations, the proposed self-powered millifluidic device works off triboelectrification. In this case, a blood-based triboelectric nanogenerator (TENG) system generates voltage off a few drops of blood, wrote the authors of a study published May 30 in Advanced Materials.

"Monitoring tools for blood conductivity can facilitate assessment of vital biological parameters such as hematocrit, erythrocyte sedimentation rate, cardiac output, and even conditions like Alzheimer's disease," noted lead author PhD candidate Jianzhe Luo and colleagues from the department of civil and environmental engineering and department of bioengineering at the University of Pittsburgh.

“Blood is basically a water-based environment that has various molecules that conduct or impede electric currents,” added Dr. Alan Wells, for a University of Pittsburgh Swanson School of Engineering blog post. Wells serves as medical director of University of Pittsburgh Medical Center (UPMC) Clinical Laboratories and executive vice chairman of laboratory medicine at the University of Pittsburgh.

Conductivity of blood is influenced by the composition and concentrations of electrolytes including salts (sodium chloride [NaCl]) and proteins, the researchers noted. Calcium (Ca) and magnesium (Mg) are minor contributors.

“Glucose, for example, is an electrical conductor," Wells explained. "We are able to see how it affects conductivity through these measurements. Thus, allowing us to make a diagnosis on the spot.”

Measuring conductivity at frequencies below 100 hertz (Hz) is particularly important for gaining a deeper understanding of the blood electrical properties and fundamental biological processes, the researchers added. Moreover, exploring blood conductivity at 20 Hz or below can contribute to the comprehension of the electrical behavior of blood at the cellular and molecular levels, they said.

Hypothesizing that electrical conductivity can be assessed by monitoring the voltage generated by the proposed blood-based TENG system, biomedical engineers manufactured portable lab-on-a-chip devices using 3D printing.

Each device consists of multiple components: a sealed hollow chamber for blood containment, a polytetrafluoroethylene (PTFE) disc, copper electrodes, polymethyl methacrylate (PMMA) elements, a spring-loaded push trigger cap, and a cap shaft. Blood taken by fingerstick is directly transferred to sealed hollow channels in the device.

Vision of the proposed research for developing a self-powered, millifluidic lab-on-a-chip device to determine blood conductivity.Vision of the proposed research for developing a self-powered, millifluidic lab-on-a-chip device to determine blood conductivity.Image courtesy of Amir Alavi, PhD, University of Pittsburgh Swanson School of Engineering

"The blood infilling the hollow channel creates a conductive layer sandwiched between two [polymethyl methacrylate] PMMA layers," Luo and colleagues explained. In a TENG system, electron transfer and charge separation generate a voltage difference that drives electric current when the materials experience relative motion such as compression or sliding.

The researchers tested efficacy of the device in two stages, first using simulated body fluid and then using human blood plasma. They also checked for measurements and performance at different temperatures as temperature fluctuations are known to influence blood properties and increase conductivity. Operating as a TENG system, the device proved optimal for applications requiring low-frequency measurements (≤1–20 Hz), the team found.

Furthermore, they used an advanced AI technique to model the intricate relationships among generated voltage, electrolyte concentrations, and blood conductivity.

Trained on a dataset of device-generated voltage and corresponding conductivity measurements obtained using a commercial benchtop conductivity meter, the developed AI model exhibited promising accuracy and potential for real-time electrical conductivity measurement, Luo and colleagues wrote. The results serve as a promising proof-of-concept; however, the researchers noted that a substantially larger database is necessary to calibrate the AI models and ensure enhanced reliability in blood conductivity measurements.

While traditional blood conductivity measurement methods are reliable, the nanogenerator device has self-powering capability and additional equipment is not needed, according to the researchers.

Currently the device is a disposable, portable, pocket-size tool to determine blood conductivity at the point of care. However, assistant professor at Swanson School of Engineering Amir Alavi, PhD, told that such blood-powered nanogenerators can function anywhere within the body where blood is present.

"This opens the exciting possibility of designing implantable, self-powered diagnostic devices," Alavi said. "These devices could use blood flow to generate electricity, powering sensors and diagnostics directly within the body.

"For instance, in theory, it might be possible to utilize the artery itself as part of a miniaturized nanogenerator system," Alavi said. "Imagine tiny triboelectric elements embedded near the artery or wrapped around it, converting the pressure fluctuations of blood flow into electricity."

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