Advancing Biomedical Engineering through High-Precision 3D Printing Innovation

The University of North Carolina (UNC) is at the forefront of medical innovation, leveraging micro-precision 3D printing technology to develop advanced healthcare solutions. Professor Roger Narayan and his team at the Joint Department of Biomedical Engineering turned to Boston Micro Fabrication’s (BMF) micro 3D printers for various applications, including lidocaine detection, pH sensing, ISF extraction, and 5-HT sensing, where resolution, accuracy, and precision were crucial and could not be achieved with traditional manufacturing methods.

Development of a Point-of-Care Device for Lidocaine Detection

Lidocaine patches have been widely used in clinical settings to alleviate discomfort and pain. While these patches offer significant benefits, overdosage can lead to severe side effects impacting the cardiovascular and central nervous systems, posing life-threatening risks. Therefore, there is a crucial need for a rapid, sensitive, and user-friendly point-of-care device capable of onsite lidocaine detection.

To address this need, the team at UNC has developed an advanced machine learning-enabled, wireless microneedle array integrated with a screen-printed electrode-based electrochemical point-of-care device. This innovative device is designed for the rapid and effective detection of lidocaine levels. Following the successful completion of their initial research project, the results confirmed the efficacy of their proposed 3D-printed microneedle array-based sensing platform. This platform demonstrated the capability to detect micromolar concentrations of lidocaine in artificial interstitial fluid.

Using a microArch S130 2µm 3D printer, the team was able to print the customized microneedle array design of different resolutions and sizes with precision and accuracy. This technological capability was instrumental in developing the microneedle array-based biosensing device for lidocaine detection.

The promising results indicate that this platform can be further explored for the development of various electrochemical sensors, facilitating the onsite detection of other biomarkers in interstitial fluid. This advancement holds significant potential for enhancing patient safety and improving clinical outcomes in diverse healthcare settings.

Schematic representation of machine learning-enabled wireless micro needle array integrated screen-printed electrode-based electrochemical point-of-care device for lidocaine detection. (a) Expanded view of components and stepwise assembly process of the micro needle array integrated device. (b) Fully assembled device on skin layer. (c) Fully assembled device connected with wireless sensor. (d) Wireless readout device for further analysis through machine learning enabled linear regression models followed by digital visualization of lidocaine concentration.

Development of a Microneedle-Based Colorimetric pH Sensing Patch

pH levels play a crucial role in various biological processes, affecting nutrient levels, wound healing, and chemical behavior. Consequently, food industries and healthcare are increasingly interested in developing low-cost optical pH sensors for applications such as meat spoilage detection and wound health monitoring.

To address this need, Narayan’s team has created a simple and affordable machine learning-enabled microneedle-based colorimetric pH sensing patch. This innovative patch is designed for dual applications: monitoring food quality and assessing wound health. Upon completing their research project, the in vitro results demonstrated the effectiveness of the microneedle-based colorimetric pH sensing patch. The data confirmed that the patch could be successfully used for both wound pH monitoring and meat spoilage detection.

The BMF 3D printer’s capability to produce parts with resolutions ranging from 2–25 micrometers using projection micro-stereolithography (PµSL) technology enabled the creation of intricate and exact microneedles. This precision was essential in developing the pH sensing devices.

The development of this versatile and cost-effective pH sensing patch has significant implications for both the healthcare and food industries. It offers a practical solution for ensuring food safety and enhancing wound care management, thereby improving overall health outcomes.

Illustration of the manufacturing process for the microneedle-based colorimetric pH sensing patch. (a) View of different components used in the manufacturing of pH sensing patch, (b) real-time images of the stepwise (i-vi) fabrication process of the micro needle array-based pH sensing patch, and (c) top and bottom view of the fully assembled pH sensing patch.

Development of a 3D Printed Microneedle Array-Based Device for ISF Extraction and Monitoring

Recent studies have explored various mechanisms for interstitial fluid (ISF) collection, including diffusion, vacuum convection, capillary action, osmosis (using a hydrogel), and hollow microneedle (MN) arrays. ISF flow rates differed based on the presence of convective forces, with technique efficiency ranked as follows: diffusion < capillary action < osmosis < applied pressure/suction. However, vacuum-driven systems proved to be complex, cumbersome, and limited by variable tissue hydration properties.

To overcome these challenges, Narayan’s team developed a 3D printed MN array-based point-of-care microscale device for ISF extraction and analyte monitoring. This innovative device employs pressure-driven convection to efficiently withdraw ISF. The MN integrated device successfully acquired a sufficient ISF volume (3.0 μL) for downstream analyses. The oblique structure of the MNs significantly stretched the epidermal layer at the MN tip, preventing skin folding near the tip and enhancing the skin penetration process.

The team at UNC was looking to create microneedles with heights between 500 micrometers and 1.4 millimeters. BMF’s 3D printing technology was the only one that could achieve the required accuracy and precision for these microneedles.

This 3D printed MN array-based device represents a significant advancement in ISF extraction and monitoring. Its efficient and user-friendly design offers great potential for various point-of-care applications, improving the accuracy and ease of ISF collection and analysis in clinical settings.

Figure 3. Optical images of MN arrays on a) square plate and b) cap . SEM micrographs of c) MN array, d) MN tip, and e) MN oblique view. Keyence laser scanning optical microscopy 3D image of the f) MN and g) dimensions of the MNs shown by the plot between height (y-axis) and width of the needle (x-axis). Optical images of trypan blue-coated punctured porcine skin using MN arrays of height h) 750 μm, i) 800 μm, j) 900 μm, and k) 950 μm.

Development of Carbon-Fiber Integrated Multi-Contact Electrodes for 5-HT Sensing

Traditional analyte detection methods utilize carbon fibers (10μm in diameter and ∼5cm in length) attached to copper wires. Despite the miniaturization, these designs have limitations, including the macroscopic scale of electrode interconnects, complex electrode assembly processes, and limited control over electrode spatial organization.

To address these challenges, the team at UNC developed carbon-fiber integrated multi-contact electrode (MCCFE) configurations specifically for 5-HT sensing. The MCCFEs feature individual recording electrodes in a flexible, higher-density configuration, overcoming the limitations of previous designs. The MCCFEs possess numerous electroactive sites, appropriate tensile strength, and chemical stability, all essential for effective electrochemical sensing on fiber-based platforms. Initial treatment of the carbon fibers with sonication induced cavitation events, facilitating the exfoliation of smooth carbonaceous layers. This process significantly enhanced interfacial electrode behavior, such as electrolyte penetration.

The development of MCCFEs represents a significant advancement in electrochemical sensing technology. Their improved design and functionality offer great potential for more accurate and reliable analyte detection, paving the way for enhanced applications in various scientific and medical fields.

Figure 4. Schematic illustration: (A) CAD models (a-c) and digital images of 3D-patterned array (d-f). (B) Assessment of the flexibility and bendability of the 3D array (a-d). (C) Palladium loading and conversion of spun carbon fibers to the biosensing electrodes (a-e).

To learn more about UNC’s work on the above projects please visit:

Shukla S, Machekposhti SA, Joshi N, Joshi P, Narayan RJ. Microneedle‐Integrated Device for Transdermal Sampling and Analyses of Targeted Biomarkers. Small Science. 2023 Jun;3(6):2200087.
https://doi.org/10.1002/smsc.202200087

Shukla S, Khanna S, Sahoo S, Joshi N, Narayan R. Nanomaterial-Coated Carbon-Fiber-Based Multicontact Array Sensors for In Vitro Monitoring of Serotonin Levels. ACS Applied Bio Materials. 2024 Jan 2;7(1):472-84.
https://doi.org/10.1021/acsabm.3c01089

Kadian S, Sahoo SS, Kumari P, Narayan RJ. Machine learning enabled onsite electrochemical detection of lidocaine using a microneedle array integrated screen printed electrode. Electrochimica Acta. 2024 Jan 20;475:143664.
https://doi.org/10.1016/j.electacta.2023.143664

Kadian S, Kumari P, Sahoo SS, Shukla S, Narayan RJ. Machine learning enabled microneedle-based colorimetric pH sensing patch for wound health monitoring and meat spoilage detection. Microchemical Journal. 2024 May 1;200:110350.
https://doi.org/10.1016/j.microc.2024.110350

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