Léonard Bezinge

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Bezinge

First Name

Léonard

ORCID

0000-0002-9733-9697

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Publications 1 - 10 of 18

Kinetics of nanocrystal synthesis in a microfluidic reactor: theory and experiment
Maceiczyk, Richard; Bezinge, Léonard; deMello, Andrew J. (2016)
Reaction Chemistry & Engineering
Pick a Color MARIA: Adaptive Sampling Enables the Rapid Identification of Complex Perovskite Nanocrystal Compositions with Defined Emission Characteristics
Bezinge, Léonard; Maceiczyk, Richard; Lignos, Ioannis; et al. (2018)
ACS Applied Materials & Interfaces
Laser-Pyrolyzed Graphenic Paper: Toward Smart Electrochemical Diagnostic Tests
Bezinge, Léonard (2023)
Microfluidic paper-based analytical devices, such as lateral flow assays, are indispensable tools for disease diagnostics. Their utility stems from their low cost, portability, and ease of operation via passive capillary flow. While nearly all tests rely on qualitative colorimetric readouts, electrochemical signal transduction offers an attractive route toward device miniaturization and quantitative signal output. Unfortunately, electrode fabrication on paper is a daunting challenge due to the inhomogeneous nature of this fibrous material, and the cost and complexity of current fabrication techniques are often prohibitive for single-use applications. Furthermore, current conventional deposition techniques result in non-porous electrodes, posing significant limitations for capillary-driven flow-based bioassays. In this thesis, we introduce an innovative platform that combines paper-based microfluidics with laser-pyrolyzed electronics and demonstrate its utility in rapid diagnostic tests. Our method involves creating electrodes embedded in paper through laser-induced pyrolysis of the cellulose itself. This approach allows us to exploit cellulose both as a substrate for driving capillary flow and as the precursor for the graphenic electrodes. The electrodes, patterned using a commercial CO2-laser engraver, exhibit high conductivity, a porous electroactive structure, and permeability to capillary flow. Combined with wax patterning of microfluidic channels, we leverage this electrofluidic platform to design clinically-relevant capillary-driven diagnostic tests. This thesis details the entire development process, from optimizing the fabrication and characterizing the material at the nano- and microscale, to constructing functional devices. In particular, we have developed two devices that capitalize on the permeable and embedded nature of the electrodes: (i) a vertical flow electrochemical immunoassay, which we apply for antibody serology testing or nucleic acid detection, and (ii) a flow injection analysis device for high-throughput detection of small molecules and enzyme in urine or serum samples. With the aim of simplifying these tests further, we showcase two-electrode detection schemes that facilitate fabrication and reader circuitry. We also focus on maximizing the capabilities of the reader to harness the wealth of data provided by the embedded sensors. Through the use of real-time algorithms, we demonstrate systems in which the synergy between test and reader unlocks novel functionalities. These include tracking fluid movement within the test and acting as an intelligent device that navigates the user through the test protocol while alerting them of irregularities. To conclude, this platform provides an accessible method for fabricating electrodes on paper without specialized equipment. The unique properties and morphology of the electrodes pave the way for novel functionalities, enhanced interconnectivity with readers, and the creation of innovative device architectures for a wide range of applications in analytical sciences.
Electrochemical Paper-Based Microfluidics: Harnessing Capillary Flow for Advanced Diagnostics
Bezinge, Léonard; Shih, Chih-Jen; Richards, Daniel A.; et al. (2024)
Small
Electrochemical paper-based microfluidics has attracted much attention due to the promise of transforming point-of-care diagnostics by facilitating quantitative analysis with low-cost and portable analyzers. Such devices harness capillary flow to transport samples and reagents, enabling bioassays to be executed passively. Despite exciting demonstrations of capillary-driven electrochemical tests, conventional methods for fabricating electrodes on paper impede capillary flow, limit fluidic pathways, and constrain accessible device architectures. This account reviews recent developments in paper-based electroanalytical devices and offers perspective by revisiting key milestones in lateral flow tests and paper-based microfluidics engineering. The study highlights the benefits associated with electrochemical sensing and discusses how the detection modality can be leveraged to unlock novel functionalities. Particular focus is given to electrofluidic platforms that embed electrodes into paper for enhanced biosensing applications. Together, these innovations pave the way for diagnostic technologies that offer portability, quantitative analysis, and seamless integration with digital healthcare, all without compromising the simplicity of commercially available rapid diagnostic tests.
Quantitative reagent monitoring in paper-based electrochemical rapid diagnostic tests
Bezinge, Léonard; deMello, Andrew J.; Shih, Chih-Jen; et al. (2024)
Lab on a Chip
Paper-based rapid diagnostic tests (RDTs) are an essential component of modern healthcare, particularly for the management of infectious diseases. Despite their utility, these capillary-driven RDTs are compromised by high failure rates, primarily caused by user error. This limits their utility in complex assays that require multiple user operations. Here, we demonstrate how this issue can be directly addressed through continuous electrochemical monitoring of reagent flow inside an RDT using embedded graphenized electrodes. Our method relies on applying short voltage pulses and measuring variations in capacitive discharge currents to precisely determine the flow times of injected samples and reagents. This information is reported to the user, guiding them through the testing process, highlighting failure cases and ultimately decreasing errors. Significantly, the same electrodes can be used to quantify electrochemical signals from immunoassays, providing an integrated solution for both monitoring assays and reporting results. We demonstrate the applicability of this approach in a serology test for the detection of anti-SARS-CoV-2 IgG in clinical serum samples. This method paves the way towards "smart" RDTs able to continuously monitor the testing process and improve the robustness of point-of-care diagnostics.
Simplifying the complex: accessible microfluidic solutions for contemporary processes within in vitro diagnostics
Khosla, Nathan K.; Lesinski, Jake M.; Colombo, Monika; et al. (2022)
Lab on a Chip
In vitro diagnostics (IVDs) form the cornerstone of modern medicine. They are routinely employed throughout the entire treatment pathway, from initial diagnosis through to prognosis, treatment planning, and post-treatment surveillance. Given the proven links between high quality diagnostic testing and overall health, ensuring broad access to IVDs has long been a focus of both researchers and medical professionals. Unfortunately, the current diagnostic paradigm relies heavily on centralized laboratories, complex and expensive equipment, and highly trained personnel. It is commonly assumed that this level of complexity is required to achieve the performance necessary for sensitive and specific disease diagnosis, and that making something affordable and accessible entails significant compromises in test performance. However, recent work in the field of microfluidics is challenging this notion. By exploiting the unique features of microfluidic systems, researchers have been able to create progressively simple devices that can perform increasingly complex diagnostic assays. This review details how microfluidic technologies are disrupting the status quo, and facilitating the development of simple, affordable, and accessible integrated IVDs. Importantly, we discuss the advantages and limitations of various approaches, and highlight the remaining challenges within the field.
Real-time, smartphone-based processing of lateral flow assays for early failure detection and rapid testing workflows
Colombo, Monika; Bezinge, Léonard; Rocha Tapia, Andres; et al. (2023)
Sensors & Diagnostics
Despite their simplicity, lateral flow immunoassays (LFIAs) remain a crucial weapon in the diagnostic arsenal, particularly at the point-of-need. However, methods for analysing LFIAs still rely heavily on sub-optimal human readout and rudimentary end-point analysis. This negatively impacts both testing accuracy and testing times, ultimately lowering diagnostic throughput. Herein, we present an automated computational imaging method for processing and analysing multiple LFIAs in real-time and in parallel. This method relies on the automated detection of signal intensity at the test line, control line, and background, and employs statistical comparison of these values to predictively categorise tests as “positive”, “negative”, or “failed”. We show that such a computational methodology can be transferred to a smartphone and detail how real-time analysis of LFIAs can be leveraged to decrease the time-to-result and increase testing throughput. We compare our method to naked-eye readout and demonstrate a shorter time-to-result across a range of target antigen concentrations and fewer false negatives compared to human subjects at low antigen concentrations.
Paper-Based Laser-Pyrolyzed Electrofluidics: An Electrochemical Platform for Capillary-Driven Diagnostic Bioassays
Bezinge, Léonard; Lesinski, Jake M.; Suea-Ngam, Akkapol; et al. (2023)
Advanced Materials
Microfluidic paper-based analytical devices (µPADs) are indispensable tools for disease diagnostics. The integration of electronic components into µPADs enables new device functionalities and facilitates the development of complex quantitative assays. Unfortunately, current electrode fabrication methods often hinder capillary flow, considerably restricting µPAD design architectures. Here, laser-induced graphenization is presented as an approach to fabricate porous electrodes embedded into cellulose paper. The resulting electrodes not only have high conductivity and electrochemical activity, but also retain wetting properties for capillary transport. Paper-based electrofluidics, including a lateral flow device for injection analysis of alkaline phosphatase in serum and a vertical flow device for quantitative detection of HPV16 with a CRISPR-based assay are demonstrated. It is expected that this platform will streamline the development of diagnostic devices that combine the operational simplicity of colorimetric lateral flow tests with the added benefits and possibilities offered by electronic signaling.
Stochastic Nucleation of Polymorphs: Experimental Evidence and Mathematical Modeling
Maggioni, Giovanni M.; Bezinge, Léonard; Mazzotti, Marco (2017)
Crystal Growth & Design
Correction: Real-time, smartphone-based processing of lateral flow assays for early failure detection and rapid testing workflows
Colombo, Monika; Bezinge, Léonard; Rocha Tapia, Andres; et al. (2024)
Sensors & Diagnostics
Correction for 'Real-time, smartphone-based processing of lateral flow assays for early failure detection and rapid testing workflows' by Monika Colombo et al., Sens. Diagn., 2023, 2, 100-110, https://doi.org/10.1039/D2SD00197G.

Publications 1 - 10 of 18

Léonard Bezinge

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