Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays
Abstract Rapid mixing and precise timing are key for accurate biomedical assay measurement, particularly when the result is determined as the rate of a reaction: for example rapid immunoassay in which the amount of captured target is kinetically determined; determination of the concentration of an e...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-58720-5 |
| _version_ | 1827277224508653568 |
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| author | David E. Williams Wei Li Mithileshwari Chandrasekhar Carsten Ma On Wong Corazza Gerrit Sjoerd Deijs Lionel Djoko Bhavesh Govind Ellen Jose Yong Je Kwon Tiffany Lowe Anil Panchal Gabrielle Reshef Matheus J. T. Vargas M. Cather Simpson |
| author_facet | David E. Williams Wei Li Mithileshwari Chandrasekhar Carsten Ma On Wong Corazza Gerrit Sjoerd Deijs Lionel Djoko Bhavesh Govind Ellen Jose Yong Je Kwon Tiffany Lowe Anil Panchal Gabrielle Reshef Matheus J. T. Vargas M. Cather Simpson |
| author_sort | David E. Williams |
| collection | DOAJ |
| description | Abstract Rapid mixing and precise timing are key for accurate biomedical assay measurement, particularly when the result is determined as the rate of a reaction: for example rapid immunoassay in which the amount of captured target is kinetically determined; determination of the concentration of an enzyme or enzyme substrate; or as the final stage in any procedure that involves a capture reagent when an enzyme reaction is used as the indicator. Rapid mixing and precise timing are however difficult to achieve in point-of-care devices designed for small sample volumes and fast time to result. By using centrifugal microfluidics and transposing the reaction surface from a chamber to a single mm-scale bead we demonstrate an elegant and easily manufacturable solution. Reagents (which may be, for example, an enzyme, enzyme substrate, antibody or antigen) are immobilised on the surface of a single small bead (typically 1–2 mm in diameter) contained in a cylindrical reaction chamber subjected to periodically changing rotational accelerations which promote both mixing and uniform mass-transfer to the bead surface. The gradient of Euler force across the chamber resulting from rotational acceleration of the disc, dΩ disc /dt, drives circulation of fluid in the chamber. Oscillation of Euler force by oscillation of rotational acceleration with period, T, less than that of the hydrodynamic relaxation time of the fluid, folds the fluid streamlines. Movement of the bead in response to the fluid and the changing rotational acceleration provides a dynamically changing chamber shape, further folding and expanding the fluid. Bead rotation and translation driven by fluid flow and disc motion give uniformity of reaction over the surface. Critical parameters for mixing and reaction uniformity are the ratio of chamber radius to bead radius, r chamber /r bead , and the product Tr chamber (dΩ disc /dt), of oscillation period and Euler force gradient across the fluid. We illustrate application of the concept using the reaction of horse radish peroxidase (HRP) immobilised on the bead surface with its substrate tetramethylbenzidine (TMB) in solution. Acceleration from rest to break a hydrophobic valve provided precise timing for TMB contact with the bead. Solution uniformity from reaction on the surface of the bead in volumes 20–50 uL was obtained in times of 2.5 s or less. Accurate measurement of the amount of surface-bound HRP by model fitting to the measured kinetics of colour development at 10 s intervals is demonstrated. |
| first_indexed | 2024-04-24T07:16:07Z |
| format | Article |
| id | doaj.art-558287d8b6a845d58f648f02a327451e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T07:16:07Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-558287d8b6a845d58f648f02a327451e2024-04-21T11:16:23ZengNature PortfolioScientific Reports2045-23222024-04-0114111310.1038/s41598-024-58720-5Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assaysDavid E. Williams0Wei Li1Mithileshwari Chandrasekhar2Carsten Ma On Wong Corazza3Gerrit Sjoerd Deijs4Lionel Djoko5Bhavesh Govind6Ellen Jose7Yong Je Kwon8Tiffany Lowe9Anil Panchal10Gabrielle Reshef11Matheus J. T. Vargas12M. Cather Simpson13School of Chemical Sciences, University of AucklandOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdOrbis Diagnostics LtdAbstract Rapid mixing and precise timing are key for accurate biomedical assay measurement, particularly when the result is determined as the rate of a reaction: for example rapid immunoassay in which the amount of captured target is kinetically determined; determination of the concentration of an enzyme or enzyme substrate; or as the final stage in any procedure that involves a capture reagent when an enzyme reaction is used as the indicator. Rapid mixing and precise timing are however difficult to achieve in point-of-care devices designed for small sample volumes and fast time to result. By using centrifugal microfluidics and transposing the reaction surface from a chamber to a single mm-scale bead we demonstrate an elegant and easily manufacturable solution. Reagents (which may be, for example, an enzyme, enzyme substrate, antibody or antigen) are immobilised on the surface of a single small bead (typically 1–2 mm in diameter) contained in a cylindrical reaction chamber subjected to periodically changing rotational accelerations which promote both mixing and uniform mass-transfer to the bead surface. The gradient of Euler force across the chamber resulting from rotational acceleration of the disc, dΩ disc /dt, drives circulation of fluid in the chamber. Oscillation of Euler force by oscillation of rotational acceleration with period, T, less than that of the hydrodynamic relaxation time of the fluid, folds the fluid streamlines. Movement of the bead in response to the fluid and the changing rotational acceleration provides a dynamically changing chamber shape, further folding and expanding the fluid. Bead rotation and translation driven by fluid flow and disc motion give uniformity of reaction over the surface. Critical parameters for mixing and reaction uniformity are the ratio of chamber radius to bead radius, r chamber /r bead , and the product Tr chamber (dΩ disc /dt), of oscillation period and Euler force gradient across the fluid. We illustrate application of the concept using the reaction of horse radish peroxidase (HRP) immobilised on the bead surface with its substrate tetramethylbenzidine (TMB) in solution. Acceleration from rest to break a hydrophobic valve provided precise timing for TMB contact with the bead. Solution uniformity from reaction on the surface of the bead in volumes 20–50 uL was obtained in times of 2.5 s or less. Accurate measurement of the amount of surface-bound HRP by model fitting to the measured kinetics of colour development at 10 s intervals is demonstrated.https://doi.org/10.1038/s41598-024-58720-5 |
| spellingShingle | David E. Williams Wei Li Mithileshwari Chandrasekhar Carsten Ma On Wong Corazza Gerrit Sjoerd Deijs Lionel Djoko Bhavesh Govind Ellen Jose Yong Je Kwon Tiffany Lowe Anil Panchal Gabrielle Reshef Matheus J. T. Vargas M. Cather Simpson Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays Scientific Reports |
| title | Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays |
| title_full | Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays |
| title_fullStr | Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays |
| title_full_unstemmed | Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays |
| title_short | Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays |
| title_sort | lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays |
| url | https://doi.org/10.1038/s41598-024-58720-5 |
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