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A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations

It is known that in many cases a combination of drugs is more effective than single-drug treatments both for reducing toxicity and increasing efficacy. With the advent of organoid screens, personalised medicine has become possible for many diseases. Automated pipetting to well plates is the pharmace...

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Autores principales: Davies, Mark, Abubaker, Mannthalah, Bible, Lorraine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603205/
https://www.ncbi.nlm.nih.gov/pubmed/33080987
http://dx.doi.org/10.3390/mi11100943
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author Davies, Mark
Abubaker, Mannthalah
Bible, Lorraine
author_facet Davies, Mark
Abubaker, Mannthalah
Bible, Lorraine
author_sort Davies, Mark
collection PubMed
description It is known that in many cases a combination of drugs is more effective than single-drug treatments both for reducing toxicity and increasing efficacy. With the advent of organoid screens, personalised medicine has become possible for many diseases. Automated pipetting to well plates is the pharmaceutical industry standard for drug screening, but this is relatively expensive and slow. Here, a rotary microfluidic system is presented that can test all possible drug combinations at speed with the use of droplets. For large numbers of combinations, it is shown how the experimental scale is reduced by considering drug dilutions and machine learning. As an example, two cases are considered; the first is a three-ring and three radii configuration and the second is a four ring and forty-eight radii configuration. Between these two, all other cases are shown to be possible. The proposed commercial instrument is shown to be flexible, the user choosing which wells to fill and which driver-computational sub-routine to select. The major issues addressed here are the programming theory of the instrument and the reduction of droplets to be generated by drug dilutions and machine learning.
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spelling pubmed-76032052020-11-01 A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations Davies, Mark Abubaker, Mannthalah Bible, Lorraine Micromachines (Basel) Article It is known that in many cases a combination of drugs is more effective than single-drug treatments both for reducing toxicity and increasing efficacy. With the advent of organoid screens, personalised medicine has become possible for many diseases. Automated pipetting to well plates is the pharmaceutical industry standard for drug screening, but this is relatively expensive and slow. Here, a rotary microfluidic system is presented that can test all possible drug combinations at speed with the use of droplets. For large numbers of combinations, it is shown how the experimental scale is reduced by considering drug dilutions and machine learning. As an example, two cases are considered; the first is a three-ring and three radii configuration and the second is a four ring and forty-eight radii configuration. Between these two, all other cases are shown to be possible. The proposed commercial instrument is shown to be flexible, the user choosing which wells to fill and which driver-computational sub-routine to select. The major issues addressed here are the programming theory of the instrument and the reduction of droplets to be generated by drug dilutions and machine learning. MDPI 2020-10-18 /pmc/articles/PMC7603205/ /pubmed/33080987 http://dx.doi.org/10.3390/mi11100943 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Davies, Mark
Abubaker, Mannthalah
Bible, Lorraine
A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations
title A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations
title_full A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations
title_fullStr A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations
title_full_unstemmed A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations
title_short A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations
title_sort flexible, microfluidic, dispensing system for screening drug combinations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603205/
https://www.ncbi.nlm.nih.gov/pubmed/33080987
http://dx.doi.org/10.3390/mi11100943
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