Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients

“Children are not tiny adults” is an adage commonly used in pediatrics to emphasize the fact that children often have different physiological responses to sickness and trauma compared to adults. However, despite widespread acceptance of this concept, diagnostic blood testing is a...

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Main Authors: Rama S. Sista, Rainer Ng, Miriam Nuffer, Michael Basmajian, Jacob Coyne, Jennifer Elderbroom, Daniel Hull, Kathryn Kay, Maithri Krishnamurthy, Christopher Roberts, Daniel Wu, Adam D. Kennedy, Rajendra Singh, Vijay Srinivasan, Vamsee K. Pamula
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/10/1/21
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author Rama S. Sista
Rainer Ng
Miriam Nuffer
Michael Basmajian
Jacob Coyne
Jennifer Elderbroom
Daniel Hull
Kathryn Kay
Maithri Krishnamurthy
Christopher Roberts
Daniel Wu
Adam D. Kennedy
Rajendra Singh
Vijay Srinivasan
Vamsee K. Pamula
author_facet Rama S. Sista
Rainer Ng
Miriam Nuffer
Michael Basmajian
Jacob Coyne
Jennifer Elderbroom
Daniel Hull
Kathryn Kay
Maithri Krishnamurthy
Christopher Roberts
Daniel Wu
Adam D. Kennedy
Rajendra Singh
Vijay Srinivasan
Vamsee K. Pamula
author_sort Rama S. Sista
collection DOAJ
description “Children are not tiny adults” is an adage commonly used in pediatrics to emphasize the fact that children often have different physiological responses to sickness and trauma compared to adults. However, despite widespread acceptance of this concept, diagnostic blood testing is an excellent example of clinical care that is not yet customized to the needs of children, especially newborns. Cumulative blood loss resulting from clinical testing does not typically impact critically ill adult patients, but can quickly escalate in children, leading to iatrogenic anemia and related comorbidities. Moreover, the tests prioritized for rapid, near-patient testing in adults are not always the most clinically relevant tests for children or newborns. This report describes the development of a digital microfluidic testing platform and associated clinical assays purposely curated to address current shortcomings in pediatric laboratory testing by using microliter volumes (<50 µL) of samples. The automated platform consists of a small instrument and single-use cartridges, which contain all reagents necessary to prepare the sample and perform the assay. Electrowetting technology is used to precisely manipulate nanoliter-sized droplets of samples and reagents inside the cartridge. To date, we have automated three disparate types of assays (biochemical assays, immunoassays, and molecular assays) on the platform and have developed over two dozen unique tests, each with important clinical application to newborns and pediatric patients. Cell lysis, plasma preparation, magnetic bead washing, thermocycling, incubation, and many other essential functions were all performed on the cartridge without any user intervention. The resulting assays demonstrate performance comparable to standard clinical laboratory assays and are economical due to the reduced hands-on effort required for each assay and lower overall reagent consumption. These capabilities allow a wide range of assays to be run simultaneously on the same cartridge using significantly reduced sample volumes with results in minutes.
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spelling doaj.art-f38eed43c4f04aaf896338d461a2a5e92022-12-22T02:57:49ZengMDPI AGDiagnostics2075-44182020-01-011012110.3390/diagnostics10010021diagnostics10010021Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric PatientsRama S. Sista0Rainer Ng1Miriam Nuffer2Michael Basmajian3Jacob Coyne4Jennifer Elderbroom5Daniel Hull6Kathryn Kay7Maithri Krishnamurthy8Christopher Roberts9Daniel Wu10Adam D. Kennedy11Rajendra Singh12Vijay Srinivasan13Vamsee K. Pamula14Baebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USABaebies, Inc., PO Box 14403, Durham, NC 27709, USA“Children are not tiny adults” is an adage commonly used in pediatrics to emphasize the fact that children often have different physiological responses to sickness and trauma compared to adults. However, despite widespread acceptance of this concept, diagnostic blood testing is an excellent example of clinical care that is not yet customized to the needs of children, especially newborns. Cumulative blood loss resulting from clinical testing does not typically impact critically ill adult patients, but can quickly escalate in children, leading to iatrogenic anemia and related comorbidities. Moreover, the tests prioritized for rapid, near-patient testing in adults are not always the most clinically relevant tests for children or newborns. This report describes the development of a digital microfluidic testing platform and associated clinical assays purposely curated to address current shortcomings in pediatric laboratory testing by using microliter volumes (<50 µL) of samples. The automated platform consists of a small instrument and single-use cartridges, which contain all reagents necessary to prepare the sample and perform the assay. Electrowetting technology is used to precisely manipulate nanoliter-sized droplets of samples and reagents inside the cartridge. To date, we have automated three disparate types of assays (biochemical assays, immunoassays, and molecular assays) on the platform and have developed over two dozen unique tests, each with important clinical application to newborns and pediatric patients. Cell lysis, plasma preparation, magnetic bead washing, thermocycling, incubation, and many other essential functions were all performed on the cartridge without any user intervention. The resulting assays demonstrate performance comparable to standard clinical laboratory assays and are economical due to the reduced hands-on effort required for each assay and lower overall reagent consumption. These capabilities allow a wide range of assays to be run simultaneously on the same cartridge using significantly reduced sample volumes with results in minutes.https://www.mdpi.com/2075-4418/10/1/21pediatricslaboratorydigital microfluidicselectrowettingnanoliterneonatal intensive care unit (nicu)bilirubinglucose-6-phosphate dehydrogenasealbuminthyroidinsulincreatininecytomegalovirus
spellingShingle Rama S. Sista
Rainer Ng
Miriam Nuffer
Michael Basmajian
Jacob Coyne
Jennifer Elderbroom
Daniel Hull
Kathryn Kay
Maithri Krishnamurthy
Christopher Roberts
Daniel Wu
Adam D. Kennedy
Rajendra Singh
Vijay Srinivasan
Vamsee K. Pamula
Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients
Diagnostics
pediatrics
laboratory
digital microfluidics
electrowetting
nanoliter
neonatal intensive care unit (nicu)
bilirubin
glucose-6-phosphate dehydrogenase
albumin
thyroid
insulin
creatinine
cytomegalovirus
title Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients
title_full Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients
title_fullStr Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients
title_full_unstemmed Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients
title_short Digital Microfluidic Platform to Maximize Diagnostic Tests with Low Sample Volumes from Newborns and Pediatric Patients
title_sort digital microfluidic platform to maximize diagnostic tests with low sample volumes from newborns and pediatric patients
topic pediatrics
laboratory
digital microfluidics
electrowetting
nanoliter
neonatal intensive care unit (nicu)
bilirubin
glucose-6-phosphate dehydrogenase
albumin
thyroid
insulin
creatinine
cytomegalovirus
url https://www.mdpi.com/2075-4418/10/1/21
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