microfluidics as an emerging platform for tackling amr · 2019. 4. 4. · lab-on-a-chip &...
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Microfluidics as an Emerging
Platform for Tackling AMR
Global-NAMRIP network conference, Uganda
Monday 4th – Thursday 7th March 2019
Prof. Xunli Zhang <[email protected]>
School of Engineering
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Outline
Introduction - Microfluidics
Challenges in tackling AMR
Our approaches
Application examples
Summary
Acknowledgements
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Lab-on-a-Chip & Microfluidics
Chip
Laborato
ry
Stanford Chip
Capillary:
1.5m, 200 30 mm
Stationary phase:
OV-101
Detector:
Thermal conductivity
Terry, et al, IEEE Trans. Electron. Devices, ED-26: 1880, 1979
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Laminar Flow within Microfluidic Channels
Whitesides, et al,
Science (1999)
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Laminar Flow and Diffusive Mixing- Unique characteristics of microfluidics
0
0.2
0.4
0.6
0.8
1
-80 -60 -40 -20 0 20 40 60 80
X/mm
C/C
0
0.568 s
0.915 s
1.41 s
2.27 s
Abs = e d C
Abs = log (I0/I1)Tetrahedron, 58, (24), 4735-4757 (2002)
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Applications
Biomicrofluidics
Microfluidics and Lab-on-a-Chip
Biomaterials
Tackling AMR
Cell Bioanalysis
Drug Delivery
Microreactors
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Applications
Tackling AMR
200 mm
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Challenges (1)- in studying pharmacokinetics/AMR
Current 2-D cell culture inaccurately
reflects conditions in man
Current drug testing protocols
• batch operation
• static media
• single concentration
Our approaches
Using a microsphere-based 3-D cell culture model
Developing a microfluidic-based platform with
precise fluidic control
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Microparticles formation by multiphase microfluidics
Microfluidic chips permit the formation of multiphaseflows, that are flows constituted of two or moreimmiscible fluids, suggesting new routes to theproduction of microparticles.
T-junction chips X-junction chips
The breakup process is driven bythe build-up of pressure upstreamof an emerging droplet
The formation of droplets is due tothe interplay between viscousforces and interfacial forces
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200 mm
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Al-Shammari et al., J Inf Dis, 2015, 212:463-473
The extracellular matrix regulates the host-pathogen interaction
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Broth culture 2-D cell culture 3-D system
Pyrazinamide kills Mtbin the 3-D model, but not in 7H9 broth or 2-D culture.
Bielecka et al., mBio, 2017, 8:e02073-16
- Testing Tuberculosis (TB) drug resistance
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Microfluidics to model physiological conditions
Media A In
Media B In
Media Out
Detection 11
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Microfluidic-based regulation of physiological conditions (1)
Pla
sm
a A
ntibio
tic
concentr
ation
12Bielecka et al., mBio, 2017, 8:e02073-16
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Microfluidic-based regulation of physiological conditions (2)
No antibiotics
Low peak concentration
Standard peak concentration
High peak concentration
Antibiotics added
13Bielecka et al., mBio, 2017, 8:e02073-16
(C) 24-well (D) 96-well tissue culture plate
Luminescence from infected PBMCs in microspheres in a single well
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Challenges (2)- in rapid detection/diagnosis of AMR
Rapid and easy to use
Low cost
High sensitivity
High specificity
Portable
Accurate
Multiplex
Our approaches To miniaturise AMR assays into microfluidics
devices and provide portable handheld systems for
rapid and high throughput AMR testing.
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Antimicrobial susceptibility testing (AST)
Minimum inhibitory concentration (MIC)
determination
Microfluidic-based AMR testing
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Microfluidic chips
1 CM
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Microfluidic sampling / quantification
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Smart phone based quantification
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Summary
Microfluidics as powerful tools for tackling AMR.
Combining microfluidics and microsphere-based
3-D cell culture model can regulate and detect
dynamic microenvironment surrounding cell
culture microspheres with precise fluidic control.
Pump-free microfluidic chips provide essay-to-use
and cost-effective approaches for rapid and high
throughput AMR testing.
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Prof Paul Elkington (Medicine)
Dr Magda Bielecka (Medicine)
Dr Liku Tezera (Medicine)
Dr Robert Zmijan (Engineering)
Dr Sammer-ul Hassan (Engineering)
Prof Suwan Jayasinghe (Biomaterials, UCL)
Network on Antimicrobial Resistance and Infection
Prevention (NAMRIP)
Acknowledgements
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