LAB ON A CHIP: A MINIATURIZATION OF LABORATORY...
Transcript of LAB ON A CHIP: A MINIATURIZATION OF LABORATORY...
LAB ON A CHIP: A MINIATURIZATION OF
LABORATORY TECHNIQUES MÉLISSANDRE BERTHELOT-DILK
1) Moschou, D.; Tserepi, A. The Lab-on-PCB Approach: Tackling the ΜTAS Commercial Upscaling
Bottleneck. Lab on a Chip 2017, 17 (8), 1388–1405.
OUTLINE
History
Main components of a chip and types of chips
Applications
Current developments
WHAT IS LAB ON A CHIP?
Miniturization and integration of laboratory
techniques.
Usually done on a device involving a microplate
no greater than a few centimetres square that allow
the use of laboratory techniques on the microscale.
1) Ghallab, Y. H.; Badawy, W. Lab-on-a-chip: techniques, circuits, and biomedical applications; Artech House: Boston,
2010, 1-11.
2) Hogan, J. A Little Goes a Long Way. Nature 2006, 442 (7101), 351–352.
A LITTLE BIT OF HISTORY
Started around the 1950s with semiconductors being miniaturized
and lithography based technology used in pressure sensors
development of chips able to handle fluids with capillary
connections allowing mixers, valves, pumps, dosing devices…
1975 : S.C. Terry developed the first Micro Total Analysis System
(TAS)
1) Labeed, F. H.; Fatoyinbo, H. O. Microfluidics in detection science: lab-on-a-chip technologies; Royal Society of Chemistry: Cambridge, 2015.
2) Ghallab, Y. H.; Badawy, W. Lab-on-a-chip: techniques, circuits, and biomedical applications; Artech House: Boston, 2010, 1-11.
MAIN COMPONENTS
Three major components:
1- actuator
mechanical or electrical force on fluid or object via electromagnetic interactions
2- pumps
3- readout device
sensors will measure thermal, optical, electrical or magneticsignals
WHAT TECHNIQUES CAN BE USED FOR LAB ON A CHIP?
ESI/ESI-MS
Microfluidics
Centrifuge
HPLC
Selection and
analysis of single
3D cell structure
Dielectrophoresis
Flow cytometry
PCR
Proteomics
Chromatography
imaging
Qian, X.; Xu, J.; Yu, C.; Chen, Y.; Yu, Q.; Ni, K.; Wang, X. A Reliable and Simple Method for Fabricating a
Poly(Dimethylsiloxane) Electrospray Ionization Chip with a Corner-Integrated Emitter. Sensors 2015, 15 (4), 8931–
8944
WHAT IS MICROFLUIDICS?
Mixing
pH
Acid-base equilibria
Flow physics
Capillarity
Electrokinetics
Electrolyte chemistry
Separation
Detection
1) Santiago, J. G.; Chen, C.-H. Special Issue on Fundamental Principles and Techniques in Microfluidics. Lab on a Chip 2009, 9 (17), 2423.
2) HOW TO CHOOSE A MICROFLUIDIC CHIP? https://www.fluigent.com/microfluidic-expertise/what-is-microfluidic/how-to-choose-a-microfluidic-
chip/?gclid=Cj0KCQiA4sjyBRC5ARIsAEHsELEoTxRN-6Axo_iMmrHZShWg1Caoxd5mkjoB0SCZRrJ9pDVzF7ynFBgaAtWyEALw_wcB (accessed Feb 23, 2020).
Liquid chemistry at a microscopic level
WHY ARE WE DEVELOPPING THESE CHIPS?
Medical advancements
Point of care
Accessibility
cost reduction
Better detection
Prevention
Personalized care
Pharmaceutical advancements
Pharmacokinetics
Shorter approval wait time
Reliability of results
Reduce cost
Waste reduction
Drug discovery
Personalized care
BASICS OF A CHIP
PDMS: polydimethylsiloxane (rubberlike medical grade silicon)
Photolithography
Thin film deposition
Etching
Substrate bonding
Glass-PDMS
Paper
1) Introduction to poly-di-methyl-siloxane (PDMS). https://www.elveflow.com/microfluidic-reviews/general-microfluidics/the-poly-di-methyl-siloxane-pdms-and-microfluidics-2/ (accessed Feb 23, 2020).
2) Labeed, F. H.; Fatoyinbo, H. O. Microfluidics in detection science: lab-on-a-chip technologies; Royal Society of Chemistry: Cambridge, 2015.
BASICS OF A CHIP
Thermoplastics
Polymethyl
methacrylate (acrylic
glass / plexi glass)
Polycarbonate
Polystyrene
Cyclic olefin
polymers/copolymers
Soft microfabrication
Micromoulding
Microcontact printing
Substrate bonding
BASICS OF A CHIP
Photolithography
Thin film deposition
Etching
1) Labeed, F. H.; Fatoyinbo, H. O. Microfluidics in detection science: lab-on-a-chip technologies; Royal
Society of Chemistry: Cambridge, 2015.
BASICS OF A CHIP
Substrate
bonding
Microcontact
printing
1) Labeed, F. H.; Fatoyinbo, H. O. Microfluidics in detection science: lab-on-a-chip technologies; Royal
Society of Chemistry: Cambridge, 2015.
PHOTOLITHOGRAPHY
ADVANTAGES
Reduces wastes and cost by using very small amounts of reagents and
sample
Good control over the interactions and concentrations
Faster response time
Allows the analysis to be done at the point of care rather than a
centralized laboratory
Reduction of human error
Ease of use
DISADVANTAGES
Interactions between surface and chemicals are greater (capillary force, surface roughness, chemical interaction, etc.)
Low signal to noise ratio if the detection needs more than microscales dynamics
We aren’t at a point yet where they can be commercialized.
Some still depend on external systems to control flow and volumes, etc.
APPLICATION OF LAB ON A CHIP – CENTRIFUGE
LAB ON A DISC V. CONVENTIONAL METHOD OF PLATELET ISOLATION
1) Kim, C.-J.; Ki, D. Y.; Park, J.; Sunkara, V.; Kim, T.-H.; Min, Y.; Cho, Y.-K.
Fully Automated Platelet Isolation on a Centrifugal Microfluidic Device for
Molecular Diagnostics. Lab on a Chip 2020.
1) Platelet Rich Plasma Centrifuges - Drucker Diagnostic.
https://druckerdiagnostics.com/prp-
prf/?gclid=Cj0KCQiA4sjyBRC5ARIsAEHsELGFNzIcOFiLYjKIbvcFOjTCFFS1uoezRN
9dKI795vq1lz8yktWdrwUaAhK5EALw_wcB (accessed Feb 23, 2020).
LAB ON A DISC : METHOD
1) Kim, C.-J.; Ki, D. Y.; Park, J.; Sunkara, V.; Kim, T.-H.; Min, Y.; Cho, Y.-K. Fully
Automated Platelet Isolation on a Centrifugal Microfluidic Device for Molecular
Diagnostics. Lab on a Chip 2020.
LAB ON A DISC: RESULTS
1) Kim, C.-J.; Ki, D. Y.; Park, J.; Sunkara, V.; Kim, T.-H.; Min, Y.; Cho, Y.-K. Fully Automated
Platelet Isolation on a Centrifugal Microfluidic Device for Molecular Diagnostics. Lab on a
Chip 2020.
A-D – method based platelets purity
E – platelet yield based on method used
F - reproducibility of method and error margin
G – white blood cell present in samples with
platelets
H-J – activation of platelets based on method
WHY IS IT HARD TO UPSCALE? AND WHY SHOULD WE CARE?
Why haven’t we commercialized?
Cost
Standardization of the design
User-friendly interface with macroscopic world
Many chips could change our lives but cannot beadopted into the mainstream and we need to adaptthem
Can we commercialize?
PCB microfluidic chips are more cost effective
Already established
Have the manufacturing capabilities
The standardization already exists
1) Moschou, D.; Tserepi, A. The Lab-on-PCB Approach: Tackling the ΜTAS Commercial Upscaling
Bottleneck. Lab on a Chip 2017, 17 (8), 1388–1405.
THANK YOU!
REFERENCES
1. Device Materials - uFluidix: Microfluidic chips and devices manufacturer. https://ufluidix.com/device-materials/ (accessed Feb 20, 2020).
2. Cheriyedath, S. What is Lab-on-a-Chip? https://www.news-medical.net/life-sciences/What-is-Lab-on-a-Chip.aspx (accessed Feb 20, 2020).
3. Liu, Z.; Zhang, P.; Ji, H.; Long, Y.; Jing, B.; Wan, L.; Xi, D.; An, R.; Lan, X. A Mini-Panel PET Scanner-Based Microfluidic Radiobioassay System Allowing High-Throughput Imaging of Real-Time Cellular Pharmacokinetics. Lab on a Chip 2020.
4. Kim, C.-J.; Ki, D. Y.; Park, J.; Sunkara, V.; Kim, T.-H.; Min, Y.; Cho, Y.-K. Fully Automated Platelet Isolation on a Centrifugal Microfluidic Device for Molecular Diagnostics. Lab on a Chip 2020.
5. Introduction to lab-on-a-chip 2015 : review, history and future. https://www.elveflow.com/microfluidic-reviews/general-microfluidics/introduction-to-lab-on-a-chip-2015-review-history-and-future/ (accessed Feb 20, 2020).
6. Hogan, J. A Little Goes a Long Way. Nature 2006, 442 (7101), 351–352.
7. Ghallab, Y. H.; Badawy, W. Lab-on-a-chip: techniques, circuits, and biomedical applications; Artech House: Boston, 2010, 1-11.
8. Labeed, F. H.; Fatoyinbo, H. O. Microfluidics in detection science: lab-on-a-chip technologies; Royal Society of Chemistry: Cambridge, 2015.
9. Chin, C. D.; Laksanasopin, T.; Cheung, Y. K.; Steinmiller, D.; Linder, V.; Parsa, H.; Wang, J.; Moore, H.; Rouse, R.; Umviligihozo, G.; Karita, E.; Mwambarangwe, L.; Braunstein, S. L.; Wijgert, J. V. D.; Sahabo, R.; Justman, J. E.; El-Sadr, W.; Sia, S. K. Microfluidics-Based Diagnostics of Infectious Diseases in the Developing World. Nature Medicine 2011, 17 (8), 1015–1019.
10. Gac Séverine Le; Berg, A. van den. Miniaturization and mass spectrometry; A Silicon-Based ESI Chip with Integrated Counter Electrode and Its Applications Combined with Mass Spectrometry; RSC Publishing: Cambridge, UK, 2009, 47-66.
11. Nguyen, T.; Andreasen, S. Z.; Wolff, A.; Bang, D. D. From Lab on a Chip to Point of Care Devices: The Role of Open Source Microcontrollers. Micromachines 2018, 9 (8), 403.
12. Demirci, U.; Khademhosseini, A.; Langer, R.; Blander, J. Microfluidic technologies for human health; World Scientific Publishing: Singapore, 2013
13. Staal, S. S.; Ungerer, M. C.; Movig, K. L. L.; Bartholomew, J. A.; Krabbe, H.; Eijkel, J. C. T. Chapter 12. Medimate Minilab, a Microchip Capillary Electrophoresis Self-Test Platform. Nanoscience & Nanotechnology Series Microfluidics for Medical Applications 259–288.
14. Moschou, D.; Tserepi, A. The Lab-on-PCB Approach: Tackling the ΜTAS Commercial Upscaling Bottleneck. Lab on a Chip 2017, 17 (8), 1388–1405.
15. Alyassin, M. A.; Moon, S.; Keles, H. O.; Manzur, F.; Lin, R. L.; Hæggstrom, E.; Kuritzkes, D. R.; Demirci, U. Rapid Automated Cell Quantification on HIV Microfluidic Devices. Lab on a Chip 2009, 9 (23), 3364.
16. Santiago, J. G.; Chen, C.-H. Special Issue on Fundamental Principles and Techniques in Microfluidics. Lab on a Chip 2009, 9 (17), 2423.
17. Berg, A. V. D.; Mummery, C. L.; Passier, R.; Meer, A. D. V. D. Personalised Organs-on-Chips: Functional Testing for Precision Medicine. Lab on a Chip 2019, 19 (2), 198–205.
18. Zhang, B.; Radisic, M. Organ-on-a-Chip Devices Advance to Market. Lab on a Chip 2017, 17 (14), 2395–2420.
19. Hachey, S. J.; Hughes, C. C. W. Applications of Tumor Chip Technology. Lab on a Chip 2018, 18 (19), 2893–2912.
20. Lu, Y.; Yang, L.; Wei, W.; Shi, Q. Microchip-Based Single-Cell Functional Proteomics for Biomedical Applications. Lab on a Chip 2017, 17 (7), 1250–1263.
21. Wu, M.; Perroud, T. D.; Srivastava, N.; Branda, C. S.; Sale, K. L.; Carson, B. D.; Patel, K. D.; Branda, S. S.; Singh, A. K. Microfluidically-Unified Cell Culture, Sample Preparation, Imaging and Flow Cytometry for Measurement of Cell Signaling Pathways with Single Cell Resolution. Lab on a Chip 2012, 12 (16), 2823.
22. Platelet Rich Plasma Centrifuges - Drucker Diagnostic. https://druckerdiagnostics.com/prp-prf/?gclid=Cj0KCQiA4sjyBRC5ARIsAEHsELGFNzIcOFiLYjKIbvcFOjTCFFS1uoezRN9dKI795vq1lz8yktWdrwUaAhK5EALw_wcB (accessed Feb 23, 2020).
23. Introduction to poly-di-methyl-siloxane (PDMS). https://www.elveflow.com/microfluidic-reviews/general-microfluidics/the-poly-di-methyl-siloxane-pdms-and-microfluidics-2/ (accessed Feb 23, 2020).
24. Qian, X.; Xu, J.; Yu, C.; Chen, Y.; Yu, Q.; Ni, K.; Wang, X. A Reliable and Simple Method for Fabricating a Poly(Dimethylsiloxane) Electrospray Ionization Chip with a Corner-Integrated Emitter. Sensors 2015, 15 (4), 8931–8944.
25. HOW TO CHOOSE A MICROFLUIDIC CHIP? https://www.fluigent.com/microfluidic-expertise/what-is-microfluidic/how-to-choose-a-microfluidic-chip/?gclid=Cj0KCQiA4sjyBRC5ARIsAEHsELEoTxRN-6Axo_iMmrHZShWg1Caoxd5mkjoB0SCZRrJ9pDVzF7ynFBgaAtWyEALw_wcB (accessed Feb 23, 2020).
ORGAN ON A CHIP INFORMATION
Microfluidics cell culture that emulates the physico-chemical microenvironment of tissue and organ-level.
Done by controlling the dynamic conditions on the chip.
Done for specific individuals representing that individual’s genetics, physiology, etc,… This is called precision medicine and is increasingly becoming important for groups that are non-responders to standard practice medicine. Many people are hospitalized due to adverse effects to their treatments or medicine = 100 000 + deaths per year. Precise medicine would reduce harm, increase quality of life and potentially reduce cost of the healthcare system. We want to recapitulate a patient's complexity in a controlled system (as we would in any organ grown culture) but this time we want to be able to go from the prep to analysis to results on one chip.
Human cells are cultured, and in engineered microenvironments mimic the tissue geometry, actuation dynamics, flow and gradients just like the human body. Eg: lung-on-a-chip breathing, vessels on a chip (tumour cells in perfused blood vessels), gut on a chip (peristaltic actuation and flowing microbes), multi-organ chips (pancreas and liver to maintain glucose liver)
Organ on a chip = high level of control of biological, physical and chemical cell culture in a single microsystem. You only need a small sample of the primary organs and fluid sample. Personalization = using patients' samples (primary tissue by biopsy or other, blood, stool)
1) Zhang, B.; Radisic, M. Organ-on-a-Chip Devices Advance to Market. Lab on a Chip 2017, 17 (14), 2395–2420.
2) Berg, A. V. D.; Mummery, C. L.; Passier, R.; Meer, A. D. V. D. Personalised Organs-on-Chips: Functional Testing for Precision Medicine. Lab on a Chip 2019, 19 (2),
198–205.
OTHER SUBJECTS OF INTEREST:
Cytometry on a chip: Wu, M.; Perroud, T. D.; Srivastava, N.; Branda, C. S.; Sale, K. L.; Carson, B. D.; Patel, K. D.; Branda, S. S.; Singh, A.
K. Microfluidically-Unified Cell Culture, Sample Preparation, Imaging and Flow Cytometry for Measurement of Cell Signaling Pathways with
Single Cell Resolution. Lab on a Chip 2012, 12 (16), 2823.
Proteomics on a chip: Lu, Y.; Yang, L.; Wei, W.; Shi, Q. Microchip-Based Single-Cell Functional Proteomics for Biomedical
Applications. Lab on a Chip 2017, 17 (7), 1250–1263.
ESI/ESI-MS on a chip: Qian, X.; Xu, J.; Yu, C.; Chen, Y.; Yu, Q.; Ni, K.; Wang, X. A Reliable and Simple Method for Fabricating a
Poly(Dimethylsiloxane) Electrospray Ionization Chip with a Corner-Integrated Emitter. Sensors 2015, 15 (4), 8931–8944.
And Gac Séverine Le; Berg, A. van den. Miniaturization and mass spectrometry; A Silicon-Based ESI Chip with Integrated Counter Electrode and
Its Applications Combined with Mass Spectrometry; RSC Publishing: Cambridge, UK, 2009, 47-66.
Electrophoresis on a chip: Staal, S. S.; Ungerer, M. C.; Movig, K. L. L.; Bartholomew, J. A.; Krabbe, H.; Eijkel, J. C. T. Chapter 12.
Medimate Minilab, a Microchip Capillary Electrophoresis Self-Test Platform. Nanoscience & Nanotechnology Series Microfluidics for Medical
Applications 259–288.
ELISA on a chip for HIV and Syphilis diagnostic: Alyassin, M. A.; Moon, S.; Keles, H. O.; Manzur, F.; Lin, R. L.; Hæggstrom, E.;
Kuritzkes, D. R.; Demirci, U. Rapid Automated Cell Quantification on HIV Microfluidic Devices. Lab on a Chip 2009, 9 (23), 3364.