Download - LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

Transcript
Page 1: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 2: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

OUTLINE

History

Main components of a chip and types of chips

Applications

Current developments

Page 3: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 4: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 5: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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

Page 6: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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

Page 7: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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

Page 8: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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

Page 9: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 10: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

BASICS OF A CHIP

Thermoplastics

Polymethyl

methacrylate (acrylic

glass / plexi glass)

Polycarbonate

Polystyrene

Cyclic olefin

polymers/copolymers

Soft microfabrication

Micromoulding

Microcontact printing

Substrate bonding

Page 11: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 12: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 13: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

PHOTOLITHOGRAPHY

Page 14: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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

Page 15: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 16: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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).

Page 17: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 18: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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

Page 19: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 20: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

THANK YOU!

Page 21: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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).

Page 22: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.

Page 23: LAB ON A CHIP: A MINIATURIZATION OF LABORATORY …home.cc.umanitoba.ca/~perreau/Chem4590_2020/2020... · only need a small sample of the primary organs and fluid sample. Personalization

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.