This document discusses the application of Internet of Things (IoT) technology to microfluidic devices, particularly in healthcare applications. It first provides background on healthcare 4.0 and the importance of integrating IoT with microfluidics. It then describes the key components and principles of an IoT-enabled microfluidic system, including sensors, actuators, and a proposed 5-layer architecture. Applications discussed include wearable microfluidic devices for analyzing biofluids and measuring biomechanics, and point-of-care microfluidic devices for medical diagnostics. Other applications highlighted are using IoT and microfluidics to aid pharmaceutical research and development, such as for personalized medicine. Challenges like security, materials limitations

1. The Application of Internet Of
Things (IOT) on Microfluidic
Devices
Chia Xun Nian
Mok Yan Ni
Teo Jin Wei

2. Content Page
01 Healthcare 4.0 & the Important of IoT on Microfluidics
02 Principle of IoT in Microfluidics & Key Developments
03 Conventional vs Digital Microfluidics & System Design on Internet of
Microfluidic Things
04 Results and discussion (Applications of Microfluidics based IOT)
05 Problems encountered
06 Conclusion and future work

3. Healthcare 4.0
Wearable & Point of Care IOT
Capture & Processing of Biological
Data in Real Time
Ambient IOT
Sensor Detection for Non Intrusive
observation of individuals
Healthcare Digitalisation
Cloud and Storage
Healthcare 2.0
Healthcare 3.0
Healthcare 4.0
Healthcare 1.0
Chen, C., Loh, E.-W., Kuo, K. N., & Tam, K.-W. (2019). The Times they Are a-Changin’ – Healthcare 4.0 Is Coming! Journal of Medical Systems, 44(2). doi:10.1007/s10916-019-1513-0
Jayaraman, P. P., Forkan, A. R. M., Morshed, A., Haghighi, P. D., & Kang, Y. (2019). Healthcare 4.0: A review of frontiers in digital health. WIREs Data Mining and Knowledge Discovery. doi:10.1002/widm.1350

4. The Importance of IoT on Microfluidics
Conventional Microfluidic
Chemical Analysis
Integration with IoT
Big Data Analytics &
Artificial Intelligence
Mejía-Salazar, J. R.; Cruz, K. R.; Vásques, E. M. M.; de Oliveira, O. N. Microfluidic Point-of-Care Devices: New Trends and Future Prospects for Ehealth Diagnostics. Sensors (Switzerland) 2020, 20 (7), 1–20. https://doi.org/10.3390/s20071951
Ibrahim, M.; Gorlatova, M.; Chakrabarty, K. The Internet of Microfluidic Things: Perspectives on System Architecture and Design Challenges: Invited Paper. IEEE/ACM Int. Conf. Comput. Des. Dig. Tech. Pap. ICCAD 2019, 2019-November, 1–8. https://doi.org/10.1109/ICCAD45719.2019.8942080..

5. Internet of Things (IOT) Hardware & Software
Microcontroller Boards/Single
Board computer
Microcontroller
Functional Module (e.g
pumps, bluetooth and Wifi)
Microfluidics
Kassis, T., Perez, P. M., Yang, C. J. W., Soenksen, L. R., TrumperPrabhu, G. R. D., & Urban, P. L. (2020). Elevating Chemistry Research with a Modern Electronics Toolkit. Chemical Reviews. doi:10.1021/acs.chemrev.0c00206
, D. L., & Griffith, L. G. (2018). PiFlow: A biocompatible low-cost programmable dynamic flow pumping system utilizing a Raspberry Pi Zero and commercial piezoelectric pumps. HardwareX, 4, e00034.

6. Complementary Metal Oxide Semiconductor
(CMOS) Chip
Interface
● Processor
● Noise Removal
● Signal amplification
● Actuator controller
Sensors
● Image sensor
● Particle/Cells detection
● pH sensor
● DNA analysis
Actuators
● Particle Actuators
● Microheater
● Flow control
Khan, S. M., Gumus, A., Nassar, J. M., & Hussain, M. M. (2018). CMOS Enabled Microfluidic Systems for Healthcare Based Applications. Advanced Materials, 30(16), 1705759. doi:10.1002/adma.201705759

7. Conventional vs Digital Microfluidics
Digital Microfluidics
Conventional Microfluidics
Flow controlled by voltage or pressure
Utilizes small droplets as on chip analyte carrier
Manipulation of the droplets done by an array of
electrodes that are electrically controllable
Droplet handling mechanism - Electrowetting on
Dielectric (EWOD)
Digital Microfluidics - reconfigurable technology
● Cyber-Physical System
● Real-time decision making
Nguyen, N.-T., Hejazian, M., Ooi, C., & Kashaninejad, N. (2017). Recent Advances and Future Perspectives on Microfluidic Liquid Handling. Micromachines, 8(6), 186. doi:10.3390/mi8060186

8. Internet of Microfluidic Things (IoMT) System Design
5 Layer Architecture
M. Ibrahim, M. Gorlatova and K. Chakrabarty, "The Internet of Microfluidic Things: Perspectives on System Architecture and Design Challenges: Invited Paper," 2019 IEEE/ACM International Conference on Computer-Aided Design (ICCAD), Westminster, CO, USA, 2019, pp. 1-8, doi: 10.1109/ICCAD45719.2019.894208

9. Perception Layer
Consists of microfluidic sensors and actuators that
interact with biochemical substances
Universal control interface has to be designed and
customised to act as “adapters”
Adapters are capable of digitizing and transferring data
to abstraction layer
Abstraction Layer
Implements coordination protocol among
Microfluidic Things
Data transferred to data storage (Middleware Layer)
5 Layer Architecture
M. Ibrahim, M. Gorlatova and K. Chakrabarty, "The Internet of Microfluidic Things: Perspectives on System Architecture and Design Challenges: Invited Paper," 2019 IEEE/ACM International Conference on Computer-Aided Design (ICCAD), Westminster, CO, USA, 2019, pp. 1-8, doi: 10.1109/ICCAD45719.2019.894208

10. Middleware Layer
Stores real-time streaming data
Implements procedures based on specific
identification information (protocol name &
microfluidic device address)
Monitors the progress of biochemical service
Application Layer
Process stored data
Map analytics decisions to
biochemical services request
Semantics Layer
Manage performance metrics and
data collected
Build decision model, graphs and
flowchart
Creates a feedback loop
5 Layer Architecture
M. Ibrahim, M. Gorlatova and K. Chakrabarty, "The Internet of Microfluidic Things: Perspectives on System Architecture and Design Challenges: Invited Paper," 2019 IEEE/ACM International Conference on Computer-Aided Design (ICCAD), Westminster, CO, USA, 2019, pp. 1-8, doi: 10.1109/ICCAD45719.2019.894208

11. Application of Internet of things (IOT) on
Microfluidic Devices In Healthcare
Microfluidic-based
Wearables
Microfluidic-based Point
of Care (POC) Devices

12. Wearable Microfluidics devices (Biofluid)
Biofluid Sweat Analysis
Skin Patch pH analysis
Yeo, J. C., Kenry, K., & Lim, C. T. (2016). Emergence of microfluidic wearable technologies. Lab on a Chip, 16(21), 4082–4090. doi:10.1039/c6lc00926c

13. Wearable Microfluidics Devices (Mechanotransduction
Force)
Foot Pressure
Wrist PressureVocal Cords
Yeo, J. C., Kenry, K., & Lim, C. T. (2016). Emergence of microfluidic wearable technologies. Lab on a Chip, 16(21), 4082–4090. doi:10.1039/c6lc00926c
Liu, Y., Yang, T., Zhang, Y., Qu, G., Wei, S., Liu, Z., Kong, T., Ultrastretchable and Wireless Bioelectronics Based on All‐Hydrogel Microfluidics. Adv. Mater. 2019, 31, 1902783. https://doi.org/10.1002/adma.201902783

14. Microfluidic-based Point of Care (POC) Devices
Electrochemical microfluidic paper-based
immunosensor device (E-μPADs)
Mejía-Salazar, J. R.; Cruz, K. R.; Vásques, E. M. M.; de Oliveira, O. N. Microfluidic Point-of-Care Devices: New Trends and Future Prospects for Ehealth Diagnostics. Sensors (Switzerland) 2020, 20 (7), 1–20. https://doi.org/10.3390/s20071951.
Zhou, J.; Tao, F.; Zhu, J.; Lin, S.; Wang, Z.; Wang, X.; Ou, J. Y.; Li, Y.; Liu, Q. H. Portable Tumor Biosensing of Serum by Plasmonic Biochips in Combination with Nanoimprint and Microfluidics. Nanophotonics 2019, 8 (2), 307–316. https://doi.org/10.1515/nanoph-2018-0173

15. Microfluidic-based Point of Care (POC) Devices
IoT lab chip on monitoring Ebola Virus
Diseases
Brangel, P.; Sobarzo, A.; Parolo, C.; Miller, B. S.; Howes, P. D.; Gelkop, S.; Lutwama, J. J.; Dye, J. M.; McKendry, R. A.; Lobel, L.; Stevens, M. M. A Serological Point-of-Care Test for the Detection of IgG Antibodies against Ebola Virus in Human Survivors. ACS Nano 2018, 12 (1), 63–73. https://doi.org/10.1021/acsnano.7b07021

16. Application of Internet of things (IOT) on Microfluidic
Devices In Research and Drug Development
Research & Development Drug Development

17. IoT and Microfluidics Aiding in Research and
Development
micrIO: an open-source autosampler and fraction
collector for automated microfluidic input–output
Longwell, S. A., & Fordyce, P. M. (2019). micrIO: an open-source autosampler and fraction collector for automated microfluidic input–output. Lab on a Chip. doi:10.1039/c9lc00512a

18. IoT and Microfluidics in Pharmaceutical
AI Aided Synthesis of Personalised Drugs
Herbal Medicine
Chemical Based
Pharmaceuticals
Protein based
Pharmaceuticals
Personalised Drugs
Zhong, J.; Riordon, J.; Wu, T. C.; Edwards, H.; Wheeler, A. R.; Pardee, K.; Aspuru-Guzik, A.; Sinton, D. When Robotics Met Fluidics. Lab Chip 2020, 20 (4), 709–716. https://doi.org/10.1039/c9lc01042d

19. Security of
Internet
Prevent hacking or
leaking of sensitive
data
Materials
Technology
Limited by the
capabilities of current
available materials
Multidisciplinary
Efforts
Incorporation of
Hardware and
Software requires
multiple skill sets
Problems and Challenges

20. Conclusion and Future Work
Incorporation of
acoustic levitation
Samples and analytes
will not touch the
surface
Reduce any chance
possible
contamination
Open Source and 3D
printing
Integration of Open Source
Platforms and 3D printing
Higher accessibility
contributes to lower cost
Synergy of IoT and
microfluidics
Effectiveness of integrating IoT
into mircofludics
Give rise to potential solution
to upgrade quality of life
Eg. wearable IoT, healthcare
4.0, personalised
pharmaceuticalsBrangel, P., Sobarzo, A., Parolo, C., Miller, B. S., Howes, P. D., Gelkop, S., … Stevens, M. M. (2018). A Serological Point-of-Care Test for the Detection of IgG Antibodies against Ebola Virus in Human Survivors. ACS Nano, 12(1), 63–73. doi:10.1021/acsnano.7b07021

21. Question and Answers

22. References
1. Chen, C., Loh, E.-W., Kuo, K. N., & Tam, K.-W. (2019). The Times they Are a-Changin’ – Healthcare 4.0 Is Coming! Journal of Medical Systems, 44(2). doi:10.1007/s10916-019-1513-0
2. Jayaraman, P. P., Forkan, A. R. M., Morshed, A., Haghighi, P. D., & Kang, Y. (2019). Healthcare 4.0: A review of frontiers in digital health. WIREs Data Mining and Knowledge Discovery.
doi:10.1002/widm.1350
3. Liu, X.; Huang, X.; Jiang, Y.; Xu, H.; Guo, J.; Hou, H. W.; Yan, M.; Yu, H. A Microfluidic Cytometer for Complete Blood Count With a 3.2-Megapixel, 1.1- Μm-Pitch Super-Resolution Image
Sensor in 65-Nm BSI CMOS. IEEE Trans. Biomed. Circuits Syst. 2017, 11 (4), 794–803. https://doi.org/10.1109/TBCAS.2017.2697451.
4. Zhao, C.; Liu, X. A Portable Paper-Based Microfluidic Platform for Multiplexed Electrochemical Detection of Human Immunodeficiency Virus and Hepatitis C Virus Antibodies in Serum.
Biomicrofluidics 2016, 10 (2). https://doi.org/10.1063/1.4945311.
5. Ibrahim, M.; Gorlatova, M.; Chakrabarty, K. The Internet of Microfluidic Things: Perspectives on System Architecture and Design Challenges: Invited Paper. IEEE/ACM Int. Conf. Comput.
Des. Dig. Tech. Pap. ICCAD 2019, 2019-November, 1–8. https://doi.org/10.1109/ICCAD45719.2019.8942080.
6. Liu, Y.; Yang, T.; Zhang, Y.; Qu, G.; Wei, S.; Liu, Z.; Kong, T. Ultrastretchable and Wireless Bioelectronics Based on All-Hydrogel Microfluidics. Adv. Mater. 2019, 31 (39), 1–7.
https://doi.org/10.1002/adma.201902783.
7. Zhong, J.; Riordon, J.; Wu, T. C.; Edwards, H.; Wheeler, A. R.; Pardee, K.; Aspuru-Guzik, A.; Sinton, D. When Robotics Met Fluidics. Lab Chip 2020, 20 (4), 709–716.
https://doi.org/10.1039/c9lc01042d.
8. Jha, A. K.; Akhter, Z.; Tiwari, N.; Muhammed Shafi, K. T.; Samant, H.; Jaleel Akhtar, M.; Cifra, M. Broadband Wireless Sensing System for Non-Invasive Testing of Biological Samples. IEEE
J. Emerg. Sel. Top. Circuits Syst. 2018, 8 (2), 251–259. https://doi.org/10.1109/JETCAS.2018.2829205.
9. Khan, S. M.; Gumus, A.; Nassar, J. M.; Hussain, M. M. CMOS Enabled Microfluidic Systems for Healthcare Based Applications. Adv. Mater. 2018, 30 (16), 1–26.
https://doi.org/10.1002/adma.201705759.
10. (Prabhu, G. R. D.; Urban, P. L. Elevating Chemistry Research with a Modern Electronics Toolkit. Chem. Rev. 2020, 120 (17), 9482–9553. https://doi.org/10.1021/acs.chemrev.0c00206.
11. Kulkarni, M. B.; Yashas; Enaganti, P. K.; Amreen, K.; Goel, S. Internet of Things Enabled Portable Thermal Management System with Microfluidic Platform to Synthesize
MnO2nanoparticles for Electrochemical Sensing. Nanotechnology 2020, 31 (42). https://doi.org/10.1088/1361-6528/ab9ed8.
12. Longwell, S. A.; Fordyce, P. M. MicrIO: An Open-Source Autosampler and Fraction Collector for Automated Microfluidic Input-Output. Lab Chip 2020, 20 (1), 93–106.
https://doi.org/10.1039/c9lc00512a.
13. Mejía-Salazar, J. R.; Cruz, K. R.; Vásques, E. M. M.; de Oliveira, O. N. Microfluidic Point-of-Care Devices: New Trends and Future Prospects for Ehealth Diagnostics. Sensors (Switzerland)
2020, 20 (7), 1–20. https://doi.org/10.3390/s20071951.
14. Lin, S.; Wang, B.; Zhao, Y.; Shih, R.; Cheng, X.; Yu, W.; Hojaiji, H.; Lin, H.; Hoffman, C.; Ly, D.; Tan, J.; Chen, Y.; Di Carlo, D.; Milla, C.; Emaminejad, S. Natural Perspiration Sampling and in Situ
Electrochemical Analysis with Hydrogel Micropatches for User-Identifiable and Wireless Chemo/Biosensing. ACS Sensors 2020, 5 (1), 93–102.
https://doi.org/10.1021/acssensors.9b01727.
15. Zhou, J.; Tao, F.; Zhu, J.; Lin, S.; Wang, Z.; Wang, X.; Ou, J. Y.; Li, Y.; Liu, Q. H. Portable Tumor Biosensing of Serum by Plasmonic Biochips in Combination with Nanoimprint and
Microfluidics. Nanophotonics 2019, 8 (2), 307–316. https://doi.org/10.1515/nanoph-2018-0173.
16. Brangel, P.; Sobarzo, A.; Parolo, C.; Miller, B. S.; Howes, P. D.; Gelkop, S.; Lutwama, J. J.; Dye, J. M.; McKendry, R. A.; Lobel, L.; Stevens, M. M. A Serological Point-of-Care Test for the
Detection of IgG Antibodies against Ebola Virus in Human Survivors. ACS Nano 2018, 12 (1), 63–73. https://doi.org/10.1021/acsnano.7b07021.
17. Edris S. (2019) Paradigm Change in the History of the Pharmaceutical Industry. In: Cantwell J., Hayashi T. (eds) Paradigm Shift in Technologies and Innovation Systems. Springer,
Singapore. https://doi.org/10.1007/978-981-32-9350-2_9