Microfluidic Devices for HIV Point-of-Care Diagnostics Xuanhong Cheng

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1 Microfluidic Devices for HIV Point-of-Care Diagnostics Xuanhong Cheng Bioengineering Materials Science and Engineering Lehigh University November 30, 2018

2 POC Diagnostics

3 Basic Water Supply Microdevices for Medicine Micronit.com

4 Advantage of Microfluidic Systems Small sample volume Small reagent volume Low production cost Portable, potential for integration and automation High surface to volume ratio Laminar flow, predictable transport property

5

6 Micro-scale Fabrication Master

7 Global Health The area of study, research and practice that places a priority on improving health and achieving equity in health for all people worldwide Koplan JP, Bond TC, Merson MH, et al; Consortium of Universities for Global Health Executive Board. Towards a common definition of global health. Lancet. 2009;373:

8 Leading causes of death, high-income countries Source: WHO, The World Health Report 2018

9 Leading causes of death, low-income countries Source: WHO, The World Health Report 2018

10 36.9 million adults living with HIV/AIDS, 2017

11

12 Cell Bacteria (TB, Typhoid) Virus (HIV, hepatitis, SARS, influenza). HIV emerging from a cell Cell HIV

13 HIV HIV Pathophysiology - Life Cycle HIV CD4 CD4 cell

14 HIV HIV Pathophysiology - Life Cycle CD4 Binding CD4 Co-receptor (CCR5 or CXCR4)

15 HIV HIV Pathophysiology - Life Cycle Fusion

16 HIV HIV Pathophysiology - Life Cycle Virion entry

17 HIV Pathophysiology - Life Cycle HIV

18 HIV HIV Pathophysiology - Life Cycle Reverse transcription HIV DNA

19 HIV HIV Pathophysiology - Life Cycle Translocation to nucleus

20 HIV HIV Pathophysiology - Life Cycle Integration

21 HIV HIV Pathophysiology - Life Cycle Transcription / Translation of HIV mrna / polyprotein

22 HIV HIV Pathophysiology - Life Cycle Protease processing and viral assembly

23 HIV infection HIV attacks CD4 cells, the generals of the immune system s army HIV inserts itself into our genes HIV creates many different strains CD4 cell

24 Impact of Treatment Begin ART CD4 Viral load (HIV RNA level) Weeks time Years

25 Impact of Treatment Before After

26 Impact of Treatment After 9 months

27 Impact of Treatment - Society Effective ARVs available Deaths per 100,000 Population Unintentional injury Cancer Heart disease Suicide HIV infection 10 Homicide Year Chronic liver disease Stroke Diabetes Source: Centers for Disease Control, 2001

28 HIV Diagnostic and Molecular Testing

29 Basic Water Supply State of the Art Technologies Viral load count: determining resistance

30 Basic Water Supply Quantitative Real Time PCR

31 Basic Water Supply Lab Diagnostics in Resource Poor Settings

32 hat is Needed Low cost Easy to use Rapid and Robust Portable Sensitive and specific

33 Portable CD4 Counter Cl - Cl - K + Cl - Cl - K + Na + K +

34 Microfluidic Cell Counting Chip CD4 counting microchip Daktari Diagnostics Inc. Cheng, X. et. al, Lab on a Chip, 2007

35 Nanoporous Membrane for Viral Processing and Sensing Controllable pore size High porosity Bio-functionality Tight pore size distribution Thin membranes

36 Viral Capture (%) Viral Capture Viral Capture in Efficiency Porous Membrane SEM Image of Porous Membrane 5 μm 0 Flatbed Device Porous Device

37 Current Voltage Current Ion Antigp120 HIV Gold Silver Low Viral Load High

38 Virus Sensing in Porous Membrane

39 Virus Sensing in Porous Membrane Peak Current Values of Control and Threshold Viral Loads

40 cm Device Assembly electrode Roof substrates outlet inlet separation membrane Finalized devices syringe tubing electrodes

41

42 Student Participants Krissada Surawathanawises, PhD Keely Heinz, graduate student Wang Yi, graduate student Thomas Reidy, graduate student BDSI summer students (2012) Aileen Bidad (BS, 2016) John Fraser (BS, 2015) Kathryn Kundrod (BS, 2015) Cyclic Solutions TE teams (2016, 2017) CINQ397 Team (2018)

43

44 Statistics of Sickle Cell Anemia

45 POC for Sickle Cell Anemia?

46 Nanoporous Membrane for Viral Processing and Sensing Controllable pore size High porosity Bio-functionality Tight pore size distribution Thin membranes

47 Embedded Nanoporous Membranes for Viral Processing 120 Percentage of Virions (%) nm Pores 20nm Pores Filtrate Absorbed on membrane Suspended above membrane 0 Viral Concentration (/ml) 8e+7 6e+7 4e+7 2e+7 0 Original Sample 1mL filtration + 10 L Wash % of Virions Captured on Membranes Bare PEG AntiCD44

48 Community-based Care Care takes place in the community. Reinforced in the clinic.

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