Microfluidic Devices for Point-of-Care Diagnostics Xuanhong Cheng
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1 Microfluidic Devices for Point-of-Care Diagnostics Xuanhong Cheng Materials Science and Engineering Bioengineering Lehigh University December 2, 2016
2 Basic Water Supply Microdevices for Medicine Micronit.com
3 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
4 POC Diagnostics
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 2012
9 Leading causes of death, low-income countries Source: WHO, The World Health Report 2012
10 36.7 million adults living with HIV/AIDS, 2015
11
12
13 Changes in Life Expectancy,
14
15 Cell Bacteria (TB, Typhoid) Virus (HIV, hepatitis, SARS, influenza). HIV emerging from a cell Cell HIV
16 Relationship Between CD4 count and Viral Load Slow: <5,000, Fast: 50,000+
17 Impact of Treatment Before After
18 Impact of Treatment After 9 months
19 HIV Diagnostics 1000 WHO Stage 2 and 3: Symptomatic HIV infection CD Mild infections Weight loss, fatigue TB, Thrush CD4 Count WHO Stage 1: Asymptomatic HIV infection CD4 >500 WHO Stage 4 AIDS CD4 < 200 TB, infections Death ~18 months 2 Time (years) 4 6
20 Impact of Treatment Begin ART CD4 Viral load (HIV RNA level) Weeks time Years
21 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
22 Number of Individuals Receiving ART Source: WHO
23 HIV Diagnostic and Molecular Testing
24 Basic Water Supply Clinical Indicators 10 7 Viral load HIV RNA level (copies/ ml plasma) CD4 cell count 600 (cells/ L blood) Weeks Years
25 Basic Water Supply State of the Art Technologies BD FACSCalibur CD4-count Priority ART initiation < 350 cells/ul Viral load count measure resistance to treatment RT PCR
26 Basic Water Supply Lab Diagnostics in Resource Poor Settings
27 hat is Needed Low cost Easy to use Rapid and Robust Portable Sensitive and specific
28 Basic Water Supply Microdevice for Medicine
29 Portable CD4 Counter Cl - Cl - K + Cl - Cl - K + Na + K +
30 Microfluidic Cell Counting Chip CD4 counting microchip Daktari Diagnostics Inc. Cheng, X. et. al, Lab on a Chip, 2007
31 Nanoporous Membrane for Viral Processing and Sensing Controllable pore size High porosity Bio-functionality Tight pore size distribution Thin membranes
32 Embedded Nanoporous Membranes for Virus Capture PDMS membrane
33 Viral Capture (%) Viral Capture Viral Capture in Efficiency Porous Membrane SEM Image of Porous Membrane 5 μm 0 Flatbed Device Porous Device
34
35 cm Device Assembly Roof substrates Finalized devices electrode outlet inlet separation membrane syringe tubing electrodes
36 Viral Capture Binding assay in functional devices Simulated virus concentrations: Control: 0 beads/ml Low: 1,000 beads/ml Medium: 10,000 beads/ml High: 100,000 beads/ml
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 Acknowledgments Collaborators Fil Bartoli Arthur Chiou (Yangming U, Taiwan) Tim Friel (LVHN) Martin Hirsch (MGH) Jim Hwang Jim Gilchrist Sabrina Jedlicka Yaling Liu Alp Oztakin Daniel Ouyang William Rodriguez (MGH) Olga Latinovic (IHV) Peikuen Wei (Academia Sinica, Taiwan) Frank Zhang Students Aileen Bidad John Fraser Keely Heinz Yi Hu, PhD Kathryn Kundrod Krissada Surawathanawises, PhD Bu Wang, PhD Chao Zhao, PhD
41
42 Nanoporous Membrane for Viral Processing and Sensing Controllable pore size High porosity Bio-functionality Tight pore size distribution Thin membranes
43 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
44 Community-based Care Care takes place in the community. Reinforced in the clinic.
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