Microchip Technology. Xuanhong Cheng Materials Science and Engineering

Transcription

1 Microchip Technology for Global l Health Diagnostics Xuanhong Cheng Materials Science and Engineering Bioengineering

2 Microchip Technology Basic Water for Medicine Supply

3 Overview of Presentation 1 Global Health Challenges 2 HIV/AIDS Statistics and Biology 3 HIV/AIDS Diagnostics 4 Microchip Technology for HIV/AIDS Diagnostics i

4 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:

5 Leading causes of death, high-income countries Deaths in millions % of deaths Ischaemic heart disease % Stroke and other cerebrovascular disease % Trachea, bronchus, lung cancers % Alzheimer and other dementias % Lower respiratory infections % Chronic obstructive pulmonary disease % Colon and rectum cancers % Diabetes mellitus % Hypertensive heart disease % Breast cancer % Source: WHO, The World Health Report 2000

6 Leading causes of death, low-income countries Death (millions) % of deaths Lower respiratory infections % Diarrhoeal diseases % HIV/AIDS % Ischaemic heart disease % Malaria % Stroke and other cerebrovascular disease % Tuberculosis % Prematurity and low birth weight % Birth asphyxia and birth trauma % Neonatal infections % Source: WHO, The World Health Report 2000

7 33 million adults living with HIV/AIDS, 2008 Source: WHO/UNAIDS, 2008

8 Growth of the AIDS Epidemic People With HIV/AIDS, Cumulative Regional Totals Millions *Western and Central Europe & North America. Source: UNAIDS/WHO, 2006.

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11 Changes in Life Expectancy,

12 AIDS Effect on African Agriculture Percent of Agricultural l Labor Force Lost to HIV/AIDS, (Projected) Namibia 26 Botswana Zimbabwe Mozambique South Africa Kenya 17 Malawi Uganda Tanzania Source: Food and Agriculture Organization (FAO), AIDS A Threat to Rural Africa: Fact Sheet ( e/aids/aids6-e.htm).

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

15 Global diversity of different HIV-1 strains Source: Los Alamos Database

16 HIV HIV Pathophysiology - Life Cycle HIV CD4 CD4 cell

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

18 HIV HIV Pathophysiology - Life Cycle Fusion

19 HIV HIV Pathophysiology - Life Cycle Virion entry

20 HIV HIV Pathophysiology - Life Cycle

21 HIV HIV Pathophysiology - Life Cycle Reverse transcription HIV DNA

22 HIV HIV Pathophysiology - Life Cycle Translocation to nucleus

23 HIV HIV Pathophysiology - Life Cycle Integration

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

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

26 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

27 HIV infection Viral load CD4 Weeks Years time

28 Relationship Between CD4 count and Viral Load Slow: <5,000, Fast: 50,000+

29 CD4 Count 1000 WHO Stage 1: Asymptomatic HIV infection CD4 >500 WHO Stage 2 and 3: Symptomatic HIV infection CD Mild infections Weight loss, fatigue TB, Thrush WHO Stage 4 AIDS CD4 < 200 TB, infections Death ~18 months Time (years) 4 6

30 Goals of HIV Treatment Improve quality of life Prevent opportunistic infections Prevent progression to AIDS Prevent death d h lk lh d f h Reduce the likelihood of transmission to others ( Secondary prevention )

31 HIV Treatment - Antiretrovirals Fusion/Entry Inhibitors (1) Maturation Inhibitors (~2008) Protease Inhibitors (8) Reverse Transcriptase Inhibitors (11) Integration Inhibitors (~2008)

32 HIV Treatment - Timing of HIV Treatment Therapy is delayed until patients develop WHO Stage 3 or Stage 4 disease Delaying therapy until Stage 3 or 4, if done carefully, does not decrease the likelihood of successful treatment Treatment is lifelong and expensive, do not want to start unnecessarily early Delayed therapy minimizes opportunity for side effects Delayed therapy minimizes opportunity for drug resistance

33 CD4 and Mortality - Zimbabwe 1.00 CD4 > 200 Survival Probability CD CD4 < Time from enrolment to death (years)

34 Impact of Treatment Before After

35 Impact of Treatment After 9 months

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

37 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

38 Number of Individuals Receiving ART Source: WHO Source: AVERT.org

39 Clinical Indicators Basic Water Supply Viral load HIV RNA level (copies/ ml plasma) Weeks Years CD4 cell count 600 (cells/μl blood)

40 State of the Art Technologies Basic Water Supply BD FACSCalibur CD4-count start treatment < 200 cells/ul Viral load count Viral load count measure resistance to treatment RT PCR

41 Lab Diagnostics Basic in Resource Water Supply Poor Settings

42 What is Needed Low cost Easy to use Rapid and Robust Portable Sensitive and specific

43 Microchip Technology Basic Water for Medicine Supply

44 CD4 counting microchip

45 Mechanism of the CD4 Counter

46 Nanoporous Membrane Fabrication Viral Concentrration (/ml) V 8e+7 6e+7 4e+7 2e+7 0 Original Sample Percentage of Virions (%) P nm Pores 1mL filtration + 10μL Wash 20nm Pores 80 Filtrate 60 Absorbed on membrane 40 Suspended above membrane 20 0 Cheng Lab: the Lab of Micro- and Nanotechnology for Medicine

47 Optically Forced Cytometry for Nanobead Counting Cheng Lab: the Lab of Micro- and Nanotechnology for Medicine