Digital Microscopy and Diagnosis on Cellphones

Transcription

1 Digital Microscopy and Diagnosis on Cellphones Aydogan Ozcan Electrical Engineering Department Bioengineering Department California NanoSystems Institute University of California, Los Angeles July,

2 Aydogan Ozcan, Ph.D. UCLA June,

3 Cell phones are now everywhere: A great potential for Telemedicine needs Afghanistan 40 Canada 68 U.K. 97 Russia 162 Mexico 78 U.S. 97 Chad 24 India 45 China 56 Bolivia 72 Brazil 90 Argentina 129 Angola 44 South Africa 94 World Bank 2009 > 5 billion cell phones are being used worldwide. UAE 232 Indonesia 69 > 70% are in developing countries. (ITU, 2010). Australia 111

4 Providing a new platform for telemedicine LUCAS: Lensfree (On-Chip Imaging) Compact, Cost-effective High-throughput Highly sensitive (Incoherent Holography) Tolerant to Misalignments LUCAS: Lensless, Ultra wide-field Cell monitoring Array platform based on Shadow imaging 4

5 Imaging of shadows Cell Shadows imaged using LUCAS 5

6 (e) (a) (a) Lymphocyte (c) (b) (b) Lymphocyte Neutrophil (d) (e) (c) Neutrophil (d) Neutrophil Neutrophil

7 Cell Density: 102K [Cells/uL] Reconstruction 10X

8 Incoherent Lensfree Holography Using Large Apertures: -Reduced speckle noise and multiple interference noise -Reduced cross-talk among cells -Tolerant to misalignments; No need for coupling optics -No need for lasers; LEDs would be sufficient -Significantly larger field of view

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10 40 µm 40 µm 40 µm 40 µm 40 µm 40 µm 10 µm 10 µm 10 µm 10 µm 10 µm 10 µm 10 µm 10 µm 10 µm 10 µm 10 µm 10 µm

11 300k 250k 200k 150k 100k 50k 0 Rec % Rec % (e) BP +0.39% (g) 10X Microscope (b) BP +2.25% -8.98% -2.25% (f) Raw Raw (d) 10X Microscope -2.25% (c) Raw Blood Analysis using LUCAS +3.15% Rec % Raw -4.57% (h) BP (i) Raw % -3.33% Rec. (b) (c) (d) (e) (f) (g) (h) (i) (j) -4.57% Rec. 0 50k 100k 150k 200k 250k 300k 350k 400k

12 CD4 cell count (cells/mm 3 ) Monitoring HIV patients in resource limited settings is an important challenge Diagnosis Combination therapy became widely available in A flow-cytometer costs on average 30K-120K $ Year of CD4 cell count A girl living with HIV in Malawi 12

13 Cell counting in microfluidic channels based on LUCAS Anti CD4 PDMS based 4-channel microfluidic device Whole blood O N O Avidin O N O S (CH 2 ) 3 Si O O O We can achieve a specificity of >90% and an efficiency of 90% for capturing CD4 cells from whole blood. Collaborator: Revzin Group UC Davis 13

14 CD4 CD8 counts using LUCAS Collaborator: Revzin Group UC Davis

15 CD8 T-cells CD4 T-cells Cell counting in microfluidic channels based on LUCAS MC=87 AC=90 40um MC=93 AC=96 40um MC=53 AC=55 40um MC=49 AC=51 40um 15

16 Number of CD4 Cellsper spot Total Number of CD4 Cells Number Of CD8 Cells per spot Total number of CD8 Cells Patient# PATIENT#1 CD8 count Microscope LUCAS Error Total CD8 Cells Micros cope LUCAS 947 Error CD4/CD8 PATIENT#1 CD4 count Microscope LUCAS Error Total CD4 Count Micros cope LUCAS 2906 Error Microscope LUCAS Error

17 Number of CD4 Cellsper spot Total Number of CD4 Cells Number Of CD8 Cells per spot Total number of CD8 Cells Patient#2 PATIENT#2 CD8 count Microscope LUCAS Error Total CD8 Cells Micros cope LUCAS 5074 Error CD4/CD8 PATIENT#2 CD4 count Microscope LUCAS Error Total CD4 Count Micros cope LUCAS 4617 Error Microscope LUCAS Error

18 Giardia Lamblia Cysts & Cryptosporidium Parvum Cryptosporidium Parvum Giardia Lamblia Cysts Lensfree Imaging of Waterborne Parasites Lensfree Holograms Reconstructed Amplitude 40X Microscope Objective 20um 20um 20um 20um 20um 20um 20um 20um 20um

19 LUCAS 2.5 (NA=0.65) 10 mm 10 mm 10 mm radians radians radians Plasmodium falciparum

20 1mm

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22 Providing a new platform for telemedicine 22

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24 Giardia Lamblia White Blood Cells Wide field fluorescent imaging on a cellphone 24

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26 Cell density (#/µl) Cell-phone counting results Coulter counting results (5100/µL) Time (s) 26

27 Water Skim Milk 27

28 Providing a new platform for telemedicine 28

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30 Integrated Rapid-Diagnostic-Test Reader Platform on a Cellphone 47mm AAA batteries LED array (transmission) Switch 34mm LED arrays (reflection) Lens

31 Integrated Rapid-Diagnostic-Test Reader Platform on a Cellphone

32 Integrated Rapid-Diagnostic-Test Reader Platform on a Cellphone

33 Integrated Rapid-Diagnostic-Test Reader Platform on a Cellphone 1x 2x 3x

34 Integrated Rapid-Diagnostic-Test Reader Platform on a Cellphone

35 An Analogy: From PCs to the Internet 35

36 The µ-internet Big Data - An opportunity or a challenge? 36

37 Diagnosis of Malaria using Crowd-Sourced Games

38 Diagnosis of Malaria using Crowd-Sourced Games More than 70 countries are playing BioGames, with ~1.5 Million cell diagnoses so far.

39 Ozcan Research Group Members & Funding 39