Next-generation lab-on-a-chip devices Samuel Sia, Ph.D. Associate Professor Department of Biomedical Engineering Columbia University APHL, Little Rock June 4, 2014 Clinical ELISA testing... ELISA ideal method low cost? - capital -per test compact? rapid? simple to operate? sensitive (pM)? distinguishes quantitative differences? amenable to parallel analysis? operable without ground electricity? works in field conditions (sunlight)? • coat surface with antigen (overnight) • block with 1% BSA or 0.05% Tween-20 (1 hr) uses accessible • add sample containing antibody to be tested (1 hr) reagents? • add enzyme-conjugated antibody (1 hr) • add substrate (10 min.) “Plug-in cartridge” (bubble-based reagent delivery) 17 pM 170 pM 1.7 nM 17 nM 170 nM 1.7 M Fluorescent antibody Sample Wash Wash Fluorescent Air spacers antibody 200 m Vacuum Antibody in sample Antigen 1200 1000 800 500-m 600 width 250-m 400 50-m width width total time = 2 min. 200 500-m (hands-free) width 0 Normalized fluorescence (a.u.) fluorescence Normalized 0.1 10 1000 Concentration of anti-rabbit IgG (nM) Linder, Sia, and Whitesides, Anal. Chem., 77:64 (2005) Silver reduction enables the use of microfluidics Angew Chemie, 43:498 (2004) ELISA mChip signal generation enzyme/substrate silver precipitation reaction (photography) light source lasers, lenses, filters LEDs (ambient lighting) detector photomultiplier tubes photodetector (photocopier) manufacturing plastic 96-well plates injection-molded plastic (consumer toys) Point-of-care ELISA Founded in 2004 (with Vincent Linder and David Steinmiller), based in Boston area raised ~$12M in VC funding First product: prostate cancer monitoring ISO-certified manufacturing facility and clean room approved in Europe (CE Mark) acquired by Opko Health in 2011 (~$50M) awaiting FDA approval and launch of PSA test and eventually 4K panel (total PSA, free PSA, intact PSA, HK2) Clinical scenario Pregnant woman in high burden-of-disease area (health clinic in U.S. inner city, village in sub-Saharan Africa) Healthcare professional sees this patient for the first time: no patient records No lab testing available Symptoms: fever, pain, sore throat, weight loss, headache Traditional response New response manage based only on precision diagnosis symptoms (syndromic management) Columbia ICAP testing sites (School of Public Health) August 2011 Chin et al, Nature Medicine, August 2011 Rwanda: 1 uL of whole blood Chin et al, Nature Medicine, August 2011 Rwanda: 7 uL of plasma/sera Chin et al, Nature Medicine, August 2011 Scale-up in manufacturing October 17, 2011 August 1, 2011 Design of a mobile device Popular Science, 2010 Mobile device for disease diagnosis and data-tracking in resource-limited settings Chin et al, Clin. Chem., 59:4, 2013 seamless integration with patient records time stamp, geotagged diagnostics results secure data transmission Whole-blood analysis... ...with real-time surveillance of diseases Head-to-head with lateral flow tests: commercial plasma panel with low and high antibody titers “Timely and accurate insight on current and emerging risks”: Network of sensors integrated with the cloud • maintain a global health perspective • strengthen partnerships Product evolution of mChip technology Reference lab test Claros mChip mChip device - ELISA Diagnostics (not automated) Year started 1970’s 2002 2005 2008 Automation yes yes no yes Specimen venipuncture finger-prick finger-prick finger-prick Speed 3 hours 15 min 15 min 15 min Accuracy high same as ELISA same as same as ELISA ELISA Device Cost $100,000 $3000 -- $200 Disposable COGS ~$1 $2 $2 $2 Target proteins proteins proteins (HIV, proteins (HIV, (PSA) STDs) STDs) Reference many (awards: 2010 Chin et al, Nature Chin et al, Clin Publications MIT Med, 2011 Chem, 2013 Tech.Review, 2011 WSJ Innovation) 2 8 Chin, Linder, and Sia, “Commercialization of microfluidic point-of-care diagnostic devices”, Lab Chip, 2012 Chin, Linder, and Sia (Lab Chip, 2012) Large public health impact Extremely cost-effective reference cost/DALY: $1000-$5000 (immunization), $1000 (ORT), $1000 (water and sanitation) (source: DCPP) source: RTI and Commons Capital analysis funded by Gates Foundation What’s in store for global health diagnostics? Technology challenges: • Device integration • User experience Business challenges: • Revenue: first-world markets • Cost: re-think target product profiles (Buffett rule) New resources in 2014 (vs. 2004): • Tech revolution in hardware and software Acknowledgments – Sia Lab Current members: Wan Laksanasopin, Tiffany Guo, Samiksha Nayak, Sau Yin Chin, Nalin Tejavibulya, Archana Sridhar, Brian Gillette, Ninna Rossen, Ziwei Song, Miguel Barreiros, Jeisun Xie, Ivan Ho, Yareeve Zemel, Wen Han Lee, Sahir Jaggi, Arnold Hwang, Kathleen Atkatsh, Hwan June Kang, Cherie Luo, Bret McCarty, Roshawn Johnson, Ritish Patnaik, Sarah Kim, Vivian Zhang, Kathryn Lau, Jiyoon Kim, Natalie Chee Past members contributing to this work: Curtis Chin, Yukkee Cheung, Zuankai Wang, Kweku Addae-Mensah, Mario Modena, Jennifer Wang, Robert Rouse, Hannah Moore, Paolo Cadinu, Olga Ordeig, Rafael zur Nieden Acknowledgments – Collaborators and Funding Claros Diagnostics: Rwanda: David Steinmiller Janneke van de Wijgert (AMC and Project Vincent Linder Ubuzima) Jason Taylor Etienne Karita (Projet San Francisco) Enqing Lee Rwanda Ministry of Health Pratt Design Incubator TDRTargets Network (WHO) Smart Design: Funding: Deb Johnson • NIH / NINR Eric Freitag • NIH / NHLBI • NIH / NIAID Columbia ICAP: • NIH/ NIAMS Wafaa El-Sadr • USAID/Gates Foundation/World Jessica Justman Bank/Governments of Canada and Ruben Sahabo Norway (Saving Lives at Birth) Veronicah Mugisha • Wallace H. Coulter Foundation David Hoos • NSF • American Heart Association Angela Christiano • WHO/TDR .