The promise of Label-Free Detection

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2 The promise of Label-Free Detection A capture molecule (or responsive chemical coating) on one sensor element is not affected by other sensor elements For the first time, this allows for detection of many targets as simply as one, given an ability to put many elements on chip (easy), an ability to address them all independently (easy), and an ability to make them different chemically (harder, depending on scale)

3 Photonic sensors can gain specificity through chemical interactions For Biosensing: Small molecule 1 kda TIR Peptide 5 kda DNA!5 kda Hemagglutinin 56 kda (trimer) Antibody 150 kda Human Papillomavirus VLP 18,000 kda (Similar strategies possible for chemical sensing) (and don t forget spectroscopy!)

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5 Sensor project consortium!!! Ben Miller (Lead; University of Rochester). Co-Personnel: Todd Stievater (NRL), Carl Meinhart (UCSB), Nate Cady (SUNY-Poly), Ray Jakubowicz (Ortho-Clinical Diagnostics), Skip Warren (Ortho-Clinical Diagnostics), Will Green (IBM), Eric Zhang (IBM), Chi Zhong (IBM), Ehsan Hosseini (Analog Photonics), Scott Holmstrom (University of Tulsa), Twan Korthorst (PhoeniX), Jason Guicheteau (Army/ECBC), Rick Stevens (Lockheed-Martin Co.), Mark Peterman (OndaVia) Intentionally draws from academia, DoD, large and small industry Also mixes expertise in different technology platforms and market spaces

6 !"#$%&'()#*+)&(%*(%,")('#()&(% Off-resonance On-resonance

7 Ring resonators as biosensors!! Very well understood photonic element from telecom industry Potential for Si 3 N 4 ring resonators to provide performance advantages =2!n eff /m n eff, 1 = res,a = res,b Expose to analyte I n eff, 2 On-resonance

8 Photonic Design Kit (PDK) Chip Design Multi-Project Wafer (MPW) Test, Assembly, and Packaging (TAP)

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10 Human serum: needles in (wet) haystacks Wikipedia: serum reference ranges IL6 reference: 4.8 pg/ml 10 8 difference Total protein: mg/ml

11 Representative biological targets Human C-reactive protein (PDB 1 GNH) Molecular weight: 25,106 (x 5) Reference range: ng/ml elevated in infection or inflammation to as much as 500 ng/ml Human Interleukin-6 (PDB 1 ALU) Molecular weight: 21,000 Reference range: 4.8 pg/ml Elevated in infection or inflammation to as much as 250 pg/ml

12 Biosensing via functionalized microring resonators '!""#%"'" / :;<709=>? &!("#%"'" &!""#%"'" %!("#%"'" %!""#%"'" $!("#%"'" $!""#%"'" #!""#%"&" : $9LD: $9LD: $9LD!!""#$""" )(*& )(*+ )(*, )((" )(() )((- )((. >1@7A72B6C9=24? Ring resonator-based selective detection of C-reactive protein in bovine serum albumin background. Data shows shifts for two replicate rings.

13 Quantitative detection of IL-6 and CRP in human serum Single ring Endpoint detection (incubate, rinse, dry, measure) All values are relative to an anti-fitc ring to normalize for nonspecific binding of serum (rather than using a cladded reference) LOD

14 A pathway to address all market segments (Siemens) Home Benchtop/ Point-of-care/ Point-of-need High-volume Clinical lab

15 Summary! Integrated photonic sensors represent a large and rapidly growing market! Potential devices range from high volume / low cost to low volume / high value! In the biosensing context, enable applications previously impossible! We are making excellent progress in realizing this vision in collaboration with AIM Photonics On-resonance

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