Cytokine Sensor Platform

Janice J. Li, Amy L. Ouellette, Laurent Giovangrandi, Antonio J. Ricco and Gregory T.A. Kovacs

Electrical Engineering Department, Integrated Circuits Lab, Stanford University

Objectives:

To develop a sensor that detects cytokines – proteins produced by the immune system – for early indications of infection or stress.
To design a system for investigating and optimizing cytokine assays that utilize up-converting phosphorescent labels, whose unique property of visible light emission upon excitation of near-infrared radiation potentially enhances assay sensitivity.

Technical Approach:

The cytokine sensor consists of a consumable sample-containing component and a reusable optical readout device. In this device, up-converting phosphor (UCP) emissions correspond to the presence of cytokines through the use of antibodies – proteins that bind specifically to only one kind of molecule. As a fluid sample flows, any cytokines present in the sample bind to the antibodies on the UCP particles and to the antibodies immobilized on the chip. Thus, UCP particles are bound to the chip only when cytokines are present, and only these UCP particles are detected by the optical system.

(a) Up-conversion process: Emission of one photon of visible light upon absorption of two near-infrared photons.

(b) Sandwich immunoassay using UCP technology: Schematic representation of the selective capture of a target cytokine molecule by a surface-confined antibody, followed by attachment of a UCP particle via a second specific antibody, thereby labeling the target for optical detection.

Results:

Quantification of the cytokine IFN-g with up-converting phosphorescent labels.
Development of an optical scanner that detects up-converting phosphors to produce 2-D images.

Publications:

A.L. Ouellette, J.J. Li, D.E. Cooper, A.J. Ricco, G.T.A. Kovacs, “Evolving Point-of-Care Diagnostics: Up-Converting Phosphor Bioanalytical Systems,” Analytical Chemistry. (Manuscript in progress)