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In Lab on a chip

Particle agglutination assays are widely adopted immunological tests that are based on antigen-antibody interactions. Antibody-coated microscopic particles are mixed with a test sample that potentially contains the target antigen, as a result of which the particles form clusters, with a size that is a function of the antigen concentration and the reaction time. Here, we present a quantitative particle agglutination assay that combines mobile lens-free microscopy and deep learning for rapidly measuring the concentration of a target analyte; as its proof-of-concept, we demonstrate high-sensitivity C-reactive protein (hs-CRP) testing using human serum samples. A dual-channel capillary lateral flow device is designed to host the agglutination reaction using 4 μL of serum sample with a material cost of 1.79 cents per test. A mobile lens-free microscope records time-lapsed inline holograms of the lateral flow device, monitoring the agglutination process over 3 min. These captured holograms are processed, and at each frame the number and area of the particle clusters are automatically extracted and fed into shallow neural networks to predict the CRP concentration. 189 measurements using 88 unique patient serum samples were utilized to train, validate and blindly test our platform, which matched the corresponding ground truth concentrations in the hs-CRP range (0-10 μg mL-1) with an R2 value of 0.912. This computational sensing platform was also able to successfully differentiate very high CRP concentrations (e.g., >10-500 μg mL-1) from the hs-CRP range. This mobile, cost-effective and quantitative particle agglutination assay can be useful for various point-of-care sensing needs and global health related applications.

Luo Yi, Joung Hyou-Arm, Esparza Sarah, Rao Jingyou, Garner Omai, Ozcan Aydogan