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A novel lab-on-a-chip detection device, based on the properties of immunoagglutination, was modified to detect malaria in the human blood through histidine-rich protein 2, an antigen expressed only by Plasmodium falciparum. Utilizing Mie scattering detection, which is angle- and size-dependent, the extent of immunoagglutination could be accurately measured while the optical disturbance from the human blood was minimized. The presence of human serum albumin in the blood is believed to further stabilize the antibody-conjugated submicron beads and/or break off the larger agglutinated beads. The lowest detection limit was 1 pg/mL in 10% of whole blood (equivalent to 10 pg/mL in undiluted whole blood), a few orders of magnitude lower than other assays. The final device is compact, with a fast assay time of approximately 8 min.