title: Metal-amplified Density Assays, (MADAs), including a Density-Linked Immunosorbent Assay (DeLISA).
abstract: This paper reports the development of Metal-amplified Density Assays, or MADAs - a method of conducting quantitative or multiplexed assays, including immunoassays, by using Magnetic Levitation (MagLev) to measure metal-amplified changes in the density of beads labeled with biomolecules. The binding of target analytes (i.e. proteins, antibodies, antigens) to complementary ligands immobilized on the surface of the beads, followed by a chemical amplification of the binding in a form that results in a change in the density of the beads (achieved by using gold nanoparticle-labeled biomolecules, and electroless deposition of gold or silver), translates analyte binding events into changes in density measureable using MagLev. A minimal model based on diffusion-limited growth of hemispherical nuclei on a surface reproduces the dynamics of the assay. A MADA - when performed with antigens and antibodies - is called a Density-Linked Immunosorbent Assay, or DeLISA. Two immunoassays provided a proof of principle: a competitive quantification of the concentration of neomycin in whole milk, and a multiplexed detection of antibodies against Hepatitis C virus NS3 protein and syphilis T. pallidum p47 protein in serum. MADAs, including DeLISAs, require, besides the requisite biomolecules and amplification reagents, minimal specialized equipment (two permanent magnets, a ruler or a capillary with calibrated length markings) and no electrical power to obtain a quantitative readout of analyte concentration. With further development, the method may be useful in resource-limited or point-of-care settings.
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University, 230 Mallinckrodt Bldg., 12 Oxford St., Cambridge, MA 02138, USA. gwhitesides@gmwgroup.harvard.edu.
authors.forename: Anand Bala
authors.initials: AB
authors.lastname: Subramaniam
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gonidec
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Shapiro
authors.forename: Kayleigh M
authors.initials: KM
authors.lastname: Kresse
authors.forename: George M
authors.initials: GM
authors.lastname: Whitesides
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000937:Antigen-Antibody Reactions; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007118:Immunoassay; D007164:Immunosorbents / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D008892:Milk / Q000737:chemistry; D019255:NADPH Oxidases / Q000097:blood / Q000276:immunology; D009355:Neomycin / Q000032:analysis / Q000276:immunology; D012834:Silver / Q000737:chemistry*; D014210:Treponema pallidum / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000032:analysis / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000906:Antibodies; D006046:Gold; D007164:Immunosorbents; D019255:NADPH Oxidases; D009355:Neomycin; D012834:Silver; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C060505:neutrophil cytosolic factor 1