TY - JOUR
T1 - Particle motion analysis reveals nanoscale bond characteristics and enhances dynamic range for biosensing
AU - Visser, E.W.A.
AU - van IJzendoorn, L.J.
AU - Prins, M.W.J.
PY - 2016/3/22
Y1 - 2016/3/22
N2 - Biofunctionalized colloidal particles are widely used as labels in bioanalytical assays, lab-on-chip devices, biophysical research, and in studies on live biological systems. With detection resolution going down to the level of single particles and single molecules, understanding the nature of the interaction of the particles with surfaces and substrates becomes of paramount importance. Here, we present a comprehensive study of motion patterns of colloidal particles maintained in close proximity to a substrate by short molecular tethers (40 nm). The motion of the particles (500-1000 nm) was optically tracked with a very high localization accuracy (below 3 nm). A surprisingly large variation in motion patterns was observed, which can be attributed to properties of the particle-molecule-substrate system, namely the bond number, the nature of the bond, particle protrusions, and substrate nonuniformities. Experimentally observed motion patterns were compared to numerical Monte Carlo simulations, revealing a close correspondence between the observed motion patterns and properties of the molecular system. Particles bound via single tethers show distinct disc-, ring-, and bell-shaped motion patterns, where the ring- and bell-shaped patterns are caused by protrusions on the particle in the direct vicinity of the molecular attachment point. Double and triple tethered particles exhibit stripe-shaped and triangular-shaped motion patterns, respectively. The developed motion pattern analysis allows for discrimination between particles bound by different bond types, which opens the possibility to improve the limit of detection and the dynamic range of bioanalytical assays, with a projected increase of dynamic range by nearly 2 orders of magnitude.
AB - Biofunctionalized colloidal particles are widely used as labels in bioanalytical assays, lab-on-chip devices, biophysical research, and in studies on live biological systems. With detection resolution going down to the level of single particles and single molecules, understanding the nature of the interaction of the particles with surfaces and substrates becomes of paramount importance. Here, we present a comprehensive study of motion patterns of colloidal particles maintained in close proximity to a substrate by short molecular tethers (40 nm). The motion of the particles (500-1000 nm) was optically tracked with a very high localization accuracy (below 3 nm). A surprisingly large variation in motion patterns was observed, which can be attributed to properties of the particle-molecule-substrate system, namely the bond number, the nature of the bond, particle protrusions, and substrate nonuniformities. Experimentally observed motion patterns were compared to numerical Monte Carlo simulations, revealing a close correspondence between the observed motion patterns and properties of the molecular system. Particles bound via single tethers show distinct disc-, ring-, and bell-shaped motion patterns, where the ring- and bell-shaped patterns are caused by protrusions on the particle in the direct vicinity of the molecular attachment point. Double and triple tethered particles exhibit stripe-shaped and triangular-shaped motion patterns, respectively. The developed motion pattern analysis allows for discrimination between particles bound by different bond types, which opens the possibility to improve the limit of detection and the dynamic range of bioanalytical assays, with a projected increase of dynamic range by nearly 2 orders of magnitude.
KW - colloidal particles
KW - Monte Carlo simulations
KW - motion analysis
KW - particle based biosensing
KW - particle-substrate interactions
KW - sensing dynamic range
KW - tethered particle motion
UR - http://www.scopus.com/inward/record.url?scp=84961943254&partnerID=8YFLogxK
U2 - 10.1021/acsnano.5b07021
DO - 10.1021/acsnano.5b07021
M3 - Article
C2 - 26913834
AN - SCOPUS:84961943254
SN - 1936-0851
VL - 10
SP - 3093
EP - 3101
JO - ACS Nano
JF - ACS Nano
IS - 3
ER -