Continuous biomarker monitoring by particle mobility sensing with single molecule resolution

Abstract

Healthcare is in demand of technologies for real-time sensing in order to continuously guard the state of patients. Here we present biomarker-monitoring based on the sensing of particle mobility, a concept wherein particles are coupled to a substrate via a flexible molecular tether, with both the particles and substrate provided with affinity molecules for effectuating specific and reversible interactions. Single-molecular binding and unbinding events modulate the Brownian particle motion and the state changes are recorded using optical scattering microscopy. The technology is demonstrated with DNA and protein as model biomarkers, in buffer and in blood plasma, showing sensitivity to picomolar and nanomolar concentrations. The sensing principle is direct and self-contained, without consuming or producing any reactants. With its basis in reversible interactions and single-molecule resolution, we envisage that the presented technology will enable biosensors for continuous biomarker monitoring with high sensitivity, specificity, and accuracy.

Rotating magnetic particles for lab-on-chip applications – a comprehensive review

“…particle-based point-of-care testing devices 2 and devices for continuous biomarker monitoring. 130 In summary, the controlled application of torque and rotation to magnetic particles has developed strongly and steadily over the past decades, delivering a range of unique actuation and probing functionalities of fluids, molecules and cells in lab on chip systems. The field is set to further develop innovative approaches for characterizing biomolecular and biological systems as well as for integrating lab on chip functionalities into advanced bioanalytical tools.…”

Stochastic electrochemistry at ultralow concentrations: the case for digital sensors

“…Early attempts have focused mostly on optical methods. [22][23][24] Purely electrical transducers are however highly desirable since they can be implemented using integrated circuits to provide massive parallelization at low cost. In the second part of the manuscript, we therefore review electrochemical sensory systems with the capability to sense analytes and particles with a digital on/off mode.…”

Conformation switching of single native proteins revealed by nanomechanical probing without a pulling force

“…The nanomechanical probing technique described in this paper can in the future be applied for bioanalysis because it is suited for measuring native proteins in biological samples, due to the use of the general concept of capturing a target molecule between two affinity binders, in a molecular sandwich arrangement. In this way the single-molecule technique may find application for biomarker characterization in near-patient testing 46 and continuous monitoring 47 technologies.…”