Magnetic particle-based bioassays

Inventors

Strong, Louis H. • Edson, Clark M. • Palamakumbura, Senerath • Hall, Daniel B. • Varadi, Gyula

Assignees

Radiation Monitoring Devices Inc

Abstract

The disclosure relates to bioassays, as well as related devices and methods for detecting targets. The targets may be molecules and/or biological products that a user is interested in analyzing to determine information such as their presence and/or concentration in a sample.

Core Innovation

The invention relates to analyzing a sample that includes unbound magnetic particles and complexes that comprise one or more magnetic particles bound to a target. The complexes and unbound particles are subjected to magnetic-field manipulation so that their orientation and relaxation after field removal can be read out optically. After applying and removing magnetic fields, the method directs light to the sample and detects at least one optical signature indicative of the magnetic-bound state of the complexes.

In one approach, the method applies a first magnetic field to the sample for a first duration in a first direction, removes the first magnetic field, then applies a second magnetic field for a second duration in a second direction substantially perpendicular to the first direction. The optical readout includes detecting at least one of birefringent phase delay in light emanating from the sample and anisotropic light scattered from the sample. The device version includes a first magnetic field source and a second magnetic field source arranged to apply the two magnetic fields, together with a light source and a detector assembly arranged to measure the birefringent phase delay and/or anisotropic light scattering.

Another approach provides a sample with unbound magnetic particles and complexes comprising magnetic particles bound to a target, applies a magnetic field, then removes the magnetic field. The detection is based on at least one of birefringent phase delay in backwardly reflected light and backscattered light from the sample. Dependent refinements expand the sample content with isothermal nucleic acid amplification components and with chemically coupled hybridization probes and chemically coupled target ligands associated with magnetic particles, and further allow sample inclusion of cells or cell fragments with protein expression systems expressing membrane-embedded recombinant proteins.

Claims Coverage

The document provides three independent claims: clm-00001 (method with two substantially perpendicular magnetic fields and forward/emanating optical detection), clm-00008 (bioassay device with two magnetic field sources and optical detection), and clm-00009 (method with a single magnetic field cycle and backward/backscattered optical detection). Across these independent claims, the main inventive features total four categories: sequential perpendicular magnetic-field alignment/relaxation, dual-direction magnetic-field bioassay device configuration, optical detection via birefringent phase delay and anisotropic/backward optical scattering, and magnetic-field apply/remove readout in conjunction with backwardly reflected/backscattered detection.

Collectively, the independent claims define label-free magnetic-particle bioassay analysis in which magnetic-field manipulation is paired with optical detection using birefringent phase delay and anisotropic/backward/backscattered light, with clm-00001 and clm-00008 using two magnetic fields or two magnetic field sources and clm-00009 focusing on backwardly reflected and backscattered detection after magnetic field removal.

Stated Advantages

Documented Applications