Device for laser analysis and separation (LAS) of particles
Inventors
Hart, Sean J. • Terray, Alexander V. • Hebert, Colin G.
Assignees
Publication Number
US-10281385-B2
Publication Date
2019-05-07
Expiration Date
2027-12-21
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Abstract
A device includes a collimated light source operable to generate a collimated light source beam, which includes a beam direction. The device includes a first channel in a first plane and a second channel in a second plane different from the first plane. The second channel communicates with the first channel and includes a flow direction. The second channel is oriented to receive the collimated light source beam. The device includes a third channel in a third plane different from the second plane and communicates with the second channel. The collimated light source beam is oriented to enter a cross-section of the first channel, then to pass through the second channel, and then to enter a cross-section of the third channel such that the beam direction is opposite to the flow direction in the second channel. The device includes a focused particle stream nozzle operably connected to the first channel.
Core Innovation
The invention provides a device and method for optical analysis and separation of particles in fluids using laser-induced optical pressure. This device employs a collimated light source that generates a beam passing through a network of microfluidic channels oriented in orthogonal planes, where the beam direction opposes the fluid flow direction. Particles in the fluid experience optical forces due to radiation pressure from the laser beam, enabling size-, shape-, refractive index-, or morphology-based separation and characterization without reliance on antibodies or fluorescent molecules.
The device includes a first channel for fluid flow, a second orthogonal channel aligned to receive the collimated laser beam, and a third channel orthogonal to the second, forming a three-dimensional microfluidic network. A focused particle stream nozzle delivers a sample flow into the first channel, and sheath flows provide hydrodynamic focusing to control the sample flow's cross-section and position. By balancing optical forces with fluid drag, particles can be retained or directed to collection channels based on their intrinsic or induced properties, enabling particle identification, separation, and analysis.
Claims Coverage
The patent includes multiple independent claims detailing a device with specific channel configurations and light source arrangements, covering laser-based particle separation using orthogonal microfluidic channels and hydrodynamic focusing features. The inventive features emphasize channel design, optical beam orientation, particle stream focusing, and sample reservoir integration.
Orthogonal multi-channel configuration for laser and fluid flow interaction
The device comprises three channels arranged in three different planes, where the second channel is oriented to receive a collimated light source beam. The collimated beam enters the first channel cross-section, passes through the second channel, and enters the third channel cross-section such that the beam direction opposes the flow direction in the second channel.
Focused particle stream nozzle with sheath flow channels
A focused particle stream nozzle operably connected to the first channel includes a plurality of sheath flow channels and a sample injection inlet, allowing control of the sample flow cross-section size and position by hydrodynamic focusing.
Collection channels and reservoirs for particle sorting and analysis
The device incorporates at least one collection channel communicating with the second or third channel, with corresponding outlet reservoirs such as outlet well plates comprising multiple grid wells and waste moats. This supports separated particle collection and further analysis.
Particle interrogation unit integration
The device includes particle interrogation units communicating with the second channel, comprising illuminators, optics, and sensors such as bright field imagers, light scatter detectors, fluorescent detectors, CCD or CMOS cameras, photodiodes, photomultiplier tubes, chemiluminescent or bioluminescent detectors, and Raman spectroscopy detectors for sample analysis.
Sample reservoir with fluid pressure control and mixing capabilities
A sample reservoir communicates with the sample injection inlet, is connected to a fluid pressure driver and controller, and may be rotatable, tilted, or horizontally oriented. It includes a mixer such as a stir bar, microfluidic mixer, impeller, or baffles to maintain particle suspension and controlled sample flow.
Use of optical elements and customizable laser beam modes
Optical elements between the collimated light source and the second channel produce various beam types including rectangular, TEM00, TEM01, TEM10, TEM21, Hermite-Gaussian, Laguerre-Gaussian, or multimodal beams. The elements can be lenses, mirrors, modulators, or wave plates, producing polarized beams (circular, linear, elliptical).
The independent claims collectively cover a particle separation device using a three-dimensional microfluidic channel arrangement receiving a collimated laser beam with opposing flow, combined with hydrodynamic focusing of particle streams, collection infrastructure, particle interrogation capabilities, and controlled sample reservoir delivery to enable precise optical-force-based particle analysis and sorting.
Stated Advantages
The invention enables sensitive and selective particle sorting based on inherent optical properties without the need for antibodies or fluorescent labels.
It offers automated analysis and sorting with a cost- and size-effective microfluidic device.
The method allows physical separation and characterization of biological and inorganic particles through balance of optical and fluidic forces.
Particles can be analyzed dynamically, including deformation and mechanical property assessment relevant to disease states such as cancer or cell aging.
Hydrodynamic focusing enables precise positioning of particle streams within the device, improving separation and interrogation efficiency.
Documented Applications
Sorting cell streams for detection of pathogens and disease based on optical force differences arising from variations in size, shape, refractive index, or morphology.
Separation and analysis of colloidal samples including organic particulates, inorganic particles like glass and metal, and biological species such as cells, bacteria, and viruses.
Biomedical analysis and bio-warfare detection by identifying biological samples according to chemical differences expressed in refractive indices and physical properties.
Dynamic monitoring of single cells or small tissue samples to assess mechanical and biochemical changes related to disease.
Automated delivery and collection of multiple samples using microfluidic well plates and controlled fluid pressures for high-throughput particle analysis.
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