Method and apparatus for measuring particle characteristics through mass detection
Inventors
Babcock, Kenneth • Burg, Thomas • Godin, Michel • Manalis, Scott
Assignees
AFFINITY BIOSENSORS LLC • Massachusetts Institute of Technology
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Abstract
Method for measuring a target particle property. A suspended microchannel resonator is calibrated to determine the relationship between a detected mass and a resonance frequency shift of the resonator. The target particle is suspended in a fluid and introduced into the resonator, and the resonator frequency shift due to the particle is measured. Target particle mass is calculated from the resonator frequency shift, the target particle density, and the fluid density. A target particle property such as size or volume is determined from the calculated target particle mass.
Core Innovation
The invention provides methods using a suspended microchannel resonator (SMR) to measure properties of target particles based on resonance frequency shifts. A target particle is introduced into the SMR and the shift in resonance frequency is measured. The SMR is calibrated to determine a relationship between the resonance frequency or shift in resonance frequency and detected mass due to the presence of a particle inside the resonator, enabling calculation of particle properties from the resonance frequency shift.
The invention includes determining particle density by introducing the target particle in a first fluid and measuring the resonance frequency shift, introducing the target particle in a second fluid having a different density and measuring the resonance frequency shift, and determining the fluid density that would produce zero resonance frequency shift as the target particle density. It also extends to measuring mean density of a population by measuring time averages or mean resonance frequency shifts for particles in first and second fluids and determining the fluid density that would produce zero mean shift as the mean density of the particle population.
The invention further includes identifying the type of an individual particle among two possible types distinguished by distinct mean densities by suspending the particle in a fluid with a density between the two types, introducing the fluid and particle into the SMR, monitoring the resonance frequency shift as the particle passes through the resonator, and identifying the particle with the corresponding type. In addition, it provides methods for measuring a fluid density using SMR calibration and seeded particles of known mass and density, and methods for measuring particle volume, diameter, and linear size from resonance-frequency shift via density-correction relations using the relationship between detected mass and the shift in resonance frequency.
Claims Coverage
The independent claims cover density measurement of a target particle and a particle population, particle-type identification between two density-distinct types, fluid-density measurement via SMR calibration and seeded particles, and particle property measurement from resonance frequency shifts using density-correction relations. In total, the claims emphasize SMR calibration to relate detected mass to resonance frequency shift and calculation of particle properties from that relationship, including zero-shift and zero mean shift density determination methods.
Target particle density from zero resonance frequency shift across two fluids
introducing a target particle in a first fluid having a first density into a suspended microchannel resonator and measuring the shift in resonance frequency; introducing the target particle in a second fluid having a second density different from the first density into the resonator and measuring the shift in resonance frequency; and determining the fluid density that would produce zero resonance frequency shift, this fluid density being the target particle density.
Mean density from zero mean resonance frequency shift across two fluids
introducing a number of particles from the particle population in a first fluid having a first density into a suspended microchannel resonator; measuring the resonance frequency shifts for the individual particles suspended in the first fluid as they pass through the resonator; determining the mean resonance frequency shift for the particles suspended in the first fluid; introducing a number of particles from the particle population in a second fluid having a second density into a suspended microchannel resonator; measuring the resonance frequency shifts for the individual particles suspended in the second fluid as they pass through the resonator; determining the mean resonance frequency shifts for the particles suspended in the second fluid; and determining the fluid density that would produce zero mean shift in resonance frequency, this fluid density being the mean density of the particle population.
Particle type identification using resonance frequency shift monitored in intermediate-density fluid
suspending the particle in a fluid whose density is between the densities of the two particle types; introducing the fluid and particle into a suspended microchannel resonator; monitoring the resonance frequency shift as the particle passes through the resonator; and identifying the particle with the corresponding type.
Fluid density calculation using SMR calibration and seeded known-mass and density particles
calibrating a suspended microchannel resonator to determine the relationship between a detected mass and the shift in resonance frequency of the resonator; seeding a target fluid with particles of known mass and density; flowing the seeded fluid through the resonator and measuring the shift in resonance frequency caused by individual particles; and calculating the fluid density from the equation fluid density=particle density×(1−(detected mass/particle mass)).
Population property calculation from detected bulk mass density change using a calibration relation
calibrating a suspended microchannel resonator to determine the relationship between bulk sample density and the shift in resonance frequency of the resonator; introducing a suspension of particles in fluid into the suspended microchannel resonator; measuring the change in bulk density caused by the presence of the particles; and calculating a property of the population of particles from the equation detected bulk mass density change=mean particle concentration×mean particle volume×(mean particle density−fluid density).
Mean density by time-averaged resonance frequency shifts in two fluids
introducing a suspension of particles in a first fluid having a first density into a suspended microchannel resonator; measuring the time average of the resonance frequency shifts for the particles suspended in the first fluid as they pass through the resonator; introducing a suspension of particles in a second fluid having a second density into a suspended microchannel resonator; measuring the time average of resonance frequency shifts for the particles suspended in the second fluid as they pass through the resonator; and determining the fluid density that would produce zero mean shift in resonance frequency, this fluid density being the mean density of the particle population.
Target particle mass from detected mass using a density-correction equation
calibrating a suspended microchannel resonator to determine the relationship between the resonance frequency of the resonator and the detected mass due to the presence of a particle inside the resonator; introducing a target particle into the resonator along with a fluid and measuring the shift in resonance frequency; and calculating a property of the target particle from the shift in resonance frequency, wherein the property is mass and mass is calculated by the equation particle mass=detected mass/(1−fluid density/particle density).
Target particle volume from detected mass using a density-difference equation
calibrating a suspended microchannel resonator to determine the relationship between the resonance frequency of the resonator and the detected mass due to the presence of a particle inside the resonator; introducing a target particle into the resonator along with a fluid and measuring the shift in resonance frequency; and calculating a property of the target particle from the shift in resonance frequency, wherein the property is volume and volume is calculated by the equation particle volume=detected mass/(fluid density−particle density).
Target particle diameter from detected mass using a density-difference relationship
calibrating a suspended microchannel resonator to determine the relationship between the resonance frequency of the resonator and the detected mass due to the presence of a particle inside the resonator; introducing a target particle into the resonator along with a fluid and measuring the shift in resonance frequency; and calculating a property of the target particle from the shift in resonance frequency, wherein the property is diameter and diameter is determined by the relationship diameter=CubeRoot(6×detected mass/(Pi*(fluid density−particle density))).
Target particle linear size from volume-to-size relations for selected shapes
calibrating a suspended microchannel resonator to determine the relationship between the resonance frequency of the resonator and the detected mass due to the presence of a particle inside the resonator; introducing a target particle into the resonator along with a fluid and measuring the shift in resonance frequency; and calculating a property of the target particle from the shift in resonance frequency, wherein the property is linear size and linear size is determined using relations between volume and size for selected shapes.
The claims center on calibrating a suspended microchannel resonator to relate resonance frequency or resonance frequency shift to detected mass, then using that relationship to determine particle properties, densities, and fluid density via zero-shift and density-correction relations. Additional coverage includes measuring population properties and identifying an individual particle type among two density-distinct types.
Stated Advantages
optics-free sensing
reduced sample volume
no pre-fractionation
direct mass/density/size measurement
MEMS cost-effectiveness
Documented Applications
measuring particle mass/size distributions using the SMR approach with resonance frequency shift calibration and density correction, including polystyrene spheres
measuring density response for gold nanoparticles
measuring density-related properties for E. coli and B. subtilis
measuring particle density by a density-response approach using resonance frequency shift behavior in fluids of different densities
measuring mean population density by using multi-particle configurations and time-averaged bulk mass density change
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