Particle agglutination assay system

Apparatus for assaying a fluid sample for an analyte, said apparatus comprising, in combination

• a first reagent including at least a first class of minute initial particles dimensioned within a predeterminedly narrow range of particle diameters and being coated with a reactant capable of entering into a reaction involving said analyte so as to generate resultant particles from said initial particles and of different dimensions than said initial particles, said resultant particles having characteristic acoustic scattering cross sections;
• at least a second class of minute, substantially spheroidal particles within a predeterminedly narrow range of substantially larger particle diameters than the diameters of said particles of said first class, the particles of said second class being coated with said reactant;
• and
• means for forming a mixture of the reactant coated particles of said first and second classes with said sample so as to initiate said reaction and form said resultant particles from said first and second classes of particles by said reaction with analyte present in said sample;
• and
• means for irradiating the mixture of said reagent and sample with compressional waves in a predetermined frequency range at which said resultant particles will cause a reduction in forward energy of said waves within a wavelength band determined in accordance with the scattering cross-sections of said resultant particles;
• and
• sensor means for detecting said reduction of said forward energy by said resultant particles.

Apparatus for assaying a fluid sample for an analyte, said apparatus comprising, in combination

• a first reagent including at least a first class of minute initial particles dimensioned within a predeterminedly narrow range of particle diameters, said particles comprising a reactant capable of entering into a reaction involving said analyte so as to generate resultant particles of different dimensions than said initial particles, said resultant particles having characteristic acoustic scattering cross sections;
• means for forming a mixture of said reagent with said fluid sample so as to initiate said reaction;
• a source of ultrasonic waves for irradiating the mixture of said reagent and sample with said waves in a predetermined frequency range at which said resultant particles will cause a reduction in forward energy of said waves within a wavelength band determined in accordance with the scattering cross-sections of said resultant particles;
• an ultrasonic delay line disposed between said source and said mixture so as to delay the propagation of said waves irradiating said mixture;
• and
• sensor means for detecting said reduction of said forward energy by said resultant particles.

Apparatus for assaying a fluid sample for an analyte, said apparatus comprising, in combination

• a first reagent including at least a first class of minute initial particles dimensioned within a predeterminedly narrow range of particle diameters, said particles comprising a reactant capable of entering into a reaction involving said analyte so as to generate resultant particles of different dimensions than said initial particles, said resultant particles having characteristic acoustic scattering cross sections;
• means for forming a mixture of said reagent with said fluid sample so as to initiate said reaction;
• a source of ultrasonic waves for irradiating the mixture of said reagent and sample with said waves in a predetermined frequency range at which said resultant particles will cause a reduction in forward energy of said waves within a wavelength band determined in accordance with the scattering cross-sections of said resultant particles;
• acoustic reflector means positioned for reflecting said ultrasonic waves back toward said source after having traversed said mixture;
• and
• sensor means for detecting said reduction of said forward energy by said resultant particles.

Apparatus for assaying a fluid sample for an analyte, said apparatus comprising, in combination

• a first reagent including at least a first class of minute initial particles dimensioned within a predeterminedly narrow range of particle diameters, said particles comprising a reactant capable of entering into a reaction involving said analyte so as to generate resultant particles of different dimensions than said initial particles, said resultant particles having characteristic acoustic scattering cross sections;
• means for forming a mixture of said reagent with said fluid sample so as to initiate said reaction, said means for forming a mixture comprising a hollow flow cell having a chamber of capillary cross-section with inlet and outlet conduits thereto for respectively introducing and removing the mixture of reagent and sample to and from said chamber;
• a source of ultrasonic waves for irradiating the mixture of said reagent and sample with said waves in a predetermined frequency range at which said resultant particles will cause a reduction in forward energy of said waves within a wavelength band determined in accordance with the scattering cross-sections of said resultant particles;
• and
• sensor means for detecting said reduction of said forward energy by said resultant particles.

Apparatus for assaying a fluid sample for an analyte, said apparatus comprising, in combination

• a first reagent including at least a first class of minute initial particles dimensioned within a predeterminedly narrow range of particle diameters, said particles comprising a reactant capable of entering into a reaction involving said analyte so as to generate resultant particles of different dimensions than said initial particles, said resultant particles having characteristic acoustic scattering cross sections;
• means for forming a mixture of said reagent with said fluid sample so as to initiate said reaction,
• means for irradiating the mixture of said reagent and sample with compressional waves in a predetermined frequency range at which said resultant particles will cause a reduction in forward energy of said waves within a wavelength band determined in accordance with the scattering cross-sections of said resultant particles, said means for irradiating comprising acoustic transducer means for providing said compressional waves;
• sensor means for detecting said reduction of said forward energy by said resultant particles, said sensor means comprising means for generating electrical signals in accordance with the detected reduction in said forward energy;
• and
• means for determining from the frequency and amplitude of said electrical signals an assay of said analyte in said sample.

Method of assaying for at least one type of analyte in a liquid sample, including the steps of

• providing a first reagent including at least a first class of minute particles dimensioned within a predeterminedly narrow range of particle diameters and being coated with a reactant capable of entering into a reaction involving said analyte so as to generate resultant particles of different dimensions than said first class of initial particles, said resultant particles having characteristic acoustic scattering cross sections;
• providing a second reagent including at least a second class of substantially larger particle diameters than the diameters of said particles of said first class, the particles of said second class being coated with said first reactant;
• forming a mixture of the reactant coated particles of said first and second classes with said sample so as to effect a specific reaction involving said reactant and said analyte to form conjugates of said first and second classes of particles, said conjugates having a characteristic acoustic scattering cross-sections;
• irradiating the conjugates with compressional waves in a predetermined frequency range at which said conjugates will cause a reduction in forward energy of said waves within a wavelength band determined in accordance with said scattering cross-sections;
• and
• detecting said reduction of said forward energy.