Microparticle-based methods and systems and applications thereof

Abstract

Microparticle-based analytical methods, systems and applications are provided. Specifically, the use of resonant light scattering as an analytical method for determining either or both a particle's identity and the presence and optionally, the concentration of one or more particular target analytes is described. Applications of these microparticle-based methods in biological and chemical assays are also disclosed.

1 - 70 . (canceled)  
     
     
         71 . A microparticle based measuring system comprising: 
 (a) at least two substantially spherical identifiable particles in solution, each particle comprising 
 a capture probe affixed to the outer surface of the particle;  
   wherein: 
 1) each particle is characterized by a unique resonant light scattering signature when scanned over an analytical wavelength range having a window spanning about 1 to about 20 nanometers, over a range of optical wavelengths from about 275 to about 1900 nanometers;  
 2) each particle is about 75 micrometers in diameter or less;  
 3) each particle has a refractive index between about 1.45 and about 2.1 over the analytical wavelength range; and  
 4) each particle has an outer optical region which is substantially transparent to light over said analytical wavelength range;  
   (b) a tunable diode laser for scanning the particle over the analytical wavelength range;    (c) an optical cell for holding the particles in a position such that the scanning diode laser efficiently illuminates said particles and scattered light is minimized;    (d) a particle handling means for placing the at least two particles into the optical cell; and    (e) an imaging means for detecting resonant light scattering from the particles and converting said light to an electrical signal.    
     
     
         72 . A system of  claim 71  optionally comprising a means for contacting the particles with reagents and analytes.  
     
     
         73 . A system of  claim 71  optionally comprising a computer operably linked to the light scanning source and the imaging means for the acquisition and analysis of said electrical signal generated by said imaging means.  
     
     
         74 . A system of  claim 71  optionally comprising a data analysis means for converting said electrical signal to the identity of the particles and optionally the presence or degree of binding of an analyte or group of analytes to the particles.  
     
     
         75 . A system of  claim 71  optionally having a data analysis means for detecting binding of or identifying said analyte or group of analytes.  
     
     
         76 . A system of  claim 71  wherein the tunable diode laser is modified with a fiber optic light coupling.  
     
     
         77 . A microparticle based measuring system comprising: 
 (a) at least two substantially spherical identifiable particles in solution, each particle comprising; 
 a capture probe affixed to the outer surface of the particle;  
   wherein: 
 1) each particle is characterized by a unique structural resonant light scattering signature when scanned over an analytical wavelength range having a window spanning about 1 to about 20 nanometers, over a range of optical wavelengths from about 275 to about 1900 nanometers;  
 2) each particle is about 75 micrometers in diameter or less;  
 3) each particle has a refractive index between about 1.45 and about 2.1 over the analytical wavelength range; and  
 4) each particle has an outer optical region which is substantially transparent to light over said analytical wavelength range;  
   (b) a tunable diode laser light source;    (c) an optical cell for holding the particles in a position such that the scanning diode laser efficiently illuminates said particles and scattered light is minimized;    (d) a means for contacting microparticles with analytes and reagents;    (e) a microscope;    (f) a digital camera and monitor;    (g) digital image acquisition hardware;    (h) a computer operably linked to the elements of (b)-(g); and    (i) software suitable for controlling the elements of (b)-(g), capturing data, and processing the data.