Ultrasound system for shearing cellular material

Abstract

A system for processing biological or other samples includes an array of transducer elements that are positioned to align with sample wells in a microplate. Each transducer element produces ultrasound energy that is focused towards a well of the microplate with sufficient acoustic pressure to cause inertial cavitation. In one embodiment, the transducers are configured to direct ultrasound energy into cylindrical wells. In other embodiments, the transducer elements are configured to direct ultrasound energy into non-cylindrical wells of a microplate.

1 - 13 . (canceled) 
     
     
         14 . A system for shearing biological materials in a sample well of a microplate, comprising:
 a number of transducer elements, each of which is constructed to receive a conical sample well of a microplate at least partially through the transducer element and to deliver ultrasound energy into the sample well at sufficient acoustic pressures to cause inertial cavitation in a biological sample.   
     
     
         15 . The system of  claim 14 , where the transducer elements are configured to create ultrasound energy with the ability to shear DNA or chromatin samples down to about 50 base pairs. 
     
     
         16 . The system of  claim 14 , where the transducer elements are configured to create ultrasound energy with the ability to shear DNA or chromatin to a range of sizes including 100-300 base pairs. 
     
     
         17 . The system of  claim 14 , wherein each transducer element is spherical. 
     
     
         18 . The system of  claim 14 , wherein each transducer element is hemispherical. 
     
     
         19 . The system of  claim 14 , wherein each transducer element is cylindrical. 
     
     
         20 . The system of  claim 19 , wherein each cylindrical transducer element includes a lens in an interior portion of the cylindrical transducer element. 
     
     
         21 . The system of  claim 14 , wherein each transducer element is disk-shaped with a hole through a central portion thereof and includes a waveguide on top of the disk to direct ultrasound energy from the transducer into a sample well of the microplate. 
     
     
         22 - 24 . (canceled) 
     
     
         25 . A microplate including a number of wells into which a samples are to be placed, wherein each well of the microplate has a bottom surface with a varying thickness that is configured to form a concave lens to focus ultrasound energy from an external unfocused ultrasound transducer towards an interior portion of the well. 
     
     
         26 . The microplate of  claim 26 , wherein the bottom surface of each well of the microplate has a thickness between 52 and 68 microns thick. 
     
     
         27 . A system for shearing cellular material, comprising
 a signal generator configured to supply ultrasound driving pulses;   an amplifier for amplifying the driving pulses; and   an number of piezoelectric elements that receive the amplified driving pulses and are configured to produce ultrasound energy that is directed into a microplate having a number of wells in which cellular material is placed, wherein each piezoelectric element is formed of a piezoelectric substrate that is larger than a single well of the microplate and smaller than an area of the microplate, whereby the number of piezoelectric elements are arranged in a pattern to underlie the wells of the microplate;   wherein the amplifier is configured to amplify the ultrasound driving pulses to a voltage sufficient to create a negative pressure in the wells of the microplate of greater than 5 MPa to shear cellular material by inertial cavitation.   
     
     
         28 . The system of  claim 27 , further comprising a gel layer between the number of piezoelectric elements and the wells of the microplate for coupling ultrasound energy into the wells of the microplate. 
     
     
         29 . The system of  claim 27 , wherein the ultrasound driving pulses produced by the signal generator have a frequency of 2 MHz and a 15 microsecond duration. 
     
     
         30 . The system of  claim 29 , wherein the amplifier is configured to amplify the ultrasound driving pulses to a field of 400 volts per mm. in the piezoelectric substrate. 
     
     
         31 . The system of  claim 27 , further comprising a plate positioned between the number of piezoelectric elements and the microplate, wherein the plate includes a number of lenses formed therein that focus the ultrasound energy produced by the piezoelectric elements into the wells of the microplate.