Multiplexable super-resolution force spectroscopy using ultrasound methods and magnetic detection
A method of measuring dissociation of the biomolecular bonds in one or multiple sample wells using super-resolution force spectroscopy (SURFS). SURFS utilizes precise ultrasound radiation to exert an acoustic radiation force on the biomolecular bonds labeled with magnetic particles. The force-induced dissociation of the protein bonds labeled with magnetic particles may be measured as a reduced magnetic signal by a magnetic sensor. The force resolution allows for differentiating biomolecular bonds with an extremely high level of precision. The biomolecular bonds include protein-protein, protein-nucleic acid, nucleic acid-nucleic acid, small molecule-protein, and small molecule-nucleic acid interactions.
1. An apparatus for measuring Apparatus to measure the dissociation of molecular bonds in an immobilized molecule said apparatus comprising:
at least one piezo plate;
grease or a compartment comprising a liquid, wherein the grease or the compartment is positioned on the piezo plate;
a sample-plate containing one or more samples of the immobilized molecule, positioned above said grease or said compartment;
a magnetic sensor;
rubber, wherein the at least one piezo plate is positioned between the rubber and the grease or the compartment comprising the liquid; and
transport apparatus configured to move the sample-plate between a first location, and a second location, wherein said magnetic sensor is configured to measure changes in magnetism proportional to bond dissociation of the molecular bonds.
2. The apparatus of claim 1 , wherein the first location is at the at least one piezo plate.
3. The apparatus of claim 1 , wherein the second location is at the magnetic sensor.
4. The apparatus of claim 1 , wherein the transport apparatus comprises a motor or multiple motors.
5. The apparatus of claim 1 , wherein the at least one piezo plate is about 1 mm-100 mm in width, about 1 mm-100 mm in length, and about 0.3 mm-10 mm in thickness.
6. The apparatus of claim 1 , wherein the magnetic sensor is a superconducting quantum interference device, a Hall probe, or a magnetoresistive-based sensor.
7. The apparatus of claim 1 , wherein said sample-plate comprises 1 to 10,000 sample wells.
8. The apparatus of claim 1 , wherein a number of the at least one piezo plate is in the range of 1-1000.
9. The apparatus of claim 1 , wherein the first location and the second location overlap.
10. The apparatus of claim 1 , wherein a force resolution of the apparatus is sub piconewton (pN), and wherein a spatial resolution for molecular motion is less than or equal to about 0.2 nm and/or wherein a time resolution for measuring bond dissociation is in a range of from about 1 to about 3 min.
11. The apparatus of claim 1 , wherein a bottom of the one or more samples contacts the grease or a liquid in the compartment prior to application of ultrasound radiation by the at least one piezo plate.
12. The apparatus of claim 1 , further comprising a function generator configured to generate an alternating current, the function generator electrically connected to the at least one piezo plate.
13. The apparatus of claim 12 , further comprising an amplifier electrically connected to the at least one piezo plate, wherein the amplifier is an ac (alternating current) amplifier.
14. The apparatus of claim 13 , wherein the function generator, and the amplifier generate an amplified alternating current, wherein the amplified alternating current has a frequency of between 20 kHz and 5 MHz, and wherein the amplified alternating current has an amplitude of between 0.01 V and 20 V, and the amplified alternating current is applied to the at least one piezo plate.
15. The apparatus of claim 13 , wherein a maximum power of the amplifier is 10-1000 watts.
16. An apparatus for generating an acoustic force and measuring bond dissociation in multiple samples of a molecule simultaneously, said apparatus comprising:
at least one piezo plate, wherein the at least one piezo plate is driven by an amplified ultrasound radiation;
a layer of a lubricant positioned on a first surface of said at least one piezo plate;
rubber in contact with a second surface of said at least one piezo plate;
a sample plate comprising at least one sample well, wherein the a piezo plate each of the at least one piezo plate is configured to generate an acoustic force onto each of the at least one sample well;
a magnetic sensor; and
transport apparatus configured to move the sample plate between a first location, and a second location;
wherein said magnetic sensor is configured to measure the changes in magnetism that are proportional to bond dissociation of the multiple samples.
17. The apparatus of claim 16 , wherein a number of the at least one piezo plate is in the range of 1-1000.
18. The apparatus of claim 16 , wherein the layer of lubricant is a vacuum grease positioned between the multiple samples and the at least one piezo plate, and wherein a thickness of the layer of vacuum grease is about 0.001-0.5 mm.
19. The apparatus of claim 16 , wherein the layer of lubricant is liquid positioned between the multiple samples and the at least one piezo plate, wherein said layer of liquid has a thickness of about 0.001 mm-5 mm.
20. The apparatus of claim 16 , wherein the first location and the second location overlap.