What is claimed is:
1. A system for dispensing precise quantities of a transfer liquid, said system comprising:
an enclosed space for holding fluids including said transfer liquid, a system liquid and a compressible fluid, said compressible fluid separating said transfer liquid from said system liquid said enclosed space having an outlet;
means for supplying said system liquid into said enclosed space;
means for introducing said compressible fluid into said enclosed space adjacent to said system liquid;
means for providing said transfer liquid into said enclosed space adjacent to said compressible fluid and on the other side of the said compressible fluid from said system liquid, such that said compressible fluid separates said system liquid from said transfer liquid; and said transfer liquid is between said outlet and said compressible fluid;
means for dispensing a quantity of said transfer liquid out of said outlet without introducing any fluid into said enclosed space during dispensing;
means for sensing pressure change in said enclosed space resulting from the volume of the transfer liquid being dispensed;
means for converting said pressure change to the volume of the transfer liquid dispensed by said dispensing means.
2. A method for dispensing from an enclosed space having a dispensing port, precise quantities of a transfer liquid and determining the precise volume of the transfer liquid,
(a) transferring into the enclosed space a system liquid;
(b) supplying into the enclosed space a compressible fluid adjacent to said system liquid;
(c) transferring into the enclosed space a transfer liquid on the other side from said system liquid such that the compressible fluid, separates said transfer liquid from said system liquid adjacent to said compressible fluid, said transfer liquid being adjacent to the dispensing port;
(d) dispensing droplets of the transfer liquid through said dispensing port;
(e) sensing pressure change in the enclosed space resulting from the droplets being dispensed;
(f) converting the pressure change sensed in step (e) into volume of liquid dispensed.
3. A method for dispensing from an enclosed space having a dispensing port precise quantities of a transfer liquid, said method comprising the following steps:
(a) introducing into the enclosed space a system liquid;
(b) introducing into the enclosed space a compressible fluid;
(c) introducing into the enclosed space a transfer liquid such that said compressible fluid separates said system liquid from said transfer liquid, said dispensing liquid being adjacent to said dispensing port;
(d) dispensing a predetermined number of droplets of the transfer liquid through the dispensing port;
(e) sensing the pressure change in the enclosed space resulting from dispensing of the drops in step (d);
(f) converting the pressure change into the volume of the transfer liquid;
(g) comparing the volume of the liquid dispensed in step (d) with the predetermined volume.
4. A microvolume liquid handling system for dispensing small quantities of liquids, comprising:
pumping means for controlling the pressure and flow of a first liquid;
microdispenser means for dispensing microvolumes of a second liquid, said first liquid and said second liquid separated by a compressible fluid;
a sensor for converting pressure changes in at least one of said first liquid and said second liquid into a signal;
tubing means for connecting said pumping means to said sensor and said sensor to said microdispenser means; and
means for converting the signal into an indication of fluid volume dispensed;
vibrating means for vibrating said microdispenser means at a frequency sufficiently high to dislodge foreign material adhering to said microdispenser.
5. The microvolume liquid handling system of claim 4 wherein said vibrating means further comprises a piezoelectric transducer.
6. The microvolume liquid handling system of claim 4 wherein said frequency is a high frequency.
7. The microvolume liquid handling system of claim 6 wherein said frequency is approximately a resonant ultrasonic frequency of said microdispenser means.
8. The microvolume liquid handling system of claim 7 wherein said resonant frequency is approximately 12 kHz.
9. A process for cleaning a microvolume liquid handling system, said microvolume liquid handling system including a microdispenser having a capillary portion for dispensing droplets and a constricting portion for constricting said capillary portion, comprising the steps of:
pulsing said constricting portion at a frequency sufficient to dislodge foreign material adhering to interior surfaces of said capillary portion, said foreign material being dislodged into a liquid in said capillary portion; and
applying positive pressure to said liquid in said capillary portion to flush said dislodged foreign material in said liquid out of said capillary portion of said microdispenser.
10. The process for cleaning a microvolume liquid handling system of claim 9, wherein said frequency is approximately a resonant frequency of said microdispenser.
11. A process for preventing clogging of a microvolume liquid handling system, said microvolume liquid handling system including a microdispenser having a capillary portion for dispensing droplets through a nozzle and a constricting portion for constricting said capillary portion, comprising the steps of:
bringing said nozzle and a source of transfer liquid containing foreign matter into operational contact;
aspirating said transfer liquid through said nozzle into said capillary portion of said microdispenser; and
pulsing constricting portion at a frequency sufficient to dislodge said foreign material adhering to said nozzle of said capillary portion.
12. The process for preventing clogging of a microvolume liquid handling system of claim 11, wherein said frequency is approximately a resonant frequency of said microdispenser.
13. A process for unclogging of a microvolume liquid handling system, said microvolume liquid handling system including a microdispenser having a capillary portion for dispensing droplets through a nozzle and a constricting portion for constricting said capillary portion, comprising the steps of:
pulsing said constricting portion at a frequency sufficient to dislodge foreign material adhering to said nozzle of said capillary portion.
14. The process for preventing clogging of a microvolume liquid handling system of claim 13, wherein said frequency is approximately a resonant frequency of said microdispenser.
15. A microvolume liquid handling system for dispensing small quantities of liquids, comprising:
a system liquid reservoir containing a system liquid;
a pressure control system having a pump capable of increasing or decreasing pressure of said system liquid in said system liquid reservoir;
a hollow tube connecting said pressure control system to said system liquid reservoir;
a distribution tube having at least one section;
a microdispenser having a capillary portion for dispensing droplets of a transfer liquid through a nozzle and a constricting portion for constricting said capillary portion;
a valve coupled at a first end to said system liquid reservoir through one section of said a distribution tube, said valve coupled at a second end to said microdispenser;
a sensor coupled to said section of said distribution tube, said sensor capable of detecting at least one of either pressure or flow of system liquid in said distribution tube and generating a corresponding signal; and
a system controller coupled to said valve to control said valve, said system controller coupled to said sensor to receive said signal, said system controller coupled to said pressure control system to direct said pressure control system to increase or decrease pressure in said system liquid, and said system controller being coupled to said constricting portion to activate said constricting portion.
16. The microvolume liquid handling system for dispensing small quantities of liquids of claim 15, wherein said constricting portion is constricted at a frequency sufficiently high to dislodge foreign material adhering to said microdispenser.
17. A microvolume liquid handling system for dispensing small quantities of liquids, comprising:
a microtitre plate having an array of wells disposed therein, said wells have a bottom portion transparent to light, said bottom portion forming bottom walls of said wells, and a top portion opaque to light, said top portion having gaps that form side walls of the wells;
a light source for emitting light adjacent to said bottom portion of said microtitre plate such that said light is transmitted through said transparent bottom portion and through said gaps in said top portion of said microtitre plate;
a microdispenser having a capillary portion for dispensing droplets of a transfer liquid through a nozzle and a constricting portion for constricting said capillary portion;
a robot connected to said microdispenser, said robot capable of moving said microdispenser adjacent to said top portion of said microtitre plate; and
a light sensor for sensing said light passing though said wells of said microtitre plate and producing a corresponding light signal when said light is sensed; and
a system controller, said system controller being electrically coupled to said light sensor for receiving said light signal, said system controller being electrically coupled to said robot, and said system controller directing said robot to position said microdispenser at a desired position above said top portion of said microtitre plate in response to said light signal to dispense one or more droplets from said nozzle of said microdispenser into one of said wells.
18. The microvolume liquid handling system of claim 4 wherein said pressure sensor contains a piezoresistive element capable of converting pressure into an electrical signal.
19. The microvolume liquid handling system of claim 4 wherein said tubing means further comprises teflon.
20. The microvolume liquid handling system of claim 4 wherein said means for dispensing further comprise a capillary and a piezoelectric transducer in substantially radial contact with a portion of said capillary.
21. The microvolume liquid handling system of claim 4 wherein said microdispenser is mounted on a robotic system capable of moving said microdispenser.
22. The microvolume liquid handling system of claim 4 wherein said robotic system is a three-axis system.
23. The microvolume liquid handling system of claim 15 wherein said constricting portion of said microdispenser is capable of vibrating said microdispenser at a frequency sufficiently high to dislodge foreign material adhering to interior surfaces of said microdispenser.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for obtaining magnetic resonance images of flowing blood in a vascular vessel comprising:
(a) positioning a radio frequency (RF) transmitter in the vascular vessel,
(b) conducting global coherent free precession (GCFP) magnetic resonance imaging (MRI) of blood flowing intravascularly in the vessel by operating the RF transmitter within the vascular vessel; and
(c) obtaining images of the flowing blood.
2. A method as in claim 1, wherein (b) comprises operating the RF transmitter at a frequency which is exactly on resonance and at a zero phase increment.
3. A method as in claim 1 or 2, wherein (b) comprises operating a MRI timing sequence which prevents magnetic field gradients required for imaging from causing excited protons to accumulate phase shifts as the protons move through three dimensional space.
4. A method of obtaining intravascular magnetic resonance images (MRI) of blood flow comprising:
(a) intravascularly positioning a radio frequency (RF) transmitter in proximity to the blood flow,
(b) causing the RF transmitter to produce a train of RF pulses so as to form a continuous stream of coherently excited protons of the blood flow,
(c) performing global coherent free precession (GCFP) magnetic resonance imaging (MRI) by continuously sampling the coherently excited protons of the blood flow as the protons freely precess while flowing through a region of three dimensional space unaffected by the ongoing RF excitation, and
(d) generating an image of the sampled coherently excited protons.
5. A method as in claim 4, wherein step (a) further comprises providing an intravascular catheter having a RF transmitter at a distal end thereof.
6. A method as in claim 4 or 5, which comprises operating a MRI timing sequence which prevents magnetic field gradients required for imaging from causing excited protons to accumulate phase shifts as the protons move through three dimensional space.
7. A system for obtaining magnetic resonance images of flowing blood in a vascular vessel comprising:
a catheter having a radio frequency (RF) transmitter at a distal end thereof configured to be positioned in the vascular vessel,
a magnetic resonance data acquisition and imaging system configured to conduct global coherent free precession (GCFP) magnetic resonance imaging (MRI) of blood flowing intravascularly in the vessel and obtain images thereof, wherein
the RF transmitter is configured to produce a train of RF pulses so as to form a continuous stream of coherently excited protons of the blood flow within the vascular vessel during operation of the data acquisition and imaging system so that images of the flowing blood therein are obtained.
8. A system as in claim 7, wherein the RF transmitter is configured to operate at a frequency which is exactly on resonance and at a zero phase increment.
9. A system as in claim 7 or 8, wherein the RF transmitter and the data acquisition and imaging system are configured to operate to achieve a MRI timing sequence which prevents magnetic field gradients required for imaging from causing excited protons to accumulate phase shifts as the protons move through three dimensional space.
10. A system for obtaining intravascular magnetic resonance images of blood flow comprising:
(a) a catheter having an RF transmitter at a distal end thereof configured to produce a train of radio frequency (RF) pulses so as to form a continuous stream of coherently excited protons of the blood flow, and
(b) a data acquisition and imaging system configured to conduct global coherent free precession (GCFP) magnetic resonance imaging (MRI) by continuously sampling the coherently excited protons of the blood flow as the protons freely precess while flowing through a region of three dimensional space unaffected by the ongoing RF excitation and further configured to generate an image thereof.
11. A system as in claim 10, wherein said RF transmitter and said data acquisition and imaging system are configured to operate to achieve a MRI timing sequence which prevents magnetic field gradients required for imaging from causing excited protons to accumulate phase shifts as the protons move through three dimensional space.