1. A method of producing valacyclovir hydrochloride in crystal form VIII, comprising the steps of:
dissolving valacyclovir hydrochloride in dimethylformamide at a temperature ranging from about 20 to 25\xb0 C.,
cooling the solution to a temperature ranging from about 0 to 5\xb0 C. and precipitating valacyclovir hydrochloride by adding ethyl acetate,
isolating valacyclovir hydrochloride from the mixture in form VIII, and
optionally drying isolated valacyclovir hydrochloride.
2. A method for producing valacyclovir hydrochloride in crystal form IX, comprising the steps of:
dissolving valacyclovir hydrochloride in methanol at a temperature ranging from about 20 to 80\xb0 C.,
cooling the solution to a temperature ranging from about 0 to 5\xb0 C. and precipitating valacyclovir hydrochloride by adding n-hexanes,
isolating valacyclovir hydrochloride from the mixture in form IX, and
optionally drying the isolated valacyclovir hydrochloride.
3. A method for producing valacyclovir hydrochloride crystals according to claim 2, wherein the dissolving step is conducted at a temperature of about 65\xb0 C.
4. A method for producing valacyclovir hydrochloride in crystal form X, comprising the steps of:
dissolving valacyclovir hydrochloride in dimethylformamide at a temperature ranging from about 20 to 25\xb0 C.,
precipitating the same by adding acetone,
isolating valacyclovir hydrochloride from the mixture in form X, and
optionally drying the isolated valacyclovir hydrochloride.
5. A method for producing valacyclovir hydrochloride in crystal form XI, comprising the steps of:
dissolving valacyclovir hydrochloride in dimethylformamide at a temperature ranging from about 20 to 25\xb0 C.,
precipitating the same by adding ethyl acetate,
isolating valacyclovir hydrochloride from the mixture in form XI, and
optionally drying the isolated valacyclovir hydrochloride.
6. A method for producing valacyclovir hydrochloride in crystal form XII, comprising the steps of:
dissolving valacyclovir hydrochloride in dimethylformamide at a temperature ranging from about 20 to 25\xb0 C.,
precipitating the same by adding a reagent selected from the group consisting of n-hexanes and diethylether,
isolating valacyclovir hydrochloride from the mixture in form XII, and
optionally drying the isolated valacyclovir hydrochloride.
7. A method for producing valacyclovir hydrochloride in crystal form XIII, comprising the steps of:
dissolving valacyclovir hydrochloride in dimethylformamide at a temperature ranging from about 20 to 25\xb0 C.,
cooling the solution to a temperature ranging from about 0 to 5\xb0 C. and precipitating the same by adding acetone,
isolating valacyclovir hydrochloride from the mixture in form XIII, and
optionally drying the isolated valacyclovir hydrochloride.
8. A method for producing valacyclovir hydrochloride in crystal form XIV, comprising the steps of:
dissolving valacyclovir hydrochloride in methanol at a temperature ranging from about 40 to 80\xb0 C.,
cooling the solution to about ambient temperature and precipitating the same by adding n-hexanes,
isolating valacyclovir hydrochloride from the mixture in form XIV, and
optionally drying the isolated valacyclovir hydrochloride.
9. A method for producing valacyclovir hydrochloride crystals according to claim 8, wherein the dissolving step is conducted at a temperature about 65\xb0 C.
10. A method according to claim 1, wherein the isolated sample is dried at a reduced pressure and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 0.5% to 3% according to Karl Fischer analysis method.
11. A method for producing valacyclovir hydrochloride in crystal form XII, comprising the steps of:
dissolving valacyclovir hydrochloride in methanol at about reflux temperature,
precipitating the same by adding a reagent selected from the group consisting of acetone and diethylether,
isolating valacyclovir hydrochloride from the mixture in form XII, and
optionally drying the isolated valacyclovir hydrochloride.
12. A method according to claim 2 wherein the isolated sample is dried at a reduced pressure, and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 6% to 10% according to Karl Fischer analysis method.
13. A method according to claim 4 wherein the isolated sample is dried at a reduced pressure, and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 3% to 7% according to Karl Fischer analysis method.
14. A method according to claim 5 wherein the isolated sample is dried at a reduced pressure, and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 1% to 3% according to Karl Fischer analysis method.
15. A method according to claim 2 wherein the isolated sample is dried at a reduced pressure, and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 0.5% to 9% according to Karl Fischer analysis method.
16. A method according to claim 11 wherein the isolated sample is dried at a reduced pressure, and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 0.5% to 9% according to Karl Fischer analysis method.
17. A method according to claim 7 wherein the isolated sample is dried at a reduced pressure, and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 3% to 5% according to Karl Fischer analysis method.
18. A method according to claim 8 wherein the isolated sample is dried at a reduced pressure, and at a temperature ranging from 20\xb0 C. to 80\xb0 C. for a duration of 1 to 24 hours to yield crystals having water content of about 6% to 9% according to Karl Fischer analysis method.
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 capturing a molecule via an integrated system, the method comprising:
applying an alternating voltage to a Paul trap device in an electrically conductive solution to generate electric fields, the Paul trap device being integrated with a nanopore device to form the integrated system;
wherein forces from the electric fields of the Paul trap device position the molecule to a nanopore in the nanopore device; and
applying a first voltage to the nanopore device to capture the molecule in the nanopore of the nanopore device;
wherein the integrated system comprises a first insulating layer disposed on top of a substrate a first conductive layer disposed on top of the first insulating layer, a second insulating layer disposed on top of the first conductive layer, a second conductive layer disposed on top of the second insulating layer, and a third insulating layer disposed on top of the second conductive layer;
wherein a first pair of contact pads and a second pair of contact pads are each formed on the second conductive layer, the alternating voltage alternating polarity between the first pair of contact pads and the second pair of contact pads; and
wherein the first pair of contact pads correspond to first windows opened through the third insulating layer stopping on the second conductive layer, the first windows being positioned on opposites sides of the nanopore.
2. The method of claim 1, further comprising applying a second voltage to sequencing pads of the nanopore device to sequence bases of the molecule in the nanopore;
wherein the second pair of contact pads correspond to second windows opened through the third insulating layer stopping on the second conductive layer, the second windows being positioned on opposites sides of the nanopore;
wherein the sequencing pads correspond to sequencing windows opened through the third insulating layer, the second conductive layer, the second insulating layer, stopping on the first conductive layer.
3. The method of claim 1, wherein the alternating voltage is applied to the Paul trap device prior to applying the first voltage to the nanopore device.
4. The method of claim 1, wherein the alternating voltage is applied to the Paul trap device while applying the first voltage to the nanopore device.
5. The method of claim 1, further comprising centering the molecule to a location of the nanopore in the nanopore device by a combination of the forces of the Paul trap device and the first voltage applied to the nanopore device.
6. The method of claim 1, wherein the electrically conductive solution fills two reservoirs connected by the nanopore; and
wherein insulating material surrounds immersed parts of the first pair of contact pads and the second pair of contact pads in the electrically conductive solution to prevent the first pair of contact pads and the second pair of contact pads from conducting electricity through the electrically conductive solution.
7. The method of claim 6, wherein applying the alternating voltage to the first pair of contact pads and the second pair of contact pads positions the molecule to the nanopore in one of the two reservoirs for capture in the nanopore; and
wherein the forces, continuously changing, act upon the molecule to force the molecule into an equilibrium position centered with the nanopore, in order to prevent the molecule from being moved out of position.
8. The method of claim 6, wherein the first voltage is applied to one electrode in one of the two reservoirs and another electrode in another one of the two reservoirs.
9. The method of claim 7, wherein the first voltage moves the molecule through the nanopore for sequencing respective bases of the molecule; and
wherein the first voltage is turned off to sequence one base and turned on again to move to a next base.