1. A circuit, comprising:
a circuit component for modulating a gain of a photomultiplier tube in association with one or more dynodes of the photomultiplier tube, utilizing a modulation signal;
a circuit component for generating a matched signal matched to the modulation signal; and
a circuit component for combining the matched signal with an anode signal at an anode of the photomultiplier tube to generate a combination signal with a photon pulse amplitude that is preserved;
wherein the modulating, the generating, and the combining are performed for photon-counting.
2. A method, comprising:
modulating a gain of a photomultiplier tube in association with one or more dynodes of the photomultiplier tube, utilizing a modulation signal;
generating a matched signal matched to the modulation signal; and
combining the matched signal with an anode signal at an anode of the photomultiplier tube to generate a combination signal with a photon pulse amplitude that is preserved;
wherein the modulating, the generating, and the combining are performed for photon-counting.
3. The method of claim 2, wherein the modulation signal is generated utilizing a cancellation circuit.
4. The method of claim 3, and further comprising a voltage divider circuit having a plurality of resistor stages, each resistor stage coupled to one of the dynodes of the photomultiplier tube.
5. The method of claim 3, wherein the cancellation circuit includes a first output coupled to a first of the dynodes and a second output connected to a second of the dynodes.
6. An apparatus, comprising:
a photomultiplier tube including a cathode, an anode, and one or more dynodes; and
a photon-counting circuit coupled to the photomultiplier tube, the circuit for generating a first modulation signal and a second modulation signal 180-degrees out-of-phase with the first modulation signal.
7. The apparatus of claim 6, wherein the circuit includes a cancellation circuit.
8. The apparatus of claim 7, and further comprising a voltage divider circuit having a plurality of resistor stages, each resistor stage coupled to one of the dynodes of the photomultiplier tube.
9. The apparatus of claim 7, wherein the cancellation circuit includes a first output coupled to a first of the dynodes and a second output connected to a second of the dynodes.
10. The apparatus of claim 6, wherein superimposition of a modulation signal upon an output signal of the photomultiplier tube is cancelled.
11. The apparatus of claim 6, wherein the first modulation signal and the second modulation signal are applied to adjacent dynodes of the photomultiplier tube.
12. The apparatus of claim 6, wherein a level of at least one of the first modulation signal and the second modulation signal is adjusted for minimizing a net AC modulation voltage at the anode of the photomultiplier tube.
13. A method, comprising:
providing a photomultiplier tube including a cathode, an anode, and one or more dynodes; and
generating a first modulation signal and a second modulation signal 180-degrees out-of-phase with the first modulation signal, for photon-counting.
14. An apparatus, comprising:
a photomultiplier tube including a cathode, an anode, and one or more dynodes including a first dynode with a first modulation signal applied thereto;
a photon-counting circuit coupled to the photomultiplier tube, the circuit for attenuating the first modulation signal, and subtracting the attenuated modulation signal from an anode signal at the anode of the photomultiplier tube;
wherein a path length of the attenuated modulation signal is matched.
15. The apparatus of claim 14, wherein the attenuated modulation signal is capacitively-coupled.
16. The apparatus of claim 14, wherein the circuit includes a cancellation circuit.
17. A method, comprising:
providing a photomultiplier tube including a cathode, an anode, and one or more dynodes including a first dynode with a first modulation signal applied thereto;
attenuating the first modulation signal; and
subtracting the attenuated modulation signal from as anode signal at the anode of the photomultiplier tube;
wherein the attenuating and the subtracting are performed for photon-counting, and a path length of the attenuated modulation signal is matched.
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 of preparing an optically active 2-alkylated cysteine represented by Structural Formula (I):
or a salt thereof;
wherein R1 is a substituted or unsubstituted alkyl group,
the method comprising:
(a) coupling a compound represented by Structural Formula (II):
\u2003or a salt thereof, with a substituted or unsubstituted aryl nitrile of the formula Ar\u2014CN, wherein Ar is a substituted or unsubstituted aryl group; thereby forming a substituted thiazoline carboxylic acid represented by Structural Formula (III):
(b) esterifying the substituted thiazoline carboxylic acid with R*\u2014OH, wherein R* is a substituted or unsubstituted alkyl group comprising one or more chiral carbon atoms; thereby forming a substituted thiazoline carboxylic acid ester represented by Structural Formula (IV):
(c) alkylating the substituted thiazoline carboxylic acid ester with one or more bases and R1X, wherein X is a leaving group and R1 is as defined above; thereby forming an alkylated substituted thiazoline carboxylic acid ester represented by Structural Formula (V):
(d) hydrolyzing the alkylated substituted thiazoline carboxylic acid ester with base or acid, thereby forming an alkylated substituted thiazoline carboxylic acid represented by Structural Formula (VI):
(e) reacting the alkylated substituted thiazoline carboxylic acid with acid, thereby forming the 2-alkylated cysteine represented by Structural Formula (I).
2. The method of claim 1, wherein Ar is a substituted or unsubstituted phenyl group.
3. The method of claim 2, wherein Ar is phenyl.
4. The method of claim 1, wherein R*\u2014OH is selected from the group consisting of (1R,2R,3R,5S)-(\u2212)-isopinocamphenol and (1S,2R,5R)-(+)-isomenthol.
5. The method of claim 1, wherein the one or more bases of step (c) are selected from the group consisting of potassium t-butoxide, sodium methoxide, sodium ethoxide, and sodium amide.
6. The method of claim 1, wherein R1 is a substituted or unsubstituted C1-C4 alkyl group.
7. The method of claim 6, wherein R1 is methyl.
8. The method of claim 1, wherein X is iodine.
9. The method of claim 1, further comprising the step of purifying the alkylated substituted thiazoline carboxylic acid ester by resolving the enantiomers of the alkylated substituted thiazoline carboxylic acid ester.
10. The method of claim 9, wherein the (S)-isomer, based on carbon atom 4 as indicated in Structural Formula (V), of the alkylated substituted thiazoline carboxylic acid ester is isolated from the enantiomers of the alkylated substituted thiazoline carboxylic acid ester.
11. The method of claim 1 further comprising the step of purifying the alkylated substituted thiazoline carboxylic acid by resolving the enantiomers of the alkylated substituted thiazoline carboxylic acid.
12. The method of claim 11, wherein the (S)-isomer of the alkylated substituted thiazoline carboxylic acid is isolated from the enantiomers of the alkylated substituted thiazoline carboxylic acid.
13. A method of preparing a compound represented by Structural Formula (II):
or a salt thereof, the method comprising:
(a) coupling a compound represented by Structural Formula (VIII):
\u2003or a salt thereof, with a substituted or unsubstituted aryl nitrile of the formula Ar\u2014CN, wherein Ar is a substituted or unsubstituted aryl group; thereby forming a substituted thiazoline carboxylic acid represented by Structural Formula (IX):
(b) esterifying the substituted thiazoline carboxylic acid with R*\u2014OH, wherein R* is a substituted or unsubstituted alkyl group comprising one or more chiral carbon atoms; thereby forming a substituted thiazoline carboxylic acid ester represented by Structural Formula (X):
(c) alkylating the substituted thiazoline carboxylic acid ester with one or more bases and CH3X, wherein X is a leaving group; thereby forming an alkylated substituted thiazoline carboxylic acid ester represented by Structural Formula (XI):
(d) hydrolyzing the alkylated substituted thiazoline carboxylic acid ester with base or acid, thereby forming an alkylated substituted thiazoline carboxylic acid represented by Structural Formula (XII):
(e) optionally, purifying the (S)-isomer of the alkylated substituted thiazoline carboxylic acid;
(f) reacting the (S)-isomer of the alkylated substituted thiazoline carboxylic acid with acid, thereby forming (S)-2-methylcysteine; and
(g) coupling (S)-2-methylcysteine with 2,4-dihydroxybenzonitrile, thereby forming the compound represented by Structural Formula (VII).