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CPSA Digest 2001

New Technologies and Approaches for Increasing Drug Candidate Survivability:
Lead Identification to Lead Optimization

October 9-11, 2001

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Proceedings -Thursday, October 11, 2001

ThOC1



Fluidic Pulsing as an Ultra Fast Serial Sample Introduction System

Thomas Covey, AB/MDS Sciex

Background
Three categories of methods to multiplex sample introduction all differ in the means by which they select the separate sample channels, namely ion beam selectors, spray selectors, and fluid selectors. A novel fluidic selector device is presented that is comprised of an array of fast valves particularly suited to high throughput sample introduction. This new system of synchronized solenoid valves rapidly gates electrospray signals for high throughput applications.

Methodology
The device described utilizes a particular type of fluidic selector employing fast solenoid valves, each one controlling the transit of sample through an independent line to the sprayer of the mass spectrometer. All lines converge within a single sprayer as a bundle, similar to a fiber optic bundle. Using this method of gating the sample streams, the transit time of the sample through the channel from the signal off/on position is reduced to the theoretical minimum without resorting to micro machining or miniaturized fluidic systems. Dispersion effects are eliminated, avoiding the most serious time delay problem associated with other fluidic selectors such as stream selector valves.

Value of the Technology
The end result of this technology is faster actuation time without valve related dispersion and channel-related transit time delay. It also provides independent and random access to each channel, unlike the rotating spray selectors and other types of fluid selectors such as stream selector valves. Signal fall times have been recorded as fast as 10 milliseconds to reduce the signal to 0.1% of maximum. This finding translates to a carry-over of signal from channel to channel in a 4-channel system of less than 0.1% with 10 milliseconds delay and 500 msec total cycle time. Longer delays will give rise to lower values of carry-over. Detailed accounting of the relationships between liquid flow rates, cycle time, and carry-over typical of this device were provided.

Since this device has high speed and offers complete random access to any channel, many applications can be employed. This system can replace stream selectors for fast serial sample introduction. Because all lines are independent, samples can be staggered much closer in time than systems where samples enter through a single line. High flow rates can be accommodated without compromise; 2000 uL/min have been demonstrated without carry-over effects. Any particular channel can be left on or off permanently, thus serving the purpose of calibrant introduction for accurate mass references. The speed of this system is superior to stepper motor driven devices, raising the possibilities for application as an indexed parallel sample introduction device.



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