WO2002044684A2 - Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams - Google Patents
Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams Download PDFInfo
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- WO2002044684A2 WO2002044684A2 PCT/CA2001/001673 CA0101673W WO0244684A2 WO 2002044684 A2 WO2002044684 A2 WO 2002044684A2 CA 0101673 W CA0101673 W CA 0101673W WO 0244684 A2 WO0244684 A2 WO 0244684A2
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- mass spectrometer
- sample
- introduction device
- valve
- fluid sample
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/04—Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components
Definitions
- the present invention relates to a sample introduction device and method for rapidly introducing a plurality of samples simultaneously into a mass spectrometer for analysis. Each of the samples is dissolved in a flowing liquid stream. Multiple parallel streams of samples are rapidly and sequentially pulsed into the ionizing region of the mass spectrometer with a system of fast fluidic valves.
- Mass spectrometers have become one of the most widely utilized instruments for analyzing chemical entities dissolved in liquids. As a consequence of the valuable information derived from such analyses, there is an incentive to process increased numbers of samples in shorter periods of time in industrial, academic, and government-based laboratories. High speed serial systems as well as systems capable of introducing multiple samples simultaneously introduced into a mass spectrometer in a parallel fashion have been reported.
- the high-speed fast serial approach does not attempt to parallel sample introduction streams. Instead, it assures that samples enter the mass spectrometer in a sequential fashion. The mass spectrometric measurement on each sample remains uninterrupted as the sample enters and passes through the mass spectrometer.
- the fast serial technique conducts both sample introduction and measurement in a sequential manner as rapidly as fluid transfer constraints will allow. However, they are always constrained by the relatively slow time scale of sequential rather than parallel sample introduction.
- a series of fast sequential mass spectrometric measurements can be made on each of the multiple samples entering the spectrometer.
- all of the samples must enter through separate and distinct fluid channels so that each channel may be rapidly turned on and off, by some means, in synchrony with the mass spectrometric measurement. In this way, every mass spectrometric measurement may be associated with a particular sample from a particular channel in an unequivocal fashion.
- the three general categories of methods for introducing multiple parallel samples are similar in that the mass spectrometric measurements are taken in rapid sequence, i.e. sequentially. However, from a sample introduction point of view, they are all parallel in nature. Since mass spectrometric measurements are very fast relative to sample introduction speeds (milliseconds versus seconds), the sample introduction becomes the bottleneck for fast analyses, so the sequential mass spectrometric measurements do not negate the speed advantage afforded by parallel sample introduction systems. With parallel systems, the mass spectrometric measurement on each sample is constantly interrupted as the system rapidly cycles from channel to channel.
- the three categories of methods to multiplex sample introduction differ in the means by which they gate i.e. turn on and off, the separate sample channels and thus obtain synchrony with the mass spectrometer.
- the first method segregates each separate channel into a distinct ion beam within the vacuum system of the mass spectrometer, and deflects or focuses the ion beam at the appropriate time.
- the second method uses a physical shutter driven by a rotating device such as a stepper motor or other mechanical device to physically block the ionization spray occurring at atmospheric pressure. A derivative of this method physically moves individual sprayers into focus also using a rotating device.
- the third method is generally referred to as fluidic selector.
- a sample introduction device for introducing one or more independent fluid sample streams into a mass spectrometer, said sample introduction device comprising: a valve located outside a direct path of fluid sample stream to the mass spectrometer, said valve being actuable between open and closed conditions to divert the fluid sample stream either toward or away from said mass spectrometer; and one or more ionizing elements to charge the sample emitting from each fluid sample stream into the mass spectrometer.
- a plurality of independent fluid sample streams is introduced to the mass spectrometer.
- the sample introduction device includes a valve associated with each independent fluid sample stream.
- the valves are actuated so that at least one fluid sample stream is directed to the mass spectrometer and so that other fluid sample streams are diverted away from the mass spectrometer.
- Each valve includes a valve gate moveable between open and closed positions. The valve gate is positioned so that the valve gate is not in the direct path of the fluid sample stream during transit to the mass spectrometer.
- the opening and closing of the valves is performed in response to a synchronous mass spectrometer data acquisition event.
- the opening of one valve may be timed with turning off of other valves to reduce channel-to-channel dead time.
- closing of a valve allows the fluid sample stream to flow along the direct path toward the mass spectrometer while opening of the valve diverts the fluid sample stream into a bypass port away from the mass spectrometer. Flow of the fluid sample stream into the by-pass port may be assisted by vacuum applied to the bypass port.
- the diameter of the direct path to the mass spectrometer may be less than the diameter of the bypass port, so that opening of the valve automatically diverts the fluid sample stream away from the mass spectrometer.
- each of the fluid sample streams is directed to the mass spectrometer via a transfer line.
- the transfer lines are arranged in a bundle that is surrounded by a nebulizer tube.
- the nebulizer tube may contain an additional conduit for purposes other than the transmission of a fluid sample stream such as for example the transport of laser radiation.
- a sample introduction device for introducing a plurality of independent fluid sample streams into a mass spectrometer, said sample introduction device comprising: a manifold having a plurality of fluid sample stream direct paths, each direct path extending between a fluid sample stream inlet and a fluid sample stream outlet, and a plurality of bypass paths, each bypass path being coupled to a respective one of said direct paths between said inlet and outlet; a plurality of transfer lines, each transfer line being coupled to a respective one of said outlets to deliver a fluid sample stream to an ionization region of said mass spectrometer; and a plurality of valves, each valve being positioned in a respective one of said bypass paths and being actuable to divert the fluid sample stream entering said direct path via said inlet from said direct path and into said bypass path.
- a method of analyzing a plurality of samples comprising of the following steps: (1) injecting samples into separate inlet sample streams of the mass spectrometer;
- the present invention provides an advantage over other fluidic selectors in that the valves used to gate the fluid sample streams are located outside of the sample path as it traverses from the injector to the mass spectrometer.
- dispersion effects from valve are significantly reduced or eliminated, thereby circumventing the most serious time delay problem associated with other fluidic selectors.
- the transit time of the sample through the channel from the signal off/signal on position is reduced to a minimum without resorting to micromachining or miniturized fluidic systems. This is due to the fact that the positions of the valves have no bearing on the distance the fluid travels between the signal on/off points. The end result is much faster cycle times without valve-related dispersion and channel related transit time delays. It also provides independent and random access to each channel, unlike the rotating member spray and fluid selectors.
- Fig. 1A is a schematic representation of a prior art ion beam selector apparatus for introducing samples into a mass spectrometer
- Fig. 1 B is a schematic representation of a prior art spray selector apparatus for introducing samples into a mass spectrometer
- Fig. 1 C is a schematic representation of a prior art fluid selector apparatus for introducing samples into a mass spectrometer
- Figs. 2A and 2B are schematic representations of a single channel fluid introduction device in accordance with the present invention
- Fig. 3 is a schematic representation of a two-channel fluid introduction device in accordance with the present invention.
- Fig. 4 is a schematic representation of four channels bundled for entry into the same ionizer of a mass spectrometer
- Fig. 5 are tables of calculated pressures and transit times for a length of channel, at different diameters.
- Fig. 6 is a schematic representation of cycling of valves for infusion of a substance, with four sprayers.
- BEST MODE FOR CARRYING OUT THE INVENTION [018]
- Figure 1 A an ion beam selector apparatus for introducing samples into a mass spectrometer is shown. As can be seen, ion beam selector apparatus toggles the separate channels 10 and 12 of samples by segregating each separate channel.
- Each channel is passed through an ionizer, 14 and 16, respectively, to form distinct ion beams 18 and 20, respectively, that enter a vacuum system chamber 22 of the mass spectrometer.
- Ion beams 18 and 20 are deflected within vacuum system chamber 22 and fed to a mass analyzer 24.
- this approach requires multiple nebulizing and ionizing sprayers, all producing ions simultaneously.
- Each sprayer is situated in front of multiple ion entrance apertures to the mass spectrometer.
- the technique suffers from the potential for fluid overload in the ion source region resulting from all introduction of streams flowing and ionizing at all times. Thus, flow rates per channel are limited.
- FIG. 1 B illustrates a spray selector apparatus for introducing samples into a mass spectrometer. As can be seen, multiple fluid channels 30 and 32 feed multiple ionizing sprayers 34 and 36. In this case, however, only a single ion entrance aperture 38 to the mass spectrometer is required, as on a conventional mass spectrometer.
- the sprayed charged droplets are gated in the atmospheric region between the sprayer and the ion entrance aperture, by a rotating shutter 40.
- a derivative of this is to rotate individual sprayers into focus in front of the ion entrance aperture, all of the above herein referred to as rotating member devices.
- This technique also suffers from the potential for fluid overload in the ion source region since all streams are flowing and ionizing simultaneously, thereby limiting liquid flow rates per channel. Also, the presence of a rapidly rotating member in front of the nebulized and ionized spray enhances the residence time of stray charged droplets circulating around the ion source, which generates cross channel memory effects, especially at higher liquid flows. Multiple sprayers result in different response factors for the different channels and, invariably, multiple sprayer systems spraying at a single ion entrance aperture compromise sensitivity, compared to a single sprayer system, because of interference effects between the sprayers.
- FIG. 1 C a fluid selector apparatus for introducing samples into a mass spectrometer is shown.
- multiple fluidic streams 50, 52 are gated upstream and into a single sprayer by a fluidic valve mechanism 54. Rapid selection of individual fluid streams in synchrony with the mass spectrometric measurement allows injection of a plurality of samples 56 simultaneously and the obtaining of mass spectrometric measurements on all samples as they pass through the ion source.
- the fluidic valve mechanism includes a rotating stream selector valve that allows multiple channel inlets into the valve to be sequentially diverted into a common channel to the ionizing sprayer of the mass spectrometer.
- the present invention provides a sample introduction device that utilizes an array of fast solenoid valves to rapidly and sequentially gate, for ionization, a plurality of liquid sample streams, all simultaneously being fed to a mass spectrometer.
- the device is believed to be applicable to any mass spectrometer that accepts liquid streams into the ion source region of the mass spectrometer, such as electrospray, atmospheric pressure chemical ionization, and other types of mass spectrometers.
- Multiple liquid streams containing samples destined for analysis are simultaneously fed into the mass spectrometer.
- the array of solenoids rapidly and sequentially gates each stream into the ionizing region of the mass spectrometer for analysis.
- the samples are analyzed by the mass spectrometer independently of one another in a rapid sequential manner, thereby increasing instrument productivity and throughput.
- the system is also capable of introducing multiple sample streams into the mass spectrometer without gating such that one or more streams are always flowing and mixing with each other.
- the system is also capable of pulsing a single sample stream into a mass spectrometer in synchrony with the mass spectrometer or some other device.
- the present device has one or more fluid lines delivering samples dissolved in continuously flowing streams.
- the number of lines may be one, preferably greater than one and typically 4 to 8.
- the sample in each line passes over a by-pass port in transit to a transfer line that transports the sample to the ionizing region of the mass spectrometer, where ionization and mass spectrometric analysis takes place.
- the transfer of the sample to the ionizing region can be rapidly turned on and off by the action of a valve located close to or directly on the by-pass port.
- the by-pass port is maintained at a lower pressure than the transfer line to the mass spectrometer.
- the valve opens, the sample diverts through the by-pass port to a by-pass line, due to a backpressure difference between the by-pass port and the transfer line. Applying a slight vacuum to the by-pass port further enhances the pressure differential between the two lines and can increase the speed of the shut-off cycle. Closing the valve, which shuts off the by-pass line, rapidly turns on the transfer of sample to the mass spectrometer via the transfer line.
- the present sample introduction device provides a separate valve, by-pass line, and sample transfer line for each inlet to the mass spectrometer allowing each line to be independently controlled and triggered by some external device, such as the mass spectrometer, to provide synchronization.
- the by-pass port and valve are preferably arranged as a "T" fitting.
- the liquid in the channel only needs be withdrawn from the ionizing tip by a distance of about 1 mm, which is believed to be the theoretical minimum transit distance any fluidic system must empty to effectively shut off the signal. Constructing a valving element at a distance of 1 mm from a high voltage ionizing tip represents a significant technological challenge that is perhaps only achievable with nanofabrication technology. No such valves having any practical utility for this application have been developed.
- the liquid is withdrawn from the ionizing tip only to the distance required to turn off the signal. It is not necessary to withdraw the liquid any further.
- the valve closes the liquid quickly reverses direction and returns to the ionizer, which is a very short distance away. This short transit distance also minimizes dispersion effects otherwise referred to as parabolic flow profiles, which contribute significantly to the rise time of the signal to a steady state level when liquids travel through long lengths of tubing.
- the retraction of the sample a small distance within the tubing assures a very rapid decay or fall time of the signal, thereby reducing channel to channel cross contamination or carryover.
- clean solvent brought to the ionizing tip by a separate line will assure no residues are momentarily left on the ends of each sample line to cause cross channel contamination.
- a bundle or array of channels also allows for the introduction of conduits other than sample or solvent channels e.g. optical fibres to transport energy such as IR laser light for the purposes of enhancing the vaporization of the spraying liquid from the sample channels or for simple visualization and tuning of the spray.
- each line may be fed to a different ionizing element.
- the first method provides a means for simultaneously analysing multiple samples injected in parallel into the mass spectrometer. During this mode of operation each channel is rapidly turned on and off in sequence on a time scale much faster than the time required for any of the samples to pass through and exit the channels. When one valve is shut, the transfer line associated with that particular valve delivers sample to the mass spectrometer. The remaining valves are open diverting the samples away from the mass spectrometer.
- the electronics used to drive the valves synchronize the opening and closing of the valves with the mass spectrometric analysis, so that the analytical results from the mass spectrometer may be correlated with the samples.
- the mass spectrometer collects data during these short bursts of sample introduction and stores the data collected from each channel in a separate location or file, referred to as indexing or indexed operation. This method of operation has the most demanding specifications for speed of channel turn-off and turn-on. Turn-off times of less than 10 milliseconds, providing a reduction of the signal level by 3 orders of magnitude, have been achieved with this technique. Similarly signal rise times of less than 10 milliseconds have been observed under similar conditions.
- Stepper motor driven spray selectors or fluid selectors have a fundamental limitation dictated by motor speeds, typically 50 - 100 milliseconds plus additional dead times introduced by other factors. [037] This method has significant advantages over the rotating member spray and fluid selector systems in being able to achieve further speed enhancements for the indexed mode of operation. As each channel is controlled independently from all others, further reductions in channel-to- channel dead time may be achieved by overlapping in time the turning off of one channel with the turning on of the next. A substantial speed advantage will be accrued, because any residual delays in fluid transfer will be compensated for by this offset in valve actuation time.
- the second method of operation provides for a superior means of optimising the speed of the fast serial sample introduction approach.
- Each channel may be operated in a non-indexed fashion, similar to a typical stream selector valve, to gate samples very rapidly but sequentially (as opposed to in parallel) into the mass spectrometer.
- the fast serial sample introduction approach also benefits from the absence of a valving element in the path of the sample as it transits to the mass spectrometer.
- the third method of operation involves both parallel sample introduction and parallel mass spectrometric data acquisition. As the valves may be independently controlled, this method of operation is available. It cannot be achieved with the rotating member spray or fluid selectors. At any time, one or more channels may be continuously left on. The samples will mix in the ionization region of the mass spectrometer and data acquisition will occur simultaneously on all channels. Although it is impossible to distinguish what signals came from what channel in this mode if the composition of the sample is completely blind, it is a useful technique for adding a known calibrant compound to one stream to be used as a reference mass for precise molecular weight calculations of the components in the other stream containing the unknown components. [040] The fourth method of operation involves any combination of the above three modes occurring simultaneously.
- the independence of control of each channel provides ultimate flexibility.
- One or multiple channels may be permanently on or off while any combination of the remaining valves are cycled in an indexed fashion.
- the present sample introduction device also provides advantages due to its mechanical simplicity, robustness and inherent reliability.
- the performance of the sample introduction device is insensitive to small leakage rates of the valves because the valve is outside the sample path in transit to the mass spectrometer.
- a leakage rate of a few percent can be tolerated i.e. several orders of magnitude worse than typical solenoid valve specifications, with virtually no effect on the rise and fall time of the sample signal and ultimately the achievable speed of cycling without excessive carryover. This translates into an important element of robustness and tolerance to performance degradation.
- on/off solenoid valves is at least 10 times faster than stepper or servo motors (sub millisecond versus several tens of milliseconds) used for spray selectors or fluidic selectors of the switching valve type. Also, lifetime and reliability of on/off solenoid valves are 10 times longer than motors and 100 times longer than switching valves.
- the sample introduction device is a single channel device and includes a "T" fitting 62 having an inlet 62 receiving a sample.
- "T" fitting 62 also has outlets 64 and 66.
- Outlet 64 is connected to a mass spectrometer (not shown) through ionization region 68.
- Outlet 66 is connected to a valve 70, which has gate 72 actuable between in a closed position as shown in Figure 2A and an open condition as shown in Figure 2B.
- Valve 70 also has an outlet port 74.
- valve 70 is a high-speed solenoid valve, which typically has an actuation time of 5 milliseconds but can be driven at rates as high as 200 microseconds.
- sample introduction device includes a manifold 84 receiving two inlet sample streams identified by reference numerals 80 and 82 respectively.
- Manifold 84 in this case includes two "T" fittings. Inlet 80 is connected to outlet 86 of manifold 84, which is directed through ionization region 88 of a mass spectrometer. Manifold 84 also has a first solenoid valve including a valve gate 90, which connects to outlet 92. In Fig. 3, valve gate 90 is shown in a closed position, so that a sample stream entering inlet 80 passes through outlet 86 to the mass spectrometer via a transfer line. Upon opening of the valve gate 90 however, a sample stream entering inlet 80 is diverted to outlet 92.
- Inlet 82 is connected to outlet 94, which is also directed to the ionization region 88 of the mass spectrometer.
- Manifold 84 additionally has a second solenoid valve including a valve gate 96, which connects to outlet 98.
- Valve gate 96 is shown in an open position so that a sample stream entering inlet 82 is diverted through outlet 98. Upon closing of the valve gate 96, a sample stream entering inlet 82 however passes through outlet 94 to the ionization region 88 of the mass spectrometer via a transfer line.
- valve gate 90 is shown in a closed position.
- a sample entering at inlet 80 passes through manifold 84 to outlet 86 and hence to the mass spectrometer.
- a sample entering at inlet 82 is diverted through valve gate 96 to outlet 98 due to the fact that the inner diameter of outlet 94 is less than the inner diameter of outlet 98.
- valve gate 96 is closed, at which time valve gate 90 is opened, the sample entering inlet 82 passes to the mass spectrometer and the sample entering inlet 80 is diverted to outlet 92.
- the fluid On subsequent cycles, when the associated valve is opened to shut off the spray from a selected transfer line, the fluid will be retracted only partially if so desired. Minimization of the retraction distance will maximize the speed. This is done by controlling the vacuum on outlets 92 and 98 or by controlling the backpressure of the outlets 92 and 98 relative to the transfer lines extending from the respective outlets 86 and 94 e.g. by use of different inner diameter tubing, needle valves or the like. [049] In the embodiment of Fig. 3, the solenoid valves are mounted on the manifold 84 in such a way that the valve gates 90 and 96 are very close to the by-pass apertures.
- the fluidic sample lines 86 and 94 are shown as converging, to allow them to be bundled into a single ionization device. These lines are typically made from fused silica tubing of ⁇ 200 microns outside diameter and inner diameters ranging from 20-150 microns.
- Figure 4 depicts four separate sample transfer lines 100, 102, 104 and 106 bundled into an electrospray ionizer.
- Sample transfer line 102 is shown delivering a sample to the mass spectrometer; the other sample transfer lines are shown as being off.
- a metal nebulizer tube 108 surrounds sample transfer lines 100 to 106.
- a gas flows at a high velocity through metal nebulizer tube 108, to atomize the liquid passing through the sample transfer lines as indicated by reference numeral 109. This gas is optional and may be avoided if the total liquid flow is sufficiently low to allow for nebulization of the liquid to occur strictly as a consequence of the disruptive power of the electric field.
- Metal nebulizer tube 108 is maintained at a high voltage to charge the liquid.
- Voltage contact is made through solvent wash delivered into the electrospay ionizer via a wash tube 110, which is shown as protruding from metal nebulizer tube 108, but in practice is recessed within metal nebulizer tube 108.
- High voltage contact is made to the solvent wash, which streams over the fluidic sample transfer lines and completes the electrical contact.
- Other means of making electrical contact to the separate sample transfer lines are also possible including making the channels of metal, by providing a metal junction upstream in the fused silica line from which sample transfer lines are formed, or by simply lowering the gas nebulizer pressure sufficiently to allow the liquid to wick back on the outside of the sample transfer lines and make contact with the metal nebulizer tube 108.
- Tube 110 can also serve other functions.
- Tube 110 for example, can serve as a conduit to transport energy such as IR laser light to enhance the vaporization of the spraying liquid, to introduce photons for sample ionization purposes, to introduce additional gases to enhance the ionization process, or to serve as a simple illumination device to enhance visualization for tuning purposes.
- each channel must then be able to turn on and off in no more than a maximum of 100 milliseconds and preferably much faster than this to allow for sufficient time to acquire mass spectrometric data on each channel.
- the rate at which a channel is turned off is very fast, because the liquid needs only to retract from the ionizer tip by 1-2 mm to shut off ionization.
- the rate at which a channel can be turned on is determined by the transit or refill time of the fluid in the transfer line from the "T" fitting to the ionizer tip.
- the velocity of the liquid through the transfer line is the major determinant of this time delay together with dispersion effects of the sample in the solvent.
- the velocities may be considered to be a function of the volumetric flow of liquid delivered to the tube, the tube inner diameter, and the length. Assuming fluids are essentially non-compressible, the rate at which the fluid accelerates to the calculated terminal velocity is very fast at the pressures commonly contained by solenoid valves, typically less than 2000 psi. [055] Table 1A in Figure 5 indicates a scenario wherein the 10 cm long fluid transfer line from the sprayer to the valve gate is completely emptied on each cycle, which may be referred to as a worst case scenario.
- FIG. 6 shows data, obtained using ultraviolet absorbance detection at 254 nm, that demonstrates that the calculated speeds are within a reasonable measure of experimental error.
- a sample of caffeine was pumped through a four-channel sample introduction device at a rate of 1000 microliters per minute. UV detection was accomplished by utilizing the last 1 millimetre at the tip of the fused silica sample transfer line as the detection cell. The total length of this transfer line was 11 cm and the inner diameter 100 microns. The rise and fall times of the signals were measured on all four valves when operating at the targeted cycling frequency of 1 Hz. Vacuum was applied to the outlet of the "T" fitting sufficient to assure that the transfer line was emptied up to the by-pass valve gate.
- valves may be opened and closed in a rapid manner, so that a rapid sequence of samples may be fed to the ionizing region of the mass spectrometer, with the analysis of samples in the mass spectrometer being co-ordinated and synchronized with the opening and closing of valves so that the analytical results may be correlated with the respective samples.
- An exception to the typical procedure would be when two, or more, samples were to be fed to the ionizing region at the same time e.g. a calibrant stream and the sample to be analyzed.
- the present invention offers the advantage over other fluidic selectors in that the valving elements used to gate the sample streams are located outside of the sample path as it traverses from the injector to the mass spectrometer. Thus, dispersion effects from valve elements may be eliminated, avoiding a serious problem that other fluidic selectors encounter. It also provides a means for minimizing the sample transit distance to the theoretical limit required to turn on and off a spray. All the advantages of fluidic selectors over other methods are maintained intact including the ability to produce ionization from a single point source rather than multiple ionizing elements. The present invention also has the advantage of mechanical simplicity and associated robustness required for the 24 hour per day multiple day operations typical of high throughput chemical analyses. [062] Although preferred embodiments of the present invention have been described, those of skill in the art will appreciate that variations and modifications may be made without departing from the spirit and scope thereof as defined by the appended claims.
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Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
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DE60144243T DE60144243D1 (en) | 2000-11-28 | 2001-11-28 | DEVICE FOR INTRODUCING LIQUID SAMPLES INTO A MASS SPECTROMETER USING A QUICK VALVE SYSTEM FOR SYNCHRONIZING MULTIPLE PARALLEL SAMPLES |
AU2002223343A AU2002223343B2 (en) | 2000-11-28 | 2001-11-28 | Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams |
CA002429007A CA2429007C (en) | 2000-11-28 | 2001-11-28 | Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams |
AT01998807T ATE502391T1 (en) | 2000-11-28 | 2001-11-28 | DEVICE FOR INTRODUCING LIQUID SAMPLES INTO A MASS SPECTROMETER USING A FAST VALVE SYSTEM FOR SYNCHRONIZING MULTIPLE PARALLEL SAMPLE STREAMS |
EP01998807A EP1338026B1 (en) | 2000-11-28 | 2001-11-28 | Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams |
US10/432,965 US6841774B1 (en) | 2000-11-28 | 2001-11-28 | Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams |
JP2002546183A JP3917938B2 (en) | 2000-11-28 | 2001-11-28 | Sample introduction device for mass spectrometry using a high-speed fluid system that synchronizes multiple parallel liquid sample flows |
AU2334302A AU2334302A (en) | 2000-11-28 | 2001-11-28 | Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams |
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US25361600P | 2000-11-28 | 2000-11-28 | |
US60/253,616 | 2000-11-28 | ||
US27006701P | 2001-02-20 | 2001-02-20 | |
US60/270,067 | 2001-02-20 |
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WO2002044684A2 true WO2002044684A2 (en) | 2002-06-06 |
WO2002044684A3 WO2002044684A3 (en) | 2003-02-27 |
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PCT/CA2001/001673 WO2002044684A2 (en) | 2000-11-28 | 2001-11-28 | Sample introduction device for mass spectrometry using a fast fluidic system to synchronize multiple parallel liquid sample streams |
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EP (1) | EP1338026B1 (en) |
JP (1) | JP3917938B2 (en) |
AT (1) | ATE502391T1 (en) |
AU (2) | AU2334302A (en) |
CA (1) | CA2429007C (en) |
DE (1) | DE60144243D1 (en) |
WO (1) | WO2002044684A2 (en) |
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- 2001-11-28 JP JP2002546183A patent/JP3917938B2/en not_active Expired - Fee Related
- 2001-11-28 CA CA002429007A patent/CA2429007C/en not_active Expired - Fee Related
- 2001-11-28 AU AU2334302A patent/AU2334302A/en active Pending
- 2001-11-28 EP EP01998807A patent/EP1338026B1/en not_active Expired - Lifetime
- 2001-11-28 DE DE60144243T patent/DE60144243D1/en not_active Expired - Lifetime
- 2001-11-28 WO PCT/CA2001/001673 patent/WO2002044684A2/en active Application Filing
- 2001-11-28 AT AT01998807T patent/ATE502391T1/en not_active IP Right Cessation
- 2001-11-28 AU AU2002223343A patent/AU2002223343B2/en not_active Ceased
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EP0886143A1 (en) * | 1998-03-27 | 1998-12-23 | SYNSORB Biotech Inc. | Apparatus for screening compound libraries |
US6066848A (en) * | 1998-06-09 | 2000-05-23 | Combichem, Inc. | Parallel fluid electrospray mass spectrometer |
Cited By (18)
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US6812458B2 (en) | 2002-08-08 | 2004-11-02 | Nanostream, Inc. | Systems and methods for high-throughput microfluidic sample analysis |
US7214320B1 (en) | 2002-08-08 | 2007-05-08 | Nanostream, Inc. | Systems and methods for high throughput sample analysis |
WO2004015411A1 (en) * | 2002-08-08 | 2004-02-19 | Nanostream, Inc. | Systems and methods for high-throughput microfluidic sample analysis |
US7132650B1 (en) | 2003-09-26 | 2006-11-07 | Nanostream, Inc. | High throughput multi-dimensional sample analysis |
WO2005062340A2 (en) * | 2003-12-13 | 2005-07-07 | Nanostream, Inc. | High throughput systems and methods for parallel sample analysis |
WO2005062340A3 (en) * | 2003-12-13 | 2006-07-06 | Nanostream Inc | High throughput systems and methods for parallel sample analysis |
US8721768B2 (en) | 2008-05-27 | 2014-05-13 | Perkinelmer Health Sciences, Inc. | Chromatography systems and methods using them |
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US8561484B2 (en) | 2009-03-24 | 2013-10-22 | Perkinelmer Health Sciences, Inc. | Sorbent devices with longitudinal diffusion paths and methods of using them |
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US8794053B2 (en) | 2010-06-14 | 2014-08-05 | Perkinelmer Health Sciences, Inc. | Fluidic devices and methods using them |
US10399030B2 (en) | 2010-06-14 | 2019-09-03 | Perkinelmer Health Sciences, Inc. | Fluidic devices and methods for modulating flow of fluid in chromatography system to provide tree way switching |
US8562837B2 (en) | 2010-09-22 | 2013-10-22 | Perkinelmer Health Sciences, Inc. | Backflush methods and devices for chromatography |
US10753913B2 (en) | 2015-06-30 | 2020-08-25 | Perkinelmer Health Sciences, Inc. | Chromatography systems with mobile phase generators |
EP3971564A4 (en) * | 2019-07-31 | 2022-07-27 | National Institute Of Advanced Industrial Science and Technology | Spray ionization device, analysis device, and surface coating device |
Also Published As
Publication number | Publication date |
---|---|
CA2429007C (en) | 2008-11-25 |
AU2334302A (en) | 2002-06-11 |
CA2429007A1 (en) | 2002-06-06 |
JP3917938B2 (en) | 2007-05-23 |
JP2004525483A (en) | 2004-08-19 |
DE60144243D1 (en) | 2011-04-28 |
ATE502391T1 (en) | 2011-04-15 |
EP1338026B1 (en) | 2011-03-16 |
AU2002223343B2 (en) | 2007-01-18 |
EP1338026A2 (en) | 2003-08-27 |
WO2002044684A3 (en) | 2003-02-27 |
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