This invention relates to devices for extracting a fluid sample from a bulk fluid container for subsequent or simultaneous optical and/or electrical interrogation of the sample.
Handheld pipettes, which are used for precision fluid volume measurement and delivery, are some of the most common and widely-used laboratory tools available to scientists today. Many procedures requiring low-volume fluid handling of biological and chemical liquid samples rely on their ease of use, precision and repeatability to ensure proper, consistent experimental processing. Commercial pipettes are available in a wide variety of fixed and adjustable volumes. When used in large-scale, high-throughput testing, commercially available pipettes are often multiple-channel, allowing for precise fluid metering of up to 12 different samples, simultaneously, with the single push of a button. Typical pipette instruments rely on positive displacement systems (e.g. either a manually operated plunger system, or an electronic pump) to generate the pressure required to urge a specified fluid volume into, or out of, a disposable pipette tip. Once the sample is ejected, the pipette tip is discarded. State-of-the-art pipette instruments are capable of accurately metering fluid volumes of less than 1 mL, and employ servo pumps for volume control and fluid metering. Digital displays with integrated electronic controls improve the pipette instrument's ease of use for the operator.
In the laboratory, pipettes are typically found in wet bench environments and are used in countless fluid-metering applications ranging from fluid mixing to sample isolation and preparation. In experimental cell biology, pipettes are routinely used to isolate small volume suspensions of cells in culture. In one of the most common procedures, manually counting (under microscope observation) a small portion of the cells in a precisely metered volume allows a user to make population and cell viability estimates for the entire volume of cells in culture. Unfortunately, counting cells under a microscope using this approach is very time and resource intensive, and count accuracy depends wholly on the number of cells a user is willing to actually count in the given volume.
Pioneering work in particle detection by measuring impedance deviation caused by particles flowing through a small aperture between two containers of electrically conductive fluids is disclosed in U.S. Pat. No. 2,656,508 to W. H, Coulter. The inventor's name is now associated with the principle of particles causing a change in electric impedance as they occlude a portion of the aperture. Since publication of his patent, considerable effort has been devoted to developing and refining sensing devices operating under the Coulter principle. Relevant US patents include U.S. Pat. Nos. 5,376,878 to Fisher; 6,703,819 to Gascoyne et al.; 6,437,551 to Krulevitch et al.; 6,426,615 to Mehta; 6,169,394 to Frazier et al.; 6,454,945 and 6,488,896 to Weigl et al.; 6,656,431 to Holl et al.; and 6,794,877 to Blomberg et al. All of the above-referenced documents are hereby incorporated by reference, as though set forth herein in their entireties, for their disclosures of technology and various sensor arrangements.
The ability of certain particles to emit radiation at a different frequency than an applied excitation frequency is commonly known as Stokes-shift. Recent US patents disclosing structure related to interrogation of such phenomena include: U.S. Pat. Nos. 7,450,238; 7,444,053; 7,420,674; 7,416,700; 7,312,867; 7,300,800; and 7,221,455. All of the above-referenced documents are hereby incorporated by reference, as though set forth herein in their entireties, for their disclosures of relevant technology and various sensor arrangements.
It would be an improvement to provide a precision fluid interrogation apparatus that is capable of metering very precise quantities of a bulk fluid to extract a fluid sample, and interrogating that sample (optically and/or electrically), to determine one or more characteristic of such sample, such as particle count per unit volume. It would be a further advance for the apparatus to be embodied as a low-cost, one-time-use, rugged, and disposable device.
The present invention provides an apparatus and method for interrogating particles entrained in a fluid sample. Certain currently preferred embodiments may extract such sample from a bulk container of fluid. Currently preferred embodiments are operable to perform certain tests on one or more portion of the fluid sample, such as particle count per unit volume, and/or may verify a volumetric size or flow rate of the sample, or a portion thereof, among other functions. Tests, or interrogation, may encompass one or both of radiation detection, and electrical property evaluation.
A currently preferred embodiment forms a pipette tip having an elongate body stretching between a proximal end and a distal end with a fluid path through the body extending from the distal end toward the proximal end. The preferred embodiment is structured to permit detection of radiation emitted from an excited, or stimulated, particle of interest that passes through an interrogation zone. In general, an interrogation zone is disposed in proximity to structure configured to urge particles into approximately single-file travel. Optionally, certain embodiments may electrically interrogate fluid flowing along the fluid path. Desirably, embodiments of an operable sensor component are configured and arranged to determine volumetric particle count. Sometimes, the sensor component may be configured and arranged to detect the presence of a fluid boundary edge at one or more particular location along the fluid path. In one such device, the sensor component may be configured and arranged to permit determination of a fluid flow rate along the fluid path.
In some cases, the body is structured to include a plurality of layers configured and arranged to provide at least a portion of the fluid path. In certain such cases, a workable sensor component can be formed by part of a first electrically conductive trace carried between first and second adjacent layers. The first sensor component can be formed by a first stretch of the first trace being disposed to contact fluid flowing along the fluid path. Further, a second electrically conductive trace may be carried between adjacent layers, with at least a stretch of the second trace being disposed to contact fluid flowing along the fluid path as a second sensor component. Sometimes, the first sensor component and the second sensor component may be spaced apart along the fluid path and carried between the same layers. Other times, the first sensor component and the second sensor component are spaced apart along the fluid path and carried between different layers. A plurality of such sensor components may be provided at a plurality of desired locations, as desired.
In certain embodiments, part of the fluid path is defined by a length of lumen encompassing a known volume between distinct points. Further, sensor components can be disposed at such distinct points effective to indicate travel through the pipette tip of an amount of fluid comprising a sample volume corresponding to that known volume. Time of flight for the fluid front between sensor components that are spaced apart along a fluid channel having known volume there-between may be used to determine volumetric flow rate of an interrogated sample.
A pipette tip structured in accordance with certain principles of the instant invention may be used to advantage in combination with a pipette that is configured and arranged to couple with the proximal end of the pipette tip. Desirably, coupling the tip to the pipette is effective to orient an interrogation zone to permit application of excitation radiation to the zone, and detection of emission radiation from the zone, as well as to permit application of suction to a proximal portion of the fluid path. Furthermore, it is sometimes desirable for the act of coupling the tip and pipette to place a sensor component in-circuit with electrical interrogation apparatus.
Some embodiments may include structure adapted to permit detection of a pipette tip when the tip is installed in a pipette. Different pipette tips may be structured to have different detectable identities, e.g. different resistance values caused between electrical contact pad pins, or different contact pads being disposed in direct electrical communication, which can be used as triggers, which, for example, may be used to perform particular tests depending upon the obtained tip identity.
A device may be used by coupling a pipette tip structured according to certain principles of the instant invention to a cooperatingly structured pipette effective to place the pipette tip into position for interrogation of particles passing through an interrogation zone of the tip by interrogation apparatus, and to place a proximal end of the fluid path through the tip in communication with a suction source. Then, a fluid-motive pressure is applied effective to draw a sample into the pipette tip. At least a portion of the sample is interrogated as that portion flows along the fluid path and past the sensor component. Data collected by the sensor component may be shown on a display screen associated with the pipette, and/or transferred to a computer, or other data collection device, for further analysis or storage. Subsequent to completion of fluid sample analysis, the used pipette tip is discarded.
A preferred method of applying suction encompasses generating an excess suction pressure that may then be down-regulated by structure associated with the pipette effective to apply: i) a first suction pressure operable to draw a sample into the pipette tip; and ii) a subsequent desired suction pressure profile over time.
These features, advantages, and alternative aspects of the present invention will be apparent to those skilled in the art from a consideration of the following detailed description taken in combination with the accompanying drawings.
In the drawings, which illustrate what are currently considered to be the best modes for carrying out the invention:
Reference will now be made to the drawings in which the various elements of the invention will be given numerical designations and in which the invention will be discussed so as to enable one skilled in the art to make and use the invention. It is to be understood that the following description is only exemplary of the principles of the present invention, and should not be viewed as narrowing the claims which follow.
As typically used in this disclosure, and unless otherwise obvious in context, the term “fluid” may include a liquid alone, one or more liquids in a mixture, or one or more liquid and particles entrained or suspended therein. In certain cases, a fluid will have electrolytic properties. A bulk fluid container is simply a container sized to hold an amount of fluid sufficient to form at least one fluid sample to be interrogated with an embodiment of the instant device.
The term “particle” and its variants, is intended to encompass a small piece of matter, nonexclusively including a live or dead biological cell, and a molecule. Unless otherwise apparent in context, “pressure” and “suction” is generally intended to be measured with respect to local atmospheric pressure.
By “controlled radiation interrogation zone” it is meant that at least an operable measure of control is exerted over the travel of particles of interest in the zone. An operable level of control physically organizes particles into an arrangement sufficient to permit detecting emitted radiation effective to distinguish, or quantify, individual particles of interest traveling through the controlled radiation interrogation zone. Such control is in stark contrast to uncontrolled radiation, such as would be the case of excitation radiation impinged into a test tube containing a plurality of particles of interest. In such case, the Stokes-shift radiation emitted from a particle might be detected, but would be uncontrolled, and one could not distinguish, or quantify, individual particles of interest. One could extract only the limited information that there are at least some particles of interest in the test tube.
An orifice may be defined broadly to encompass any sort of constricting structure effective to organize or arrange particles of interest into a desirably compact cross-section as such particles travel through a portion of a pipette tip. In one currently preferred embodiment, an orifice is essentially a hole-through-a-plate. Desirably, the particles of interest are urged for travel in at least approximately single-file order by structure of the orifice.
A schematic illustrating a generalized operable arrangement of structure employed in certain embodiments of the invention is indicated generally at 100 in
The thickness, T1, of an opaque member and characteristic size, D1, of an orifice are typically sized in agreement with a size of a particle of interest to promote single-file travel of the particle through the opaque member, and to have substantially only one particle inside the orifice at a time. In the case where the apparatus is used to interrogate blood cells, the thickness of the opaque member may typically range between about 10 microns and about 300 microns, with a thickness of about 125 microns being currently preferred. The diameter, or other characteristic size of the orifice, may range between about 5 and 200 microns, with a diameter of about 50 microns being currently preferred.
An operable opaque member 102 may function, in part, to reduce the quantity of primary radiation 118 (or sometimes, excitation radiation) that is emitted by source 104, which is received and detected by radiation detector 106. Primary radiation 118 is illustrated as a vector having a direction. Desirably, substantially all of the primary radiation 118 is prevented from being detected by the radiation detector 106. In any case, operable embodiments are structured to resist saturation of the detector 106 by primary radiation 118. As illustrated in the arrangement depicted in
The opaque member 102 illustrated in
A workable core 122 for use in detecting small sized particles can be formed from a thin polymer film, such as PET having a thickness of about 0.005 inches. Such polymer material is substantially permeable to radiation, so one or more coatings, such as either or both of coating 124 and 126, can be applied to such core material, if desired. A workable coating includes a metal or alloy of metals that can be applied as a thin layer, such as by sputtering, vapor deposition, or other well-known technique. Ideally, such a layer should be at least about 2-times as thick as the wavelength of the primary radiation, e.g. about 1 μm in one operable embodiment. The resulting metallized film may be essentially impervious to transmission of radiation, except where interrupted by an orifice. Aluminum is one metal suitable for application on a core 122 as a coating 124 and/or 126.
The apparatus 100 is configured to urge a plurality of particles 130 in substantially single-file through orifice 108. A particle 130 typically passes through an excitation zone as the particle approaches, passes through, and departs from the orifice 108. Of note, the direction of particle-bearing fluid flow may be in either direction through orifice 108. An excitation zone typically includes the through-channel defined by orifice 108. An excitation zone may also include a volume indicated by lower cloud 134, which encompasses a volume in which a particle may reside and be in contact with primary radiation. An excitation zone may further include a volume indicated by upper cloud 136, which also encompasses a volume in which a particle may reside and be in contact with primary radiation.
In certain cases, e.g. where there may be a plurality of orifices, the term “zone” may include a plurality of such distributed zones. That is, it is within contemplation to perform interrogation in a plurality of hydraulically parallel zones. However, the appropriate meaning of the term “zone” is believed to be aduceable in context. In the excitation zone, primary radiation 108 impinged upon particles causes certain particles to fluoresce (undergo a Stokes-shift), thereby emitting radiation at a different wavelength compared to the primary radiation 108 and in substantially all three ordinate directions. The fluorescence radiation emitted by those certain particles is then detected by the radiation detector 106.
It should be noted, for purpose of this disclosure, that the term “wavelength” is typically employed not necessarily with reference only to a single specific wavelength, but rather may encompass a spread of wavelengths grouped about a characteristic, or representative, wavelength. With reference to
With reference again to
The multi-layered embodiment, generally indicated at 140 and illustrated in
Plumbing arrangement 140 includes five layers configured and arranged to form a channel system effective to direct flow of particle bearing fluid from a supply chamber 142, through orifice 108 in an opaque member 102, and toward a waste chamber 144. Desirably, a depth of fluid guiding channels 146 and 148 are sized in general agreement with a size of a particle 150, to resist “stacking” particles near the orifice 108. Fluid can be moved about on the device 140 by imposing a difference in pressure between chambers 142 and 144, or across orifice 108 disposed in opaque member 102. For example, a positive pressure may be applied to the supply chamber 142. Alternatively, a negative pressure may be applied to the waste chamber 144. Both positive and negative pressures may be applied, in certain cases. Alternative fluid motive elements, such as one or more pumps, may be employed to control particle travel through opaque member 102.
Although both of supply chamber 142 and waste chamber 144 are illustrated as being open to the atmosphere, it is within contemplation for one or both to be arranged to substantially contain the fluid sample within a plumbing device that includes a multilayer element 104. Also of note, although a top-down fluid flow is illustrated in
The multilayer plumbing arrangement 140 illustrated in
In any case, at least a portion of bottom layer 160 is adapted to form a bottom window 162, through which excitation radiation 118 may be transmitted into an excitation zone. Similarly, top layer 154 includes a portion forming a window 164, through which fluorescence may be transmitted. Therefore, the assembly 140 is arranged to form a window permitting radiation to pass through its thickness. Such window includes window portions 162, 164, certain portions of channels 146 and 148 disposed in the vicinity of orifice 108, and the orifice 108 itself. Radiation can therefore be directed through the thickness of the assembly 140 in the vicinity of the orifice 108.
The plumbing arrangement illustrated in
As illustrated in
Because fluorescence propagates from a tagged and excited particle of interest in substantially all directions, the primary radiation 118 may be directed to an excitation zone from a side, instead of only from directly below such zone. With reference now to
A radiation source 104 may be formed from a broad spectrum radiation emitter, such as a white light source. In such case, it is typically preferred to include a pre-filter 188 adapted to pass, or transmit, radiation only in a relatively narrow band encompassing the characteristic value required to excite a particular fluorescing agent associated with a particle of interest. It is generally a good idea to limit the quantity of applied radiation 118 that is outside the excitation wavelength to reduce likelihood of undesired saturation of the radiation detector, and consequent inability to detect particles of interest.
In one embodiment adapted to interrogate blood cells, it is currently preferred to use a red diode laser, and to include a short pass filter (after the diode laser) that passes primary light radiation with wavelengths shorter than about 642 nm. It is also currently preferred to include a band pass filter (prior to the photodetector) with a peak that matches a particular selected fluorescence peak. Commercially available dyes may be obtained having characteristic fluorescent peaks at 660, 694, 725, and 775 nanometers. Long pass filters are also often used in place of band-pass filters prior to the photodetector. The pipette tip “cap layer” and “substrate” can also be designed to act as optical filters to aid or eliminate the need for the traditional excitation and emission filters. In this disclosure, “Post filter” may more conventionally be referred to as an “emission filter”.
With continued reference to
It is within contemplation that a device structured according to certain principles of the instant invention may, or may not, include one or more sensor component, such as an electrode, disposed in various patterns, and at various places, for contact with the fluid flowing through a conduit in the device, e.g. for impedance-based particle interrogation. Selected operable arrangements of such interrogation structure is disclosed in U.S. patent application Ser. No. 11/800,167, titled “THIN FILM PARTICLE SENSOR, and filed on May 4, 2007, the entire contents of which are hereby incorporated as though set forth herein in its entirety.
With reference to
Certain components that are operable to construct an apparatus according to certain principles of the instant invention are commercially available. For example, one operable source of radiation 104 includes a red diode laser available under part number VPSL-0639-035-x-5-B, from Blue Sky Research, having a place of business located at 1537 Centre Point Drive, Milpitas, CA 95035. Filter elements 188, 190 are avilable from Omega Optical, having a place of business located at 21 Omega Dr., Delta Campus, Brattleboro, Vt. 05301. Preferred filters include part numbers, 660NB5 (Bandpass filter), and 640ASP (shortpass filter). An operable radiation detector includes a photomultiplier tube available from the Hamamatsu Corporation, having a place of business located at 360 Foothill Rd., Bridgewater, N.J. 08807, under part number H5784-01. Molecular Probes (a division of Invitrogen Corporation, www.probes.invitrogen.com) supplies a plurality dyes that are suitable for use in tagging certain particles of interest for interrogation using embodiments structured according to the instant invention. In particular, AlexaFluor 647, AlexaFluor 700, and APC-AlexaFluor 750 find application to interrogation of blood cells. These dyes are also commonly used in flow cytometric applications and have specific excitation and emission characteristics. Each dye can be easily conjugated to antibodies for labeling, or tagging, different cell types.
The illustrated pipette tip 200 is operable to interrogate particles using either impedance or fluorescence, or both in combination. The illustrated opaque member 102 (sometimes alternatively called an interrogation layer or sheet) carries electrically conductive traces, e.g. 210 configured to form an electrode sensor component 212 in electrical communication with an electrical contact pad 214 (see
The contact pads illustrated in
In general, the term “fluid” is used in this disclosure to encompass particles entrained in a fluid. Sometimes, that fluid may be an electrolyte. With reference to
Fluid flowing in channel 231 wets a first driving electrode 233 and first interrogation electrode 234, in series. After passing transversely through the orifice 108 in the interrogation sheet 102, fluid then flows along the indicated direction 235 in the channel 236, disposed in the bottom channel sheet 158, and wets second interrogation electrode 238 and second driving electrode 240, in series.
At the distal end 242 of channel 236, fluid wets a first electrode 248 and a second electrode 250, in series. Electrodes 248 and 250 are configured cooperatively to indicate the presence of a fluid front at a known position along the fluid conduit extending proximally from the distal end of the device 200. As illustrated, electrodes 248 and 250 can indicate the arrival of a leading edge of fluid at a known position (essentially at the entrance to the fluid channel 252 disposed in the substrate 202). For example, impedance between electrodes 248 and 250 may be monitored to detect a change from an open-circuit condition. The monitored signal, which shows a discontinuity from an open-circuit value as the fluid boundary wets the second electrode 250, may be used as a trigger signal to start recording or processing data to interrogate fluid as such fluid continues to be inspired into the device 200. An impedance signal between such electrodes may be monitored to detect either a leading or trailing fluid boundary edge. Due to the close proximity of stimulus electrode 248, an electrical signal available at measurement electrode 250 can be monitored for the duration of a test to detect the presence of air bubbles in the sample. Absence of a trailing boundary signal can be used to verify freedom of bubbles in a fluid sample, among other uses.
Interrogation of a fluid sample may be terminated by a subsequent trigger signal that is monitored, for example, to determine completion of interrogation of a known volume of fluid. In the illustrated device 200, after a known volume (downstream of electrode 250, and indicated at arrow 251) has entered the substrate channel 252, the associated fluid front wets a confirmation electrode 254 (see
A trigger signal from illustrated confirmation electrode 254 may be used to terminate suction applied to air vent 222 to resist potential contamination of a pipette, or other interrogation device, by fluid inspired completely through the device 200. It is also, or alternatively, within contemplation to provide a fluid resistant barrier or membrane (not illustrated) disposed to resist further flow of fluid beyond a desired location in device 200, such as at an exit from storage chamber 255. A workable such barrier permits air molecules to pass, but resists passage of the inspired fluid, to resist drawing inspired fluid into the pipette, or other interrogation device.
Structure to provide a validation signal may be included in a device 200 to confirm proper installation of the pipette tip 200 in a pipette. For example, an electrical continuity signal between electrical contact pad #1 and electrical contact pad #10 may provide the desired feedback. As illustrated in
With reference now to
As illustrated in
The thin film assembly 266 illustrated in
It is currently preferred to manufacture a thin film assembly, such as assembly 266 in
In an exemplary sensor assembly 266 used in connection with interrogation of blood cells, it is currently preferred to use layers made from Polyamide or Mylar film. A workable range in thickness for Polyamide layers is believed to be about 0.1 micron to about 500 microns. A currently preferred Polyamide cap layer 154 is about 52 microns in thickness. It is currently preferred to make the interrogation layer 102 from Polyamide also. However, alternative materials, such as Polyester film or Kapton, which is less expensive, are also workable. A film thickness of about 125 microns for a channel layer 156, 158 has been found to be workable in a sensor used to interrogate blood cells. Desirably, the thickness of the spacer layer is approximately on the order of the particle size of the dominant particle to be interrogated. A workable range is currently believed to be within about 1 particle size, to about 15 times particle size, or so, although a larger range may also be feasible.
The radiation interrogation assembly 264 in
Interrogation structure may be arranged in alternative ways, e.g. fiber optic cable may be incorporated to transmit radiation from a more remote source 104 toward an interrogation zone. Such an arrangement may permit construction of the distal portion of the pipette 288 to present a more slim form factor. Similarly, such cable may be employed in alternative devices to transmit radiation from the interrogation zone to a remotely disposed radiation detector 106.
The fiber 302 (or light pipe) in the pipette tip will deliver the laser light directly to the vicinity of the detection orifice 108 and shine straight across the orifice 108, essentially transverse to the direction of fluid flow in the orifice 108. Particles (or cells) will flow through this light path as they travel into (or out of) the detection orifice 108. Because the excitation radiation 118 is emitted in a direction substantially parallel to the interrogation layer 102, the transversely located detector 106 is out of the path of such radiation. Therefore, layer 102 may even be formed from a material that is entirely permeable to excitation radiation. Radiation emitted (in all directions) from particles undergoing a Stokes-shift will still be detected by detector 106. Again, a lens 192 and/or a filter 190 may be included, as desired.
Devices structured according to certain principles of the instant invention may be employed in a method for interrogating one or more particle. To use the device in one such method, a user would be provided with a device structured to urge particles, entrained in a fluid flowing through a radiation interrogation zone of the device, toward substantially single-file travel to permit detection of emission radiation that is emitted by a particle undergoing a Stokes-shift in that radiation interrogation zone. The user would use the device to extract a fluid sample from a bulk container of fluid. Then excitation radiation, comprising a first characteristic wavelength, would be impinged into the radiation interrogation zone as a portion of the fluid sample flows therethrough. Radiation having a second characteristic wavelength, corresponding to emission radiation from a particle undergoing a Stokes-shift, would be detected effective to gain information about the particle.
In one use of the device, the pipette tip 276 is inserted into the distal end of a pipette 278 to form an air tight seal for air vent 228 and to establish the necessary alignment between the disposable fluorescence-sensing pipette tip and the pipette optics. Next, the plunger 284 is depressed to draw up an excess volume of the sample to be analyzed from a bulk fluid container. This sample will typically be stored in the input reservoir 220 prior to analysis, although simultaneous analysis is possible. Then, the plunger 284 is released, and/or a second button or other control may be actuated, to start the cell counting or interrogation. A controlled vacuum profile will desirably be applied to the sensor/pipette tip 276 to draw cells through the fluorescence detection zone. Single or multiple color fluorescence detection methods could be incorporated. Fluorescent particles are detected and counted. In general, a fixed volume of fluid is interrogated. This may be done optically or using multiple electrodes and electric impedance. This enables volumetric cell counts to be performed. Analytical results may be displayed on a small screen 280, typically in the form of a histogram or scatter plot. Finally, the pipette tip is discarded.
A preferred method of applying suction encompasses generating an excess suction pressure that may then be down-regulated by structure associated with the pipette effective to apply: i) a first suction pressure operable to draw a sample into the pipette tip; and ii) a subsequent desired suction pressure profile over time to cause a desired fluid flow through the sensor portion of the pipette tip.
Embodiments structured according to certain principles of the instant invention may be used to: count particles; verify sample integrity (e.g. freedom from bubbles); estimate or monitor sample flow rate; confirm an inspired volume; determine cellular viability of individual cells in a liquid suspension of known volume; identify/detect specific cells stained with fluorescent dyes (i.e., antibody-conjugated dyes); and determine the presence of a fluorescent analyte or molecule in a liquid suspension of known volume, among other uses.
While the invention has been described in particular with reference to certain illustrated embodiments, such is not intended to limit the scope of the invention. The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. For non-limiting examples, a layer may have a non-flat conformation, and may only extend along only a portion of the length of a pipette tip. The described embodiments are to be considered only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.
This application claims the benefit of the filing date of U.S. Provisional Patent Application Ser. No. 61/004,630, filed Nov. 27, 2007, for “Fluorescence-based pipette instrument”, the entire contents of which are incorporated herein by this reference.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US08/13003 | 11/21/2008 | WO | 00 | 5/21/2010 |
Number | Date | Country | |
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61004630 | Nov 2007 | US |