US20050042760A1 - System and method for providing improved event reading and data processing capabilities in flow cytometer - Google Patents
System and method for providing improved event reading and data processing capabilities in flow cytometer Download PDFInfo
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- US20050042760A1 US20050042760A1 US10/953,677 US95367704A US2005042760A1 US 20050042760 A1 US20050042760 A1 US 20050042760A1 US 95367704 A US95367704 A US 95367704A US 2005042760 A1 US2005042760 A1 US 2005042760A1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Electro-optical investigation, e.g. flow cytometers
- G01N15/1456—Electro-optical investigation, e.g. flow cytometers without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals
- G01N15/1459—Electro-optical investigation, e.g. flow cytometers without spatial resolution of the texture or inner structure of the particle, e.g. processing of pulse signals the analysis being performed on a sample stream
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- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06F—ELECTRIC DIGITAL DATA PROCESSING
- G06F18/00—Pattern recognition
- G06F18/20—Analysing
- G06F18/23—Clustering techniques
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N2015/1006—Investigating individual particles for cytology
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Electro-optical investigation, e.g. flow cytometers
- G01N2015/1477—Multiparameters
Abstract
A system and method for use with a flow cytometer to improve event reading and data processing capabilities of the flow cytometer, while also providing efficient system configuration assessment capabilities. The system and method enables the flow cytometer to capture and sample an entire waveform representative of an event being read, and provides improved processing and analysis of the sampled data in a real time or near real-time basis. The system and method further enable the flow cytometer to assess its configuration and provide assessment results to an operator in an efficient and effective manner.
Description
- The present invention claims benefit under 35 U.S.C. § 119(e) of a U.S. Provisional Patent Application of Dwayne Yount et al. entitled “Hardware and Electronics Architecture for a Flow Cytometer”, Ser. No. 60/203,515, filed May 11, 2000, of a U.S. Provisional Patent Application of Michael Lock et al. entitled “Cluster Finder Algorithm for Flow Cytometer”, Ser. No. 60/203,590, filed May 11, 2000, of a U.S. Provisional Patent Application of Michael Goldberg et al. entitled “User Interface and Network Architecture for Flow Cytometer”, Ser. No. 60/203,585, filed May 11, 2000, and of a U.S. Provisional Patent Application of John Cardott et al. entitled “Digital Flow Cytometer”, Ser. No. 60/203,577, filed May 11, 2000, the entire contents of each of said provisional patent applications being incorporated herein by reference.
- Related subject matter is disclosed in a copending U.S. patent application of Pierce 0. Norton entitled “Apparatus and Method for Verifying Drop Delay in a Flow Cytometer”, Ser. No. 09/346,692, filed Jul. 2, 1999, in a copending U.S. patent application of Kenneth F. Uffenheimer et al. entitled “Apparatus and Method for Processing Sample Materials Contained in a Plurality of Sample Tubes”, Ser. No. 09/447,804, filed Nov. 23, 1999, and in a copending U.S. patent application of Michael D. Lock et al. entitled “System for Identifying Clusters in Scatter Plots Using Smoothed Polygons with Optimal Boundaries”, Attorney Docket No. P-5100, filed even date herewith, the entire contents of each of these applications are incorporated herein by reference.
- 1. Field of The Invention
- The present invention relates to a system and method for providing improved event reading, data processing and system configuration capabilities in a flow cytometer. In particular, the present invention provides a system and method for use with a flow cytometer that enables the event reading components of the flow cytometer to capture and digitize substantially the entire optical waveform of each detected event, and provides improved, near real-time processing of the digitized waveform data and automated system configuration assessment capabilities.
- 2. Description of the Related Art
- Flow cytometers known in the art are used for analyzing and sorting particles in a fluid sample, such as cells of a blood sample or particles of interest in any other type of biological or chemical sample. A flow cytometer typically includes a sample reservoir for receiving a fluid sample, such as a blood sample, and a sheath reservoir containing a sheath fluid. The flow cytometer transports the particles (hereinafter called “cells”) in the fluid sample as a cell stream to a flow cell, while also directing the sheath fluid to the flow cell.
- Within the flow cell, a liquid sheath is formed around the cell stream to impart a substantially uniform velocity on the cell stream. The flow cell hydrodynamically focuses the cells within the stream to pass through the center of a laser beam. The point at which the cells intersect the laser beam, commonly known as the interrogation point, can be inside or outside the flow cell. As a cell moves through the interrogation point, it causes the laser light to scatter. The laser light also excites components in the cell stream that have fluorescent properties, such as fluorescent markers that have been added to the fluid sample and adhered to certain cells of interest, or fluorescent beads mixed into the stream.
- The flow cytometer further includes an appropriate detection system consisting of photomultipliers tubes, photodiodes or other light detecting devices, which are focused at the intersection point. The flow cytometer analyzes the detected light to measure physical and fluorescent properties of the cell. The flow cytometer can further sort the cells based on these measured properties.
- To sort cells by an electrostatic method, the desired cell must be contained within an electrically charged droplet. To produce droplets, the flow cell is rapidly vibrated by an acoustic device, such as a piezoelectric element. The droplets form after the cell stream exits the flow cell and at a distance downstream from the interrogation point. Hence, a time delay exists from when the cell is at the interrogation point until the cell reaches the actual break-off point of the droplet. The magnitude of the time delay is a function of the manner in which the flow cell is vibrated to produce the droplets, and generally can be manually adjusted, if necessary.
- To charge the droplet, the flow cell includes a charging element whose electrical potential can be rapidly changed. Due to the time delay which occurs while the cell travels from the interrogation point to the droplet break-off point, the flow cytometer must invoke a delay period between when the cell is detected to when the electrical potential is applied to the charging element. This charging delay is commonly referred to as the “drop delay”, and should coincide with the travel time delay for the cell between the interrogation point and the droplet break-off point to insure that the cell of interest is in the droplet being charged.
- At the instant the desired cell is in the droplet just breaking away from the cell stream, the charging element is brought up to the appropriate potential, thereby causing the droplet to isolate the charge once it is broken off from the stream. The electrostatic potential from the charging circuit cycles between different potentials to appropriately charge each droplet as it is broken off from the cell stream.
- Because the cell stream exits the flow cell in a substantially downward vertical direction, the droplets also propagate in that direction after they are formed. To sort the charged droplet containing the desired cell, the flow cytometer includes two or more deflection plates held at a constant electrical potential difference. The deflection plates form an electrostatic field which deflects the trajectory of charged droplets from that of uncharged droplets as they pass through the electrostatic field. Positively charged droplets are attracted by the negative plate and repelled by the positive plate, while negatively charged droplets are attracted to the positive plate and repelled by the negative plate. The lengths of the deflection plates are small enough so that the droplets which are traveling at high velocity clear the electrostatic field before striking the plates. Accordingly, the droplets and the cells contained therein can be collected in appropriate collection vessels downstream of the plates.
- Known flow cytometers similar to the type described above are described, for example, in U.S. Pat. Nos. 3,960,449, 4,347,935, 4,667,830, 5,464,581, 5,483,469, 5,602,039, 5,643,796 and 5,700,692, the entire contents of each patent being incorporated by reference herein. Other types of known flow cytometer, are the FACSVantage™, FACSort™, FACSCount™, FACScan™ and FACSCalibur™ systems, each manufactured by Becton Dickinson and Company, the assignee of the present invention.
- Although the flow cytometers described above can be suitable for reading events as intended, these existing systems do suffer from certain drawbacks. For example, in these types of instruments, the controller or central processing unit (CPU) does not ordinarily process the data obtained from reading the events in “real time”. However, it is desirable to process the data in real time or near real time to improve the efficiency of the flow cytometer and the ability to compare the readings of the events on a real-time or near real-time basis.
- These existing systems also do not capture the entire image of the event. That is, when each event is read by detecting, for example, light fluorescing from the cell or particle of interest, these systems capture the “peak point” or peak intensity of the detected light. These systems also typically measure the duration during which the light is detected. By detecting these two parameters, the existing systems can use this data to determine characteristics of the event, such as the identity and size of a cell of interest. However, these techniques do not enable the existing systems to sample individual regions of the cell or particle of interest, nor are they capable of being performed on a real-time or near real-time basis. Furthermore, these systems are typically incapable of comparing data from multiple events effectively and in a real time or near real-time manner.
- In addition, these types of existing systems do not provide a mechanism that indicates the configuration of the system to the operator effectively. For example, these types of systems are typically configured with multiple detector and filter arrangements that enable the different detectors to detect light having wavelengths within different wavelength regions. In such an arrangement, one detector can detect light with having a wavelength within the range of blue light, for example, while another detector can detect light having a wavelength within the range of green light. However, if an incorrect filter is placed in front of a particular detector, the detector will detect the incorrect light (e.g., green light instead of blue light). The system will therefore give erroneous results. However, the operator of the system will have difficulty determining which filters are arranged incorrectly, and in the worst case, the error may go unnoticed.
- Accordingly, a need exists for an improved system and method for use with a flow cytometer to improve the event reading and data processing features of the flow cytometer to eliminate the above drawbacks.
- An object of the present invention is to provide a system and method for use with a flow cytometer to improve event reading and data processing capabilities of the flow cytometer, while also providing efficient system configuration assessment capabilities.
- Another object of the present invention is to provide a system and method that enables a flow cytometer to capture and sample an entire waveform representative of an event being read, and which provides improved processing and analysis of the sampled data in a real-time or near real-time basis.
- A further object of the present invention is to provide a system and method that is capable of indicating the configuration of a flow cytometer to an operator in an efficient and effective manner.
- These and other objects are substantially achieved by providing a system and method for processing at least one signal representative of an event detected by at least one detector in a flow cytometer. The system and method employs a sampling device which is adapted to receive portions of the signal from the detector in time sequence and to generate a respective value representative of the respective magnitude of each respective portion of the signal as the respective portion of the signal is being received. The system and method further employ a storage device which is adapted to store the values generated by the sampling device. The sampling device can receive substantially all of the signal, and can generate the values which represent the portions of substantially all of the signal. The signal can be an analog signal representative of a light signal emitted from the event as detected by the detector. The system and method can further employ an arithmetic device which is adapted to, for example, subtract a designated value from each of the values generated by the sampling device. The designated value can be representative of an unwanted signal, such as crosstalk, detected by the detector, or can be representative of a characteristic of the detector. The sampling device can further be adapted to receive portions of a second signal from a second detector in time sequence and to generate a respective second value representative of the respective magnitude of each respective portion of the second signal as the respective portion of the second signal is being received, and the storage device can store the second values generated by the sampling device. The sampling device can receive the portions of the signal at a time different from that during which it receives at least some of the portions of the second signal, and the system and method can employ a comparator which is adapted to compare each of the second values with a respective one of the values to compare the signal to the second signal.
- These and other objects are further substantially achieved by providing a system and for identifying a configuration of a detector unit of a flow cytometer. The system and method employ a port which is adapted to couple to a removable device that includes an optical element, such as a mirror or filter, and a memory adapted to store information pertaining to the optical element. The system and method further employ a reader which is adapted to read the information stored in the memory when the removable device is coupled to the port. The system and method can also employ an indicator which adapted to provide an indication of the information read by the reader.
- These and other objects are also substantially achieved by providing a removable device which is adapted for coupling with a port of a flow cytometer, and comprises an optical element, such as a filter or mirror, and a memory adapted to store information pertaining to the optical element.
- The various objects, advantages and novel features of the present invention will now be more readily appreciated from the following detailed description when read in conjunction with the accompanying drawings, in which:
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FIG. 1 is a conceptual block diagram of the flow cytometer employing a system and method according to an embodiment of the present invention; -
FIG. 2 is a cross-sectional view of the flow cytometer shown inFIG. 1 ; -
FIG. 3 is a detailed view of an example of an emission block according to an embodiment of the present invention which is employed in the flow cytometer shown inFIGS. 1 and 2 ; -
FIG. 4 is a top perspective view of an example of a support ring and flex circuits employed in the emission block shown inFIG. 3 ; -
FIG. 5 is a bottom perspective view of the support ring and flex circuits shown inFIG. 4 ; -
FIG. 6 is a side view of the support ring and flex circuits shown inFIGS. 4 and 5 ; -
FIG. 7 is a conceptual top plan view of the emission block shown inFIG. 3 ; -
FIG. 8 is a perspective view of an example of a removable mirror assembly for use with the emission block shown inFIG. 3 in accordance with an embodiment of the present invention; -
FIG. 9 is a perspective view of an example of a removable mirror assembly for use with the emission block shown inFIG. 3 in accordance with an embodiment of the present invention; -
FIG. 10 is a conceptual top view of the emission block shown inFIG. 3 illustrating exemplary paths in which light entering the emission block is reflected and propagates; -
FIG. 11 is a block diagram illustrating an example of the electronic components employed in the flow cytometer shown inFIGS. 1 and 2 according to an embodiment of the present invention; -
FIG. 12 is a block diagram illustrating anther example of the electronic components employed in the flow cytometer shown inFIGS. 1 and 2 according to another embodiment of the present invention; -
FIGS. 13-16 are conceptual illustrations of an exemplary relationship between multiple lasers and multiple emission blocks in the flow cytometer shown inFIGS. 1 and 2 according to an embodiment of the present invention; -
FIGS. 17-20 are conceptual block diagrams showing exemplary relationship between certain components shown inFIGS. 11 and 12 ; -
FIG. 21 illustrates an example of a waveform as captured and sampled by the circuitry shown inFIGS. 11 and 12 ; -
FIG. 22 is a conceptual block diagram of control circuitry for a PMT detector; and -
FIGS. 23-27 illustrate exemplary waveforms and their processing by the circuitry shown inFIGS. 11 and 12 . - A
flow cytometer 100 employing an embodiment of the present invention is illustrated inFIGS. 1 and 2 . As discussed in the background section above, theflow cytometer 100 includes anozzle 102 having aflow cell 104 therein. The flow cytometer further includes asample reservoir 106 for receiving a fluid sample,. such as a blood sample, and asheath reservoir 108 containing a sheath fluid. The flow cytometer transports the cells in the fluid sample in the cell stream to theflow cell 104, while also directing the sheath fluid to theflow cell 104. - Within the
flow cell 104, the sheath fluid surrounds the cell stream, and the combined sheath fluid and cell stream exits theflow cell 104 via anopening 110 as a sample stream. Theopening 110 can have a diameter of, for example, 50 μm, 70 μm, 100 μm, or any other suitable diameter. As illustrated, due to characteristics of the sheath fluid, such as surface tension and the like, the sample stream remains intact until breaking off into droplets at the droplet break-offpoint 112, which is at a certain distance fromopening 110. The distance from opening 110 at which the droplet break-offpoint 112 occurs, and the frequency or rate at which the droplets are formed, are governed by the fluid pressure, as well as the amplitude and frequency of oscillation ofoscillating device 114 which can be, for example, a piezoelectric element. - As shown in
FIG. 2 , theoscillating device 114 is connected to an alternatingvoltage source 116 whose output voltage amplitude, frequency and phase is controlled by acontroller 118 which can include, for example, a microprocessor or any other suitable controlling device. Further details of thecontroller 118 are described below. The amplitude of the alternating voltage signal output by alternatingvoltage source 116 can be increased or decreased bycontroller 118 to in turn increase or decrease the distance from opening 110 at which the droplet break-off 112 occurs. Likewise, the frequency of the alternating voltage signal output by alternatingvoltage source 116 can be increased or decreased bycontroller 118 to increase or decrease the rate at which droplets of sample fluid are formed at the droplet break-offpoint 112. - To view the droplet break-off
point 112, alight source 119, such an LED array, can be positioned in the region of the sample fluid stream containing the droplet break-offpoint 112. Thecontroller 118 can control thelight source 119 to strobe at a described frequency, so that thedetector 120, such as a camera or other special viewing device, can be used to view the region of the sample fluid stream containing the droplet break-offpoint 112. Theflow cytometer 100 further includes at least onelaser 122, such as a diode laser, which is controlled bycontroller 118 to emit laser light. The emitted laser light intersects the sample stream at a point ofinterest 124 commonly referred to as a the interrogation point. - The
laser 122 can be, for example, a red laser that emits light having a wavelength of at or about 633 nm, which is in the red light spectrum. Alteratively,laser 122 can be a blue laser that emits light having a wavelength of at or about 488 nm, which is in the blue light spectrum.Laser 122 also can be an ultraviolet laser that emits light having a wavelength of at or about 325 nm, or within the range of at or about 351 nm to at or about 364 nm, all of which are within the ultraviolet spectrum. As discussed in more detail below,flow cytometer 100 can includemultiple lasers 122 that each emit their respective laser light to a respective interrogation point along the fluid flow stream. Also, if desired, a lens or filter 126 can be positioned between thelaser 122 and theinterrogation point 124 to filter out light of unwanted wavelengths from the laser light prior to its reaching theinterrogation point 124. - As further illustrated, the flow cytometer includes at least one
fiberoptic cable 130 that receives laser light that has intersected the sample stream at theinterrogation point 124 and has been scattered by the sample stream fluid and, in particular, by any cells or particles of interest present in the sample stream. Theinput port 132 of thefiberoptic cable 130 in this example is located in the same plane as the laser light being emitted fromlaser 122, and at a 90° angle or about a 90° angle with respect to the direction of propagation of the laser light being emitted fromlaser 122. The laser light scattered by the fluid stream and any cells or particles of interest at theinterrogation point 124 is commonly referred to as side-scatter laser light. - As further illustrated, a
detector 134 and filter 136 arrangement can be used to detect a portion of the laser light that has passed through theinterrogation point 124 along the direction of propagation of the laser light being emitted bylaser 122, which is commonly referred to as the forward-scatter laser light. Also, if desired, anobscuration bar 138 can be position in the path of the forward-scatter laser light, in the path of the side-scatter laser light, or in both paths, to reduce the amount of side-scatter laser light enteringfiber optic cable 130 or to reduce the amount of forward-scatter laserlight entering detector 134. The side-scatter laser light entering thefiberoptic cable 130 is input to anemission block 140 as described in more detail below. - As further shown in
FIGS. 1 and 2 , theflow cytometer 100 can includedeflection plates controller 118 to allow droplets to pass todroplet collection container 146, or to deflect droplets that have been charged by chargingunit 147 towardsdroplet collection containers 148 and 150, as appropriate. In additional, a laser andfilter arrangement filter arrangement filter arrangement - Further details of the
emission block 140 will now be discussed with reference toFIGS. 3-10 . As illustrated,emission block 140 includes asupport ring 142 which can be made from stainless steel or any other suitable material. As shown, in particular, inFIGS. 4-6 ,support ring 142 hasinner groves 144 in its inner surface andouter groves 146 in its outer surface. Afirst flex circuit 148 is mountable insupport ring 142. Specifically, thefirst flex circuit 148 includes projections 150 that are received intoinner groves 144 ofsupport ring 142 to thus mount thefirst flex circuit 148 insidesupport ring 142. As can be appreciated by one skilled in the art,first flex circuit 148 is an integrated circuit board arrangement that includes a plurality of integrated circuits (not shown) andcontact pads 152 that havecontacts 154 which are adapted to provide connections to the circuitry in thefirst flex circuit 148. - As further illustrated, a
second flex circuit 156 is mountable to thesupport ring 142. That is, thesecond flex circuit 156 includesprojections 158 that can be received in theouter groves 146 of thesupport ring 142 to thus mount thesecond flex circuit 156 to the exterior ofsupport ring 142. An adhesive can be used to secure thefirst flex circuit 148 and thesecond flex circuit 156 to thesupport ring 142. Likefirst flex circuit 148,second flex circuit 156 is also an integrated circuit arrangement that includesintegrated circuits 160 that are capable of carrying out certain data processing operation as discussed in more detail below. Thesecond flex circuit 156 further includescontact pads 162 that includecontacts 164 which provide connections to the circuitry in thesecond flex circuit 156. - As further illustrated, the
emission block 140,first flex circuit 148 andsecond flex circuit 156 are housed within anouter housing 166 andinner housing 168. As illustrated, the combination of thesupport ring 142,first flex circuit 148, second 156,outer housing 166 andinner housing 168form openings FIG. 7 . Each of theopenings 170 is configured to receive amirror assembly 174 which includes adichroic mirror 176, the purpose of which is described in more detail below. Furthermore, eachopening 172 is configured to receive afilter assembly 180, the purpose of which is described in more detail below. In this example,emission block 140 is capable of receiving six mirror assemblies 174-1 through 174-6 and seven filter assemblies 180-1 through 180-7 (seeFIGS. 7 and 10 ). However, theemission block 140 can be configured to include any suitable number ofmirror assemblies 174 andfilter assemblies 180. - An example of a
mirror assembly 174 is shown inFIG. 8 . As stated above, eachmirror assembly 174 includes adichroic mirror 176 that is capable of passing light having a particular wavelength (e.g., blue light) while reflecting light of all other wavelengths. Thediachronic mirror assembly 174 includes a memory, such as an electrically, erasable read-only memory (EEPROM), in which is stored information pertaining to the type ofdichroic mirror 176 in themirror assembly 174, along with other information such as the company of manufacture, the date and place of manufacture and so on, for purposes described in more detail below. Themirror assembly 174 further includescontacts 178 that provide electrical connection with the memory embedded in themirror assembly 174. Accordingly, when themirror assembly 174 is inserted into anopening 170 as shown, for example, inFIG. 3 , thecontacts 178 ofmirror assembly 174 engage with thecontact 154 on thecontact pads 152 of thefirst flex circuit 148. Accordingly, the circuitry in thefirst flex circuit 148 can thus access the information stored in the memory of themirror assembly 174 for the purposes described in more detail below. - A
filter assembly 180 is shown in more detail inFIG. 9 .Filter assembly 180 includes afilter 182 that is capable of passing light of a certain wavelength (e.g., blue light) while blocking light of all other wave lengths. Furthermore, likemirror assembly 174,further assembly 180 includes a memory, such as ROM, in which is stored information pertaining to the type offilter 182 in thefilter assembly 180, the date, place, and company of manufacture, and so on.Further assembly 180 also includescontacts 184 which provide electrical contact to the memory embedded in thefilter assembly 180. Accordingly, when thefilter assembly 180 is inserted into anopening 172 as shown, for example, inFIG. 3 , thecontacts 184 of thefilter assembly 180 engage with thecontacts 164 on acontact pad 162 of thesecond flex circuit 156. Hence, the circuitry in thesecond flex circuit 156 can then access the information stored in the memory of thefilter assembly 180 for reasons discussed below. - As further shown in
FIG. 3 , for example,emission block 140 include a plurality ofdetectors 186 which, in this example, are photomultiplier tubes (PMTs). Eachphotomultiplier tube detector 186 has an opening therein (not shown) which is aligned with adichroic mirror 176 in itsrespective mirror assembly 174, and with afilter 182 in itsrespective filter assembly 180, so that thedetector 186 will receive light passing through its respectivedichroic mirror 176 andfilter 182. Eachdetector 186 further includes acircuit board assembly 188 that include circuitry for processing the light received by itsrespective PMT detector 186, as well as power and control circuitry for the PMT, as discussed in more detail below. - As shown in
FIG. 3 , for example, and in more detail inFIG. 10 , themirror assemblies 174 are angled so that the side-scatter laser light entering theemission block 140 fromfiber optic cable 130 is reflected to all of themirror assemblies 174 and to all of thefilter assemblies 180. Specifically, when the laser light enters theemission block 140 fromfiber optic cable 130, the laser light propagates to mirror assembly 174-1. The dichroic mirror of mirror assembly 174-1 allows light having a certain wavelength to pass to filter assembly 180-1, which also allows light of that wavelength to be detected by its respective detector 186-1. Detector 186-1 outputs a signal representative of the detected light, which is processed as described in more detail below. - As further illustrated, the portion of the laser light reflected by mirror assembly 174-1 propagates to mirror assembly 174-2, which functions in a manner similar to
mirror assembly 174. That is, the dichroic mirror of mirror assembly 174-2 allows light of a certain wavelength (e.g., green light) to pass to filter assembly 180-2 while reflecting light of all other wavelengths. Accordingly, the light passing to filter assembly 180-2 will pass through the filter of filter assembly 180-2 and be received by detector 186-2, while the reflected light will propagate to mirror assembly 174-3. As can be appreciated from the above description, mirror assemblies 174-3 through 174-6 will each allow light within a certain respective wavelength range to pass through to the corresponding filter assemblies 180-3 through 180-6, respectively, while reflecting light of all remaining wavelengths. It is noted that the light reflected by mirror assembly 174-6 will propagate directly into filter assembly 180-7, because no further reflection is necessary. Filter assembly 180-7 will therefore allow light within a respective wavelength to pass to its corresponding detector 186-7. - As discussed above, each laser 122 (see
FIG. 1 ) of theflow cytometer 100 is associated with a respectivefiber optic cable 130 andemission block 140. Accordingly, as discussed in more detail below, ifflow cytometer 100 includes, for example, fourdifferent lasers 122, then the flow cytometer will also include fouremission blocks 140, with eachemission block 140 being associated with arespective laser 122 to receive side-scatter laser light in the manner described above. - An example of the electronics included in the
flow cytometer 100 is shown in block diagram format inFIG. 11 . As discussed above, theflow cytometer 100 includes acontroller 118 which, in this example, includes adata acquisition unit 190, a status andcontrol unit 192, adroplet control module 222 and afluidics control module 224. As indicated, thedata acquisition unit 190 includes aprocessor 194 which, in this example, is a real-time or near real-time CPU, such as a Pentium III processor or any other suitable processor. Theprocessor 194 is coupled to thescreen LCD 196 of theflow cytometer 100, as well as asample loader 198 andsample output device 200. Theprocessor 194 is further coupled to ahub 202 which provides data to and fromwork station 204 andprocessor 194 as described in more detail below. It is noted that theprocessor 194 provides the data pertaining to the event readings to thework station 204 in packet format in real-time or near real-time. Thehub 202 further provides data to and fromprocessor 194 and aprepper unit 206 which can be, for example, any type of sample preparation unit such as that described m U.S. patent application Ser. No. 09/447,804, referenced above. - The
data acquisition unit 190 further include a plurality ofdata acquisition modules 208 that are each capable of acquiring data from respectivecircuit board assemblies 188 of thedetectors 186 discussed above as described in more detail below. Thedata acquisition unit 190 further includes a masterdata acquisition module 210 that gathers the data from all of the otherdata acquisition modules 208 via a plurality of link-ports 211 and provides the data toprocessor 194 as discussed in more detail below. - As further illustrated, the
processor 194 ofdata acquisition unit 190 communicates with thecontroller 212 of status andcontrol unit 192 to control, for example, the fluid flow, drop delay, PMT driving voltage, and so on as described in more detail below. The status andcontrol unit 192 includePMT modules 214 which, under the control ofcontroller 212, control the driving voltage of thePMT detectors 186 as discussed in more detail below. The status andcontrol unit 192 further include alaser control module 216 which, under control ofcontroller 212, controls operation oflaser 122. The status andcontrol unit 192 also includes a power andtemperature control module 218 that controls, for example, the power to components of theflow cytometer 100, as well as the temperature of the sheath and sample fluid. - In addition, status and
control unit 192 further includes an emission identification (ID)module 220 that receives information from thefirst flex circuit 148 andsecond flex circuit 156 indicative of the locations of themirror assemblies 174 andfilter assemblies 180. in theemission block 140. That is, as discussed above, eachmirror assembly 174 andfilter assembly 180 includes a memory in which is stored information pertaining to its respective mirror or filter. The circuitry in thefirst flex circuit 148 is capable of accessing the memory in thefilter assemblies 180, and providing the content of this memory to theemission ID module 220. Likewise, the circuitry in thesecond flex circuit 156 is capable of accessing the memories in thefilter assemblies 180 and providing that information to theemission ID module 220. Theemission ID module 220 then can determine whether each of themirror assemblies 174 andfilter assemblies 180 are in the appropriate positions based on information pertaining to a desired configuration stored in a memory that was provided, for example, bywork station 204. If theemission ID module 220 determines that amirror assembly 174 orfilter assembly 180 is missing or in an incorrect location in theemission block 140, or if an erroneous orfaulty mirror assembly 174 orfilter assembly 180 has been installed in theemission block 140,emission ID module 220 will provide the appropriate data to, for example, thecontroller 212, which can then provide the data to theprocessor 194. Theprocessor 194 can then provide this data to, for example,work station 204, which can display an appropriate error message. This error message can indicate the location of the incorrect mirror or filter assembly in theemission block 140, and thework station 204 can also display the filter and mirror configuration, which therefore greatly simplifies troubleshooting. - As further shown in
FIG. 11 , the masterdata acquisition module 210, which is described in more detail below, receives from thedata acquisition modules 208 event data that has been provided to thedata acquisition modules 208 from thePMT detectors 186 of the emission blocks 140. Prior to running theflow cytometer 100 to detect events, thework station 204 can download data via thehub 202 andprocessor 194 to the masterdata acquisition module 210. This downloaded data is stored in a memory in the masterdata acquisition module 210 and indicates to the masterdata acquisition module 210 the channel configuration of thedata acquisition modules 208, so that the masterdata acquisition module 210 can recognize which channels of thedata acquisition modules 208 are active, and the type of data (e.g., representative of side scatter blue light, side scatter red light and so on) that the data from each channel represents, as discussed in more detail below. - The master
data acquisition module 210 further provides and receives data to and from thedroplet control module 222 and thefluidics control module 224 to control the operation of theflow cytometer 100 in the manner described above. For example, the masterdata acquisition module 210 can receive high-speed clock data from thedroplet control module 222 that gives the master data acquisition module 210 a time reference as to the rate of drop formation (e.g., 50 thousand drops per second). Masterdata acquisition module 210 can use this time base to synchronize a direction command signal which can be, for example, a four bit binary code, that the masterdata acquisition module 210 sends to thedroplet control module 222 so that thedroplet control module 222 can control the charging unit 147 (seeFIG. 2 ) as appropriate to achieve the desired charging of the appropriate droplets containing a cell or particle of interest. By charging the droplet with the appropriate charge, thedroplet control module 222 thus controls the amount and direction of deflection that thedeflection plates 142 and 144 (seeFIG. 2 ) deflect the charged droplet. Thedeflection plates hardware 235 shown inFIG. 11 . The droplet can be deflected, for example, to be received in one of any suitable number (e.g., sixteen)collection vessels - In addition, the master
data acquisition module 210 can receive data from theprocessor 194 that has been acquired by, for example,detectors FIG. 1 ) as well as information pertaining to the droplet sorting. Based on this data, the masterdata acquisition module 210 can provide control signal to thedroplet control module 222 to control, for example, drop delay, droplet formation and so on as discussed above with regard toFIGS. 1 and 2 .processor 194 can further control thedroplet control module 222 to control, for example, acooling module 234 and anaerosol management module 236 to control the temperature of the sorted sample, for example, as well as to control sorting and aerosol containment management and safety devices in theflow cytometer 100. It is also noted that thefluidics control module 224 can control the valve and pumpdrivers 226, theagitation module 228, thetemperature control module 230 and themultiport valve HPLC 232 to control the temperature of the fluid sample and sheath fluids, to agitate the sample in the sample reservoir 106 (seeFIG. 1 ), and to control the flow of fluids in theflow cytometer 100. - It is further noted that the
flow cytometer 100 need not include all of the electronics shown inFIG. 11 . For example, if theflow cytometer 100 is not equipped to perform droplet sorting, certain components shown inFIG. 11 can be omitted. As shown inFIG. 12 , the hardware of thedata acquisition unit 190 and status andcontrol unit 192 can consolidated into a data acquisition unit 190-1. The components of the data acquisition unit 190-1, such as theprocessor 194,data acquisition modules 204 and masterdata acquisition module 210 operate in a manner similar to those described above with regard toFIG. 11 . However, the data acquisition module 190-1 includes anSCI controller 238 which performs the operations performed by status and control I/F unit 192 shown inFIG. 11 , such as controlling the driving voltages of thelasers 122 and power andtemperature sensor module 218 which operates as described above. TheSCI controller 238 further controls operation of the driving voltage ofdetectors 186 in a manner described below, and receives and processes the mirror and filter assembly position information received from theemission block 140 in a manner similar to theemission ID module 220 described above. - The operation of the above components in relation to the operation of
flow cytometer 100 will now be described. As discussed above,flow cytometer 100 will typically employ more than onelaser 122 to sample more than one type of cell or particle of interest, or more than one characteristic of a cell or particle of interest. The following discussion will assume that theflow cytometer 100 includes fourlasers 122, each emitting light having a different wavelength. - As discussed above and as shown conceptually in
FIGS. 13-16 , if theflow cytometer 100 includes four lasers 122-1 through 122-4, then theflow cytometer 100 will include four corresponding fiber optic cables 130-1 through 130-4 that feed the respective side-scatter laser lights to the respective emission blocks 140-1 through 140-4. As further shown, the laser light emitted from these respective lasers 122-1 through 122-4 strike respective interrogation points 124-1 through 124-4 on the fluid stream. In this example, the interrogation points are displaced by about 133 micrometers along the direction of flow of the fluid stream, which translates into a spacing of about 22 microseconds for a fluid stream flowing at a rate of 6 meters per second. As shown inFIG. 16 , this spacing also permits inter-laser mixing to occur. For example, the side scatter laser light from interrogation point 124-3 can enter the fiber optic cable 130-4 dedicated to receive side scatter laser light from interrogation point 124-4. Themirror assemblies 174 andfilter assemblies 180 in the emission blocks 140-1 through 140-4 can be configured to eliminate any light of undesired wavelengths as discussed above, in the event that unwanted inter-laser mixing occurs. - Further details of the relationship between the
detectors 186, adata acquisition module 208, masterdata acquisition module 210, processor 194 (real time CPU) and the work station will now be described with regard toFIGS. 17-21 . In this arrangement, eachdata acquisition module 208 can receive data from fourdetectors 186 from any of the emission blocks 140. For purposes of this discussion,data acquisition module 208 is configured to receive side scatter laser light that has been generated by the four different wavelength lasers 122-1 through 122-4. - As illustrated, the analog data signals from the
detectors 186 are input to their respectivedata acquisition module 208 as 2 MHz bandwidth (BW) analog signals. Further details of the data acquisition module are shown inFIGS. 18 and 19 . That is, the signal from eachdetector 186 is input to a respective analog-to-digital (A/D)converter 240 where the analog data is converted into digital data. As illustrated, each A/D converter 240 have differential inputs to maximize common mode rejection of the received analog signals. The frequency (e.g., 10 MHz) at which the A/D converters 240 are operating enable the A/D converters 240 to take multiple samples (e.g., 10 or 20, or more) of the waveform as shown inFIG. 21 in real-time or near real-time. As indicated, the intensity of the signal will typically increase to a maximum when the particle or cell of interest is at the center of the interrogation point, and then drop-off to a minimum as the cell passes out of theinterrogation point 124. Accordingly, each individual sample of the waveform will have a value representing the characteristic (e.g., height) of that sampled portion of the waveform. This sampling of the entire or substantially the entire waveform improves the details at which the waveforms can be analyzed and compared, for example, to other waveforms representative of other events. Accordingly, this sampling allows for a more detailed sampling of the characteristics of each event. - The digital data output by each A/
D converter 240 is provided to arespective delay circuit 244 which imposes a respective delay on the digital data as described in more detail below. As shown, for example, inFIG. 19 , the delay imposed by eachdelay circuit 244 is set to compensate for the delays between the interrogation points 124-1 and 124-4 as shown inFIG. 15 or, in other words, to compensate for the time delay that occurs between when the side scatter light representative of a particle or cell of interest at interrogation point 124-1 is received by adetector 186 in emission block 140-1 and when the side scatter light representative of that particle or cell of interest reaching interrogation points 124-2 through 124-4 are subsequently received bydetectors 186 in their respective emission blocks 140-2 through 140-4. - The digital data from each
delay circuit 244 is provided to a respective channel field programmable gate array (FPGA)circuit 246, which provide the data to a Super Harvard Architecture Computer (SHARC)unit 248. It is noted that eachchannel FPGA circuit 246 can process the characteristics of the data samples to produce data representing a single characteristic of the analog waveform, such as the width or height of the waveform, if desired, instead of passing all of the samples (e.g., 20 samples per waveform as discussed above) to theSHARC unit 248. Also, thechannel FPGA circuits 246 will add a time stamp to their respective data prior to passing the data to theSHARC 248. Under the control of a programmable logic device, versa-module Eurocard interface (PLD VME I/F)unit 250 and atrigger FPGA unit 252, theSHARC unit 248 provides the digital data via alink port 211 to the masterdata acquisition module 210 as indicated. - Specifically, prior to running the
flow cytometer 100 to detect the events, theworkstation 204 can download channel data to thetrigger FPGA unit 252 of eachdata acquisition module 208 via thehub 202 andprocessor 194. This channel data indicates to thechannel FPGA circuits 246 whether they should collect the data from theirrespective delay circuits 244, that is, whether they are receiving data on an active channel. The channel data further indicates to thetrigger FPGA unit 252 when thetrigger FPGA unit 252 should trigger theSHARC 248 to transfer the event data received in parallel from thechannel FPGAs 246 to the masterdata acquisition module 210 via thelink port 211. - Details of the master data
acquisition data module 210 are shownFIG. 20 . That is, the masterdata acquisition module 210 includes amulti-SHARC unit 256 that includes a SHARCevent classification unit 258, a SHARCdrop classification unit 260 and a SHARCevent assembly unit 262, the details of which are described below. The masterdata acquisition module 210 further include agate FPGA 264, a logarithmic look-up table 266, and adata FIFO unit 268. Furthermore, the master dataacquisition data module 210 includes anFPGA module 270 that includes adrop control FPGA 272 and atrigger FPGA 274. The master data acquisition module further include a PLD VME I/F 276. The details of these components are described below. - Specifically, prior to running the
flow cytometer 100 to detect the events, theworkstation 204 can download channel data to thetrigger FPGA unit 274 of masterdata acquisition module 210 via thehub 202 andprocessor 194. This channel data indicates to thetrigger FPGA units 252 of eachdata acquisition module 208 whether they should trigger theirrespective SHARC 248 to transfer the event data received in parallel from thechannel FPGAs 246 to the masterdata acquisition module 210 via theirrespective link port 211. That is, when thetrigger FPGA units 252 provide their respective indications to thetrigger FPGA unit 274 indicating that event data has been received on their appropriate respective channels, thetrigger FPGA unit 274 will signal thetrigger FPGA units 252 to trigger theirrespective SHARCs 248 to transfer the event data received in parallel from thechannel FPGAs 246 to the masterdata acquisition module 210 via thelink port 211. - When the master
data acquisition module 210 receives the event data via thelinkports 211, the event data is input to theSHARC event assembly 262. TheSHARC event assembly 262 assembles the data into lists, tables or buffers based on their time-stamp that has been added by thechannel FPGAs 246. That is, theSHARC event assembly 262 uses the time stamps to determine which data is associated with which event. - If no sorting of cells is to be performed, the
SHARC event assembly 262 passes the lists, tables or buffers of data to thedata FIFO unit 268. Thedata FIFO unit 268 sends the lists, tables or buffers of the data via theVME bus 254 to theprocessor 194. Theprocessor 194 can then provide the data to thework station 204 for further display in, for example, a scatter plot diagram, a graphical representation, and so on. - However, if cell sorting is to be performed, data received by the SHARC
event assembly unit 262 is processed by the SHARCevent classification unit 258 and SHARCdrop classification unit 260. For example, theflow cytometer 100 can be run to sample a portion of the cell sample to therefore provide initial sample data to thework station 204 as discussed above. Thework station 204 can display the detected events on, for example, a scatter plot which can be reviewed by the operator. The operator can select certain cells of interest to be sorted by selecting, for example, a region on an interactive display screen of thework station 204. Thework station 204 can then pass the desired cell sorting data to the masterdata acquisition module 210 viahub 202 andprocessor 194. The masterdata acquisition module 210 stores this cell sorting data in, for example, thelogarithmic lookup SRAM 266. - When the operator reactivates the
flow cytometer 100 to continue processing the sample, the SHARCevent classification unit 258 and SHARCdrop classification unit 260 can access the data in thelogarithmic lookup SRAM 266 in real-time or near real-time to determine which data received by the SHARCevent assembly unit 262 represents cells to be sorted. The SHARCevent classification unit 258 and SHARCdrop classification unit 260 can then provide signals to theDrop Control FPGA 272 which can provide the appropriate direction command signal to thedroplet control module 222 so that thedroplet control module 222 can control sorting as discussed above. TheSHARC event assembly 262 can then pass the lists, tables or buffers of data to thedata FIFO unit 268, which sends the lists, tables or buffers of the data via theVME bus 254 to theprocessor 194 as discussed above. Theprocessor 194 can then provide the data to thework station 204 in real-time or near real-time for further display in, for example, a scatter plot diagram, a graphical representation, and so on. - Additionally, the event data can be used to process the sample waveforms in various ways. For example, the above system, in particular, the controller 212 (
FIG. 11 ) or SCI controller 238 (FIG. 12 ) can adjust system can adjust the voltages applied to the detector 186 (PMTs) to adjust the relative zero point of thePMT detector 186. For example, as shown inFIG. 22 , the PMT andcircuit board 188 includes a DC highvoltage power supply 280 that provide the driving voltage to thePMT socket 282 that drives the PMT. The current from the PMT generated upon, for example, detection of side scatter light as described above is converted by acurrent voltage converter 284 so that the voltage signal is provided to the respective channeldata acquisition module 208 as described above. Voltage control and serial control signal are provided from thePMT controllers 214 in, for example, the respective channeldata acquisition module 208 to adjust the base voltage of the PMT, to therefore adjust the relative zero point of the PMT. —Accordingly, this adjustment can be used to perform the gain adjustment as shown, for example, inFIG. 23 to increase the height of the smaller waveform to be consistent with the heights of the red and blue waveforms. - In addition, as shown in
FIGS. 24-27 , theSHARC event assembly 262 the masterdata acquisition module 210 can compare the entire sample wave form of data obtained fromdifferent detectors 186 and can perform different types of processing functions on this data in a real time or near-real time basis. For example, the event data representative of the red side scatter light signal received at time T can be delayed so that it can be compared with the event data representative of the blue side scatter light signal received at time T+1 as shown inFIG. 24 , so that the signals can be time correlated as shown inFIG. 25 . Furthermore, as shown inFIGS. 26 and 27 , the data signals can be processed to remove crosstalk that can occur as discussed above. In this event, the blue data represented as the “blue+red crosstalk” can be processed to remove a percentage of the red signal that is affecting the magnitude of the blue data, so that the magnitudes of the blue and red data can be made similar for comparison as shown inFIG. 27 . - Although only a few exemplary embodiments of the present invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the following claims.
Claims (34)
1. A system for processing at least one signal representative of an event detected by at least one detector in a flow cytometer, the system comprising:
a sampling device, adapted to receive portions of said signal from said detector in time sequence and to generate a respective value representative of the respective magnitude of each respective portion of said signal as said respective portion of said signal is being received; and
a storage device, adapted to store said values generated by said sampling device.
2. A system as claimed in claim 1 , wherein:
said sampling device receives a number of said portions totaling substantially all of said signal, and generates said values which represent said portions of substantially all of said signal.
3. A system as claimed in claim 1 , wherein:
said signal is an analog signal representative of a light signal emitted from said event as detected by said detector.
4. A system as claimed in claim 1 , further comprising:
an arithmetic device, adapted to arithmetically combine a designated value with each of said values.
5. A system as claimed in claim 4 , wherein:
said arithmetic device includes a subtractor which is adapted to subtract said designated value from each of said values.
6. A system as claimed in claim 4 , wherein:
said designated value is representative of an undesired signal detected by said detector.
7. A system as claimed in claim 4 , wherein:
said designated value is representative of a characteristic of said detector.
8. A system as claimed in claim 1 , wherein:
said sampling device is adapted to receive portions of a second said signal from a second said detector in time sequence and to generate a respective second value representative of the respective magnitude of each respective portion of said second signal as said respective portion of said second signal is being received; and
said storage device is adapted to store said second values generated by said sampling device.
9. A system as claimed in claim 8 , wherein:
said sampling device receives said portions of said signal at a time different from that during which said sampling device receives at least some of said portions of said second signal.
10. A system as claimed in claim 9 , further comprising:
a comparator, adapted to compare each of said second values with a respective one of said first values to compare said signal to said second signal.
11. A system for identifying a configuration of a detector unit of a flow cytometer, the system comprising:
a port, adapted to couple to a removable device, said removable device including an optical element and a memory adapted to store information pertaining to said optical element; and
a reader, adapted to read said information stored in said memory when said removable device is coupled to said port.
12. A system as claimed in claim 11 , wherein:
said optical element includes an optical filter.
13. A system as claimed in claim 11 , wherein:
said optical element includes a mirror.
14. A system as claimed in claim 11 , further comprising:
an indicator, adapted to provide an indication of said information read by said reader.
15. A removable device, adapted for coupling with a port of a flow cytometer, the removable device comprising:
an optical element; and
a memory adapted to store information pertaining to said optical element.
16. A removable device as claimed in claim 15 , wherein:
said optical element includes an optical filter.
17. A removable device as claimed in claim 15 , wherein:
said optical element includes a mirror.
18. A method for processing at least one signal representative of an event detected by at least one detector in a flow cytometer, the method comprising:
receiving portions of said signal from said detector in time sequence;
generating a respective value representative of the respective magnitude of each respective portion of said signal as said respective portion of said signal is being received; and
storing said values.
19. A method as claimed in claim 18 , wherein:
said receiving receives a number of said portions totaling substantially all of said signal; and
said generating generates said values which represent said portions of substantially all of said signal.
20. A method as claimed in claim 18 , wherein:
said signal is an analog signal representative of a light signal emitted from said event as detected by said detector.
21. A method as claimed in claim 18 , further comprising:
arithmetically combining a designated value with each of said values.
22. A method as claimed in claim 21 , wherein:
said arithmetic combining includes subtracting said designated value from each of said values.
23. A method as claimed in claim 21 , wherein:
said designated value is representative of an undesired signal detected by said detector.
24. A method as claimed in claim 21 , wherein:
said designated value is representative of a characteristic of said detector.
25. A method as claimed in claim 18 , further comprising:
receiving portions of a second said signal from a second said detector in time sequence;
generating a respective second value representative of the respective magnitude of each respective portion of said second signal as said respective portion of said second signal is being received; and
storing said second values.
26. A method as claimed in claim 25 , wherein:
said receiving steps are performed such that said portions of said signal are received at a time different from that during which at least some of said portions of said second signal are received.
27. A method as claimed in claim 26 , further comprising:
comparing each of said second values with a respective one of said first values to compare said signal to said second signal.
28. A method for identifying a configuration of a detector unit of a flow cytometer, comprising:
coupling a removable device to a port of said flow cytometer, said removable device including an optical element and a memory adapted to store information pertaining to said optical element; and
reading said information stored in said memory when said removable device is coupled to said port.
29. A method as claimed in claim 28 , wherein:
said optical element includes an optical filter.
30. A method as claimed in claim 28 , wherein:
said optical element includes a mirror.
31. A method as claimed in claim 28 , further comprising:
providing an indication of said information read from said memory.
32. A method for manufacturing a removable device, adapted for coupling with a port of a flow cytometer, the method comprising:
coupling an optical element to said removable device; and
including a memory in said removable device, said memory being adapted to store information pertaining to said optical element.
33. A method as claimed in claim 32 , wherein:
said optical element includes an optical filter.
34. A method as claimed in claim 32 , wherein:
said optical element includes a mirror.
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110221892A1 (en) * | 2010-03-09 | 2011-09-15 | Neckels David C | Calculate Drop Delay for Flow Cytometry Systems and Methods |
US20130337575A1 (en) * | 2012-06-07 | 2013-12-19 | Bio-Rad Laboratories, Inc. | Automated and accurate drop delay for flow cytometry |
US20140051064A1 (en) * | 2011-04-29 | 2014-02-20 | Becton, Dickinson And Company | Cell Sorter System and Method |
US20140329265A1 (en) * | 2013-03-15 | 2014-11-06 | Iris International, Inc. | Flowcell, sheath fluid, and autofocus systems and methods for particle analysis in urine samples |
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Families Citing this family (77)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6683314B2 (en) * | 2001-08-28 | 2004-01-27 | Becton, Dickinson And Company | Fluorescence detection instrument with reflective transfer legs for color decimation |
US6838289B2 (en) * | 2001-11-14 | 2005-01-04 | Beckman Coulter, Inc. | Analyte detection system |
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US20060219873A1 (en) * | 2005-04-01 | 2006-10-05 | Martin Steven M | Detection system for a flow cytometer |
US20070043510A1 (en) * | 2005-08-19 | 2007-02-22 | Beckman Coulter, Inc. | Assay system |
US7996188B2 (en) | 2005-08-22 | 2011-08-09 | Accuri Cytometers, Inc. | User interface for a flow cytometer system |
US8017402B2 (en) | 2006-03-08 | 2011-09-13 | Accuri Cytometers, Inc. | Fluidic system for a flow cytometer |
US8303894B2 (en) | 2005-10-13 | 2012-11-06 | Accuri Cytometers, Inc. | Detection and fluidic system of a flow cytometer |
US7780916B2 (en) | 2006-03-08 | 2010-08-24 | Accuri Cytometers, Inc. | Flow cytometer system with unclogging feature |
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US7414248B1 (en) * | 2006-06-23 | 2008-08-19 | Siemens Medical Solutions Usa, Inc. | Electrical penetration of nuclear detector tub |
US8077310B2 (en) * | 2006-08-30 | 2011-12-13 | Accuri Cytometers, Inc. | System and method of capturing multiple source excitations from a single location on a flow channel |
US8715573B2 (en) | 2006-10-13 | 2014-05-06 | Accuri Cytometers, Inc. | Fluidic system for a flow cytometer with temporal processing |
US8445286B2 (en) | 2006-11-07 | 2013-05-21 | Accuri Cytometers, Inc. | Flow cell for a flow cytometer system |
US7739060B2 (en) | 2006-12-22 | 2010-06-15 | Accuri Cytometers, Inc. | Detection system and user interface for a flow cytometer system |
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US8140300B2 (en) * | 2008-05-15 | 2012-03-20 | Becton, Dickinson And Company | High throughput flow cytometer operation with data quality assessment and control |
US8864725B2 (en) | 2009-03-17 | 2014-10-21 | Baxter Corporation Englewood | Hazardous drug handling system, apparatus and method |
US8507279B2 (en) | 2009-06-02 | 2013-08-13 | Accuri Cytometers, Inc. | System and method of verification of a prepared sample for a flow cytometer |
US8004674B2 (en) * | 2009-06-02 | 2011-08-23 | Accuri Cytometers, Inc. | Data collection system and method for a flow cytometer |
US8779387B2 (en) * | 2010-02-23 | 2014-07-15 | Accuri Cytometers, Inc. | Method and system for detecting fluorochromes in a flow cytometer |
WO2011159708A1 (en) | 2010-06-14 | 2011-12-22 | Accuri Cytometers, Inc. | System and method for creating a flow cytometer network |
ES2897531T3 (en) | 2010-10-25 | 2022-03-01 | Accuri Cytometers Inc | Systems and user interface for collecting a data set in a flow cytometer |
US9874514B2 (en) * | 2012-11-05 | 2018-01-23 | Shimadzu Corporation | Atomic absorption spectrophotometer and signal voltage optimization method used by the same |
EP2984468B1 (en) | 2013-04-12 | 2021-11-17 | Becton, Dickinson and Company | Automated set-up for cell sorting |
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US9446159B2 (en) | 2013-10-03 | 2016-09-20 | Becton, Dickinson And Company | Flow cytometer biosafety hood and systems including the same |
JP6102783B2 (en) * | 2014-02-14 | 2017-03-29 | ソニー株式会社 | Particle sorting apparatus, particle sorting method and program |
US9575050B2 (en) | 2014-04-21 | 2017-02-21 | Becton, Dickinson And Company | Slider tape sealing cartridge for adjustably sealing a flow cytometer sample manipulation chamber |
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US20230046207A1 (en) | 2021-08-10 | 2023-02-16 | Becton, Dickinson And Company | Outlet fittings for reducing bubbles at the interface with a flow cell, and flow cytometers and methods using the same |
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Family Cites Families (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3596275A (en) | 1964-03-25 | 1971-07-27 | Richard G Sweet | Fluid droplet recorder |
US3373437A (en) | 1964-03-25 | 1968-03-12 | Richard G. Sweet | Fluid droplet recorder with a plurality of jets |
US3344406A (en) | 1964-11-09 | 1967-09-26 | Ibm | Sampled data reduction and storage system |
US3454953A (en) | 1967-08-21 | 1969-07-08 | Varian Associates | Graphic recorder apparatus having means for printing an elapsed time code on the recording |
US3609379A (en) | 1969-05-13 | 1971-09-28 | Gen Electric | Photoelectric drop sensing and timing control for intravenous feed and other flow control applications |
US3719086A (en) | 1971-01-12 | 1973-03-06 | Damon Corp | Liquids sampler with probe-bathing chamber |
US3885438A (en) | 1972-02-04 | 1975-05-27 | Sr Rano J Harris | Automatic fluid injector |
US3872730A (en) | 1972-03-10 | 1975-03-25 | Becton Dickinson Co | Sampling apparatus |
US4000973A (en) | 1974-09-09 | 1977-01-04 | Beckman Instruments, Inc. | Sample residue cleaning system for biological analyzers |
US3954341A (en) | 1974-09-30 | 1976-05-04 | Technicon Instruments Corporation | Liquid sample analyzer with improved optical characteristics |
US3960449A (en) | 1975-06-05 | 1976-06-01 | The Board Of Trustees Of Leland Stanford Junior University | Measurement of angular dependence of scattered light in a flowing stream |
DE2810587C2 (en) | 1978-03-11 | 1984-11-08 | Siebtechnik GmbH, 4330 Mülheim | Sieving machine |
US4244919A (en) | 1979-03-19 | 1981-01-13 | Hyperion Incorporated | Sample diluting apparatus |
US4347935A (en) | 1979-05-16 | 1982-09-07 | The United States Of America As Represented By The United States Department Of Energy | Method and apparatus for electrostatically sorting biological cells |
JPS5630650A (en) | 1979-08-22 | 1981-03-27 | Hitachi Ltd | Automatic chemical analyzer |
US4525673A (en) | 1979-12-26 | 1985-06-25 | Varian Associates, Inc. | NMR spectrometer incorporating a re-entrant FIFO |
US4311484A (en) | 1980-04-09 | 1982-01-19 | Cortex Research Corporation | Specimen sampling apparatus |
US4367043A (en) | 1980-05-05 | 1983-01-04 | Leland Stanford Junior University | Method and means for delivering liquid samples to a sample scanning device |
SE428609B (en) | 1981-03-20 | 1983-07-11 | Coulter Electronics | SAMPLES FOR MIXING AND SAMPLING BLOOD OR SIMILAR SEDIMENTAL LIQUID |
US4667830A (en) | 1981-06-15 | 1987-05-26 | The Board Of Trustees Of The Leland Stanford Junior University | Method and means for sorting individual particles into containers for culturing, cloning, analysis, or the like |
US4357301A (en) | 1981-07-20 | 1982-11-02 | Technicon Instruments Corp. | Reaction cuvette |
DE3229118A1 (en) | 1981-08-05 | 1983-03-24 | Varian Techtron Proprietary Ltd., 3170 Mulgrave, Victoria | DEVICE FOR HANDLING SAMPLES |
FR2523746B1 (en) | 1982-03-17 | 1987-07-10 | Inst Francais Du Petrole | DEVICE ASSOCIATED WITH A COMPUTER FOR CONTROLLING DATA TRANSFERS BETWEEN A DATA ACQUISITION SYSTEM AND AN ASSEMBLY INCLUDING A RECORDING AND READING APPARATUS |
US4683212A (en) | 1982-09-30 | 1987-07-28 | Technicon Instruments Corporation | Random access single channel sheath stream apparatus |
SE434700B (en) | 1983-05-20 | 1984-08-13 | Bengt Gustavsson | DEVICE FOR AIRED TRANSFER OF SUBSTANCE FROM A KERLE TO ANOTHER |
US4808381A (en) | 1983-05-13 | 1989-02-28 | E. I. Du Pont De Nemours And Company | Fluid transfer device |
US4599307A (en) | 1983-07-18 | 1986-07-08 | Becton, Dickinson And Company | Method for elimination of selected cell populations in analytic cytology |
NL8303564A (en) * | 1983-10-17 | 1985-05-17 | Philips Nv | DEVICE FOR DISPLAYING INFORMATION FROM AN OPTICALLY READABLE RECORD CARRIER. |
US4660971A (en) | 1984-05-03 | 1987-04-28 | Becton, Dickinson And Company | Optical features of flow cytometry apparatus |
US4727020A (en) | 1985-02-25 | 1988-02-23 | Becton, Dickinson And Company | Method for analysis of subpopulations of blood cells |
US4602995A (en) | 1985-05-20 | 1986-07-29 | Technicon Instruments Corporation | Liquid level adjusting and filtering device |
US4748573A (en) | 1985-06-28 | 1988-05-31 | Honeywell Inc. | Test management system to acquire, process and display test data |
US4989977A (en) | 1985-07-29 | 1991-02-05 | Becton, Dickinson And Company | Flow cytometry apparatus with improved light beam adjustment |
US4799393A (en) | 1985-09-03 | 1989-01-24 | Technicon Instruments Corporation | Combined closed and open tube sampling apparatus and method |
US4756201A (en) | 1985-09-03 | 1988-07-12 | Technicon Instruments Corporation | Apparatus and method for combined closed and open tube sampling |
US4811611A (en) | 1985-09-03 | 1989-03-14 | Technicon Instruments Corporation | Apparatus and method for pressure equalization in closed tube sampler |
DE3536031A1 (en) | 1985-10-09 | 1987-04-09 | Bbc Brown Boveri & Cie | METHOD FOR ANALYZING AND SYNTHESISING BINARY SIGNS |
US4774057A (en) | 1985-10-25 | 1988-09-27 | Technicon Instruments Corporation | Dual liquid dispenser package |
US4863066A (en) | 1986-06-02 | 1989-09-05 | Technicon Instruments Corporation | System for dispensing precisely metered quantities of a fluid and method of utilizing the system |
US4758409A (en) | 1986-07-10 | 1988-07-19 | Techicon Instruments Corporation | Microsample cup |
US4867908A (en) | 1986-08-29 | 1989-09-19 | Becton, Dickinson And Company | Method and materials for calibrating flow cytometers and other analysis instruments |
US4704891A (en) | 1986-08-29 | 1987-11-10 | Becton, Dickinson And Company | Method and materials for calibrating flow cytometers and other analysis instruments |
FR2604789B1 (en) | 1986-10-06 | 1989-07-28 | Abx Sa | DEVICE FOR AUTOMATICALLY TAKING LIQUID FROM A BOTTLE |
US4764687A (en) | 1987-06-30 | 1988-08-16 | Data General Corporation | Variable timing sequencer |
US4987539A (en) | 1987-08-05 | 1991-01-22 | Stanford University | Apparatus and method for multidimensional characterization of objects in real time |
US4987086A (en) | 1987-11-30 | 1991-01-22 | Becton, Dickinson And Company | Method for analysis of subpopulations of cells |
US4836038A (en) | 1988-03-18 | 1989-06-06 | Aim Instruments Ltd. | Automated sampler-injector apparatus and method for sampling a quantity of sample and testing portions of said quantity |
US5215714A (en) | 1988-04-08 | 1993-06-01 | Toa Medical Electronics Co., Ltd. | Immunoagglutination measurement apparatus |
US4907229A (en) | 1988-06-23 | 1990-03-06 | The United States Of America As Represented By The Secretary Of The Navy | Selective multimode/multiconfigurable data acquisition and reduction processor system |
US5229074A (en) | 1988-07-25 | 1993-07-20 | Precision Systems, Inc. | Automatic multiple-sample multiple-reagent chemical analyzer |
US5012845A (en) | 1988-08-18 | 1991-05-07 | Dynatech Precision Sampling Corporation | Fluid injector |
AU635547B2 (en) | 1988-12-29 | 1993-03-25 | Miles Inc. | Integrated sampler for closed and open sample containers |
US5010560A (en) | 1989-01-17 | 1991-04-23 | Marconi Instruments, Inc. | Data logging apparatus |
US4984475A (en) | 1989-07-24 | 1991-01-15 | Tritech Partners | Ultra low carryover sample liquid analysis apparatus and method |
ES2116268T3 (en) | 1989-07-24 | 1998-07-16 | Bayer Ag | NEW IMPROVED PROBE FOR SUCTION AND DISTRIBUTION OF SAMPLE LIQUIDS. |
US5101673A (en) | 1989-07-24 | 1992-04-07 | Tritech Partners | Ultra low sample liquid analysis apparatus and method |
US5150313A (en) * | 1990-04-12 | 1992-09-22 | Regents Of The University Of California | Parallel pulse processing and data acquisition for high speed, low error flow cytometry |
US5845639A (en) | 1990-08-10 | 1998-12-08 | Board Of Regents Of The University Of Washington | Optical imaging methods |
US5231426A (en) | 1990-12-26 | 1993-07-27 | Xerox Corporation | Nozzleless droplet projection system |
US5466572A (en) | 1992-09-03 | 1995-11-14 | Systemix, Inc. | High speed flow cytometric separation of viable cells |
US5483469A (en) | 1993-08-02 | 1996-01-09 | The Regents Of The University Of California | Multiple sort flow cytometer |
US5464581A (en) | 1993-08-02 | 1995-11-07 | The Regents Of The University Of California | Flow cytometer |
DE69429230T2 (en) | 1993-09-29 | 2002-07-18 | Becton Dickinson Co | DEVICE AND METHOD FOR AUTOMATICALLY TESTING SAMPLES |
US5485639A (en) | 1994-02-28 | 1996-01-23 | Cavazos; Frank G. | Modular innerspring and box spring assemblies |
US5700692A (en) | 1994-09-27 | 1997-12-23 | Becton Dickinson And Company | Flow sorter with video-regulated droplet spacing |
US5643796A (en) | 1994-10-14 | 1997-07-01 | University Of Washington | System for sensing droplet formation time delay in a flow cytometer |
US5602349A (en) | 1994-10-14 | 1997-02-11 | The University Of Washington | Sample introduction system for a flow cytometer |
US5602039A (en) | 1994-10-14 | 1997-02-11 | The University Of Washington | Flow cytometer jet monitor system |
US5682038A (en) | 1995-04-06 | 1997-10-28 | Becton Dickinson And Company | Fluorescent-particle analyzer with timing alignment for analog pulse subtraction of fluorescent pulses arising from different excitation locations |
US5675517A (en) | 1995-04-25 | 1997-10-07 | Systemix | Fluorescence spectral overlap compensation for high speed flow cytometry systems |
US5726751A (en) | 1995-09-27 | 1998-03-10 | University Of Washington | Silicon microchannel optical flow cytometer |
US6014904A (en) | 1996-05-09 | 2000-01-18 | Becton, Dickinson And Company | Method for classifying multi-parameter data |
US5726404A (en) | 1996-05-31 | 1998-03-10 | University Of Washington | Valveless liquid microswitch |
US6139800A (en) | 1997-06-23 | 2000-10-31 | Luminex Corporation | Interlaced lasers for multiple fluorescence measurement |
US5880474A (en) | 1997-08-29 | 1999-03-09 | Becton Dickinson And Company | Multi-illumination-source flow particle analyzer with inter-location emissions crosstalk cancelation |
WO1999031488A1 (en) * | 1997-12-12 | 1999-06-24 | Chemunex S.A. | Digital flow cytometer |
AU3996299A (en) | 1998-05-14 | 1999-11-29 | Luminex Corporation | Diode laser based measurement apparatus |
JP3946444B2 (en) | 1998-05-14 | 2007-07-18 | ルミネックス コーポレイション | Configuration and method for zero dead time of flow cytometer |
FR2799654B1 (en) | 1999-10-13 | 2002-01-11 | Sod Conseils Rech Applic | DEVICE FOR RECONSTRUCTING A THERAPEUTIC SOLUTION, SUSPENSION OR DISPERSION AND PREPARATION AND PACKAGING METHOD THEREOF |
-
2001
- 2001-05-11 US US09/853,043 patent/US6809804B1/en not_active Expired - Lifetime
-
2004
- 2004-09-29 US US10/953,677 patent/US20050042760A1/en not_active Abandoned
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---|---|---|---|---|
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US20110221892A1 (en) * | 2010-03-09 | 2011-09-15 | Neckels David C | Calculate Drop Delay for Flow Cytometry Systems and Methods |
US9453789B2 (en) | 2011-04-29 | 2016-09-27 | Becton, Dickinson And Company | Cell sorter system and method |
US9200334B2 (en) * | 2011-04-29 | 2015-12-01 | Becton, Dickinson And Company | Cell sorter system and method |
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US9696257B2 (en) * | 2012-06-07 | 2017-07-04 | Bio-Rad Laboratories, Inc. | Automated and accurate drop delay for flow cytometry |
US20130337575A1 (en) * | 2012-06-07 | 2013-12-19 | Bio-Rad Laboratories, Inc. | Automated and accurate drop delay for flow cytometry |
US10508990B2 (en) | 2012-06-07 | 2019-12-17 | Bio-Rad Laboratories, Inc. | Automated and accurate drop delay for flow cytometry |
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US20140329265A1 (en) * | 2013-03-15 | 2014-11-06 | Iris International, Inc. | Flowcell, sheath fluid, and autofocus systems and methods for particle analysis in urine samples |
US9857361B2 (en) * | 2013-03-15 | 2018-01-02 | Iris International, Inc. | Flowcell, sheath fluid, and autofocus systems and methods for particle analysis in urine samples |
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