|Publication number||US20070236682 A9|
|Application number||US 10/953,197|
|Publication date||Oct 11, 2007|
|Filing date||Sep 28, 2004|
|Priority date||Aug 21, 2002|
|Also published as||CN101065656A, CN101065656B, DE602005017914D1, EP1794569A1, EP1794569B1, US7283223, US20060066840, WO2006036896A1|
|Publication number||10953197, 953197, US 2007/0236682 A9, US 2007/236682 A9, US 20070236682 A9, US 20070236682A9, US 2007236682 A9, US 2007236682A9, US-A9-20070236682, US-A9-2007236682, US2007/0236682A9, US2007/236682A9, US20070236682 A9, US20070236682A9, US2007236682 A9, US2007236682A9|
|Original Assignee||Fritz Bernard S|
|Export Citation||BiBTeX, EndNote, RefMan|
|Classifications (5), Legal Events (3)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates generally to flow cytometers. More particularly, the present invention relates to flow cytometers that sense optical properties of microscopic particles or components in a flow stream with light.
This invention is related to U.S. patent application Ser. No. 10/225,325, by Bernard Fritz et al., filed Aug. 21, 2002, and entitled “Optical Alignment Detection System”, which is incorporated herein by reference; and the invention is related to U.S. patent application Ser. No. 10/304,773, by Aravind Padmanabhan et al., filed Nov. 26, 2002, and entitled “Portable Scattering and Fluorescence Cytometer”, which is incorporated herein by reference. This invention also is related to U.S. Pat. No. 6,549,275 B1, by Cabuz et al., issued Apr. 15, 2003, and entitled “Optical Detection System for Flow Cytometry”; U.S. Pat. No. 6,597,438 B1, by Cabuz et al., issued Jul. 22, 2003, and entitled “Portable Flow Cytometer”; U.S. Pat. No. 6,382,228 B1, by Cabuz et al., issued May 7, 2002, and entitled “Fluid Driving System for Flow Cytometry”; U.S. Pat. No. 6,700,130 B2, issued Mar. 2, 2004, by Fritz, and entitled “Optical Detection System for Flow Cytometry”; and U.S. Pat. No. 6,240,944 B1, by Ohnstein et al., issued Jun. 5, 2001, and entitled “Addressable Valve Arrays for Proportional Pressure or Flow Control”; all of which are incorporated herein by reference. The above-noted applications and patents are owned by the same entity. The term “fluid” may be used here as a generic term that includes gases and liquids as species.
The invention may be a mechanism for moving and positioning a light source so that its light impinges a target as it moves on or off axis of an optical system. A detector may receive scattered light at a same position whether the light impinging the target is on or off axis due to, as an illustrative example, a telecentric optical system. Further, the light may be positioned so that the detector is maximally impinged with scattered light. An output may go to a processor that sends a signal to the light source to move the emitted light so as to continually impinge the target as it moves on or off axis. An array of light sources may used in lieu of the moving light source. To move the light beam, another light at another position in the array may be selected to replace a previously selected light source.
The telecentric condition is where the aperture stop 22 of an optical system 10 is located at the focal point or focus of the lens 21 and the focal point of lens 23. Having the optical system meet this condition on both the source 11 side and the detector 12 side of the flow cytometer allows equivalence of the optical system for off-axis field points.
The optical system 10 of
Illumination along the solid line paths 13 may emanate on axis from a source 17 of array 11 and proceed through a collimating lens 21. Source 17 illumination may proceed through an aperture stop 22 onto a lens 23. A source 17 light beam may be focused on flow channel 16 and detector 12, along solid-line paths 13. Scattered light due to the beam along paths 13 may proceed through a lens 24 to be focused on detector array 12 at places 44 and 45 of detector 12.
If a core stream in the cytometer channel 16 is shifted off axis to a position 25 of channel 16, the illumination may be shifted to off-axis dotted-line paths 14. Light from a source 18 may proceed along the light paths 14 through lens 21, aperture 22 and lens 23 to channel 16. Illumination from paths 14 may be scattered in channel 16 and focused on detector array 12 at positions 44 and 45 of detector 12.
If the core stream 38 in the cytometer channel 16 is at a position 26 of the channel, the focus of illumination may be shifted to position 26 of the channel. Illumination from a source 19 of array 11 may proceed along dashed-line paths 15 through lens 21, aperture 22 and lens 23 to position 26 of channel 16. Scattered light from position 26 may proceed along paths 15 through lens 24 to be focused on detector array 12 at positions 44 and 45.
The optical elements of system 10 are coincident focal lengths apart. For instance, lens 21 is a focal length (f1) 31 from the light source or array 11 and focal length (f1) 32 from aperture stop 22. The lengths 31 and 32 may each be the focal length (f1) of lens 21. Lengths 33 and 34 of lens 23 from the aperture stop 22 and channel 16, respectively, may each be the focal length (f2) of lens 23. Lengths 35 and 36 of lens 24 from channel 16 may each be the focal length (f3) of lens 24. Line 46 indicates the conjugate planes 11 and 16 at the light source and the channel. Line 47 indicates the conjugate planes 22 and 12 at the aperture and detector, respectively.
Light array 11 may have light sources 17, 18 and 19 which are turned on one at a time according to the location of the core stream in channel 16. There may be more light sources in the array for a more refined adjustment of the location of the light beam impinging the channel 16. Array 11 may be two-dimensional.
Instead, detector array 11 may have one source, e.g., source 17, which moves across the array structure in an x and/or y direction to provide an adjustment of the location of the light impinging the channel 16. The light source may be incremented with a stepper motor like mechanism 37 laterally across the array to move the location of impinging light in channel 16 laterally.
Light beams along paths 13, 14 and 15 may be scattered by particles in channel 16 to portions 44 and 45 of detector 12. Detector 12 may convert the light detected at portions 44 and 45, and positions 41, 42 and 43, into electrical signals which may be sent to a processor 10 which may process the electrical signals into information about the particles of flow stream 38 in the channel 16.
When the light sensor is aligned with the core stream 38, the light beam impinging particles in the core stream 38 may be scattered by the particles. Detector 12 may be a scattered light detector and a direct light detector, such as a linear array or an annular-shaped detector array. Detector 12 may have independent detector portions for various angles of scattered light and for non-scattered light. The annular array may provide a 360 range of detection by the various portions for the telecentricity system. Detector 12 may provide an electrical signal representative of the scattered light impinging the detector. If the light beam from the light source of assembly 11 is not impinging particles of the core stream 38, then there may be little scattered light detected by detector 12 with little electrical signal from this detector but rather non-scattered light. Detector 12 may detect forward-angle light scatter (FALS), small-angle light scatter (SALS), and large-angle light scatter (LALS).
The electrical signal from detector 12 may go to a computer/processor 20. The computer/processor 20 may send a signal to light source array 11 to indicate the selection of another light source or the movement of a single light source to shift the position of where the light beam is impinging in the channel 11. The position may be located and the light beam moved so that there is a maximum signal at the output of detector 12. That may mean that the light beam is creating a maximum scattering signal at detector 12. The computer 20 may send a signal that changes the position or location of the light beam in channel 16 by selecting a different light source of array 11 or moving a light source to seek out a maximum scattering signal from detector 12 to computer 20. Effectively, there is a feedback loop consisting of computer 20 to light source 11, light beam from the source scattering in the channel 16, a detector 12 providing the electrical representation of the scattered light to the computer. The computer 20 may send a signal to light source 11 to maximize the scattering signal which tends to keep the light beam focused on the core stream 38, whether on-axis or not.
Although the invention has been described with respect to at least one illustrative embodiment, many variations and modifications will become apparent to those skilled in the art upon reading the present specification. It is therefore the intention that the appended claims be interpreted as broadly as possible in view of the prior art to include all such variations and modifications.
|Cooperative Classification||G01N15/1459, G01N2015/1452|
|Sep 28, 2004||AS||Assignment|
Owner name: HONEYWELL INTERNATIONAL INC., NEW JERSEY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:FRITZ, BERNARD S.;REEL/FRAME:015850/0661
Effective date: 20040927
|Mar 23, 2011||FPAY||Fee payment|
Year of fee payment: 4
|Mar 25, 2015||FPAY||Fee payment|
Year of fee payment: 8