CN104034648A - Hydrodynamic focusing apparatus used for diffraction imaging flow cytometer - Google Patents
Hydrodynamic focusing apparatus used for diffraction imaging flow cytometer Download PDFInfo
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Abstract
The invention provides a hydrodynamic focusing apparatus used for a diffraction imaging flow cytometer. The hydrodynamic focusing apparatus comprises a sheath flow tube, a nuclear flow tube and a fluid chamber made of an optically transparent material, wherein the upper part of the sheath flow tube is located out of the upper port of the fluid chamber, the lower part of the sheath flow tube is embedded into the upper port of the fluid chamber, the lower part of the nuclear flow tube axially penetrates the center of the sheath flow tube from the upper port of the sheath flow tube and is located in the fluid chamber, the upper part of the nuclear flow tube is located out of the upper port of the sheath flow tube, and the lower port of the fluid chamber is provided with a liquid discharging pipe. The cross section of a liquid flow channel in the fluid chamber is a polygon, the outer wall of each edge is a plane, and the fluid chamber is prepared from the optically transparent material through bonding or sintering. According to the invention, processing of the sheath flow tube and the nuclear flow tube is simple; the hydrodynamic focusing apparatus can realize hydrodynamic focusing of nuclear flow in a great flow velocity adjusting range and obtain a stable layer fluid with accurately controllable nuclear flow position and flow velocity, so a high-contrast diffraction image of a to-be-measured particle can be obtained eventually.
Description
Technical field
The present invention relates to a kind of fluid dynamics focalizer for diffraction imaging flow cytometer.Particularly relate to a kind of assurance and under low flow velocity, obtain the stably stratified flow with pinpoint core stream, core stream is realized to the fluid dynamics focalizer for diffraction imaging flow cytometer that fluid dynamics focuses on.
Background technology
Since the sixties in last century, to take the particulate that cell is representative, in carrying fluid laminar flow, under rapid flow state, carried out deep optical measurement research.On these Research foundations, formed low cytometric analysis, be a kind of collector mechanics, laser technology, the great achievement of photoelectric measurement and Study on Data Processing achievement can carry out to a large amount of individual cells the instrument of Quick Measurement analysis.The poor laminar flow being formed by sample stream and sheath stream that forms in sample chamber of the concentric fluid pipeline of flow cytometer utilization and fluid pressure.The sheath stream that ring wraps in outside sample stream reduces containing fine-grained sample flow diameter by pressure difference; force carried particulate to flow through exactly excitation beam in single-row mode; the particulate of the light beam irradiates that is excited can produce the scattered light identical with excitation wavelength, and its intensity scattering angle changes and changes.The scattered light that this wavelength equates with excitation wavelength is also referred to as elastic scattering light, is the radiation that molecule electric dipole that the light beam electromagnetic field inducing that is excited due to particulate inside forms produces.The induction molecule electric dipole CONCENTRATION DISTRIBUTION of particulate inside is by its inner optical index distribution and expression, so particulate interior three-dimensional structure can be expressed by its optical index distributed in three dimensions.Carrier material optical index as inhomogeneous in the optical index distributed in three dimensions of particulate inside or that suspended from it is different, and scattered light exists, and normally particulate by the strongest signal in the various light signals that produced under the condition of illumination.The particulate of the light beam irradiates that is excited also can produce fluorescence as contained fluorescence molecule, is the radiant light producing after fluorescence molecule due to particulate inside is excited, and its wavelength is generally greater than excitation wavelength.Many particulates that comprise cell not containing or contain fluorescence molecule seldom, so these particulates only just can produce sufficient intensity fluorescence signal after dyeing.The fluorescence signal that after current low cytometric analysis mainly dyes by measurement, particulate produces carries out express-analysis to particulate to be distinguished, its processing speed can reach thousands of particulate per second.In analysis package, during containing the group of a large amount of particulates, flow cytometer method can be done single particulate analysis, and its speed is much larger than optical micro analysis method, therefore in acquisition, has aspect the data of statistical significance and has its unique advantage.Since last century the eighties, flow cytometer, in RESEARCH ON CELL-BIOLOGY, is used widely in pollution monitoring and other field field.
At present flow cytometer product can be divided into two kinds, angle integral form and incoherent imaging type by its optical signalling metering system.Most existing flow cytometers are angle integral form, in this flow cytometer, the scattered light signal that the particulate that flows produces under incident beam irradiates and fluorescence signal produce corresponding output electrical signals by different monomer photoelectric sensor (as photodiode, photomultiplier etc.) acceptance.Monomer sensor is for only exporting the sensor of 1 electric signal, its signal intensity be proportional to scattered light or fluorescence signal intensity sensor area with respect to light source the integrated value in formed three-dimensional viewpoin, referred to as scattered light or fluorescence signal.The specific molecular that fluorescence signal comprises with particulate inside (as certain protein molecule that can be combined with fluorescence molecule in cell) whether exist and quantity relevant, scattered light signal after angle integration is only that granularity is relevant with particulate volume and interior lights refractive index uniformity coefficient, cannot reflect the distributed in three dimensions of particulate interior lights refractive index.By scattered light and fluorescence signal combination, by computing machine, carry out data analysis, can carry out automatic analysis to the group that comprises a large amount of particulates and distinguish, reach the object of the particulate in group being carried out to quick kind differentiation.Angle integral form flow cytometer can be measured 2 to 10 fluorescence signals and 2 scattered light signals conventionally at present.Fluorescence signal does not comprise structural information, although 2 scattered light signals (forward direction and lateral scattering light signal) can provide the information of volume and internal particle degree, but its structural information content is extremely limited, thereby angle integral form flow cytometer mainly relies on fluorescence signal to carry out express-analysis to particulate to distinguish.And in incoherent imaging type flow cytometer, its fluoroscopic image is because wavelength of fluorescence is with respect to the incoherent image of being changed to of excitation beam wavelength, bright field or dark field image generally obtain under incoherent white light condition, also belong to incoherent image, cannot analyze the Three Dimensions Structure of particulate to be measured.
To comprise cell particulate light scattering theory and test for many years on Research foundation, a kind of novel diffraction imaging type flow cytometer method is announced recently, discuss visible list of references (X.H.Hu for example in detail, K.M.Jacobs, J.Q.Lu, " Flow cytometer apparatus for three dimensional diffraction imaging and related methods ", PCT Application No.WO 2009/151610 by East Carolina University; Dong Ke, Hu Xinhua, " diffraction image measuring and analysis system and the method for automatic identification particulate ", Chinese invention patent, CN201010221714.7).This novel diffraction imaging type flow cytometer need to form the stable laminar flow being comprised of sheath stream and core stream under different in flow rate, to carrying the core stream of particulate to be measured, realize fluid dynamics focusing, make particulate to be measured can on ad-hoc location, with single-row form, flow through the focus of relevant incident beam.Diffraction imaging type flow cytometer method has proposed to use as the image sensor elements such as ccd camera are noted down the space angle distribution that particulate to be measured produces coherent scattering light, obtain the diffraction image signal of high-contrast, for treating analysis and the identification of micrometer grain.Experimental result shows that this novel diffraction imaging flow cytometer can distinguish the particulate with different Three Dimensions Structure according to the signal analysis of particulate diffraction image, discuss visible list of references (K.M.Jacobs for example in detail, L.V.Yang, J.Ding, A.E.Ekpenyong, R.Castel lone, J.Q.Lu, X.H.Hu. " Diffraction imaging of spheres and melanoma cells with a microscope objective ", Journal of Biophotonics, vol.2, pp.521-527 (2009); K.M.Jacobs, J.Q.Lu, X.H.Hu, " Development of a diffraction imaging flow cytometer ", Optics Letters, vol.34, pp.2985-2987 (2009); K.Dong, Y.Feng, K.M.Jacobs, J.Q.Lu, R.S.Brock, L.V.Yang, F.E.Bertrand, M.A.Farwell, X.H.Hu, " Label-free classification of cultured cells through diffraction imaging ", Biomedical Optics Express, vol.2, pp.1717-1726 (2011); Y.Sa, J.Zhang, M.S.Moran, J.Q.Lu, Y.Feng, X.H.Hu, " A novel method of diffraction imaging flow cytometry for sizing microspheres ", Optics Express, vol.20, pp.22245-22251 (2012)).By the particulate photon diffusion models based on classical electrodynamics theory and extensive numerical evaluation, the particulate two dimension diffraction image and its Three Dimensions Structure height correlation that by diffraction image type flow cytometer, are obtained have now been proved, can therefrom extract the many features relevant to particulate Three Dimensions Structure, discuss visible list of references (J.Q.Lu for example in detail, P.Yang, X.H.Hu, " Simulations of Light scattering from a biconcave red blood cell using the FDTD method ", Journal of Biomedical Optics, vol.10, 024022 (2005), R.S.Brock, X.H.Hu, D.A.Weidner, J.R.Mourant, J.Q.Lu, " Effect of detailed cell structure on light scattering distribution:FDTD study of a B-cell with 3D structure constructed from confocal images ", Journal of Quantitative Spectroscopy & Radiative Transfer, vol.102, pp.25-36 (2006)).
Angle integral form flow cytometer only need be measured several light signals for each particulate to be measured at present, its photoelectric sensor response time is shorter, the data volume of each the particulate signal to be measured obtaining is little, therefore under the high condition of the core stream flow velocity that contains particle to be measured, a large amount of particulates to be measured is realized to Quick Measurement.The measuring speed of angle integral form flow cytometer can reach for 10,000 particulate/seconds, and its core Flow Velocity can reach 10,000 mm/second.The general sheath stream pipe design form at afterbody with taper nozzle that adopts of fluid dynamics focalizer that angle integral form flow cytometer is used, it is inner that core stream pipe is positioned at sheath stream pipe, and the taper nozzle diameter of sheath stream pipe afterbody is less than core stream pipe diameter, be beneficial to realize fluid dynamics and focus on, as shown in Figure 1.In the fluid containment structure design of general flow cytometer, sheath stream pipe exit 9 need to form taper jet hole, with reduce sheath stream 7 flow, accelerate converging of sheath stream 7, form the hydrodynamics focal region 8 for core stream 5, as shown in Figure 1.Make by after the core stream 5 particulate defileds to be measured that carry through incident beam 10, produce optical signalling.Compare with angle integral form flow cytometer, diffraction imaging type flow cytometer need to be used imageing sensor to gather coherent scattering light space angle distribution that each produces through the particulate to be measured of incident beam focus, as one or more diffraction image signal, transfers to image processing system., transmission great amount of images data long in the imageing sensor response time need under longer condition of time, diffraction imaging type flow cytometer needs to form fluid dynamics fluid dynamics that focus on, can regulate core Flow Velocity on a large scale to core stream and focuses on or fluid control device, general needed core stream velocity of flow adjust scope is 1 to 1,000 mm/second.Make diffraction imaging type flow cytometer when outfit has the imageing sensor of different response times, all can obtain the diffraction image data of high-contrast.
Summary of the invention
Technical matters to be solved by this invention is, provide a kind of and calculate and experimental result based on hydrodynamic simulation model, make diffraction imaging type flow cytometer can in a big way, regulate core stream flow velocity and measure and obtain the fluid dynamics focalizer for diffraction imaging flow cytometer with high-contrast diffraction image.
The technical solution adopted in the present invention is: a kind of fluid dynamics focalizer for diffraction imaging flow cytometer, comprise sheath stream pipe and core stream pipe, also be provided with the fluid chamber being formed by optically transparent material, described core stream pipe is arranged on the axis in sheath stream pipe, and the lower port that sheath stream pipe is stretched out in the bottom of core stream pipe, described sheath stream pipe is inserted in fluid chamber along axis, and the upper end of fluid chamber is stretched out in the upper end of sheath stream pipe, lower end is positioned at fluid chamber inside, in described fluid chamber, be positioned at below the core stream pipe outlet of the core stream pipe that stretches out sheath stream infratubal port and also along axis, be provided with discharging tube, the outlet of the upper port of described discharging tube and described core stream pipe is oppositely arranged, for what formed by optical transparent liquid laminar flow, for incident beam, irradiate the fluid dynamics focal region of particulate to be measured in the middle of fluid chamber, the bottom that the lower port of described discharging tube runs through fluid chamber is positioned at the outside of fluid chamber.
The laminar flow that sheath stream and core stream form and fluid dynamics focal region the core stream pipe of described core stream pipe export and the upper port of described discharging tube between.
Described sheath stream pipe is straight tube, and internal diameter is between 0.1mm to 10mm.
The inner flow passage xsect of described fluid chamber is polygon, and every limit outer wall is plane, and by optically transparent material, bonding or sintering forms.
The outlet outer wall of described core stream pipe is rounding off structure.
A kind of fluid dynamics focalizer for diffraction imaging flow cytometer, comprise sheath stream pipe, core stream pipe, also be provided with the fluid chamber being formed by optically transparent material, the upper part of described sheath stream pipe is positioned at the outside of fluid chamber's upper port, under sheath stream pipe, be partly embedded in the upper port of fluid chamber, the inside that is centered close to described fluid chamber of sheath stream pipe is axially run through in the lower end of described core stream pipe from the upper port of sheath stream pipe, and the upper end of core stream pipe is positioned at the outside of sheath stream pipe upper port, the lower port place of described fluid chamber is provided with discharging tube.
Described sheath stream pipe is straight tube, and internal diameter is between 0.1mm to 10mm.
The inner flow passage xsect of described fluid chamber is polygon, and every limit outer wall is plane, and by optically transparent material, bonding or sintering forms.
Described core stream pipe is straight tube, and internal diameter is between 0.02mm to 5mm, and the core stream pipe outlet of core stream pipe is positioned at the axis centre of sheath stream pipe, and described core stream pipe outlet outer wall is rounding off structure.
Sheath stream is positioned at laminar flow and fluid dynamics focal region that core stream forms the region that core flows pipe exit below 0.1mm to 100mm.
The core stream pipe outlet of core stream pipe is more than or equal to 5mm apart from the distance of sheath inflow entrance.
The core stream pipe outlet of core stream pipe is more than or equal to 1mm apart from the distance of discharging tube upper port.
The fluid dynamics focalizer for diffraction imaging flow cytometer that the present invention implements, sheath stream Guan Buxu in it has taper nozzle, can be column type or square, the processing of sheath stream Guan Yuhe stream pipe is simple, fluid dynamics focalizer can be realized fluid dynamics to core stream and focus within the scope of larger velocity of flow adjust, the resistant strata fluid of core stream position and flow velocity can be accurately controlled in acquisition, the final particulate diffraction image to be measured with high-contrast that obtains.Mesotheca stream pipe of the present invention outlet needn't be processed into taper nozzle or small structure; Sheath stream Guan Keyu core stream pipe is coaxially placed in fluid chamber; Sheath stream pipe also can only be placed in outside fluid chamber, makes sheath flow liquid body directly enter in fluid chamber by fluid chamber's entrance; The length range that sheath stream pipe allows is larger; Incident laser light beam can pass optically transparent fluid locular wall, in the constant liquid of light refractive index, irradiates and excites particulate to be measured, the diffraction image signal can obtain clearly, contrast being larger; In addition formed fluid dynamics focal zone is longer, can make particulate to be measured in very long region, form single-row flow, and position stability makes space allocation wider range of incident laser light beam, is convenient to regulate.
Accompanying drawing explanation
Fig. 1 is the structural representation of the fluid dynamics focalizer mesotheca stream Guan Yuhe stream pipe position of prior art;
Fig. 2 is that the present invention is for the structural representation of fluid dynamics focalizer one embodiment of diffraction imaging flow cytometer;
Fig. 3 is that the present invention is for the structural representation of another embodiment of fluid dynamics focalizer of diffraction imaging flow cytometer;
Fig. 4 is the inner structure schematic diagram of Fig. 3;
Fig. 5 (a) is the core stream gabarit streamline of Fig. 3 shown device mesotheca stream flow while being 27.7uL/s;
Fig. 5 (b) is the core stream gabarit streamline of Fig. 3 shown device mesotheca stream flow while being 100uL/s;
Fig. 6 is the simulation result figure of velocity flow profile in the fluid dynamics focal region that obtains of Fig. 3 fluid dynamics focalizer, and wherein transverse axis x represents x axial coordinate, longitudinal axis U express liquid flow velocity, and sheath stream flow is 27.7uL/s.The coordinate position of core stream pipe export center is made as x=1.5mm, y=0mm, z=0mm; Article three, curve is presented at y=0 and manages with core stream the relation that exports the flow rate of liquid U of different distance place (z=0.2mm, z=0.5mm, z=1mm) and x axial coordinate.
In figure
1: sheath stream pipe 2: core stream pipe
3: sheath inflow entrance 4: core stream tube inlet
5: core stream 6: the outlet of core stream pipe
7: sheath stream 8: fluid dynamics focal region
9: there is the sheath stream pipe outlet 10 of taper nozzle: incident beam
11: fluid chamber 12: discharging tube
Embodiment
Below in conjunction with embodiment and accompanying drawing, the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention is described in detail.
As shown in Figure 2, the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention, comprises sheath stream pipe 1 and core stream pipe 2, and the fluid chamber 11 consisting of optically transparent material.Described core stream pipe 2 is arranged on the axis in sheath stream pipe 1, and the upper/lower terminal mouth of sheath stream pipe 1 is stretched out in the bottom of core stream pipe 2.The outlet of described core stream pipe 2 is the rounding off structure of taper or other shapes.Described sheath stream pipe 1 is straight tubule, internal diameter is between 0.1mm to 10mm, tubule as straight in stainless steel, sheath stream pipe 1 is vertically inserted in fluid chamber 11, and the upper end of fluid chamber 11 is stretched out in the upper end of sheath stream pipe 1, lower end is positioned at the middle part of fluid chamber 11, in described fluid chamber 11, be positioned at below the core stream pipe outlet 6 of the core stream pipe 2 that stretches out sheath stream pipe 1 lower port and be also vertically installed with discharging tube 12, the outlet of the upper port of described discharging tube 12 and described core stream pipe 2 is oppositely arranged, the fluid dynamics focal region for incident beam 10 irradiation particulate to be measured for being formed by optical transparent liquid laminar flow in the middle of fluid chamber 11, the bottom that the lower port of described discharging tube 12 runs through fluid chamber 11 is positioned at the outside of fluid chamber 11.The inner flow passage xsect of described fluid chamber 11 is polygon, and as square, outer wall is plane, and by clear glass, bonding or sintering forms.The laminar flow that sheath stream 7 and core stream form and fluid dynamics focal region 8 the core stream pipe of described core stream pipe 2 export 6 and the upper port of described discharging tube 12 between.
The fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention as shown in Figure 2, core stream pipe 2 and sheath stream pipe 1 together can be inserted among fluid chamber 11, its mesotheca stream pipe 1 can be straight tubule, tubule as straight in stainless steel, its endpiece does not need to have taper nozzle, core stream pipe 2 can protrude from outside sheath stream pipe, can under the condition that suitably regulates sheath stream and core stream flow, between the pipe outlet 6 of core stream and discharging tube entrance, form for the fluid dynamics of core stream 5 and learn focal region 8.At this region kernel, flowing 5 interior comprised particulates to be measured can defiled, stable by incident beam 10 and produce optical signalling as diffraction image signal.
As shown in Figure 3, Figure 4, the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention, can also adopt following structure, comprises sheath stream pipe 1, core stream pipe 2, and the fluid chamber 11 consisting of optically transparent material.Described sheath stream pipe 1 is straight tubule, internal diameter between 0.1mm to 10mm, tubule as straight in stainless steel, sheath stream pipe 1 is directly connected with fluid chamber 11, the upper part of sheath stream pipe 1 is positioned at the outside of fluid chamber's 11 upper port, under sheath stream pipe 1, is partly embedded in the upper port of fluid chamber 11.Described core stream pipe 2 is straight tubule, and as capillary Stainless Steel pipe, internal diameter is between 0.02mm to 5mm, and the core stream pipe outlet 6 of core stream pipe 2 is positioned at the center of sheath stream pipe 1, and described core stream pipe outlet 6 is the rounding off structure of taper or other shapes.The inside that is centered close to described fluid chamber 11 of sheath stream pipe 1 is axially run through in the lower end of described core stream pipe 2 from the upper port of sheath stream pipe 1, and the upper end of core stream pipe 2 is positioned at the outside of sheath stream pipe 1 upper port, and the lower port place of described fluid chamber 11 is provided with discharging tube 12.The inner flow passage xsect of described fluid chamber 11 is polygon, and as square, size can be 3x3mm, and sidewall thickness can be 1mm, and every limit outer wall is plane, and by optical clear glass, bonding or sintering forms, and the present embodiment is to form for BK7 optical glass sintering.
Core stream 5 enters core stream pipe 2 through core stream tube inlet 4, by core stream pipe outlet 6 ejections, sheath stream 7 enters sheath stream pipe 1 by sheath inflow entrance 3 places, and then enter fluid chamber 11, at core stream pipe outlet 6 places and core stream 5, meet, by suitable pressure difference, reduce the diameter of core stream 5, the region that the laminar flows that sheath stream 7 and core stream 5 form and fluid dynamics focal region 8 are positioned at core stream pipe outlet 6 below, places 0.1mm to 100mm, can be below core stream pipe exit forms fluid dynamics to core stream 5 in the region of 0.1mm to 100mm and learns and focus on.Now core flow 5 interior comprised particulates to be measured can defiled, stable by incident beam and produce optical signalling as diffraction image signal.
Described core stream pipe outlet is more than or equal to 5mm apart from the distance of sheath inflow entrance.And described core stream pipe outlet (6) is more than or equal to 1mm apart from the distance of discharging tube (12) upper port.
No matter adopt which kind of structural design, the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention all can be realized stable fluid dynamics to core stream and focus within the scope of larger velocity of flow adjust.
What Fig. 5 (a), Fig. 5 (b) were shown is the core stream gabarit calculation of streamlines result obtaining according to the structure of the fluid dynamics focalizer for diffraction imaging flow cytometer shown in Fig. 3, use hydrodynamic simulation model, and its center flows 5 diameters and represented by its gabarit streamline.Diameter value of tending towards stability of core stream 5 after entering fluid dynamics focal region 8; Therefore within incident laser light beam can be placed in the region of 1mm to 100mm in core stream pipe outlet 6 belows, fluid chamber, along y axle (or x axle) direction, excite particulate to be measured, can obtain coherent scattering light and the corresponding diffraction image signal of particulate; And sheath stream 7 finally passes through discharging tube effluent fluid chamber with the laminar flow that core flows 5 synthesizeds.Comparison diagram 5 (a) and Fig. 5 (b) can find out the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention, can guarantee to obtain stable core stream in larger sheath stream flow adjustment range, in Fig. 5 (a), Fig. 5 (b), show the fluid dynamics focusing effect that sheath stream flow flows for core while being 27.7uL/s and 100uL/s.The fluid dynamics focalizer (seeing Fig. 1) adopting than general flow cytometer, the advantage of the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention is: the outlet of sheath stream pipe needn't be processed into taper nozzle or small structure; Sheath stream Guan Keyu core stream pipe is coaxially placed in fluid chamber, as shown in Figure 2; Sheath stream pipe also can be placed in outside fluid chamber, makes sheath flow liquid body directly enter in fluid chamber, as shown in Figure 3 and Figure 4 by fluid chamber's entrance; The length range that sheath stream pipe allows is larger; Incident laser light beam can pass optically transparent fluid locular wall, in the constant liquid of light refractive index, irradiates and excites particulate to be measured, the diffraction image signal can obtain clearly, contrast being larger; In addition formed fluid dynamics focal zone is longer, can make particulate to be measured in very long region, form single-row flowing, and position stability, makes the adjustment wide region of incident laser light beam wider, is convenient to regulate.
Shown in Fig. 6 is that flow rate of liquid according to the structure of the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention shown in Fig. 4, while using the stream of sheath in fluid dynamics focal zone flow that hydrodynamic simulation model obtains for 27.7uL/s is along the distribution result of calculation of x axle.Contrast is in the velocity flow profile at core stream pipe outlet different distance place, can find out and be positioned at the supercentral core stream of fluid chamber (centre coordinate position is x=1.5mm) when by fluid dynamics focal zone, its flow velocity constantly increases when gradually away from the outlet of core stream pipe, according to the incompressible characteristic of fluid, sectional area and the respective diameters of core stream can constantly reduce, this and Fig. 5 (a), core stream gabarit calculation of streamlines result shown in Fig. 5 (b) matches, the structure that has proved the fluid dynamics focalizer for diffraction imaging flow cytometer of the present invention has the features such as stability that can realize the particulate to be measured position that fluid dynamics focuses on and assurance core flows and carry under low flow velocity.
Claims (12)
1. the fluid dynamics focalizer for diffraction imaging flow cytometer, comprise sheath stream pipe (1) and core stream pipe (2), it is characterized in that, also be provided with the fluid chamber (11) being formed by optically transparent material, described core stream pipe (2) is arranged on the axis in sheath stream pipe (1), and the lower port of sheath stream pipe (1) is stretched out in the bottom of core stream pipe (2), described sheath stream pipe (1) is inserted in fluid chamber (11) along axis, and the upper end of fluid chamber (11) is stretched out in the upper end of sheath stream pipe (1), lower end is positioned at fluid chamber (11) inside, in described fluid chamber (11), be positioned at below the core stream pipe outlet (6) of the core stream pipe (2) that stretches out sheath stream pipe (1) lower port and also along axis, be provided with discharging tube (12), the outlet of the upper port of described discharging tube (12) and described core stream pipe (2) is oppositely arranged, for what formed by optical transparent liquid laminar flow, for incident beam (10), irradiate the fluid dynamics focal region of particulate to be measured in the middle of fluid chamber (11), the bottom that the lower port of described discharging tube (12) runs through fluid chamber (11) is positioned at the outside of fluid chamber (11).
2. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 1, it is characterized in that, the core stream pipe that the laminar flow that sheath stream (7) and core stream form and fluid dynamics focal region (8) are positioned at described core stream pipe (2) exports between (6) and the upper port of described discharging tube (12).
3. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 1, is characterized in that, described sheath stream pipe (1) is straight tube, and internal diameter is between 0.1mm to 10mm.
4. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 1, it is characterized in that, the inner flow passage xsect of described fluid chamber (11) is polygon, and every limit outer wall is plane, and by optically transparent material, bonding or sintering forms.
5. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 1, is characterized in that, the outlet outer wall of described core stream pipe (2) is rounding off structure.
6. the fluid dynamics focalizer for diffraction imaging flow cytometer, comprise sheath stream pipe (1), core stream pipe (2), it is characterized in that, also be provided with the fluid chamber (11) being formed by optically transparent material, the upper part of described sheath stream pipe (1) is positioned at the outside of fluid chamber (11) upper port, under sheath stream pipe (1), be partly embedded in the upper port of fluid chamber (11), the inside that is centered close to described fluid chamber (11) of sheath stream pipe (1) is axially run through in the lower end of described core stream pipe (2) from the upper port of sheath stream pipe (1), and the upper end of core stream pipe (2) is positioned at the outside of sheath stream pipe (1) upper port, the lower port place of described fluid chamber (11) is provided with discharging tube (12).
7. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 6, is characterized in that, described sheath stream pipe (1) is straight tube, and internal diameter is between 0.1mm to 10mm.
8. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 6, it is characterized in that, the inner flow passage xsect of described fluid chamber (11) is polygon, and every limit outer wall is plane, and by optically transparent material, bonding or sintering forms.
9. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 6, it is characterized in that, described core stream pipe (2) is straight tube, internal diameter is between 0.02mm to 5mm, the core stream pipe outlet (6) of core stream pipe (2) is positioned at the axis centre of sheath stream pipe (1), and described core stream pipe outlet (6) outer wall is rounding off structure.
10. the fluid dynamics focalizer for diffraction imaging flow cytometer according to claim 6, it is characterized in that, sheath stream (7) is positioned at laminar flow and fluid dynamics focal region (8) that core stream (5) forms the region that below 0.1mm to 100mm is located in core stream pipe outlet (6).
The 11. fluid dynamics focalizers for diffraction imaging flow cytometer according to claim 6, is characterized in that, the core stream pipe outlet (6) of core stream pipe (2) is more than or equal to 5mm apart from the distance of sheath inflow entrance (3).
The 12. fluid dynamics focalizers for diffraction imaging flow cytometer according to claim 6, is characterized in that, the core stream pipe outlet (6) of core stream pipe (2) is more than or equal to 1mm apart from the distance of discharging tube (12) upper port.
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| CN107091800A (en) * | 2017-06-06 | 2017-08-25 | 深圳小孚医疗科技有限公司 | Focusing system and focus method for micro-imaging particle analysis |
| CN108444897A (en) * | 2018-03-06 | 2018-08-24 | 山东大学 | Label-free micro-current controlled cell instrument and method based on mating plate illumination and sheath Flow Technique |
| WO2021017673A1 (en) * | 2019-07-31 | 2021-02-04 | 珠海真理光学仪器有限公司 | Laser particle size analyzer having liquid sheath flow measuring cell |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107091800A (en) * | 2017-06-06 | 2017-08-25 | 深圳小孚医疗科技有限公司 | Focusing system and focus method for micro-imaging particle analysis |
| CN108444897A (en) * | 2018-03-06 | 2018-08-24 | 山东大学 | Label-free micro-current controlled cell instrument and method based on mating plate illumination and sheath Flow Technique |
| WO2021017673A1 (en) * | 2019-07-31 | 2021-02-04 | 珠海真理光学仪器有限公司 | Laser particle size analyzer having liquid sheath flow measuring cell |
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