CN1811425A - Silicon microchannel array erythrocyte rheological analyzing method and apparatus - Google Patents
Silicon microchannel array erythrocyte rheological analyzing method and apparatus Download PDFInfo
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- CN1811425A CN1811425A CN 200610054065 CN200610054065A CN1811425A CN 1811425 A CN1811425 A CN 1811425A CN 200610054065 CN200610054065 CN 200610054065 CN 200610054065 A CN200610054065 A CN 200610054065A CN 1811425 A CN1811425 A CN 1811425A
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Abstract
The present invention provides a red blood cell deformability analysis method based on silicon microchannel array chip and its equipment for implementing said method. Said equipment includes the following several portions: microchannel array chip closed in base seat, flow path control system containing speed detector, pressure pump and pressure sensor, computer and its interface, microscope and image collecting device. Said invention also provides the concrete connection relationship of all the above-mention portions and its working principle. Besides, said invention also provides the concrete steps of said analysis method.
Description
Technical field
The invention belongs to test, the analysis field of blood, be specifically related to a kind of method and apparatus of measuring red cell deformability.
Background technology
The technology of measuring at present red cell deformability in the world mainly contains following several:
1. the micro pipette method is measured red blood cell that micro pipette sucks length partly under constant negative pressure, determines erythrocytic mechanical property and deformation performance with this.Because this method is only measured single red blood cell, complicated operation, time-consuming should not be promoted.
2. laser diffractometry: blood sample is put into flow chamber,, measure and see through laser intensity between deformation phases and erythrocytic length and width are recently determined erythrocytic deformability because tangential stress causes red blood cell deformation.This method can only be measured the erythrocytic deformation performance of colony, and the cost of instrument is very expensive.
3. filtration method: under certain temperature and pressure, measure the red blood cell suspension of certain volume and measure erythrocytic deformability by the utensil that filter membrane, metallic screen etc. has filtration.The filter membrane processing stability that this method adopts is difficult to guarantee that the filter opening size is uneven, influence repeatability.
4. conductance method: red blood cell has deformability, thereby so red blood cell pH in the flow field can align the change that causes the cell suspending liquid conductivity, so conductivity can characterize out erythrocytic deformability.This method also can't the erythrocytic distortion situation of Real Time Observation.
In a word, all be left to be desired in order to the method for observing red cell deformability up to now, still there is not a kind of method both can be by easy micro imaging system Direct observation red blood cell deformation process, provide single again simultaneously and parameter colony's red blood cell deformation situation, provide abundanter rheology information to clinic diagnosis.
Summary of the invention
The purpose of this invention is to provide a kind of more perfect red cell deformability detection method and device, it can pass through microscope direct observing cytomorphosis situation, can measure single red cell deformability by computer image analysis, and obtain the colony red cell deformability by the stream population parameter and distribute, this method is measured simple, and can obtain more rheology information, can be widely used in clinical.
Normocyte has the deformability of height, can comparatively fast pass through the capillary more much smaller than its diameter.But cause at a variety of causes under the situation of deformability attenuating, red blood cell can increase by the time of capillary, even stopped up.The present invention is in conjunction with the MEMS process technology, detects requirement by red cell deformability, etching parallel microchannels simulation capillary network on silicon chip.Because under uniform pressure drives, the red blood cell that deformability is different is also different by the time of passage, and single like this red blood cell can be measured by image analysis system by the time of passage, and fluctuations in discharge can reflect the situation of colony's red cell deformability again in the overall flow paths.
Ripe silicon chip process technology has guaranteed the accurate control of channel size, and precision can reach submicron order, and channel size also can be according to the different needs flexible design, and with low cost.The microchannel chip design is surperficial Open architecture, can pass through micro imaging system Direct observation red blood cell deformation situation, is convenient to the collection and the analysis of image.
The concrete technical scheme of the present invention is as follows:
Micro path array chip as the core is enclosed in the pedestal, and micro path array chip connects sample channel and waste liquid chamber respectively by two outlets of pedestal, is connected with the photovoltaic array that detects flow velocity on the sample channel.The afterbody of sample intake passage is a sample cell and a buffering liquid bath by T-valve control, a two common cushion chamber and positive pressure pumps of connecting of groove, another outlet of cushion chamber connects a reduction valve, pressure transducer is set in the cushion chamber, and photovoltaic array is gone into module with pressure transducer by mould and is connected with computing machine.The top of chip base is a viewing plane, connects microlens, and microscope connects image capture device and computing machine outward.
When detecting beginning, T-valve switches to the state that sample cell, buffering liquid groove, sample channel all communicate, and positive pressure pump drives the speed detector of flowing through after the damping fluid of red blood cell sample in buffering liquid groove in the sample cell mixes by cushion chamber, enters chip at last.Pressure transducer in the cushion chamber is regulated stream pressure by computing machine instant playback channel inner pressure situation by reduction valve, reaches the pressure limit that detection needs.Microscopically Real Time Observation red blood cell deformation situation, synchronous signal acquisition and recording system starts working: a. view data: through being installed in CCD camera on the microscope under the supervision of company monitor, picked-up sample cell by the microchannel procedural image and import computing machine and carry out the image storage and analyze, b. data on flows: the photovoltaic array test sample flow that on the sample introduction stream, is provided with, cell is imported computing machine by the variation of flow in the chip system process after amplifying.Finish the work that aggregation of data is analyzed on the last computing machine.Detection finishes, and T-valve switches to buffering liquid groove, and malleation drives buffer solution for cleaning stream and chip.
Advantage of the present invention is:
1. can be by reaching cytomorphosis and mobility status in the passage near the microscope direct observing passage;
2. can measure the precise information of single red cell deformability, also can obtain the distribution situation of colony's red cell deformability;
3.MEMS the microchannel size of technology processing can accurately be controlled, but channel shape and size flexible design;
4. the microchannel of simulation capillary is as detector, and experiment condition is the interior condition of analogue body basically, can intuitively reflect microcirculating state.
Description of drawings
Fig. 1 is a micro path array chip structure partial synoptic diagram
Fig. 2 is the synoptic diagram of data (signal) acquisition processing system, and wherein scheming A is the image data acquiring disposal system, and figure B is pressure-electric signal and pulse signal acquisition disposal system
Fig. 3 is the structural representation of single unit system
Embodiment
Describe the detailed process that realizes that concrete device of the present invention and method realize in detail below in conjunction with each synoptic diagram:
Fig. 1 is the partial schematic diagram of micro path array chip 7, A indication part among its rectangular channel such as the figure, its width 5um, degree of depth 5.2um, length 30um is to adopt the MEMS process technology, detect requirement by red cell deformability, simulation capillary network, etching forms on silicon chip.
In the A of Fig. 2 figure, metaloscope 9 is connected with CCD camera 10 through optical interface, the CCD camera links to each other with video frequency collection card 13 through video output cable, and CCD camera 10 is input to computing machine 14 through the image document of metaloscope 9 picked-up red blood cell via hole deformation processes by video frequency collection card 13 and carries out picture archiving and Flame Image Process; Among the figure B, the pressure that positive pressure pump 1 produces passes to cushion chamber 16, the pressure sensitivity of cushion chamber 16 and pressure transducer 11 is measured end and is connected, and pressure transducer 11 output terminals are gone into module 12 with mould and linked to each other, and carries out importing computing machine 14 after the amplification, A/D conversion process of pressure signal and carries out data processing.When the pressure of positive pressure pump 1 generation is higher than the pressure of our setting, by reduction valve 15 relief pressures.Simultaneously, cross pulse signal that infrared electro array 5 produced when blood flow and also import mould and go into module 12, go into module 12 input computing machines 14 by mould again and carry out signal analysis and subsequent treatment.
Fig. 3 is the one-piece construction synoptic diagram of device.Red blood cell suspension is positioned in the sample cell 2, damping fluid is positioned in the buffering liquid groove 3, sample cell 2 links to each other with the inside passage aisle of chip base 6 by T-valve 4 with buffering liquid bath 3, and the inside passage aisle of chip base 6 links to each other with the bottom aperture of micro path array chip 7.Under the pressure-driven that positive pressure pump 1 produces, the red blood cell suspension of sample cell 2 flows through the A end of T-valve 4, and the damping fluid in the buffering liquid groove 3 flows through the B end of T-valve 4, and two kinds of liquid mix at the C of T-valve 4 end.Under pressure-driven, flow into detection micro path array chip 7 through sample channel 17, the waste liquid after the detection flows into waste liquid pool 8.Its course of work is with regard to as shown in Fig. 2: the image document that red blood cell is flow through the process of micro path array chip channel deformation is imported computing machine 14 by CCD camera 10 and video frequency collection card, crosses the process of passage through the image processing program pair cell and carries out real-time observation and graphical analysis dynamically.Simultaneously, the pulse signal that the pressure-electric signal of positive pressure pump 1 and red blood cell suspension produce by photovoltaic array 5 is also real-time is input to computing machine 14, through in establish mensuration and the analysis that handling procedure carries out red blood cell rheological characteristics dynamic real-time.
Claims (3)
1. silicon microchannel array erythrocyte rheological analyzing method, method is to adopt MEMS process technology etching parallel microchannels simulation capillary network on silicon chip, form micro path array chip, with sample channel that chip links to each other in detect the sample introduction flow velocity, and the pressure of detection and control sample intake passage, gather image simultaneously by the sample of micro path array chip, above-mentioned detection information offers Computer Analysis, can obtain the size of single erythrocyte deformability by the time of red blood cell by the microchannel, change the erythrocytic deformability situation of reflection colony by bulk flow in the stream simultaneously.
2. silicon microchannel array erythrocyte rheological analyzing device, it is characterized in that: it has a pedestal, the pedestal inner sealing has the micro path array chip of simulation capillary network, micro path array chip connects sample channel and waste liquid chamber respectively by two outlets of pedestal, be connected with the photovoltaic array that detects flow velocity on the sample channel, the afterbody of sample intake passage is by the sample cell of T-valve control and buffering liquid bath, a two common cushion chamber and positive pressure pumps of connecting of groove, another outlet of cushion chamber connects a reduction valve, pressure transducer is set in the cushion chamber, and photovoltaic array is gone into module with pressure transducer by mould and is connected with computing machine; The top of pedestal is a viewing plane, connects microlens, and microscope connects image capture device and computing machine outward.
3. analytical equipment according to claim 1 is characterized in that: described micro path array chip is to adopt the MEMS process technology, and etching 5um is wide on silicon chip, and 5.2um is dark, the parallel microchannels simulation capillary network that 30um is long.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200610054065 CN1811425A (en) | 2006-01-28 | 2006-01-28 | Silicon microchannel array erythrocyte rheological analyzing method and apparatus |
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| CN 200610054065 CN1811425A (en) | 2006-01-28 | 2006-01-28 | Silicon microchannel array erythrocyte rheological analyzing method and apparatus |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102854094A (en) * | 2012-10-10 | 2013-01-02 | 重庆大学 | Multichannel microfluidic blood rheological analysis chip as well as analysis system and analysis method of chip |
| CN108445200A (en) * | 2018-02-12 | 2018-08-24 | 南方医科大学 | A kind of influence based on micro-fluidic chip detection pentoxifylline to Erythrocytes from Coronary Heart Disease deformability and biochemical index |
| CN113447337A (en) * | 2020-07-05 | 2021-09-28 | 上海宏勃生物科技发展有限公司 | Detection system integrated with dyeing function and used for microscopic examination |
-
2006
- 2006-01-28 CN CN 200610054065 patent/CN1811425A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102854094A (en) * | 2012-10-10 | 2013-01-02 | 重庆大学 | Multichannel microfluidic blood rheological analysis chip as well as analysis system and analysis method of chip |
| CN102854094B (en) * | 2012-10-10 | 2014-09-10 | 重庆大学 | Multichannel microfluidic blood rheological analysis chip as well as analysis system and analysis method of chip |
| CN108445200A (en) * | 2018-02-12 | 2018-08-24 | 南方医科大学 | A kind of influence based on micro-fluidic chip detection pentoxifylline to Erythrocytes from Coronary Heart Disease deformability and biochemical index |
| CN113447337A (en) * | 2020-07-05 | 2021-09-28 | 上海宏勃生物科技发展有限公司 | Detection system integrated with dyeing function and used for microscopic examination |
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