CN205917285U - A device for detecting with partitioning cycle melanoma cell - Google Patents
A device for detecting with partitioning cycle melanoma cell Download PDFInfo
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- CN205917285U CN205917285U CN201620609017.1U CN201620609017U CN205917285U CN 205917285 U CN205917285 U CN 205917285U CN 201620609017 U CN201620609017 U CN 201620609017U CN 205917285 U CN205917285 U CN 205917285U
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- melanoma cell
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Abstract
The utility model relates to a device for detecting with partitioning cycle melanoma cell, the photoelectric detection system that is connected including computer control system, with computer control system electricity and with the blood flow circulation unit of photoelectric detection with a system use, the photoelectric detection system include pulse laser, set gradually the post lens between pulse laser and blood flow circulation unit, mechanical slit, convex lens, speculum, objective and the relative ultrasonic probe who sets up with objective, this ultrasonic probe is connected with computer control system is electric. Compared with the prior art, the utility model has the advantages that the whole structure is simple single, convenient operation can realize intelligent control, and it is high to detect the precision, and wicresoft's security is high, and economical and practical can sneak into the measuring that realizes circulation tumor cells under the circumstances of tag in not to blood to the micro - blood that will contain circulation melanoma cell is isolated, but wide application in clinical medicine and foundation medicine research field.
Description
Technical field
This utility model belongs to Cell Measurement Technique field, is related to a kind of cell detection and segregation apparatuss, especially relates to
A kind of device for detecting and separating circulation melanoma cell.
Background technology
Melanoma is a kind of very high tumor of grade malignancy, is mostly primary in the positions such as skin, eye, nasal cavity, can be swollen
Neoplasia early stage is transferred to the significant points such as lung, brain.Circulating tumor cell (English abbreviation: ctc) refers to primary from tumor
Stove separates and enters the cell of blood circulation, has and adheres at other positions of body and form the ability of metastatic lesion.Circulation
Melanoma cell is an important indicator of reaction melanoma metastasis, and the number of circulation melanoma cell is swollen for judging
The process of tumor metastasiss is significant, removes circulating tumor cell in time and will be helpful to suppress the early stage of melanoma to shift
Journey, reduces the probability of tumor recurrence.
The number of circulating tumor cell is considerably less, and in every milliliter of blood, the quantity containing hemocyte is about 5,000,000,000, but
The content of circulating tumor cell is typically less than 10, therefore, is difficult to be detected by traditional medical instrument in clinic.For example,
Computer tomography, the resolution of nuclear magnetic resonance determine it and cannot observe micron-sized cell.Positron tomography becomes
As transmitting imaging can detect the tumor focus of early stage using radionuclide in the enrichment of tumor focus, but equally cannot examine
Measure the motion conditions of circulating tumor cell, and nucleic has certain injury to human body.In biomedical research, often by means of
The method mark cycle tumor cell of cell fluorescence labelling, ultimate principle is using the specific antibody mark coupling with fluorescent probe
Some specific position of note tumor cell, are detected by means of fluorescence analysis.At present, examine for circulating tumor cell
The research of survey technology enjoys the extensive concern of scientific worker.
The Chinese patent of Application No. 201410787928.9 discloses a kind of dress of detection circulating tumor cell (ctc)
Put, including silicon chip and sealing-in polymer cover plate square on a silicon substrate, also include being arranged at the Magnet below silicon chip;Institute
State polymer cover plate and be provided with fluid issuing and entrance, the one side of contact silicon chip is provided with fluid storage chamber, fluid issuing and entrance
Connected with fluid storage chamber respectively by fluid passage;Described silicon chip contacts the one side of polymer cover plate, corresponding to fluid
The position of storage chamber, arranges silicon nanowires region;The installation site of described Magnet is corresponding with silicon nanowires region.Above-mentioned patent is public
The technical scheme of cloth is combined by silicon nanowire array and magnetic field, for improving the efficiency catching ctc.Fluorescence signal is not carried on the back
Scape autofluorescence disturbs, and the sensitivity effectively increasing ctc detection is it is possible to be used for into one by the ctc that eluting separates and collects
The Molecular Detection of step.Although the technical scheme of above-mentioned patent disclosure can realize detection and the separation of circulating tumor cell, need
Will be by specific marker substance markers ctc, and the detection time that this device spends on each ctc can be very long.
The Chinese patent of Application No. 201510908410.0 discloses multifunctional tumor cell or other pathological cells inspection
Survey device and its detection method, described device includes LASER Light Source, laser mirror, post lens, unicellular liquid fluid system, thin
Born of the same parents' separating trap micro-fluidic chip, fluorescent reflection mirror, photomultiplier tube, data handling system, described photomultiplier tube and data
Processing system is connected, and also includes pulsed laser source, ultrasonic probe, described ultrasonic probe is connected with data handling system, described sharp
Radiant, laser mirror, post lens forming are by the focusing system on laser focusing to unicellular liquid fluid system, described fluorescence
Reflecting mirror and photomultiplier tube form and collect collection system, described pulsed laser source and the post that unicellular liquid fluid system sends fluorescence
Another focusing system on pulse laser focusing to unicellular liquid fluid system, described ultrasonic probe are located at unicellular by lens forming
On liquid fluid system, described cell separation captures the port that micro-fluidic chip is located at unicellular liquid fluid system.Above-mentioned patent disclosure
Technical scheme be mixed with traditional Flow Cytometry, ultrasonic signal detection and microfluidic chip technology, but lack necessary
Ins and outs.Lack the implementation detail forming sheath streaming system essential to unicellular liquor stream first, do not possess feasibility;Secondly should
Patent is split based on the Flow Cytometry of fluorescence to highly developed, related to fluorescent labeling and detection
Content has all been announced;The detection range of the 1hz-100mhz in ultrasound detection has substantially been intentionally enlarged detection range, and this is special
Profit does not announce testing result, and the enforcement of this technical scheme remains a need for blood or other Yang Ping are carried out with the process of complexity
To obtain unicellular liquor stream.
Therefore no matter that method above-mentioned, the material being required for being mixed into synthetic in blood carries out to circulating tumor cell
Labelling or the process that blood sample is carried out with complexity, lead to detection speed slower, greatly limit it and be applied to
Circulating tumor cell under condition of living organism separates.Research shows, the melanin content in most of melanoma cell with normal
Cell has larger difference, therefore, it can using photoacoustic signal, it be detected.Light voice phenomenon refers to using intracellular certain
After a little materials (mainly melanin) absorb pulse laser, temperature raises rapidly, and volume expands therewith and sends faint ultrasonic letter
Number, cell can be detected by detecting ultrasonic signal.It has been one based on the photoacoustic imaging that light voice phenomenon grows up
Plant the means of comparative maturity, abroad have Research Team to be applied to clinical breast cancer inspection.
Utility model content
In order to overcome existing cell analysis isolation technics to need by means of being mixed into special marking in blood and be difficult to
Realize the deficiency of the separation circulating tumor cell under condition of living organism, this utility model provide a kind of for detection with to separate circulation black
The device of pigment oncocyte, in the case that this device can be mixed into label in not to blood, realizes circulation melanoma thin
The detection of born of the same parents, and the micro blood containing circulating tumor cell is separated.
The purpose of this utility model can be achieved through the following technical solutions:
A kind of for detect and separate circulation melanoma cell device, this device include computer control system and
The photodetector system of computer control system electrical connection and the blood circulation unit using cooperatively with photodetector system, institute
The post that the photodetector system stated includes pulse laser, be successively set between pulse laser and blood circulation unit is saturating
Mirror, mechanical slot, convex lenss, reflecting mirror, object lens and the ultrasonic probe being oppositely arranged with object lens, this ultrasonic probe and computer
Control system electrically connects;
Under in working order, pulse laser that described pulse laser is launched sequentially pass through post lens, mechanical slot,
Convex lenss, reflecting mirror and object lens, focus in blood circulation unit, and produce focal spot, when the circulation in blood circulation unit is black
When melanoma cell flows through focal spot position, strongly can absorb pulse laser, and produce ultrasonic signal, described ultrasonic probe receives
Ultrasonic signal is simultaneously sent to computer control system and is identified.
The wavelength of the pulse laser that described pulse laser produces is 820-1064nm, and < 10ns repeats frequency to pulse width
Rate is about 10khz.
Described mechanical slot is located at the focal length of post lens.
Described mechanical slot is equal with the spacing of convex lenss and the focal length of convex lenss.
Described reflecting mirror is in 45 ° with the optical axis of pulse laser.
Described blood circulation unit includes blood circulation conduit and is arranged on the double outlet blood on blood circulation conduit
Liquid pump, this pair of exit blood pump is electrically connected with computer control system, and described computer control system passes through double exit blood
Pump regulates and controls to the blood flow in blood circulation conduit or blood flow rate, and can control blood flow at two of double exit blood pumps
Switching between outlet.
Described blood circulation unit also includes the waste liquid cylinder being connected with the one outlet of double exit blood pumps.
Described pulse laser focusing is on blood circulation conduit, and produces focal spot, and this focal spot is to cover blood circulation to lead
The strip focal spot of inside pipe wall arbitrary diameter.
Described ultrasonic probe and object lens are oppositely arranged, and are separately positioned on the both sides of blood circulation conduit.
Computer workstation that described computer control system includes electrically connecting with double exit blood pumps, successively with ultrasonic
The amplifier of probe electrical connection and data acquisition unit, this data acquisition unit is connected with computer workstation by circuit.
In this utility model, circular light spot is organized into by the pulse laser of pulse laser transmitting through post lens and slit
Approximate thin-and-long, object lens are by laser focusing to blood circulation conduit.The blood of blood sample or living animal is by blood circulation
Duct entry enters, and double exit blood pumps control the flowing of blood.When circulation melanoma cell flows through focal spot position, can be strong
Strong absorption pulse laser simultaneously produces ultrasonic signal, by ultrasonic probe, amplifier and high speed data acquisition system, is converted into electricity
Signal by computer workstation real-time processing, when signal peak, indicates that circulating tumor cell passes through;Computer workstation
After identification signal, the double exit blood pump of Synchronization Control the micro blood containing circulation melanoma cell can be pumped out to waste liquid receipts
Collection passage, delivers to waste liquid cylinder side by side.
Specifically, when actually used, the pulse laser that pulse laser produces, after post lens, can become ellipse
Circular laser, its output wavelength can be 820~1064nm, and < 10ns, repetition rate is about 10khz to pulse width;In post lens
Focal length at have mechanical slot, by adjustment width control hot spot size, hot spot be modulated into width be about 400 μm approximately long
Bar shaped;The distance of convex lenss and mechanical slot is the focal length of convex lenss, and reflecting mirror is mainly used in changing key light direction of principal axis to save
Space, the optical axis of reflecting mirror and pulse laser is in 45 ° of placements, and pulse laser eventually passes through 40 times of object lens and focuses on blood circulation leads
One inner wall diameter position of pipe, this position is designated as focal spot position.The blood of blood sample or experiment made on the living animal is by blood
Circulation conduit entrance enters blood circulation conduit, and under the control of double exit blood pumps, remain a constant speed flowing, wherein, described
Double exit blood pumps with precise control velocity of blood flow or flow and can control blood accurate switching between two outlets;When
When circulation melanoma cell flows through focal spot position, can be because optoacoustic effect produce specificity ultrasonic signal, ultrasonic probe is pressed close to
Blood circulation conduit is placed, and is in 30 ° of angles with the pulse laser direction of propagation, and ultrasonic signal is converted to telecommunications by ultrasonic probe
Number, after through amplifier amplify and denoising, be converted to after digital signal by high speed data acquisition system, known by computer workstation
Not.
This utility model device be currently only used in blood sample circulate melanoma cell detection with separate, Yi Jishi
Test the detection of the circulation melanoma cell under the laboratory animal condition of living organism in room and separate.But it is as being applied to clinical practice
Prototype, have human circulation melanoma cell is carried out detection and detached potentiality.
Compared with prior art, this utility model has the following characteristics that
1) detection of circulating tumor cell can be realized in the case of being mixed into label in not to blood, and will be containing following
The micro blood of ring melanoma cell is separated;
2) have and be widely used in immunology, hematology, oncology, cytobiology, cytogeneticss, biochemistry etc.
Clinical medicine and the potentiality in basic medical research field;
3) overall structure is simple, easy to operate, is capable of intelligentized control method, minimally invasive safe, economical and practical, has
Application prospect well.
Brief description
Fig. 1 is this utility model device overall structure diagram;
Fig. 2 is the photoacoustic signal figure of the circulation melanoma cell using the detection of this utility model device;
In figure description of symbols:
1 pulse laser, 2 post lens, 3 mechanical slot, 4 convex lenss, 5 reflecting mirrors, 6 object lens, 7 surpass
Sonic probe, 8 blood circulation conduits, 9 pairs of exit blood pumps, 10 waste liquid cylinders, 11 computer workstations, 12 amplifications
Device, 13 data acquisition units, 14 waste collection passages.
Specific embodiment
With specific embodiment, this utility model is described in detail below in conjunction with the accompanying drawings.
Embodiment:
As shown in figure 1, a kind of device for detecting and separating circulation melanoma cell, this device includes computer control
The photodetector system that system processed is electrically connected with computer control system and the blood flow being used cooperatively with photodetector system are followed
Ring element, photodetector system includes pulse laser 1, is successively set between pulse laser 1 and blood circulation unit
Post lens 2, mechanical slot 3, convex lenss 4, reflecting mirror 5, object lens 6 and the ultrasonic probe 7 being oppositely arranged with object lens 6, this is ultrasonic
Probe 7 is electrically connected with computer control system;Wherein, mechanical slot 3 is located at the focal length of post lens 2;Mechanical slot 3 and convex lens
The spacing of mirror 4 is equal with the focal length of convex lenss 4;Reflecting mirror 5 is in 45 ° with the optical axis of pulse laser.
Blood circulation unit includes blood circulation conduit 8 and is arranged on the double exit blood pumps on blood circulation conduit 8
9, this pair of exit blood pump 9 is electrically connected with computer control system, and computer control system passes through double exit blood pumps 9 to blood
Blood flow in circulation conduit 8 or blood flow rate are regulated and controled, and blood flow can be controlled to export it in two of double exit blood pumps 9
Between switching.Blood circulation unit also includes the waste liquid cylinder 10 being connected with the one outlet of double exit blood pumps 9.Pulse laser
Focus on blood circulation conduit 8, and produce focal spot, this focal spot is strip Jiao covering blood circulation conduit 8 inner diameter
Speckle.Ultrasonic probe 7 is oppositely arranged with object lens 6, and is separately positioned on the both sides of blood circulation conduit 8.
Computer workstation 11 that computer control system includes electrically connecting with double exit blood pumps 9, successively with ultrasonic spy
The amplifiers 12 of 7 electrical connections and data acquisition unit 13, this data acquisition unit 13 passes through circuit with computer workstation 11 even
Connect.
Under in working order, the wavelength of the pulse laser that pulse laser 1 produces is 820-1064nm, pulse width <
10ns, repetition rate is about 10khz.The pulse laser that pulse laser 1 is launched sequentially pass through post lens 2, mechanical slot 3,
Convex lenss 4, reflecting mirror 5 and object lens 6, focus in blood circulation unit, and produce focal spot, the circulation in blood circulation unit
When melanoma cell flows through focal spot position, strongly can absorb pulse laser, and produce ultrasonic signal, ultrasonic probe 7 receives super
Acoustical signal is simultaneously sent to computer control system and is identified.
When actually used, the pulse laser that pulse laser 1 produces, after post lens 2, ovalisation can be become and swash
Light;There is mechanical slot 3 at the focal length of post lens 2, control the size of hot spot by adjustment width, hot spot is modulated into width about
For 400 μm of approximate strips;The distance of convex lenss 4 and mechanical slot 3 is the focal length of convex lenss 4, and reflecting mirror 5 is mainly used in changing
Key light direction of principal axis is in 45 ° of placements to save space, reflecting mirror 5 with the optical axis of pulse laser, and pulse laser eventually passes through 40 times of things
Mirror 6 focuses on an inner wall diameter position of blood circulation conduit 8, and this position is designated as focal spot position.Blood sample or live body
The blood of laboratory animal enters blood circulation conduit 8 by the entrance of blood circulation conduit 8, under the control of double exit blood pumps 9,
Remain a constant speed flowing, and wherein, double exit blood pumps 9 with precise control velocity of blood flow or flow and can control blood to go out at two
Accurate switching between mouthful;When circulation melanoma cell flows through focal spot position, can be because optoacoustic effect produces specificity and surpasses
Acoustical signal, ultrasonic probe 7 is pressed close to blood circulation conduit 8 and is placed, and is in 30 ° of angles with the pulse laser direction of propagation, ultrasonic signal
The signal of telecommunication is converted to by ultrasonic probe 7, after through amplifier 12 amplify and denoising, number is converted to by high speed data acquisition system 13
After word signal, signal peak (as shown in Figure 2) occurs, indicates that circulating tumor cell passes through, computer workstation 11 identifies signal
Afterwards, the double exit blood pump 9 of Synchronization Control the micro blood containing circulation melanoma cell can be pumped out to waste collection passage
14, deliver to waste liquid cylinder 10 side by side, thus completing the detection to circulation melanoma cell and detached job.
When carrying out data concrete analysis, computer workstation 11 can record circulation melanoma tumors cell and pass through focal spot position
The time putAnd the moment t just past focal spot position, wherein d represents cell dia, and l represents spot width,
V represents blood flow rate.The distance of the waste liquid outlet to double exit blood pumps 9 for the focal spot position is l, and this pair of exit blood pump 9 willBlood in time period is pumped out to waste liquid cylinder 10.If there being multiple circulation melanoma tumors cells in this time period
(probability actually occurring is minimum), then double exit blood pumps 9 are before first circulation melanoma tumors cell enters inlet/outlet
1ms, the 1ms after being pumped out to last circulation melanoma tumors cell terminates, and blood is pumped out to waste liquid cylinder 10.Using this
Method, if within each circulation melanoma tumors cell of separation needs the blood pumping out can control 10 μ l, separating 1000 and follow
Oligemia 10ml that ring melanoma tumors cell needs pump out.
The present embodiment device be currently only used in blood sample circulate melanoma cell detection with separate, and experiment
Circulation melanoma cell under laboratory animal condition of living organism in room detects and separates.But it is as being applied to clinical practice
Prototype, has and human circulation melanoma cell is carried out detect and detached potentiality.
The above-mentioned description to embodiment is to be understood that and use practicality for ease of those skilled in the art
New.Person skilled in the art obviously easily can make various modifications to these embodiments, and here is illustrated
General Principle be applied in other embodiment without through performing creative labour.Therefore, this utility model be not limited to above-mentioned
Embodiment, those skilled in the art according to announcement of the present utility model, the improvement made without departing from this utility model category and
Modification all should be within protection domain of the present utility model.
Claims (10)
1. a kind of for detect and separate circulation melanoma cell device it is characterised in that this device includes computer control
The photodetector system that system processed is electrically connected with computer control system and the blood flow being used cooperatively with photodetector system are followed
Ring element, described photodetector system includes pulse laser (1), is successively set on pulse laser (1) and blood circulation
Post lens (2) between unit, mechanical slot (3), convex lenss (4), reflecting mirror (5), object lens (6) and relative with object lens (6)
The ultrasonic probe (7) of setting, this ultrasonic probe (7) is electrically connected with computer control system.
2. according to claim 1 a kind of for detection with separate circulation melanoma cell device it is characterised in that
The wavelength of the pulse laser that described pulse laser (1) produces is 820-1064nm, and < 10ns, repetition rate is about for pulse width
For 10khz.
3. according to claim 1 a kind of for detection with separate circulation melanoma cell device it is characterised in that
Described mechanical slot (3) is located at the focal length of post lens (2).
4. according to claim 3 a kind of for detection with separate circulation melanoma cell device it is characterised in that
Described mechanical slot (3) is equal with the focal length of convex lenss (4) with the spacing of convex lenss (4).
5. according to claim 1 a kind of for detection with separate circulation melanoma cell device it is characterised in that
Described reflecting mirror (5) is in 45 ° with the optical axis of pulse laser.
6. a kind of device for detecting and separating circulation melanoma cell according to any one of claim 1 to 5, its
It is characterised by, described blood circulation unit includes blood circulation conduit (8) and is arranged on double on blood circulation conduit (8)
Exit blood pump (9), this pair of exit blood pump (9) is electrically connected with computer control system, and described computer control system is led to
Cross double exit blood pumps (9) blood flow in blood circulation conduit (8) or blood flow rate are regulated and controled, and blood flow can be controlled to exist
Switching between two outlets of double exit blood pumps (9).
7. according to claim 6 a kind of for detection with separate circulation melanoma cell device it is characterised in that
Described blood circulation unit also includes the waste liquid cylinder (10) being connected with the one outlet of double exit blood pumps (9).
8. according to claim 6 a kind of for detection with separate circulation melanoma cell device it is characterised in that
Described pulse laser focusing is on blood circulation conduit (8), and produces focal spot, and this focal spot is to cover blood circulation conduit (8)
The strip focal spot of inner diameter.
9. according to claim 6 a kind of for detection with separate circulation melanoma cell device it is characterised in that
Described ultrasonic probe (7) and object lens (6) are oppositely arranged, and are separately positioned on the both sides of blood circulation conduit (8).
10. a kind of device for detecting and separating circulation melanoma cell according to claim 6, its feature exists
The computer workstation (11) that includes electrically connecting with double exit blood pumps (9) in, described computer control system, successively with super
Amplifier (12) and data acquisition unit (13) that sonic probe (7) electrically connects, this data acquisition unit (13) passes through circuit and calculating
Machine work station (11) connects.
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CN201620609017.1U CN205917285U (en) | 2016-06-20 | 2016-06-20 | A device for detecting with partitioning cycle melanoma cell |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN106085962A (en) * | 2016-06-20 | 2016-11-09 | 上海交通大学 | A kind of device for detecting and separate circulation melanoma cell |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN106085962A (en) * | 2016-06-20 | 2016-11-09 | 上海交通大学 | A kind of device for detecting and separate circulation melanoma cell |
CN106085962B (en) * | 2016-06-20 | 2022-03-22 | 上海交通大学 | Device for detecting and separating circulating melanoma cells |
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