CN103278365A - Drum type biochip spotting device and method thereof - Google Patents
Drum type biochip spotting device and method thereof Download PDFInfo
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- CN103278365A CN103278365A CN2013102271003A CN201310227100A CN103278365A CN 103278365 A CN103278365 A CN 103278365A CN 2013102271003 A CN2013102271003 A CN 2013102271003A CN 201310227100 A CN201310227100 A CN 201310227100A CN 103278365 A CN103278365 A CN 103278365A
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Abstract
The invention relates to a drum type biochip spotting device and a method thereof. The device comprises: a drum having an outer circumference surface, wherein a biochip matrix can be coated on the outer circumference surface of the drum; a drum driving mechanism used for rotating the drum; a spotting needle rack arranged over the drum and provided with a spotting needle array; and a spotting needle rack driving mechanism used for making the spotting needle rack move relative to the drum. The device uses the surface of the drum as the bearing surfaces of biochips in the invention, so the space utilization rate is substantially increased, a spotting pipeline is shortened, and the bubble generation possibility is reduced. A slide block provided with a spotting needle does not move in the vertical spotting process, so a pipeline system is always in a stationary state, and the pressure change influencing the spotting precision is very small, thereby the spotting precision and the spotting efficiency are greatly increased.
Description
Technical field
The present invention relates to the biochip point sample device and method.
Background technology
Crack human inheritance's secret, drug screening etc. many aspect, biochip point sample instrument (or also can be called " spot sample device ") has become requisite basic equipment.Therefore, the quality of the height of biochip point sample instrument technical merit, performance index also affects the process of life science to a certain extent.Only with regard to function, which kind of biochip point sample instrument no matter, all be for can be the DNA that will study or check usefulness, RNA, many skins, protein and other biological composition are fixed on the solid phase compact substance carriers such as silicon chip, glass sheet or pottery sheet with high density and high-precision mode by desirable matrix dot, thereby form the biomolecule dot matrix.
Physical construction plays a part very important in biochip point sample instrument as support and the executor of precision, speed, function etc.Reasonably physical construction not only can make and pursue high precision and become possibility at a high speed, and should have higher space availability ratio for equipment provides enough rigidity.Up to the present, the physical construction of biochip point sample instrument generally all will relate to the three-dimensional motion of X/Y/Z axle.Such physical construction layout more complicated is loose, and the slide holder range of movement of carrying biochip (matrix) is very big, and space availability ratio is not high.The point sample instrument of this structure actual floor area in use is very big, and because the point sample pipeline of spotting needle (in the existing point sample instrument, usually link to each other by the tediously long pipeline of bending between spotting needle and the sampling receptacle, this pipeline can abbreviate " point sample pipeline " as) very long, the possibility that produces bubble during point sample is also bigger.In addition, in the point sample process, spotting needle will constantly move, and pipe system is also unstable, and the pressure that influences the point sample precision changes greatly; This has caused point sample efficient low again, and the point sample precision is not high, and biochip is long process time, thereby makes that most of scientific research institutions are difficult to accept.
Summary of the invention
One of purpose of the present invention provides a kind of biochip point sample device, and it can overcome certain or some shortcoming of above-mentioned existing spot sample device.
Drum-type biochip point sample device according to the present invention comprises:
Cylinder with external peripheral surface, wherein biochip matrix is suitable for being coated on the external peripheral surface of cylinder;
Drum drive is used for rotary drum;
Be arranged on cylinder top and the point sample punch block of spotting needle array is installed; And
Point sample punch block driving mechanism is used for making the point sample punch block with respect to roller shifting.
The present invention is owing to used the loading end of cylinder surface as biochip, therefore improved space availability ratio greatly, and shortened the point sample pipeline greatly, reduced the possibility of generation bubble (when 1. for the first time spraying sample, the residual bubble of meeting in the pipeline, if pipeline is long, the time of removing bubble is just more long, and the possibility of leaving over bubble is also more big; 2. when varying product, if pipeline is long, the time of cleaning is also more long, and this also is the key factor that bubble produces; 3. pipeline is long, makes to change instability for sample pipe system pressure in the point sample process, also can cause pipeline to produce bubble.The present invention directly is integrated into point sample punch block or spotting needle with the point sample pipeline, probe in the sample box by the spotting needle syringe needle and to take a sample, effectively shortened the point sample pipeline and avoided the existence of the problems referred to above, made pipe system pressure stability in the point sample process, so reduced to produce the possibility of bubble greatly.)。Simultaneously, in vertical point sample process, because it is mobile that the slide block of spotting needle is housed, pipe system keeps stationary state, and the pressure variation that influences the point sample precision is very little, so significantly improved point sample precision and point sample efficient.
In a preferred embodiment of the invention, drum drive comprises the cylinder servomotor that directly links to each other with cylinder, is used for making cylinder rotate preset angles at every turn.The direct-connected advantage of cylinder and servomotor is that driving error is little, bearing accuracy is high.
In another preferred embodiment of the present invention, spot sample device can also comprise the vacuum device that links to each other with cylinder, and the external peripheral surface of its intermediate roll is provided with a plurality of perforation so that biochip matrix can be fixed on the external peripheral surface of cylinder in the vacuum suction mode by described a plurality of perforation.The vacuum suction fixed form makes that the replacing of biochip matrix is more convenient.
In another preferred embodiment of the present invention, the external peripheral surface of cylinder can be provided with at least one circumferential groove.Because circumferential groove corresponding to the zone of blotting of biochip matrix, therefore can make spotting needle avoid damaging when action is blotted in execution.
In another preferred embodiment of the present invention, point sample punch block driving mechanism can comprise: the cross slide way of installing above cylinder; Be slidably mounted in the vertical guide on the cross slide way, wherein the point sample punch block is slidably mounted on the vertical guide; Horizontal drive motor is used for vertical guide is horizontally slipped along cross slide way; And vertical drive motor, be used for the point sample punch block is slided up and down along vertical guide.This type of drive makes that spotting needle can be along laterally and vertically moving freely to desired location.
In another preferred embodiment of the present invention, spot sample device can also comprise rinse bath, sample box and the drop recording geometry that is arranged on the cross slide way below and is arranged side by side with cylinder, wherein when the point sample punch block moved to rinse bath, the spotting needle array on the point sample punch block can obtain cleaning in rinse bath; When the point sample punch block moved to sample box, the spotting needle array on the point sample punch block can be drawn sample from sample box; When the point sample punch block moves to the drop recording geometry, carry out pre-point sample and whether meet the point sample requirement with the drop of observing pre-point sample.This mode that is arranged side by side is both compact, has improved point sample efficient again.
In another preferred embodiment of the present invention, spot sample device can also comprise that CCD (Charge-coupled Device) detector lens that is installed on the vertical guide is to monitor the point sample situation of spotting needle array on biochip matrix.In this case, the point sample punch block also can be installed on the vertical guide by slide block, and the CCD detector lens is installed on the slide block.(at a high speed) correctly and whether the use of CCD detector lens can effectively detect whether leak source sample etc. of point sample position.
Another object of the present invention provides a kind of biochip point sample method, and it can be realized at a high speed and high-precision point sample.
Biochip point sample method according to the present invention comprises step:
With biochip matrix vacuum suction on the cylinder external peripheral surface;
By the spotting needle array sample is injected on the biochip on the biochip matrix on the cylinder external peripheral surface;
With the preset angles rotary drum and repeat above-mentioned injecting step.
Method of the present invention is owing to adopt rotating cylinder external peripheral surface as the surface of carrying biochip, so can reduce the volume of spot sample device significantly.In addition, in vertical point sample process, because it is mobile that the slide block of point sample punch block is housed, the point sample pipe system keeps stationary state, and the pressure variation that influences the point sample precision is very little, so significantly improved point sample precision and point sample efficient, save the point sample time greatly, made things convenient for the making of biochip.
The method according to this invention also preferably includes step: use the CCD detector lens to detect the sample of spotting needle array on biochip and spray situation.As mentioned above, correctly and whether the use of CCD detector lens can effectively detect whether leak source sample etc. of point sample position.
Description of drawings
Fig. 1 is the structural representation according to drum-type biochip point sample device of the present invention;
Fig. 2 is the partial structurtes synoptic diagram of the drum-type biochip point sample device of Fig. 1;
Fig. 3 is the structural representation of cylinder; And
Fig. 4 is the synoptic diagram of biochip matrix (film).
Embodiment
Describe drum-type biochip point sample device of the present invention in detail below in conjunction with accompanying drawing.It will be appreciated by those skilled in the art that the embodiment that describes below only is to exemplary illustration of the present invention, but not be used for it is made any restriction.
Fig. 1 shows drum-type biochip point sample device of the present invention, and it comprises cylinder 1 and point sample punch block 8.Biochip matrix 16 shown in Figure 4 can be coated on the external peripheral surface of cylinder 1.The spotting needle 11 of array format is installed on the point sample punch block 8 usually.
Can also be provided with the temporary storage chamber of sample (not specifically illustrating) on point sample punch block 8 or the spotting needle 11, be used for the temporary transient sample that spotting needle 8 is drawn from the sample box of hereinafter mentioning 4 of storing, like that sample is wherein sprayed the corresponding biomolecule dot matrix of formation by the biochip 18 of spotting needle 11 on biochip matrix 16 as described later.In this case, compare with the crooked tediously long point sample pipeline from sampling receptacle to spotting needle of traditional point sample instrument, of the present invention not only short but also straight to the point sample pipeline of spotting needle from the temporary storage chamber of sample that is arranged on point sample punch block 8 or the spotting needle 11, this has reduced to produce in the point sample pipeline possibility of bubble as previously mentioned greatly.
Fig. 1 also shows the cross slide way of installing 6 above cylinder 1.Vertical guide 10 is slidably mounted on the cross slide way 6, and by being installed in the driving of the horizontal drive motor 12 on the cross slide way 6, vertical guide 10 can be along cross slide way 6 move left and right.Point sample punch block 8 is slidably mounted on the vertical guide 10 by slide block 13 (referring to Fig. 2), and by being installed in the driving of the vertical drive motor 9 on the vertical guide 10, slide block 13 can move up and down along vertical guide 10.
Fig. 1 also shows the drum drive motor 2 that is arranged in cylinder 1 left side.Drum drive motor 2 also adopts servomotor, and is directly connected in cylinder 1.
In addition, the left side of the cylinder 1 in Fig. 1 also shows the rinse bath 3, sample box 4 and the strobe apparatus 5 that are arranged side by side with cylinder 1 respectively.Rinse bath 3 is used for cleaning the spotting needle 11 that moves to wherein with for example ultrasound wave form.Sample box 4 is used for holding biological sample for example DNA or RNA.When point sample punch block 8 moved to sample box, the spotting needle 11 on the point sample punch block 8 can be drawn biological sample from sample box 4.After sampling was finished, point sample punch block 8 moved to drop recording geometry 5 and carries out pre-point sample, and whether the auxiliary drop of the pre-point sample of observation down of for example strobe apparatus that comprises therein meets the point sample requirement.This drop recording geometry of strobe apparatus that comprises detects information such as the size of pre-point sample drop, quantity, flight angles, handles by image and judges whether the hydrojet effect is qualified automatically; It is well-known in the art, and at this its structure and principle of work is described in further detail no longer.
Fig. 1 also shows the CCD detector lens 7 that is installed on the vertical guide 10.Certainly, CCD detector lens 7 also can be directly installed on the slide block 13 shown in Fig. 2.CCD detector lens 7 is for detection of the point sample situation of spotting needle 11 on the biochip 18 on the biochip matrix 16.CCD detector lens 7 can also link to each other to monitor the point sample situation of spotting needle 11 in real time according to detection case with control system (not specifically illustrating).As mentioned above, CCD detector lens 7 both can be mounted to point sample punch block 8 up and down or move left and right, also can be mounted to only laterally mobile with vertical guide about 10, as long as its can actual detected to the point sample situation of spotting needle.
Fig. 3 shows cylinder 1 of the present invention.As shown in the figure, the external peripheral surface of cylinder 1 is provided with a plurality of circumferential grooves 14 and a plurality of perforation 15.Biochip matrix 16 shown in Figure 4 can be the diaphragm that suitable sorptive material is made.Be formed with multiple row biochip 18 on the biochip matrix 16, separated by the represented zone 17 of blotting of imaginary dotted line between every row biochip 18.During point sample, biochip matrix 16 is coated on the outer circumference surface of cylinder 1, and the zone 17 of blotting of biochip matrix 16 overlaps with the circumferential groove 14 of cylinder 1.Under the effect of the pull of vacuum that the vacuum extractor (not specifically illustrating) that links to each other with cylinder 1 produces, perforation 15 firmly is adsorbed on biochip matrix 16 on the external peripheral surface of cylinder 1.
Describe the principle of work of spot sample device of the present invention below in detail.
At first, biochip matrix 16 is fixed on the external peripheral surface of cylinder 1 in the vacuum suction mode as mentioned above, thereby can rotate with cylinder 2.
Start-up point sampling device subsequently, under the effect of horizontal drive motor 12, make vertical guide 10 move to the position of rinse bath 3 along cross slide way 6 together with the point sample punch block 8 on it earlier, moved downward along vertical guide 10 by vertical drive motor 9 control point sample punch blocks 8, ultrasound wave cleans to make spotting needle 11 for example finish in rinse bath 3.After finishing, cleaning make point sample punch block 8 move right the position of sample box 4 so that spotting needle 11 is drawn the sample DNA for example in the sample boxs 4 along cross slide way 6 again.
Then, the point sample punch block moves to drop recording geometry 5 and carries out pre-point sample, and whether the drop of the pre-point sample of observation meets the point sample requirement under the help of strobe apparatus.If pre-point sample effect is qualified, then control the position that point sample punch block 8 moves to the circumferential groove 14 of the leftmost side on the cylinder 1, moved downward by vertical drive motor 9 control spotting needles 11 and on contact biochip matrix 16, blot zone 17.Can adhere to some remaining samples because of absorption or injection at aforementioned absorption sample or pre-point sample process mid-point sample pin 11, if it is not blotted, the remaining sample of these on the spotting needle 11 can influence point sample precision subsequently.Because biochip matrix 16 has good adsorption, therefore the remaining sample on the spotting needle 11 can be blotted.Again owing to blot zone 17 as mentioned above and overlap or cover (being unsettled setting) on the circumferential groove 14, so spotting needle 11 blotted regional 17 o'clock in contact, only contacted bio-based plasma membrane 16 itself, can directly not contact the main body of cylinder 1 and damaged spotting needle 11.
Spotting needle 11 blot the action finish after, control punch block 8 moves to the initial point sample position of biochip 18 along cross slide way 6, adopts contactless spray printing method (principle of similar ink-jet printer) sample to be ejected into by spotting needle 11 on the precalculated position of biochip 18 to form desired biomolecule dot matrix.In point sample, the point sample circumstance or state on the high-speed CCD detector lens 7 detection of biological chips 18.Every intact biochip 18, drum drive motor 2 index drums 1 rotate preset angles with corresponding to next biochip 18, and spotting needle 11 continues this biochip 18 is carried out point sample.Cylinder 1 whenever turns around and finishes vertical point sample of biochip matrix 16 previous column biochips 18.
Then, move right second of biochip matrix 16 by horizontal drive motor 12 control point sample punch blocks 8 along continuous straight runs and blot the zone to carry out blotting of spotting needle 11.Spotting needle 11 blots after action finishes, and control point sample punch block 8 along continuous straight runs move right a dot matrix apart from arriving another row biochip 18, begin the point sample of this row biochip 18.So circulation finishes until biochip 18 point samples of all row.Finish the biochip matrix 16 of point sample and take off from cylinder 1, change a new biochip matrix 16 and be adsorbed on cylinder 1 external peripheral surface, for the point sample of next round is got ready.Simultaneously, the cleaning of spotting needle 11 is carried out in point sample punch block 8 fast return rinse baths 3 positions, prepare the beginning next round cleaning, take a sample, blot with point sample and move.
Claims (10)
1. drum-type biochip point sample device comprises:
Cylinder with external peripheral surface, wherein biochip matrix is suitable for being coated on the external peripheral surface of cylinder;
Drum drive is used for rotary drum;
Be arranged on cylinder top and the point sample punch block of spotting needle array is installed; And
Point sample punch block driving mechanism is used for making the point sample punch block with respect to roller shifting.
2. the described drum-type biochip point sample of claim 1 device, wherein drum drive comprises the cylinder servomotor that directly links to each other with cylinder, for make cylinder rotate preset angles at every turn.
3. the described drum-type biochip point sample of claim 1 device, also comprise the vacuum device that links to each other with cylinder, the external peripheral surface of its intermediate roll is provided with a plurality of perforation so that biochip matrix can be fixed on the external peripheral surface of cylinder in the vacuum suction mode by described a plurality of perforation.
4. the described drum-type biochip point sample of claim 1 device, the external peripheral surface of its intermediate roll is provided with at least one circumferential groove.
5. the described drum-type biochip point sample of claim 1 device, wherein point sample punch block driving mechanism comprises:
The cross slide way of above cylinder, installing;
Be slidably mounted in the vertical guide on the cross slide way, wherein the point sample punch block is slidably mounted on the vertical guide;
Horizontal drive motor is used for vertical guide is horizontally slipped along cross slide way; And
Vertical drive motor is used for the point sample punch block is slided up and down along vertical guide.
6. the described drum-type biochip point sample of claim 5 device, also comprise the rinse bath, sample box and the drop recording geometry that are arranged on the cross slide way below and are arranged side by side with cylinder, wherein when the point sample punch block moved to rinse bath, the spotting needle array on the point sample punch block can obtain cleaning in rinse bath; When the point sample punch block moved to sample box, the spotting needle array on the point sample punch block can be drawn sample from sample box; When the point sample punch block moves to the drop recording geometry, carry out pre-point sample and whether meet the point sample requirement with the drop of observing pre-point sample.
7. the described drum-type biochip point sample of claim 5 device comprises that also the CCD detector lens that is installed on the vertical guide is to monitor the point sample situation of spotting needle array on biochip matrix.
8. the described drum-type biochip point sample of claim 7 device, wherein the point sample punch block is installed on the vertical guide by slide block, and the CCD detector lens is installed on the slide block.
9. biochip point sample method comprises step:
With biochip matrix vacuum suction on the cylinder external peripheral surface;
By the spotting needle array sample is injected on the biochip on the biochip matrix on the cylinder external peripheral surface;
With the preset angles rotary drum and repeat above-mentioned injecting step.
10. the method for claim 9 also comprises step:
Use the CCD detector lens to detect the sample of spotting needle array on biochip and spray situation.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310227100.3A CN103278365B (en) | 2013-06-08 | 2013-06-08 | Drum type biochip spotting device and method thereof |
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| CN201310227100.3A CN103278365B (en) | 2013-06-08 | 2013-06-08 | Drum type biochip spotting device and method thereof |
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| CN103278365B CN103278365B (en) | 2015-06-24 |
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