CN105567560A - Integrated liquid drop microfluidic chip - Google Patents
Integrated liquid drop microfluidic chip Download PDFInfo
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- CN105567560A CN105567560A CN201511024081.XA CN201511024081A CN105567560A CN 105567560 A CN105567560 A CN 105567560A CN 201511024081 A CN201511024081 A CN 201511024081A CN 105567560 A CN105567560 A CN 105567560A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
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Abstract
An integrated liquid drop microfluidic chip comprises one or more liquid drop generation structures, every liquid drop generation structure is connected with a corresponding collection cavity structure through a corresponding connection channel, a water phase reagent and an oil phase reagent respectively go through the one or more liquid drop generation structures to generate liquid drops with uniform dimension, an emulsion including the liquid drops goes through the connection channel and directly or indirectly enters the collection cavity structure, and is adaptively arranged to form a regular liquid drop array in the collection cavity structure, the liquid drop array undergoes a biochemical reaction under constant temperature control or temperature circulation control in an air heating refrigeration or Peltier semiconductor heating refrigeration mode, and real time monitoring or timed optical detection is also carried out. The integrated liquid drop microfluidic chip reduces the sample transfer process, can be conveniently integrated with a thermometric module and an optical detection module, greatly improves the reaction and detection speed, and also simplifies the complex degree of a whole apparatus system.
Description
Technical field
The invention belongs to biochemical microfluidic art, be specifically related to a kind of integrated form drop micro-fluidic chip.
Background technology
At present, the biochemical analysis detection based on drop microflow control technique has obtained sufficient application and development, such as QX200
tMand Raindrop
tMdigital pcr system, sensitivity, the accuracy and can surveying in concentration dynamicrange that these two systems are detecting all is greatly improved, but still fully cannot meet the demand of biochemistry detection in actual applications.On the one hand, the requirement that these two system external contain member is higher, causes system complexity to rise, and system cost is difficult to reduce; On the other hand, these two systems do not make full use of the advantage that microflow control technique is easy to integrated, and sample to be checked often needs to shift between different instrument, makes the automatization of system and integration degree not high.In addition, the amplified reaction of system and the time of flow cytometer detection longer, also limit the flux of instrument system, make it be difficult to meet high-throughout application demand.
At Labonachip, 2011, the 11st volume, No. 22,3838-3845 page, the people such as AndrewC.Hatch once described a kind of micro-fluidic chip and the fluorescence detecting system that can be used for high-throughput drop formula digital pcr, can at 8 – 12cm
2scope in complete millions of skins upgrade other drop reaction with detect, greatly promote the dynamic detection range of digital pcr.But there are some problems equally in this system.First, this chip inevitably can cause the loss of drop, and has an impact to detected result; Secondly, easily produce bubble in the cavity of chip, these bubbles are meeting constantly Swelling and contraction in pcr amplification process, and this very likely causes the failure of testing.Finally, in this chip cavity the arrangement of drop depend critically upon early stage drop formation in water oil phase ratio, and this will inevitably bring operational difficulty and to the later stage application produce restriction.
A kind of making method of the digital pcr chip based on the saturated PDMS material of mineral oil is referred in document CN103343092, but because PDMS material has superpower receptivity to oiliness molecule, and the intensity of PDMS material is poor, very easily deform, so be used for laboratory study, the application demand of industrialization cannot be met.Therefore, a kind of micro-fluidic chip with actual application value must be provided to solve the difficult problem run at present.
Summary of the invention
In order to overcome the shortcoming of above-mentioned prior art, the object of the invention is to propose a kind of integrated form drop micro-fluidic chip, while guarantee detection sensitivity, improve the efficiency detected, reduce complexity and the system cost of the existing system based on microfluidic chip technology, simplify the operation step simultaneously.
In order to achieve the above object, the technical scheme that the present invention takes is:
A kind of integrated form drop micro-fluidic chip, comprise more than one drop formation structure 1, each drop formation structure 1 is communicated with corresponding collection chamber structure 3 by corresponding connecting passage 2, water oil two phase reagents generate the drop 10 of size uniformity respectively via drop formation structure 1, the emulsion comprising drop 10 enters in collection chamber structure 3 through connecting passage 2 directly or indirectly, and regular droplet array is arranged into adaptively in collection chamber structure 3, droplet array is freezed by air heating or the mode such as Peltier semi-conductor heating and cooling realizes thermostatic control or temperature cycle controls biochemical reaction, carry out the optical detection of real-time monitoring or timing simultaneously.
Described drop formation structure 1 is provided with the first entrance 4, second entrance 5 and fluid channel 7, first entrance 4, second entrance 5 is communicated with fluid channel 7 entrance, first entrance 4 and the second entrance 5 place are provided with reservoir 8 so that water oil two-phase reagents loaded, or water oil two phase reagents are placed in chip exterior, have been connected with the second entrance 5 loading by air-tight interfaces and the first entrance 4.
Described connecting passage 2 is provided with valve 9, in order to enable emulsion keep synchronous flowing in collection chamber structure 3, connecting passage 2 comprise one-to-two, two points four, four points eight, the parallel channel being divided into 64 tunnels is at the most connected with collection chamber structure 3.
Described collection chamber structure 3 is included in relative first wall 11, second wall 12 of two of separating each other, and be connected with multiple corbeling 13 between first wall 11, second wall 12, collection chamber structure 3 is provided with exhaust outlet 6.
Described collection chamber structure 3 vacuumizes process.
Described collection chamber structure 3 distributes at grade with drop formation structure 1.
Described collection chamber structure 3 place plane and drop formation structure 1 place plane is in 90 ° or other angles, form three-dimensional three-dimensional arrangement layout, now collection chamber structure 3 is also provided with oil-bearing structure 14.
Described fluid channel 7 comprises " ten " font or " T " font flow passage structure, by regulating the width of runner and height, can form the drop 10 of diameter dimension in the stable homogeneous of below 150um.
Distance h between described first wall 11, second wall 12 needs to determine according to the diameter of drop 10, is no more than 3 times of droplet dia, thus makes drop 10 between first wall 11, second wall 12, form the arrangement of individual layer, bilayer or three layers.
The size of described oil-bearing structure 14 in first wall 11, second wall 12 vertical direction relative with two be not then by the restriction of droplet dia.
Beneficial effect of the present invention is: drop formation and biochemical reaction and detection are integrated into a chip and complete by (1), decrease the transfer of sample, contaminated solution problem, also improve the level of automation of system; (2) adopt low cost, can the disposable chip of batch machining, some biochemistry detection occasion can be met to the demand of Environmental capacity; (3) drop 10 of single dispersing (drop size is homogeneous) can be formed, meet the requirement of biochemistry detection occasion highly sensitive and high-throughput qualitative and quantitative detection; (4) adopt rational chip layout and collection chamber structure 3 is designed, effectively prevent the formation of bubble in cavity, and utilizing the density variation of water oil two phase reagents, being provided with oil-bearing structure 14, in order to reduce the overall dimensions of chip; (5) by the distance between two of adjustment collection chamber structure 3 relative walls 11,12, can control the arrangement mode of drop 10, improve the density of drop arrangement and can testing process be completed by the imaging of image capturing system 18 single or multiple, substantially increasing the detection efficiency of liquid drop microfluidic system.
Accompanying drawing explanation
Fig. 1 is the structural representation of drop micro-fluidic chip.
Fig. 2 is three-dimensional single passage drop micro-fluidic chip stereo figure.
Fig. 3 is each view of three-dimensional single passage drop micro-fluidic chip, and wherein Fig. 3 (a) is the vertical view of three-dimensional single passage drop micro-fluidic chip; Fig. 3 (b) is the side-view of three-dimensional single passage drop micro-fluidic chip; Fig. 3 (c) is respectively the sectional view of three-dimensional single passage drop micro-fluidic chip collection chamber structure.
Fig. 4 is planar multichannel drop micro-fluidic chip stereo figure.
Fig. 5 is each view of planar multichannel drop micro-fluidic chip, and wherein Fig. 5 (a) is the front view of planar multichannel drop micro-fluidic chip; Fig. 5 (b) is the partial enlargement of planar multichannel drop micro-fluidic chip front view; Fig. 5 (c) is the sectional view of planar multichannel drop micro-fluidic chip reagent trough.
Fig. 6 is the partial schematic diagram of collection chamber structure.
The each figure of Fig. 7 is respectively front view and the side-view of the different arrangement mode of droplet array, and wherein Fig. 7 (a) is individual layer drop; Figure (b), figure (c) are double-deck drop; Figure (d) is three layers of drop.
Fig. 8 is the structural representation of drop micro-fluidic chip Systems for optical inspection.
Fig. 9 is the operating diagram of drop micro-fluidic chip.
Figure 10 is the experimental observations of individual layer droplet array under bright field and fluorescence visual field in chip collection chamber structure, and wherein Figure 10 (a) is the imaging effect of droplet array under bright field; Figure 10 (b) is the imaging effect after the droplet array amplification adopting PCR reagent to prepare under bright field and fluorescence visual field; Figure 10 (c) is the imaging effect of droplet array under fluorescence visual field.
Embodiment
The present invention is set forth further below with reference to drawings and Examples.
With reference to Fig. 1, a kind of integrated form drop micro-fluidic chip, comprise drop formation structure 1, drop formation structure 1 is communicated with collection chamber structure 3 by connecting passage 2, drop formation structure 1 drop formation structure 1 is provided with the first entrance 4, second entrance 5 and fluid channel 7, first entrance 4, second entrance 5 is communicated with fluid channel 7 entrance, first entrance 4 and the second entrance 5 place are provided with reservoir 8 so that water oil two-phase reagents loaded, water oil two phase reagents are respectively via the first entrance 4 in drop formation structure 1, second entrance 5 enters drop formation structure 1, generate the drop 10 of size uniformity, the emulsion comprising drop 10 enters in collection chamber structure 3 through connecting passage 2 directly or indirectly, connecting passage 2 is provided with valve 9, in collection chamber structure 3, synchronous flowing is kept in order to enable emulsion, connecting passage 2 comprises one-to-two, two point four, four point eight, the parallel channel being divided into 64 tunnels is at the most connected with collection chamber structure 3, drop 10 is arranged into regular droplet array adaptively in collection chamber structure 3, droplet array is freezed by air heating or the mode such as Peltier semi-conductor heating and cooling realizes thermostatic control or temperature cycle controls biochemical reaction, carry out the optical detection of real-time monitoring or timing simultaneously, collection chamber structure 3 is provided with exhaust outlet 6, collection chamber structure 3 is supported by corbeling 13, prevent caving in of cavity,
Embodiment 1, three-dimensional single passage drop micro-fluidic chip: with reference to Fig. 2 and Fig. 3 (a), three-dimensional single passage drop micro-fluidic chip comprises drop formation structure 1, drop formation structure 1 is communicated with collection chamber structure 3 by connecting passage 2, drop formation structure 1 is provided with the first entrance 4, second entrance 5 and fluid channel 7, first entrance 4, second entrance 5 is communicated with fluid channel 7 entrance, first entrance 4 and the second entrance 5 place are integrated with reservoir 8 respectively, connecting passage 2 is made up of a passage, fluid channel 7 is exported and is connected with collection chamber structure 3 entrance by connecting passage 2, collection chamber structure 3 is provided with an exhaust outlet 6, with reference to Fig. 3 (b) and Fig. 3 (c), collection chamber structure 3 comprises the relative first wall 11 of two of separating each other, second wall 12, at first wall 11, plural corbeling 13 is connected with for supporting collection chamber structure 3 between second wall 12, prevent caving in of cavity, collection chamber structure 3 place plane and drop formation structure 1 place plane in 90 °, form three-dimensional three-dimensional arrangement layout, the bottom of collection chamber structure 3 is provided with oil-bearing structure 14, oil-bearing structure 14 is to store oil phase reagent unnecessary in emulsion, reduce the cavity area of collection chamber structure 3.
Water oil two phase reagents will be loaded previously in reservoir 8 respectively, then drop 10 is generated via fluid channel 7, the emulsion comprising drop 10 directly fills collection chamber structure 3 by connecting passage 2 gradually under fluid driving forces and action of gravity, air is then discharged via exhaust outlet 6, so both ensure that emulsion is all collected, also effectively prevent the formation of bubble.
Three-dimensional single passage drop micro-fluidic chip adopts macromolecule polymer material--and COC injection molding makes, long 75mm, wide 25mm, thickness 2mm, reservoir height is 8mm, internal diameter is 5mm, the long 50mm of collection chamber structure 3, wide 20mm, wherein, the side of collection chamber structure 3 completes cavity by the film 15 of one deck COC material and seals, and under the prerequisite satisfied the demands, the most I of thickness reaches for 100um, like this just there is good heat conductivility with during calorifics module integration, be convenient to the temperature control demand meeting various biochemical reaction.Fluid channel 7 is the structure of " ten " font, the width of fluid channel 7 be highly 100um, distance between drop 10, two relative first wall 11, second walls 12 that can form diameter dimension about 100um is 100um, to form the droplet array arrangement of individual layer in cavity.
Embodiment 2, planar multichannel drop micro-fluidic chip: with reference to Fig. 4 and Fig. 5, planar multichannel drop micro-fluidic chip includes the parallel organization of 4 passages, be distributed in four of discoid chip in the radial direction, angle is each other 90 °, the chip structure of each passage includes drop formation structure 1, connecting passage 2, collection chamber structure 3, drop formation structure 1 is communicated with collection chamber structure 3 by connecting passage 2, drop formation structure 1 comprises the first entrance 4, second entrance 5 and fluid channel 7, reservoir 8 is integrated with respectively at the first entrance 4 and the second entrance 5 place, connecting passage 2 is by an one-to-two, the parallel stream of two point four is connected with collection chamber structure 3, can make emulsion in collection chamber structure 3, keep synchronous flowing, many corbelings 13 are provided with in collection chamber structure 3, corbeling 13 is not only for supporting collection chamber structure 3, prevent caving in of cavity, also according to its position distribution for adjusting the flowing of emulsion in collection chamber structure 3, the formation of further suppression bubble, simultaneously, the collection chamber structure 3 of each passage is all respectively equipped with an exhaust outlet 6.
Aqueous phase reagent is loaded in the reservoir 8 of the second entrance 5 correspondence in advance respectively, and four passages will share first entrance 4, and the reservoir 8 of the first entrance 4 correspondence is only for being tightly connected with external interface, to complete oil phase reagents loaded.Then under external motivating force effect, water oil two phase reagents generate drop 10 via fluid channel 7, the emulsion comprising drop 10 directly fills collection chamber structure 3 by connecting passage 2 gradually under fluid driving forces and surface tension gradient effect, and air is then discharged via exhaust outlet 6.
Planar multichannel drop micro-fluidic chip adopts macromolecule polymer material--and PC injection molding makes, diameter 85mm, thick 1.5mm, reservoir height is 8mm, and internal diameter is respectively 1.5mm and 5mm, wherein, chip bottom completes the sealing of chip structure by the film 15 of one deck PC material, under the prerequisite satisfied the demands, most I reaches for 100um, like this with just there is during calorifics module integration good heat conductivility, be convenient to the temperature control demand meeting various biochemical reaction.Fluid channel 7 is the structure of " ten " font, the width of fluid channel 7 be highly 100um, the drop 10 of diameter dimension about 100um can be formed, distance between two relative first wall 11, second walls 12 is 150um, to form double-deck droplet array arrangement in cavity, under the prerequisite not affecting observation, improve drop arrangement density as far as possible.
With reference to Fig. 6, described collection chamber structure 3 is included in the relative first wall 11 of two of separating each other, second wall 12, forming thickness is the cavity of h, mating surface tension gradient or gravity and two relative first walls 11, the restriction effect of the second wall 12, drop 10 will be arranged into regular droplet array adaptively in collection chamber structure 3, due to the needs of observation, two relative first walls 11, distance h between second wall 12 is no more than 3 times of droplet dia, such as: 1 times, 1.5 doubly, 1.8 doubly, 2.6 times etc., drop 10 so just can be made in collection chamber structure 3 to form one deck, the two-layer even arrangement of three layers, meanwhile, in actually operating, oil phase is normally excessive, because water oil two-phase exists density variation, therefore unnecessary oil phase will with creaming of emulsion, be in top or the bottom of emulsion, because only need to observe the drop 10 in emulsion, so arrange oil-bearing structure 14 in collection chamber structure 3, so just greatly can reduce the size of collection chamber structure 3.
With reference to Fig. 7 (a), the diameter of drop 10 is at about 100um, and the thickness h of cavity is set to 100um, and drop 10 forms monolayer array arrangement in collection chamber structure 3.With reference to Fig. 7 (b) and Fig. 7 (c), the diameter of drop 10 is at about 100um, the thickness h of cavity is set to 170um or 180um, drop 10 forms two-layer structure in collection chamber structure 3, while raising droplet array arrangement density, also can not have an impact to optical observation.With reference to Fig. 7 (d), the diameter of drop 10 is at about 100um, and the thickness h of cavity is set to 260um, and drop 10 forms the structure of three layers in collection chamber structure 3, improve droplet array arrangement density to greatest extent, also can not affect the optical observation to each drop simultaneously.
With reference to figure 8, for the detection of described integrated form drop micro-fluidic chip, image capturing system 18 is relied on, image capturing system 18 comprises imaging system or even the mobile phone camera of various CCD, image capturing system 18 carries out the Real-Time Monitoring of bright field or reacted fluoroscopic examination by the droplet array in collection chamber structure 3, drop 10 is at two of collection chamber structure 3 relative first walls 11, individual layer is formed between second wall 12, double-deck or the arrangement of three layers at the most, lighting source 17 45 ° from chip oblique upper throws light on to collection chamber structure 3, the whole collection chamber structure 3 of region overlay of illumination, region to be observed can be sufficiently illuminated, image capturing system 18 is arranged on the direction vertical with the collection chamber structure 3 of described chip, the one-time detection to droplet array in collection chamber structure 3 can be completed by single imaging.
With reference to figure 9, the operating process of integrated form drop micro-fluidic chip: first, needs the PCR reagent needed for preparation experiment and oil phase reagent, and PCR reagent can be mixed in proportion by PCRMasterMix general on market and primer, probe and template DNA and obtain; Oil phase reagent is obtained by the fluorocarbon surfactant adding 2 ~ 5% in fluorinated oil.Then by the oil phase agent transfer of the PCR reagent of 25uL and 60ul in the reservoir 8 of described chip, and chip is placed in instrument, under pressure-driven effect, PCR reagent forms the drop 10 of upgrading of receiving of tens thousand of consistent size of being wrapped up by oil phase reagent through fluid channel 7, drop 10 moves adaptively and self-assembly in collection chamber structure 3 simultaneously, and is full of whole cavity gradually.Temperature control module 16 starts afterwards, temperature control module 16 adopts Peltier semiconductor refrigeration sheet to carry out temperature control, chip side and temperature control module 16 fit tightly, make the drop in collection chamber structure 3 complete 30 ~ 40 PCR temperature cycle thereupon, each drop in such collection chamber structure 3 just can as one independently PCR reaction member complete amplification procedure, after having increased, the drop comprising different target DNA profiling will send the fluorescence of different wave length, the drop not comprising target template DNA then can not send fluorescence, image capturing system 18 so just can be utilized to carry out fluoroscopic image collection from described chip opposite side to the droplet array collection chamber structure 3, and subsequent disposal is done to the data collected, obtain sample starting point concentration, the important informations such as rare mutation.
With reference to Figure 10, this is shown for the imaging effect of individual layer droplet array under bright field and fluorescence visual field utilizing described chip to prepare.Wherein, Figure 10 (a) embodies drop prepared by described chip and has good consistence; Figure 10 (b) contrasts the imaging effect of droplet array under bright field and fluorescence visual field, and has found a small amount of droplet coalescence phenomenon; Figure 10 (c) embodies the fluorescence imaging effect of droplet array, obviously can tell the shade distinctions of single drop, can apply well and drop formula digital pcr field.
Claims (10)
1. an integrated form drop micro-fluidic chip, comprise more than one drop formation structure (1), it is characterized in that: each drop formation structure (1) is communicated with corresponding collection chamber structure (3) by corresponding connecting passage (2), water oil two phase reagents generate the drop (10) of size uniformity respectively via drop formation structure (1), the emulsion comprising drop (10) enters in collection chamber structure (3) through connecting passage (2) directly or indirectly, and regular droplet array is arranged into adaptively in collection chamber structure (3), droplet array is freezed by air heating or the mode such as Peltier semi-conductor heating and cooling realizes thermostatic control or temperature cycle controls biochemical reaction, carry out the optical detection of real-time monitoring or timing simultaneously.
2. a kind of integrated form drop micro-fluidic chip according to claim 1, it is characterized in that: described drop formation structure (1) is provided with the first entrance (4), second entrance (5) and fluid channel (7), first entrance (4), second entrance (5) is communicated with fluid channel (7) entrance, first entrance (4) and the second entrance (5) place are provided with reservoir (8) so that water oil two-phase reagents loaded, or water oil two phase reagents are placed in chip exterior, to be connected with the second entrance (5) loading by air-tight interfaces and the first entrance (4).
3. a kind of integrated form drop micro-fluidic chip according to claim 1, it is characterized in that: described connecting passage (2) is provided with valve (9), in collection chamber structure (3), synchronous flowing is kept in order to enable emulsion, connecting passage (2) comprise one-to-two, two points four, four points eight, the parallel channel being divided into 64 tunnels is at the most connected with collection chamber structure (3).
4. a kind of integrated form drop micro-fluidic chip according to claim 1, it is characterized in that: described collection chamber structure (3) is included in two of separating each other relative first wall (11), the second wall (12), be connected with multiple corbeling (13) between first wall (11), the second wall (12), collection chamber structure (3) is provided with exhaust outlet (6).
5. a kind of integrated form drop micro-fluidic chip according to claim 1, is characterized in that: described collection chamber structure (3) vacuumizes process.
6. a kind of integrated form drop micro-fluidic chip according to claim 1, is characterized in that: described collection chamber structure (3) and drop formation structure (1) distribute at grade.
7. a kind of integrated form drop micro-fluidic chip according to claim 1, it is characterized in that: described collection chamber structure (3) place plane and drop formation structure (1) place plane is in 90 ° or other angles, form three-dimensional three-dimensional arrangement layout, now collection chamber structure (3) is also provided with oil-bearing structure (14).
8. a kind of integrated form drop micro-fluidic chip according to claim 2, it is characterized in that: described fluid channel (7) comprises " ten " font or " T " font flow passage structure, by regulating the width of runner and height, the drop (10) of diameter dimension in the stable homogeneous of below 150um can be formed.
9. a kind of integrated form drop micro-fluidic chip according to claim 4, it is characterized in that: the distance h needs between described first wall (11), the second wall (12) are determined according to the diameter of drop (10), be no more than 3 times of droplet dia, thus make drop (10) between first wall (11), the second wall (12), form the arrangement of individual layer, bilayer or three layers.
10. a kind of integrated form drop micro-fluidic chip according to claim 7, is characterized in that: the size of described oil-bearing structure (14) in the first wall (11) relative with two, the second wall (12) vertical direction be not then by the restriction of droplet dia.
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