CN1569304A - Apparatus for deposition and crystallization of continuous flow biochemical products - Google Patents

Abstract

The invention is a continuous biochemical product sediment and crystallizing device, belonging to biochemical sediment or crystallization device. It includes a clamp cover reaction pot with disturber. The cone cylinder is converted in the cylinder; the pot inner cavity is divided into cone sediment reaction area and outer sediment crystallization area, a pipe mixer. The material liquid and the circular mother liquor out of from the reaction pot are added in continuously, the volume flow ratio is between 1:1 and 1:100, they are added into the reaction pot continuously after being mixed; a buffer liquid groove and a sediment storing groove; the buffer liquor and sediment agent in the two grooves are added into the reaction pot continuously; a valve arranged on the out-going pipe on the bottom of the reaction pot and correspondent control mechanism which controls the reaction material to be discharged with quantity velocity of material liquid, buffer liquid and sediment agent.

Description

Continuous Flow biochemical product precipitated crystal device

One, technical field

The present invention relates to biology, medicine and chemical industry class precipitation or crystallization reaction device, in particular for the precipitation or the crystallization reaction device of blood plasma or protein solution.

Two, background technology

The depositing technology of existing blood plasma or protein belongs to constant volume and criticizes adding batch production technology (abbreviation batch process).Whole precipitation reaction process and equipment are as follows: blood plasma or protein solution constant volume are criticized and are added the precipitation reaction jar, adjust and measure the protein concentration of solution, add cushioning liquid then at regular time and quantity and adjust the ionic strength and the acid-base value of solution, add the concentration of precipitating reagent control precipitating reagent in solution at regular time and quantity, control reaction temperature in the entire reaction course, like this, the target protein that needs precipitation or remove will condense by selective precipitation, just target protein can be separated by follow-up centrifugal process or filtration method.

The shortcoming of above-mentioned technical process device is: (1) is because protein-based solution is batch adding, and precipitating reagent and buffer solution gradually add, the time that reaches stable precipitation parameter condition (5 parameters: temperature, acid-base value, ionic strength, alcohol concentration, protein concentration) in the retort depend on precipitating reagent and buffer solution joining day and jar in a stirring.Generally speaking, the joining day of precipitating reagent is quite long, and in other words, the transit time of reaching between the stable precipitation parameter condition is very long, and the major defect that brings thus is that the production cycle is elongated.In addition, in the transit time that has parameter gradients to change or fluctuate, target protein can produce precipitation and dissolving replaces situation about occurring, and easily makes the target protein sex change influence yield rate.Moreover, in transit time, non-target protein (foreign protein) may with the target protein co-precipitation, influence the recovery purity and the difficulty of target protein.(2) batch processing albumen precipitation technology be with the precipitation parameter reach (reaction), precipitation growth is placed within the same space, the precipitation of uncontrollable formation uniformity and crystallization, promptly Chen Dian size distribution is uncontrollable.Add the means of not eliminating or handle tiny precipitation, the condition that judges whether to carry out follow-up Protein Separation so is that the minimum particle size that reaches separation condition distributes, and causes the production cycle elongated.Simultaneously, because the size distribution broadness of albumen precipitation causes the later stage separating difficulty of protein suspending liquid to increase.(3) the batch processing characteristics of producing are, the size of production capacity depends on the size of production equipment volume under certain situation of production time.At present, amplify about the plasma protein depositing technology parameter of batch processing and volume of equipment and not set up science and rigorous scale-up model, day by day under the condition of enlarged, the wasting of resources that production experiment brought and economic loss are huge in production scale.(4) market sale of the productivity effect of enterprise decision product and the fund input of production.Can only be than the decision of handling the protein production device capability according to the marketability decision of maximum possible.When its market demand reduced, the ability of process units was left unused and is caused the very big waste of enterprise.Little but if the ability of process units is determined, when its market demand increased, the performance of enterprises can reduce again.In a word, batch processing plasma protein production technology is too little to the production elasticity of enterprise's adaptation to market variations.

Three, summary of the invention

The objective of the invention is at the existing problem of existing plasma protein settler and defective and a kind of Continuous Flow biochemical product precipitated crystal device is provided, the production process serialization is carried out.The object of the present invention is achieved like this: a kind of continuous biochemical product precipitated crystal system and device, and it comprises: a retort that is provided with agitator, reacting tank body is provided with chuck, is used for increasing and reducing reaction temperature;

A tube mixer, material solution and the circulating mother liquor of extracting out through power from retort all add tube mixer in a continuous manner, wherein the ratio of the volume flow of material solution and circulating mother liquor is between 1: 1～100, and the two inputs in the retort after mixing continuously;

A buffer solution storage tank and a precipitating reagent storage tank, buffer solution in two storage tanks and precipitating reagent are respectively by technological requirement and proportion relation above-mentioned raw materials solution, in the adding retort of continuous and quantitative;

A valve and a control corresponding mechanism that is installed on the retort outlet at bottom pipe, the control reactant is discharged the speed of the adding total amount of retort with material solution, buffer solution, precipitating reagent.

Be provided with inverted awl tube in the above-mentioned retort of being made up of end socket and tank body, it is divided into a precipitation reaction district and the outer precipitated crystal of an awl tube district in the awl tube with the retort inner chamber; The retort tank body is provided with the feed liquid that is used in the outer precipitated crystal of the awl tube district and extracts the mouth of pipe that adds tube mixer as circulating mother liquor in a continuous manner through power out.

The pairing precipitation of the present invention/the crystallization processes process is as follows:

Blood plasma behind adjustment and the mensuration protein concentration or protein solution are that material solution adds tube mixer with certain continuous a small amount of, enter precipitation reaction district in the retort with (jar outward) circulating mother liquor (from retort, extracting out) in the tube mixer after mixing, meanwhile, by with the related calculating of blood plasma or protein solution addition after, by adding amount of calculation and computing time buffer solution respectively, add precipitating reagent synchronously with the concentration of control precipitating reagent in solution to adjust the ionic strength and the acid-base value of solution.Control reaction temperature with the cold and hot matchmaker's changes in flow rate in the retort chuck in the entire reaction course.So, needing the removable target protein of precipitation will optionally precipitate cohesion comes out.

The precipitation suspension that bulky grain in the retort distributes is discharged with the speed that adds total amount (material solution, buffer solution, precipitating reagent three sum) by the outlet of bottom, by follow-up centrifugal process or filtration method target protein is separated.The precipitation suspension that the retort small particles distributes then through the outlet on the retort by circulating pump and tube mixer with after initiate a small amount of blood plasma or protein solution mix, send retort again back to and continue precipitation reaction and precipitate growth.Therefore the precipitation process of blood plasma and protein solution has formed continuous charging, successive reaction, the grow up classification and the continuous process of discharging continuously continuously.

The present invention has following advantage: (1) is for continuous flow process, usually the circulating mother liquor volume that forms the initial precipitation condition can not surpass 100L, Continuous Flow retort volume is little more a lot of than batch processing retort, cooperate certain stirring, the time that reaches stable precipitation parameter condition (5 parameter) in jar is very short.After initial target albumen precipitation suspension mother liquor forms, because adding with circulating mother liquor continuously in a small amount, plasma protein solution is mixed into retort, and precipitating reagent and buffer solution add with the synchronization association amount, all the time can not change in the initial precipitation parameter condition precipitation reaction afterwards of system, finish up to whole blood plasma or protein solution reaction.The preceding transitional period of having avoided occurring in the batch process of deposition condition that reaches influences albuminous degeneration and very long shortcoming of production cycle.(2) continuous flow process is except the key concept proposition of " adding in a small amount continuously ", and " jar outer Recycling Mother Solution " is second key concept.The outer Recycling Mother Solution of jar has solved the uncontrollable problem of the size distribution of albumen precipitation in the batch process, promptly have and eliminate or handle the means that tiny precipitation distributes, the even particle size distribution unanimity of feasible precipitation, shortened the production cycle greatly, and made that the separation of follow-up protein suspending liquid is easier.The adjusting of jar outer circulation mother liquor amount has simultaneously determined the high efficiency and the operability of " adding in a small amount continuously ".(3) continuous flow process has solved depositing technology parameter and the scale-up problem of production capacity expansion on device.What the production capacity of batch process was amplified at first consideration is how much amplifications, and then consideration dynamics is amplified.The production capacity of continuous flow process depends mainly on dynamics amplifies, and the problem of how much amplifications is not a subject matter.In production scale day by day under the condition of enlarged, the wasting of resources and the economic loss that can avoid production experiment greatly and brought.(4) the continuous flow process device is much smaller with respect to batch process from volume and needed factory building, but the elasticity of production capacity is but very big.Enterprise can tackle the changes in demand of market to institute's article of manufacture cheaply calmly.

In brief, distinguishing feature of the present invention: add in a small amount continuously; The jar outer circulation mixes; Relevant parameter control; Thin brilliant (precipitation) heavily blendes together length; Precipitation fractionation is discharged; System is little and compact; Production elasticity is very big.

Four, description of drawings

Fig. 1 is the system layout of one embodiment of the invention;

Fig. 2 is the profile of the embodiment of retort shown in Figure 1;

Fig. 3 is the system layout of existing batch processing reaction.

Five, the specific embodiment

Fig. 1 illustrates, apparatus of the present invention comprise, retort 1: preferably adopt retort shown in Figure 2, it is made up of end socket and tank body, be provided with inverted awl tube 19 in the tank body, awl tube top clamping is installed between the connecting flange 25 of end socket and tank body, and tank body is provided with agitator 3, square shaft is adopted in the shaft lower end, and stirring vane 18 liftably is installed on it; Tank body is provided with chuck 2, is used for increasing or reducing reaction temperature, and the awl tube is divided into precipitation reaction district and the outer precipitated crystal of awl tube district in the awl tube with the retort inner chamber; Tank body is provided with two mouths of pipe of drawing circulating mother liquor, one is upper orifice 24, one is the middle part mouth of pipe 23, awl tube bottom opening is provided with flow control device, can be fixed on this aperture position through three adjusting support 21 (uniform) by the plug 22 identical and constitute with boring the tube bottom opening, feed pipe 16 on the retort extends downward contiguous awl tube position in the awl tube, its underpart open end and awl tube wall surface almost parallel make charging mild.The top in retort precipitation reaction district is provided with rotating wash bowl, and top, precipitated crystal district is provided with and cleans ring 17 in (not shown, standarized component) retort;

A tube mixer 11: material solution and the circulating mother liquor extracted out through measuring pump 10 from retort add tubular reactor through measuring pump 9,10 in the continuous and quantitative mode respectively, wherein, the ratio of the volume flow of material solution and circulating mother liquor is between 1: 1～100, after the two mixes, input in the retort continuously, usually, measuring pump 10 can extract mother liquor through the mouth of pipe 24 or the mouth of pipe 23, and mainly the height according to the outer precipitated crystal district of tank body inner conical-tube liquid level determines; The amount of circulating mother liquor often exceeds the manyfold of material solution; Be material solution in a small amount of Continuous Flow mode with after a large amount of circulating mother liquors mix in tube mixer, add again in the precipitation reaction district in the retort awl tube, like this, direct influence has reduced precipitating reagent greatly to material solution, helps precipitated crystal to grow up and homogeneous, and reaction is directly finished rapidly, meanwhile, the outer feed liquid of retort awl tube shifts out again outside the tank body in a continuous manner, like this, helps the precipitation reaction balance to move to the target product direction;

Buffer solution in buffer solution storage tank 4 and precipitating reagent storage tank 6, two storage tank and precipitating reagent by technological requirement and proportion relation above-mentioned raw materials solution, input in the retort through measuring pump 5,7 respectively respectively continuously, quantitatively;

A valve 12 and a control corresponding mechanism that is installed on the retort outlet at bottom pipe, the control reactant is quantitatively discharged through measuring pump 8 speed of the adding total amount of retort with material solution, buffer solution, precipitating reagent.

Above-mentioned retort is provided with acid-base value metering device 13, temperature measurement device 14, Weight metering device 15 and visor 20, manhole 26 etc.

Shown in Fig. 3 is existing protide batch processing reaction unit, in contrast, the retort that is used for Continuous Flow of the present invention is (it proposes patent application by the inventor: name is called " precipitated crystal reactor ", and application number is 03252888.4, and the applying date is on September 23rd, 2003) as shown in Figure 2.

Human plasma protein fraction precipitate and separate example: the different protein composition of five steps of human plasma protein fraction, represent with FI-FV respectively, the control of employing isoelectric point, means such as organic solvent deposit and salting out, in the precipitate and separate mode, earlier component FI+FII+FIII is removed, again component FIV is removed, realize target product FV at last.Specifically, the first step precipitates FI+FII+FIII, under certain temperature and pH value and precipitating reagent concentration conditions, the precipitation growth also forms epigranular, solid particle and crystallization, after discharging this device, through centrifugation, remove FI+FII+FIII precipitation, again with this supernatant as this device (in the reality, adopt another set of device, the two establishes under the surge tank same) raw material, send back in the retort of this device, and under certain process conditions, finish the precipitation growth of component FIV, discharge this device at last, through centrifugation, remove the FIV precipitation, again its supernatant is sent into this device, finish the precipitation growth of component FV, discharge this device at last,, obtain target product protein FV through centrifugation.

With above-mentioned technology is example, and from the production capacity aspect: throwing under 450～500 tons of/year situations of slurry amount, the total measurement (volume) of the existing required retort of batch processing mode demand respectively is 4500L, 8000L, 9000L; And the total measurement (volume) of retort of the present invention is respectively 200L, 200L, 200L, only is the former about percent 3, and (reaction time of above-mentioned FI+II+III first settling step: batch processing is 6-12 hour, and the present invention was less than 0.4 hour; The deadline of FIV second settling step, batch processing 6-12 hour, the present invention was less than 0.4 hour; The deadline of FV the 3rd settling step: batch processing 6-12 hour, the present invention was less than 0.4 hour); And, retort total measurement (volume) of the present invention is under the 200L prerequisite, will throw the slurry amount continuously and increase to 3.7 tons/day from 0.93 ton/day, throws the slurry amount and can rise to 1000 tons/year from 250 tons/year, under the long-pending constant prerequisite of outfit of equipment, production capacity can be adjusted in 4 times scope freely.Form the time of separable target precipitation, batch processing average out to 6～12 hours, and Continuous Flow＜0.5 hour.In addition, when production capacity when 450 tons/year are increased to 1000 tons/year, batch processing must increase the total measurement (volume) of equipment, increases to 4500L+8000L+9000L from 2500L+5000L+6000L, promptly consersion unit must be made great adjustment.And total volume of equipment of Continuous Flow is constant, only needs feed rate and auxiliary reagent speed and discharging speed made adjustment just can reach.

Concrete parameter sees the following form.

The present invention produces continuously with batch processing and produces enforcement parameter summary sheet (human plasma protein fraction separates)

The mode of production	The continuous mode of production				Batch processing mode
										Throw the slurry amount	Ton/year	250	?500	?1000	Ton/year	250		?450
Throw the slurry amount	Ton/sky	0.93	?1.85	?3.70	Ton/sky	0.93		?1.67
										Year is produced day	My god	270	?270	?270	My god	270		?270
Production time day	Hour	24	?24	?24	Hour	24		?24

Operation or computational item	Unit	Calculate and result of implementation			Unit	Result of calculation	Volume of equipment	Result of calculation	Volume of equipment
										One, blood plasma allotment
Plasmaflux	kg/h	?38.58	?77.16	?154.32	Kg/ days	925.93		?1666.67
										The physiological saline flow	kg/h	?2.70	?5.40	?10.80	Kg/ days	64.81		?116.67
Allotment back load	kg/h	?41.28	?82.56	?165.12	Kg/ days	990.74		?1783.33
										Control alcohol concentration (making precipitating reagent)	％
Add alcohol concentration	％
										Control PH scope		Certain limit	Certain limit	Certain limit		Certain limit		Certain limit
The control reaction temperature	℃	Appropriateness	Appropriateness	Appropriateness		Appropriateness		Appropriateness
										Buffer solution is formed		Acetic acid/sodium acetate	Acetic acid/sodium acetate	Acetic acid/sodium acetate		Acetic acid/sodium acetate		Acetic acid/sodium acetate
Reaction or time of repose in the equipment	hours
										The equipment total measurement (volume)	L	?200	?200	?200			?1500		?2500
Two, FI+ II+III albumen precipitation
										Allotment back plasmaflux (as material solution)	kg/h	?41.28	?82.56	?165.12	Kg/ days	990.74		?1783.33
The alcohol flow	kg/h	?11.01	?22.00	?44.03	Kg/ days	264.20	?1728.29	?475.56	?3110.93
										The buffer solution flow	kg/h	?0.86	?1.72	?3.44	Kg/ days	41.28	?74.31
Circular flow	kg/h	?412.8	?825.6	?1651.2	Kg/ days	0.0		?0.0

FI+II+ III discharging flow	??kg/h	??53.15	??106.30	??212.60	Kg/ days	??1296.22		??2333.19
										The control alcohol concentration	??％	??20.00	??20.00	??20.00		??20.00		??20.00
Add alcohol concentration	??％	??95.00	??95.00	??95.00		??95.00		??95.00
										Control PH scope		Certain limit	Certain limit	Certain limit		Certain limit		Certain limit
The control reaction temperature	??℃	Appropriateness	Appropriateness	Appropriateness		Appropriateness		Appropriateness
										Buffer solution is formed		Acetic acid/sodium acetate	Acetic acid/sodium acetate	Acetic acid/sodium acetate		Acetic acid/sodium acetate		Acetic acid/sodium acetate
Reaction or time of repose in the equipment	??hours	??＜0.3	??＜0.4	??＜0.5		??6-12		??6-12
										The equipment total measurement (volume)	??L	??200	??200	??200			??2500		??4500
Cold	??kcal/h	??385.07	??770.13	??1540.26	Kg/ days	??15683.15		??28229.67
										Three, FIV albumen precipitation
FI+II+ III supernatant flow	??kg/h	??94.82	??147.96	??254.26	Kg/ days	??1828.29	??3425.74	??2890.13	??5415.34
										The alcohol flow	??kg/h	??34.48	??53.81	??92.46	Kg/ days	??664.83	??1050.96
The buffer solution flow	??kg/h	??1.98	??3.08	??5.30	Kg/ days	??76.18		??120.42
										Circular flow	??kg/h	??948.2	??1479.6	??2542.6	Kg/ days	??0.0	??0.0
The FIV discharging flow	??kg/h	??131.27	??204.85	??352.02	Kg/ days	??2569.31		??4061.51
										The control alcohol concentration	??％	??40.00	??40.00	??40.00		??40.00		??40.00
Add alcohol concentration	??％	??95.00	??95.00	??95.00		??95.00		??95.00
										Control PH scope		Certain limit	Certain limit	Certain limit		Certain limit		Certain limit
The control reaction temperature	??℃	Appropriateness	Appropriateness	Appropriateness		Appropriateness		Appropriateness
										Buffer solution is formed		Acetic acid/sodium acetate	Acetic acid/sodium acetate	Acetic acid/sodium acetate		Acetic acid/sodium acetate		Acetic acid/sodium acetate

The equipment total measurement (volume)	I	200	?200	?200			?5000		?8000
										Reaction or time of repose in the equipment	hours	＜0.3	＜0.4	＜0.5		6-12		6-12
Cold	kcal/h	951.05	1484.16	2550.38		31086.42		49140.76
										Four, FV albumen precipitation
FIV supernatant flow (as material solution)	kg/h	172.94	246.52	393.69	Kg/ days	3101.22	?4252.43	4617.87	?6332.08
										The alcohol flow	kg/h	1.31	1.87	2.98	Kg/ days	23.49	34.98
The buffer solution flow	kg/h	3.60	5.14	8.20	Kg/ days	64.61		96.21
										Circular flow	kg/h	1729.4	2465.2	3936.9	Kg/ days	0.0	0.0
The FIV discharging flow	kg/h	177.85	253.52	404.87	Kg/ days	3189.32		4749.06
										The control alcohol concentration	％	40.00	40.00	40.00		40.00		40.00
Add alcohol concentration	％	95.00	95.00	95.00		95.00		95.00
										Control PH scope		Certain limit	Certain limit	Certain limit		Certain limit		Certain limit
The control reaction temperature	℃	Appropriateness	Appropriateness	Appropriateness		Appropriateness		Appropriateness
										Buffer solution is formed		Acetic acid/sodium acetate	Acetic acid/sodium acetate	Acetic acid/sodium acetate		Acetic acid/sodium acetate		Acetic acid/sodium acetate
The equipment total measurement (volume)	L	200	200	200			?6000		?9000
										Average response or time of repose in the equipment	hours	＜0.3	＜0.4	＜0.5		?6-12		6-12
Cold	kcal/h	1288.52	1836.77	2933.29		38588.11		57459.60

Implement from human blood protein's precipitate and separate, the present invention in the albumen precipitation separation process of adopting isoelectric point control, organic molten precipitation and salting out to exist, than the batch process of same principle, advantage is very tangible.Its conclusion is as follows:

Sequence number	Project	Continuous Flow compares batch processing	Reason
				????1	The albumen recovery rate	Improve 5～10%	In a single day the protein liquid precipitation parameter of continuous little quantitative response is reached hardly and is changed in time
????2	Purity of protein	Increase	The direct touch opportunity of initiate blood plasma or protein solution and precipitating reagent reduces because of Recycling Mother Solution, and non-target protein co-precipitation reduces
				????3	Reaction or time of repose	Shorten greatly	The time of reaching the precipitation parameter shortens and has the structure of the tiny precipitation of processing greatly
????4	Size distribution control	More even	The structure of handling tiny precipitation is arranged
				????5	The albumen later separation	Easier	Precipitate evenly solid
????6	Device volume	Dwindle greatly	The process units batch processing of same scale is long-pending than being about 45: 1 with the amount large population of Continuous Flow
				????7	Production elasticity	Very big	As long as adjust the production capacity that control software just can form the different market demands, the letter price ratio height of device

Claims (10)

1, a kind of Continuous Flow biochemical product precipitated crystal device is characterized in that described device comprises:

A retort (1) that is provided with agitator (3), reacting tank body is provided with chuck (2), is used for increasing or reducing reaction temperature;

A tube mixer (11), material solution and the circulating mother liquor of extracting out through power from retort (1) all add tube mixer in a continuous manner, wherein the ratio of the volume flow of material solution and circulating mother liquor is between 1: 1～100, the two inputs in the retort (1) after mixing continuously;

A buffer solution storage tank (4) and a precipitating reagent storage tank (6), buffer solution in two storage tanks and precipitating reagent are respectively by technological requirement and proportion relation above-mentioned raw materials solution, in the adding retort (1) of continuous and quantitative;

A valve (12) and a control corresponding mechanism that is installed on retort (1) the outlet at bottom pipe, the control reactant is discharged the speed of the adding total amount of retort with material solution, buffer solution, precipitating reagent.

2, according to the described precipitated crystal device of claim 1, it is characterized in that, be provided with inverted awl tube (19) in the described retort of being made up of end socket and tank body (1), it is divided into precipitation reaction district and the outer precipitated crystal of awl tube district in the awl tube with the retort inner chamber; The tank body of described retort is provided with the feed liquid that is used in the outer precipitated crystal of the awl tube district and extracts the mouth of pipe that adds tube mixer (11) as circulating mother liquor in a continuous manner out;

According to the described precipitated crystal device of claim 2, it is characterized in that 3, the bottom opening of described awl tube (19) is provided with flow control device.

4, according to the described precipitated crystal device of claim 3, it is characterized in that described flow control device is: its top is fixed on this aperture position through three adjusting supports (21) with the plug that awl tube (19) bottom opening coincide.

According to the described precipitated crystal device of claim 3, it is characterized in that 5, described retort is provided with a feed pipe (16), feed pipe extends downward contiguous awl tube position in awl tube (19), its underpart open end and awl tube wall surface almost parallel.

According to the described precipitated crystal device of claim 5, it is characterized in that 6, the shaft lower end of described agitator (3) is a square shaft, stirring vane liftably is installed on it; Described awl tube (19) top clamping is installed between the connecting flange of end socket and tank body.

According to the described precipitated crystal device of claim 6, it is characterized in that 7, the top in precipitation reaction district is provided with rotating wash bowl in the described retort; Top, precipitated crystal district is provided with and cleans ring (17) in the described retort.

According to the described precipitated crystal device of the arbitrary claim of claim 2-7, it is characterized in that 8, the mouth of pipe of drawing circulating mother liquor on the tank body of described retort is two, one is upper orifice (24), and one is the middle part mouth of pipe (23).

9, described according to Claim 8 precipitated crystal device is characterized in that, also comprises measuring pump (10), and measuring pump (10) is quantitatively extracted the feed liquid in the retort out as circulating mother liquor, delivers in the tube mixer (11); Also comprise measuring pump (9), measuring pump (9) is quantitatively transferred to material solution in the tube mixer (11); Also comprise measuring pump (5,7), measuring pump (5,7) is quantitatively transferred to buffer solution and precipitating reagent in the retort (1) respectively; Also comprise the measuring pump (8) that is arranged on the retort outlet, measuring pump (8) is quantitatively discharged reactant.

According to the described precipitated crystal device of claim 9, it is characterized in that 10, described retort (1) is provided with acid-base value metering device (13) and temperature measurement device (14) and Weight metering device (15).