Friday, May 30, 2008


Lately or for the past few years I have heard of a Japanese company selling a concoction of microorganisms which are supposed to solve all or almost all problems of the environment from pollution to even providing nutrients for agriculture. It seems to claim everything positive using the application of the magic mixture of the microorganisms

I have been trained in microbiology especially in fermentation and industrial microbiology and I really do have my doubts about the effectiveness of the microorganisms which are claimed to be very effective

Firstly I seemed to observe in their references that no significant publications apperaed in the well reviewd scientific journals of academic respect

Secondly, the proof of the magical microorganisms have never really been demonstrated scientifically and conclusively in the laboratories or in the fields

Most of the demonstrations are just briefly shown and it is more of our faith to believe in what they say

The field experiments carried out by the promoters are not really observed and recorded daily weekly or monthly or with real scientific data really being shown. No proper experimental design was really carried out. What I saw pictures of people pouring tons of the microbial solutions into the rivers or the claims the kitchen waste will be fully disintegrated within two weeks. Why dont they carry out such experiments in a perspex or glass container and take daily pictures of the progress of the decomposition for everyone to see?

Thirdly,it seems these demonstrations are only carried out in the developing countries and not thorougly in advanced scintific countries

Personally I really doubt the claims made by these sponsors but then its not my money or reputation that is going down the drain.

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Sunday, May 25, 2008



There are various limitations which we faced in practicing conventional agriculture for our plant food sources. Other problems include environmental factors such as drought, floods, diseases, political and labour instabilities in the producing countries. There are then also the problems of uncontrollable variations in the crop quality, inability of authorities to prevent crop adulteration, losses in storage and handling

In view of these problems there are attempts to find better ways of plant production or producing valuable metabolites from the plants using more modern technology. It is only natural and logical to try to apply what technology that have been acquired in fermentation technology to be applied in the cultivation of plant or plant cells for their products. The similarity of microbial cells and single plant cells makes it a natural prigression in the attempts to cultivate the plant cells in fermentors. This is especially so after the success of plant tissue culture in generating calluses and plantlets from explants

While it is inconceivable to grow large plants in fermentors,the situation is very practicable for the culture of plant cells itself. In trying to grow plant cells in fermentors there are problems faced especially with regard to different physical and physiological characteristics between plant cells and microbial cells


----------------------MICROBIAL CELL------------------------PLANT CELL
Size --------------------2 u-------------------------------- >10 u
Shear stress ----------Insensitive----------------------------Sensitive
Water content ------------75% ------------------------------>90%
Duplication time--------<1 hour ------------------------------------days
Aeration ---------------1-2 vvm -----------------------------------0.3 vvm
Fermentation time --------Days -----------------------------------Weeks
Product accumulation ----Medium --------------------------------Vacuole
Production phase -------Uncoupled --------------------------Often growth-linked
Mutation ----------------Possible-----------------------------Requires haploids
Medium cost ($)
(MS medium)----------------8-9/m -------------------------------65-70/m

Source: Zenk, M.H., Plant Cell Culture Conference, Oyez Sci, Tech. Serv. (1982)

From the aspects of fermentation technology, the key problem areas are:
1 Plant cells are too fragile compared to microbial cells
2 Plant cells takes too long to grow in fermentors compared to microbial cells
3 Oxygen consumption is lower compared to microbial cells

As for product formation it will be a downstream problems of fermentation technology

The consequences of the three main points above are:
Since plant cells are shear sensitive supplying air or mixing will be a problems as those processes are intense shear generating forces
Too long a growth time in the fermentor will lead to the potential problem of microbial contamination to occur and fermentation disaster
Oxygen supply will have to be provided by a more suitable and controlled system

Note: In our discussion here we are more towards the cultivation of plant cells that originate from multicellular plants and not from single cell plants such as the unicellular or filamentous algae

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Saturday, May 24, 2008


There is a tradition in this country where almost everyone wants to ride the gravy train. Research is treated as a fashion where you jump on the bandwagon or wave of popularity. And everything is glorified with hype sounding names and terms such as rebranding of courses in universities with hype sounding terms such as technology. Its a perpetual re branding exercise with good dollops of marketing and massive politicking.Media blitz and self advertising or promotion rules. And as ABBA puts it "The winner takes it all". But in the end, nothing significant really resulted from all these grand ambitious projects . After all it is just the plain useless old denatured wine in a new bottle

The truth remains as long as there are "politicians" on the decision board to decide which way or priority the nations research, the face of research in this country will always remain in a time warp where nothing moves or changes or the state of research will always be static or re engineering the wheel

We will now discuss the problems of incubation units and technology parks in Malaysia. Ever since the success of the Silicon valley in USA in spurring technology and its commercialization many nations including Malaysia also try to ride the bandwagon/ While some countries like Taiwan succeeded in establishing the technology parks and proved its viability, there are many other countries trying to have their own imitation technology parks but did not succeed.

Technology parks or incubators are supposed to be the engine of growth which should propel and contribute to the commercialization of the products generated. Technology parks are just not just large swath of lands planted in some large tracts of former rubber or palm oil plantations where you provide roads, buildings, utilities to attract investors

Technology parks are areas of research and technology which help facilitate the translation of viable research or technological projects into economic viability

While facilities and support services are important the best asset in any business investment in such parks are BRAINS + IDEAS

Which party is really to gain? In most technology parks it is more a place where the new companies hope to get 'free money' and escape from various forms of tax reliefs
Is the partnership exploitive or one sided?

If this is so then the Technology park fails

At least from the internet we can get the following technology parks in Malaysia

Technology Park Malaysia Corporation Sdn. Bhd.
Seri Iskandar Development Corporation. Sdn. Bhd.
Port of Tanjung Pelepas (PTP), Port of Tanjung Pelepas (PTP), Gelang Patah, Johor
Technology Park Malaysia Corpn Sdn. Bhd Kuala Lumpur
Kulim Technology Park Corporation Sdn. Bhd. Kulim, Kedah Darul Aman
Selangor Science Park 1 Petaling Jaya Selangor Darul Ehsan
Malaysian Technology Development Corporation Serdang Selangor Darul Ehsan

The question is how successful are they in meeting their objectives and how do they compare with the technology parks of other countries? Maybe our technology parks are more beautiful in form than substance

It is simply going to ne a waste of money and exercise in futility if these technology parks are not monitored. In the real corporate sectors 'heads must roll' in the event of business failure, but here....well....;)

One thing I have observed in most of these technology parks and incubator units are more into plant tissue culture propagations which I personally think can be done by a trained educated farmer with some basic facilities

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Friday, May 23, 2008


In a way, nothing much has changed in the fermentation research scenario in Malaysia today compared to the late 50s and in the sixties.There is really no shift in paradigm or real progress in the fermentation field despite the " biotechnology explosion " of the post 70s era.

The main thrust in the fermentation research is still traditional involving mainly taxonomic studies such as isolation, identification of microorganisms involved in the fermentation. Partially this may be the poor reflection of the existing paradigm of taxonomists turned fermentation technologists wannabes.

Once the isolation,characterization studies are completed the next step carried out are just the routine standard of the mill research involving very basic laboratory scale studies which are more befitting of fermentation practicals for college undergraduates. In most cases after this stage is reached no real further studies are carried out in terms of refining the scaling up studies or the industrialization of the research translated into industries

At the end of the days and after investments of millions and millions of dollars all that can be shown are just tons and tons of reports gathering dusts on the shelves

Where did we go wrong? Why cant we escape this 'blackhole' in fermentation research. Why are our research shallow, lateral and cannot be industrialized?

If we analyse the situation or quagmire we are in which steps did we failed in making the progress?

We shall look for the possible causes of the failure in the following questions?

1 Dont we send or have enough people trained in fermentation research?

In my opinion we have more than enough people sent for their PhDs in the relevant fermentation research in the good or even excellent universities in UK

2 Dont we have enough research infrastructure for fermentation research?

Looking at the various local universities I have observed that the fermentation technology course is popular, relevant and even mandatory for various courses ranging from microbiology to bioprocess engineering. In fact judging from the websites I seem to see at least two or three universities have fully equipped fermentation pilot plant. Most universities offering the courses have a large array of bioreactors or fermentors

3 Dont we have sufficient research fundings for fermentation research?

The government is having its own Intensive Research Priority funding in the tune of millions of dollars every tear to support the programme.

4 Are our fermentation research vertical or lateral research?

Sad to say from what I observed the stress on isolation, characterization and identification of fermentation and looking for strain biodiversity is lateral research. In depth vertical research or completing the fermentation study from Petrl dish right up to the industrialization is lacking

Personally I cannot find fault generally in terms of funding and research for fermentation. The only reason why I feel too little progress are really being made in this field lies with the conservative mentality, poor research ideas, failure to be creative and inability to think outside the box. This sad state of affairs could be seen by the poor quality and quantity of fermentation research papers submitted and accepted by renowned international journals.

(Dont believe me? just check the CVs of the researchers or professors in fermentation technology of the local universities in the internet )

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Wednesday, May 21, 2008


As you traveled across the globe you will see almost each nation prides itself of their own unique fermented food heritage. The Malaysians are proud of their stinking but tasty belacan, the Thais with their unique fish sauce and the Chinese with their kicap and the Germans with their outrageous sauerkraut.

In fact you will see in most cases they are referring to the same fermented food but in their own language. The conditions of fermentation and the microorganisms involved are the same. Predominant among the common microorganisms are yeasts, lactic acid bacteria among others

In the alcoholic beverage the diversity of the alcoholic drinks are more attributed to the use of different carbohydrates or cereals for their fermentation. In wine you use grapes, in bear you use wheat and in sake or tuak you use rice or even pulut

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While it is generally accepted that food fermentation is food preservation, but in the serious context food fermentation is not truly a method of food preservation. This is in the view when food materials are undergoing fermentation process, it is being acted upon by various types of microorganisms that hydrolyze and degrade the food substrate as their source of their energy.

The preservation aspects of food fermentation lies in the fact that as consequences of fermentation these microorganisms produce fermentation products which are acidic which will retard the growth of other microorganisms.

If this acidification process continue even the fermentative microorganisms which produce the organic acids will ultimately retard the fermentative microorganisms themselves.

In view of the preservative action of the fermentation products in inhibiting spoilage microorganisms from proliferating in the fermented food, why do spoilage of fermented food occur?

Spoilage of fermented food occurs because often the fermentation conditions are not strictly maintained. For example exposure to air or oxygen during the process of fermentation allows other facultative or aerobic microorganisms to thrive.

In pickling such as sauerkraut fermentation where the salt content is high would under aerobic conditions allow fungus to grow on substrate exposed to oxygen. It is important therefore that the salt concentration is maintained and not diluted as by then the lactic acid bacteria will not be to compete effectively against other microbial contaminants

Changes in ph by exposure to oxygen will allow the change in microbial succession to occur

In the case of tempe, the so called food spoilage is not really food spoilage as it does not involve microbial contaminants but merely the fungi sporulating to give it a dark appearence

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We will now discuss in detail on how to go about industrializing a hypothetical traditional fermentation industry. We will approach this by asking a few questions

1 What are the various types of fermented foods available in the region?
2 Which fermented food has the highest demand or consumption?
3 Is there a projected increase in the demand for the fermented food in the future?
4 Is the profit margin high enough to make the project viable?
5 Can the marketing be extended to larger areas?

1 What are the raw materials needed for the fermented food?
2 Is the raw material easily available locally?
3 Is the cost economical and stable?

1 Is the production a low level fermentation technology?
2 Outline the process flow in the production of the fermented food
3 What are the rate limiting steps or bottlenecks in the production process?
4 Can these rate limiting steps be improved through use of manpower or mechanization?
5 Will the increase in production costs justify increase in profit by increasing volume of production and lowering of cost per unit produced
6 Will scaling up or economy of scale work?
7 Can SOP be introduced to the production process for better consistency and quality control?
8 Can the production process be improved from batch to continuous production?

1 What is the shelf life of the fermentation products?
2 Can the shelf life be improved by better packaging and refrigerating

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As we have discussed earlier although the traditional roots of fermentation lies in food and beverage fermentations, with modern industrial fermentations it encompasses other products such as organic chemicals, antibiotics and even vaccines. The key point in all these diverse types of fermentations are that they are all organic based and depends on microorganisms to carry out the transformations process. Secondly, these industrial fermentations are carried out intensively on a large scale to produce high volume of products

In all these fermentation industries it is unavoidable that huge amounts of wastewaters are generated within a small area, that is the fermentation plants. The source of these wastewaters are at various points of the fermentation activities right from upstream to downstream activities. Usually included in the fermentation wastewaters are:
1 Raw materials or fermentation stocks
2 End products of fermentation
3 The washing and cleaning components
4 Microbial cells and its products

The type and concentration of the fermentation waste waters of course depends very much on the type of fermentation carried out. But generally the waste waters have very high pollution load in terms of BOD and COD, high solids and very colored.

The additional physical characteristics of wastewater often associated are high temperature and even ph differences

The wastewaters from fermentation industries are usually generated in high volumes and with fluctuations in flow variations as the function of production

All these factors usually complicate the treatment option of the wastewaters

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Sunday, May 11, 2008


Traditional fermentation industries have somehow always been considered as small cottage backyard industries carried out at small scale and fulfilling the needs and demands of the local areas. Sadly. this mindset have been existing undisturbed for decades. What most forget is that the huge mega industrial fermentation industries in fact have its roots and origins from the traditional small scale fermentation industries. In fact we can look at each small traditional fermentation industries as having potential to develop into mega industries if investors dare take the gamble to exploit the traditional industries and transform it ultimately into million dollars industries. And rationally there is no reason why this cannot be achieved.

Maybe it is not feasible or practical when only one individual is thinking of doint it from the point of capital, technical and marketing support. But just imagine when the number of individuals is united in a concerted effort to pool their resources then nothing becomes impossible. After all large mega industries started small...
Wasnt it Ford who discovered the automobile and Wright who started the aviation industries? Even Kentucky fried chicken and McDonald started small??

Its more about the willingness to start and facing the slight risks and gambles.

The advantage of small fermentation industries is that they have diversity ot products not bound by the rigidity and standards of major players which is so engrossed with standards and consistency of products that they failed to be more creative and exploit new tastes....

The few important components of attempting to upgrade or industrialize the traditional fermentation industries are:
1 Improving the hardware of the fermentation by improving the size and quality of the fermentors and downstream vessels and equipments
2 Finding the rate limiting steps in the traditional fermentation process and improving it
3 Increasing the scientific and technological understanding and know how so as to improve the traditional fermentation industries
4 Combining the individuals involved into clusters so bigger fermentation industries can be carried out and pooling of common resources
5 Improving the GMP aspects of the fermentation production
6 Appointing consultants to carry out technical and marketing aspects of the fermentation industries
7 Try to improve the R&D of the process especially with respect to improving the shelf life of products, pacjaging and quality of products

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Saturday, May 10, 2008


I am looking for university or college students to help me in one of my consultation projects. We will be doing water tracing studies on a wastewater treatment plant, somewhere in Selangor.

This is a valuable opportunity for the students to be exposed to the operation of a wastewater treatment plant and experiencing various methodologies of flow measurements, and applied water tracing techniques. Students doing civil and environmental engineering, biotechnology,environmental science, microbiology would get positive benefits out of this exposure

The successful student will be provided with attractive allowance, free food and transport costs.

Preference would be given to hardworking male students from colleges or universities as it will involve fieldworks,

If interested please contact me at my email address as soon as possible:

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Friday, May 9, 2008


Validation is a very important component in any manufacturing industries especially in the fermentation industries involved in the production of health care products and food products. In fact validation is one part of GMP and TQM and help in the HACCP requirements of the industries concerned. By carrying out the validation procedures we automatically ensure the standard, quality and consistency of products manufactured. As for the manufacturers it will ensure that their production are under optimum process control in terms of quality and efficiency and as for the consumers they are assured of receiving quality products that comply all the time.

When we talk about 'validation' in general, it simply means that it is a documentary evidence supporting or confirming that all equipments, processes are carried out
according to the set specifications or SOP. This means that that the equipments and the manufacturing processes are functioning as designed.

In reality, validation is a complex but schematic process that encompasses the whole process of manufacturing from A to Z.The validation studies carried out in the fermentation industries include analytical test, equipment, facility systems such as air, water, steam, process; manufacturing processes, cleaning, sterilization, sterile filling, lyophilization. In fact every step of the manufacturing process such as cleaning of glasswares, sterilization process and maintaining cultures has its own set of SOP to be complied Validation involves various stages of design and execution

In discussing validation procedures for a particular manufacturing or fermentation process we must first bear in mind that a manufacturing process are made up of various steps in the production which involve various components such as equipments,operators, material inputs and what ever. So before a proper process validation is carried out, the following components need to be qualified first:

Design qualification (DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
At each of these stage validation activities are carried out on the equipment and facilities

In the design qualification it is important to ask these questions:
1Have all components needed for the process been properly selected?
2Do all the components have adequate capacity to function for the intended purpose?
3 Will all the components selected adequately serve the operations or functions of another piece of EQ or operation?.

In the installation qualification it is important we ask the following:
1 Are all the relevant and proper proper information, instructions or written directives are carried out for all the identification information, location, utility requirements, and any safety features of EQ adequately provided?
2 Do these information provided verify that the item tally with the purchase specifications?

In the case of operational qualifications, the following questions need to be asked: 1 Do you need provide all information that all component of a system or of a piece of EQ operate as specified.
2 Do you have all the listings of SOPs for operation, maintenance and calibration?.
3 Do you define the specification and acceptance criteria Include information on EQ or system calibration, pre-operational activities, routine operations and their acceptance criteria?

For the performance Qualification, it is only carried out after both IQ and OQ have been completed, reviewed and approved. This stage describes the procedures for demonstrating that a system or piece of EQ can consistently perform and meet required specification under routine operation and, where appropriate, under worst case situations. At this stage it will include:
1 description of preliminary procedures required,
2detailed performance tests to be done,
3acceptance criteria and other supporting EQ used during qualification have been validated.

Now we will come to the validation of the process of manufacturing itself. We will define the process of manufacturing as a series of interrelated functions and activities using a variety of specified actions and EQ which is designed to produce a defined result. The process validation studies will involve the following activities or stages:
examine a process under normal operating conditions to prove that the process is in control
which will be carried out if the process undergoes the following changes:
1 Any modification to the process
2 Anyproblems occurring in the existing process
3 If there are changes in the EQ or systems

The process validation procedures must be carried out scientifically so that the study does done should show consistency and reproducibility. These studies and usually involve:
1 Using validated EQ on the fully defined process
2 Studies carried out at least three times under established procedure
3 The process must successfully and consistently meet all acceptance criteria at all steps throughout the procedure. This must be shown to operate at least 3 times consecutively

In carrying out the validation of the process, studies must be carried to show the behaviour of the process is still acceptable under worst case scenario

The validation of the process must cover every step of the production process from A to Z such as cleaning, sanitization, fumigation, depyrogenation, sterilization, sterile filling, fermentation, bulk production, purification, inactivation, filling, capping, sealing and lyophilization

At each of the above steps detailed SOP must be carried out as required. These will normally involve various tests, analyses and experiments

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Tuesday, May 6, 2008



With the exception of mixed culture and open fermentations, there is the need for filters in most types of fermentations. The need for filtration is even more extreme and demanding in cases of highly aseptic fermentations such as in pharmaceutical fermentations.

The main purpose of these filters is either to sterilize the incoming fluids or the containment of microorganisms from being released to the surrounding environment from the fermentor. In between these functions are the maintenance of aseptic integrity of the fermentor throughout the fermentation process.

There are many types of filters used for different function of the fermentor. The common function is the exclusion of microscopic particles or microorganisms such as bacteria, spores and other solids by being excluded entrance through the pores of the filters. The physical exclusion of microbial contaminants is achieved either through size exclusion of the particles that exceed the pore size of the filters or by the adsorption of the particles on the filtering media through electrostatic interactions between the filter and the particles.

Filters are essential in the maintenance of a successful fermentation process but at the same time it got to be admitted that filters used in the fermentation process are subjected to a lot of physical and chemical stresses such as high heat, pressure and chemicals. It is also in certain cases subjected to biofouling by microorganisms.

The use of filters is subjected to its life span. Intense and extreme exposure to various stress will result in the rapid deterioration of the filter function. In such situations and as filters are expensive it is very important that the life span of the filters must be extended as long as possible. However, in the process of extending the life span of filters it is not worth the cost of fermentation failures due to the malfunctioning filters. Thus filters need to be examined periodically to avoid failed fermentation which could be disastrous especially at the production scale.

In order to prolong the life span and the filtration efficiency of the filters it is common to introduce prefilters before the filters used. These prefilters are really filters but they are more coarser and durable and will help remove significant load of particles to be filtered by the filters after the prefilters

In most filters used in the fermentation process,various types of fluids are pumped through the filters

In discussing air filtration in any fermentation system we must see it from the perspective of air inlet and air outlet. The inlet and outlet air have different physical, chemical and microbiological characteristics and particle loads.

The objective of filtration of air in the inlet line is more the towards the prevention of entry of particles, spores and microorganisms that would interfere the fermentation process. Whereas in the case of the outlet air it is more towards the prevention or escape of microorganisms from the internal environment of the fermentor to the surrounding environment. This is more the problem of microbial containment especially in fermentations involved with the cultivation of pathogenic microorganisms

While on a small laboratory scale fermentation the use of millipore type membrane filters is suitable, in large scale fermentations sartridge or even ceramic filters are more applicable.

In membrane filters usually the filter membrane is hydrophobic material to prevent the filter from getting wet and affect the filtration process. However at times, even such filters could be affected by the formation of droplets of water on the membrane surface which interfere in the filtration efficiency.


Liquid filtration are normally carried out in very sensitive filtration such as pharmaceutical fermentation. Under such conditions the fermentor are often sterilized before the media or nutrient are added . Conventional heat sterilization is not applicable as it could denature the components before the process of fermentation is carried out.

Further in pharmaceutical fermentations the scale of fermentation is small and not as big as in most industrial fermentations

Under such situations the filtration load is drastically reduced by using pure fine grade chemicals as its fermentation media. This will eliminate solids and sources of impurities to be faced by the liquid filters. Additionally the use of various units of prefilters helped in extending the efficiency and life of the filters.

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The fermentor or the bioreactor has always been referred as the heart of the fermentation process. It refers to the central position and function of the fermentor where all the microbiological and biochemical reactions take place. However, the fermentor is just the vessel to support the growth of the high concentration of microorganisms and its success depends a lot on the input of various components such as nutrients, oxygen and the removal of products such as spent broth and gases among others

The dynamic flux which occur between the fermentor environment and the external environment are crucially maintained by the various pumps that serviced the fermentor . The pumps are the heart of the fermentor itself as much as the fermentor is the heart of the fermentation process

The pumps deliver,removes and maintain the fermentor environment through its control of fluids in and out of the fermentor. The success of the pumps in doing its function depends on other factors such as tubings and pipes in servicing the fermentors.

There are various types of pumps to carry out the different function in the fermentor. But important in the choice of the pumps to be selected are the:

1 The nature of fluid that is being pumped
2 The degree of contact or sterility required of the fluid

The rheology or viscosity of fluid being pumped is important. If the liquid is too viscous it might require a more powerful pump to pump the fluid. A liquid which contain high amount of solids could be a problem in pumping as if the velocity is too low then it might result in the solids settling down due to gravity and creating problems of pumping

This will be a major problem in aseptic fermentation where sterility demand is very stringent. Only pumps which are not in contact with the fluid or are in high sanitary conditions are permissible

In small scale fermentations, the most ideal mode of pumping will be by using peristaltic pumps. Fluids are moved through the tube by peristalsis action of rollers acting in pulses on the tube. The fluid is never in contact with the pump

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