Case Study: Materials for Blood Bags

Transcription

1 Case Study: Materials for Blood Bags This case study of good practice in learning and teaching in materials focuses on polymeric materials for use in blood bags. Author: Dr Nigel Mills Institution: University of Birmingham Background to the case study Biomedical materials science is an interdisciplinary area. The case study involves materials science and processing, as well as the effects of plastics on blood products. Plasticised-PVC blood bags have been used since the 1950s for the collection of whole blood, the processing of this into plasma, platelets etc., and storage. The phthalate plasticisers, when fed in large quantities to rats, can cause cancer. This does not prove that the storage of whole blood in plasticised PVC bags is a health risk. However, there has been a search for alternative polymers for blood bags. Relevance of the case study to the study of materials science It is a vehicle for student-centred learning in the areas of the 1. mechanical design of flexible containers 2. permeability of plastics to gases, water etc 3. processes for fabricating plastics film 4. blood products used in the Health Service. Objectives After completing the case study you should be able to: 1. Discuss the properties of plastics relevant to blood bags. 2. Select from grades of PE, plasticised PVC, and rubbers, which is most suitable for blood bags. 3. Select processing routes for plastics film, and for joining film. 1st Session (2 Hour Lecture) Introduction: Glass bottles were initially used for storing whole blood. The Americans began to use plasticised PVC bags in the Korean War, circa Since 1990 other polymers have been considered. One design of a blood bag set is provided for inspection. Useful Web sites for background information:! The Blood Transfusion Service at The manufacturer Baxter Medical at Haemonetics at make a bowl-type blood centrifuge! Haemotronic at make some fluid bags (link currently unavailable) There may be a local blood processing lab of the Blood Transfusion service.

2 Basic requirements (not in any particular order) 1. Translucency so can check if full, and see layers in centrifuged bags Materials property - translucency: Metals act as mirrors, since they have conduction electrons. Plastics, which are electrical insulators, can be transparent (if a single phase glass) or translucent (if 2-phase semi-crystalline with light scattering). Thin films scatter less light than thick mouldings, so appear more transparent. There must be no added pigments. Thermoplastics do not need pigments, but rubbers often need mineral fillers (carbon black, etc) for strength. Silicone rubber can be transparent. 2. Flexibility (low bending stiffness) so can process by squeezing the bag. It should only require a small force to bend the bag wall. Material property: Young's modulus E (and beam property I second moment of area). For the blood bag and tubing, the formulae for the bending stiffness EI are shown below. Neutral surface Fig. 1 a) cross section of film b) of tubing If the bag is thin (say 0.1 mm), it will be flexible whatever polymer is used; consider the 0.13 mm thick PET sheet of an OHP, which has E = 3 GPa. However thin films made from low crystallinity PE copolymers or plasticised PVC have E < 0.1 GPa, and are much more flexible. The tubing, linking the bags, has a higher bending stiffness than the bags, since the material is further from the neutral surface; the typical outer diameter is 4 mm, and inner diameter is 3 mm. 3. No damage when bent to a small radius Material property- strain at yield: If an initially flat sheet, of thickness t, is bent so the neutral surface has a radius of curvature R, the maximum tensile strain e max is at the outer surface If e max < e yield, where e yield is the yield strain of the material, the deformation will be permanent. Semi-crystalline thermoplastics, such as PE and PP, have tensile yield strains of about 0.1, whereas plasticised PVC has a value about 0.2. As the sheet thickness t is small, the bags can be bent to a small radius.

3 4. Heat resistance, so can steam sterilise prior to use The most common sterilisation method is by steam (in an autoclave at 10 bar pressure) at 121 C. The alternative is the more expensive radiation sterilisation. Materials property- melting temperature: The plastic must not melt at 12 C. For glassy PS, the glass transition temperature T g is 100 C. For semicrystalline PE and PP, the crystal melting temperatures (130 and 170 C respectively) are just high enough for the plastic to survive steam sterilisation. For PVC the 10% crystals melts at 220 C. The glass transition temperature T g is 80 C if the is unplasticised, but can be below -40 C if it is plasticised. 5. Must not burst in the centrifuge, or tear on handling Material property - tensile strength: Centrifugation is used to separate out the white and red cells, which are slightly denser than the plasma. The high speed centrifuge generates 5000 g linear acceleration, where one g is the acceleration of gravity. Several bags are placed in a strong 'bucket'. When this is rotated at speed, at the end of an arm, the 0.5 kg unit of blood experiences a centripetal force of 25 kn. The hydrostatic pressure p, at the base of the bag of depth h = 0.2 m, is With a linear acceleration of g = 5000 x 9.8 m s-2 = 50,000 m s-2 and blood of density rho = 1000 kg m-3, the pressure p = 10 MPa. If, at the base of a rigid container, there is an unsupported corner of radius r = 2 mm and wall thickness t = 0.5 mm, the hoop stress in the wall would be = 40 MPa Hence a rigid blood container needs to be made of a strong material. This stress would cause most thermoplastics to yield and fail. If a flexible bag is used, it rests against the bucket wall, and the maximum stress will be of the order of the pressure p i.e. about 10 MPa. While handling, full blood bags are sometimes supported by the tubing. Allowing a handling acceleration of 5 g, the peak load on the tubing is 5 times the full bag weight, eg 25 N. If the plastic has a tensile strength of 10 MPa, what is the minimum wall thickness of a 6 mm diameter tube? 6. Permeable to oxygen, but not too permeable to water Material property- permeability: The platelets need oxygen to survive. All plastic films are permeable to some extent. The gas flow rate Q through a wall of area A and thickness L, is given by Values of polymer permeability P are given in Plastics chapter 10. Reference D of task 1 gives transmission rates for particular film thicknesses. Polymer Film thickness mm oxygen transmission rate cm3/m2 water vapour transmission rate

4 g /m2 Metallocene PE EVA Plasticised PVC The oxygen rates are high for semi-crystalline polymers, of low crystallinity, above T g (PE copolymers, EVA - copolymer of Ethylene with Vinyl Acetate, and plasticised PVC). The water vapour transmission rates should be low, to prevent water loss. The values are lowest for the metallocene PE of density 905 kg m Moderate cost Materials property - cost per kg: The cost restriction means that the bag material is likely to be a commodity plastic or a derivative thereof (PVC, PE, PP, PS), which have costs of the order of 50p/kg. 8. Processing and welding The blood bags are disposable and must be made economically. Polymer processing methods are described in the references for task 4. It is difficult to create strong welds between different plastics. Hence, if the tubing is welded to the bag, a single plastic should be used for both tubing and bag. 2nd and 3rd Sessions The class is split into groups of between 4 and 6. Each group studies one materials selection task (1 to 3) and one processing task (4 to 6) in successive sessions. Staff are present to answer questions and to check progress. It is suggested that 2 students write the report and 2 prepare the presentation. 1st Set of Tasks The answers to the questions in each area may depend on the answers to others, so communication between groups is essential. One or more group members may wish to use the internet or library resources. 1. Which plastic should be selected for the bags and tubing? 1. Pp 1-2 of R. Carmen The Selection of plastics materials for blood bags. Transfusion medicine reviews, 7 (1993) 2. Lipsitt, Metallocene PE films for medical devices - Plastics Eng. 53, (1997) L. Czuba, Opportunities for PVC replacement in medical solution containers, Med. Device & Diagnostic Industry, (1999) at 4. B. Lipsitt, Performance properties of Metallocene PE, EVA and flexible PVC films, Med. Plast & Biomaterials, (1998) at 5. JH Ko and L Odegaard, Chlorine free blends for flexible medical tubing, Med. Plast & Biomaterials (1997) at Refer back to the introductory lecture. The minimum wall thickness and internal diameter of the connecting tubes are specified in the British Standard (task 3). You may wish to eliminate unsuitable materials until one is left, or find a material with all the required properties. If PE is to be used, specify the density (or % crystallinity). Tubing made from rubber (natural and silicone - both contain fillers), plasticised PVC, low density polyethylene, nylon, and rigid PVC are provided. Observe their relative bending resistance, and that some nylon ones will kink

5 when bent to small diameters. 2. Are there risks from using plasticiser in PVC? 1. Health risks posed by the use of DEHP in PVC medical devices, JA Tickner et al, Amer. J. Ind. Med. 39 (2001) A Scientific evaluation of health effects of 2 plasticisers used in medical devices, CE Koop and Juberg, at 3. Citric acid esters as plasticisers for medical grade PVC, Hull & Mahn, Modern Plastics Intl. 14 (1984) 42-5 Why is a high plasticiser content necessary in PVC? What is good and what is bad about the phthalate plasticisers? Should plasticisers other than phthalate be used in PVC, or should PVC be replaced altogether? 3. What are the main performance requirements of the blood bag? 1. BS 2463:1990 Transfusion equipment for medical use; part 1. Specification for collapsible containers for blood and blood components 2. K Shah et al, Gas permeability and medical film products, Med. Plast. & Biomaterials (1998) at Outline the mechanical property requirements, and those on the transmission of liquids, gases and solids to and from the blood, giving reasons where possible. See the web sites at the beginning of this case study. 2nd Set of Tasks: Processing 4. Which processes should be used to manufacture the tubing and the bag? 1. Polymer processing by DH Morton Jones, Chapman and Hall, US patent (1988) to Baxter, Heat sterilizable plastic container with non-stick internal surfaces. 3. Chapter 4 on Processing in Plastics by NJ Mills, E Arnold, 2nd edition, There are different processes for rubber and thermoplastics, so you need to know from group 1 which is to be used. The bags could be tubular or they could be made from flat sheet. How is the surface texture on the commercial blood bag achieved, and what is its purpose? 5. Which processes should be used to weld the tubing and the bag walls? 1. The use of the Sterile Connecting device in transfusion medicine, FC Kothe & GJ Platmann, Transfusion Medical Review 8 (1994) page on fluid-containing PVC bags (link currently unavailable) 3. Ultrasonics in Plastics joining technology, Herfurth booklet, Hamburg, Ultrasonic welding techniques at (link currently unavailable) What is the best process to make the bags from plastic film? Why is there a need to make

6 welds between the tubing from bags? What process is used to make the tamperproof needle inlet to the top of the bags? It can be peeled back to allow access. The outlet tube needs to be flexed to open it. 6. What are the main blood products and what is their shelf life? 1. Guidelines for the Blood Transfusion Service in the UK, HMSO. 2. Components of blood at 3. The National Blood Service, report by the National Audit office, 2000 at tap.ccta.gov.uk/doh/point.nsf/publications What are the main products used for? What limits the shelf life of the different products? Under what conditions are the products stored, and how does this affect their shelf life? What information should be on the blood product packs? What is the effective price of a unit of blood? 4th Session (3 Hours) The first hour consists of 6 presentations of 5 mins, with 5 mins of questions. The reports are then finalised, possibly adding information from the presentations. There is assessment of student presentations by students. Evaluation Student reactions to the case study were positive; they learnt about polymers that were relevant to their course, and they could link the discussion of blood components to their lectures on cell biology. They searched for information about plastics processes for the specific medical product; this produced a better reaction than traditional lectures covering a catalogue of processes. There was a positive reaction when a visit to the Blood Transfusion Service laboratories was included. Students needed to attend the 2nd and 3rd sessions to access the resource material, and complete the task under time pressure. There was significant interaction with the member of staff, and it was possible to observe their group activities. With the small size of the student groups, it was easy for them to control the various activities. The self-assessment of the presentations provided quite critical comments about speed of talking, contact with the audience, and use of visual aids, as well as recognition of good features UK Centre for Materials Education