The Blood Bag Case Study

Length: 2 weeks (introductory lecture, independent study and presentations)

Level: 2nd year Biomaterials/Bioengineering

Aims: To introduce to students the areas of mechanical design on flexible containers, permeability of plastics to gases, water etc., processes for fabricating plastics film, and blood products used in the health service.

Key Skills: Group working, independent study and communication

Assessment: Group report and presentation



This is a group-based case study that involves science and processing, as well as the effects of plastics on blood products. Plasticised-PVC blood bags have been used since this 1950’s for the collection of whole blood, the processing of this in to 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.

Session 1 (Introductory lecture)

Background to topic (see below for additional information)

Group allocation

Setting of case study tasks

Session 2

Independent study (supervisor is available for any help needed)

Session 3

Presentations

Tasks

After completing the case study you should be able to:

  • Discuss the properties of plastics relevant to blood bags
  • Select from grades of PE, plasticised PVC, and rubbers, which is most suitable for blood bags.
  • Select processing routes for plastic film, and joining film.

Background Information on Blood Bags

Glass bottles were initially used for storing whole blood. The Americans began to use plasticised PVC bags in the Korean War, circa 1950. Since 1990 other polymers have been considered.

Useful Web sites for background information:

* The Blood Transfusion Service at www.blood.co.ukhttp://www.blood.co.uk

* The manufacturer Baxter Medical at www.baxter.com

* Haemonetics at www.haemonetics.com make a bowl-type blood centrifuge

* Haemotronic at www.haemotronic.com make some fluid bags (link currently unavailable)

(There may be a local blood processing lab of the Blood Transfusion service).

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.

Neural surface

Fig. 1 

              a) cross section of film                                              b) of tubing

bags1

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 emax is at the outer surface

bags2

If emax < eyield, where eyield 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.

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 Tg 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 Tg is 80°C if the PVC 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

bags3

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

bags4

 

=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

bags5

 
Values of polymer permeability P are given in Plastics chapter 10.

Polymer Film thickness mm oxygen transmission rate cm3/m2 water vapour transmission rate g /m2
Metallocene PE 0.35 1100 3
EVA 0.25  1200 4
Plasticised PVC  0.25 550 20

The oxygen rates are high for semi-crystalline polymers, of low crystallinity, above Tg (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-3.

7. 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.

Assessment

Each group must submit a single written report addressing the above tasks and summarising the main findings and conclusions drawn. The report is to be 1500 words long (about 4 pages) not including diagrams. Each group must also give a 10 minute presentation (40% of the case study mark). Ensure you introduce who you are and the main areas of your talk. Finish with a slide showing the main conclusions. Click for tips on presentations and reports.

Resources

Material Selection

Pp 1-2 of Carmen, R. (1993) The Selection of plastics materials for blood bags. Transfusion medicine reviews, 7.

Lipsitt (1997) Metallocene PE films for medical devices, Plastics Eng. 53,  p25-8.

Czuba, L.  (1999) Opportunities for PVC replacement in medical solution containers, Med. Device & Diagnostic Industry,  at www.devicelink.com/mddi/archive/99/04/008.html

Lipsitt, B. (1998) Performance properties of Metallocene PE, EVA and flexible PVC films, Med. Plast & Biomaterials,  at www.devicelink.com/mpb/archive/98/09/004.html

Ko, J.H.  and Odegaard, L. (1997) Chlorine free blends for flexible medical tubing, Med. Plast & Biomaterials  at www.devicelink.com/mpb/archive/97/03/004.html

Health Risks

Tickner, J. A. et al. (2001) Health risks posed by the use of DEHP in PVC medical devices,  Amer. J. Ind. Med. 39  p100-111

Koop, C. E.  and Juberg, A.  Scientific evaluation of health effects of 2 plasticisers used in medical devices,  at www.medscape.com/viewarticle/407990

Hull & Mahn (1984) Citric acid esters as plasticisers for medical grade PVC,  Modern Plastics Intl. 14,  p42-5

Performance Requirements

BS 2463:1990 Transfusion equipment for medical use; part 1. Specification for collapsible containers for blood and blood components

Shah, K.  et al (1998) Gas permeability and medical film products, Med. Plast. & Biomaterials at www.devicelink.com/mpb/archive/98/09/005.html

Process and Manufacture:

Morton Jones, D. H. (1989) Polymer Processing, Chapman and Hall, .

US patent 4790815 (1988) to Baxter, Heat sterilizable plastic container with non-stick internal surfaces.

Chapter 4 on Processing in Plastics by Mills N. J., E Arnold, 2nd edition, 1993.

Kothe, F. C. and Platmann, G. J. (1994)  The use of the Sterile Connecting device in transfusion medicine,  Transfusion Medical Review, 8  117-122

www.haemotronic.com page on fluid-containing PVC bags (link currently unavailable)

Ultrasonics in Plastics joining technology, Herfurth booklet, Hamburg, 1981

Ultrasonic welding techniques at www.twi.co.uk/bestprac/datashts/ultrason.html (link currently unavailable)

Blood Products

Guidelines for the Blood Transfusion Service in the UK, HMSO.

Components of blood at www.blood.co.uk