Originally published March 1996
Plastics have been used in medical devices for more than 40 years, from the time that plasticized PVC first replaced natural rubber and glass. Since then, rapid developments in technology have stimulated the increased use of plastics in a variety of medical applications. The global market for medical devices currently exceeds $100 billion, with average annual growth rates of 8%. In Western Europe and the United States, the advent of better health care has resulted in a higher proportion of both very young and aging populations--groups that form the majority of those receiving treatment by invasive surgical and after-care techniques. Along with the recent rise in infectious diseases, this trend has led to a substantial increase in the use of presterilized, disposable medical products.
Many medical procedures involve the transfer of fluids to or from the patient, and employ a wide range of flexible tubing products. Examples include taking/giving sets (for transfusion, infusion, dialysis); catheters (intravenous, cardiovascular); endotracheal tubes (for intubation or anesthesia); tracheostomy tubes; and cystoscopy instruments.
Although the use of plastics in medical applications represents less than 2% of total consumption, the high "added value" of the final products is of considerable commercial interest to material suppliers and end processors. In achieving this value, the medical market makes stringent quality demands on manufacturers that require a commitment to continuous material and process development. This is particularly true for current extrusion technology used to produce a wide range of disposable medical devices.
Today's extruded medical products require the careful application of precision processing concepts, especially for multilumen, microbore, coextruded, or cross-head- extruded tubes, for which the diameter tolerances can be as small as ±5 µm. Such products are part of the increasing trend toward minimally invasive surgery, examination by miniaturized optics, or microsurgery using laser techniques. Catheter tubes are also receiving attention, with tighter tolerances being set on tube dimensions. With medical plastic compounds costing as much as $10,000/tn, large cost savings can be an added incentive to attaining higher levels of accuracy in tube extrusion.
A considerable variety of materials are available for medical tube extrusion, with properties to satisfy most end-user requirements while meeting strict regulations relating to biocompatibility and nontoxicity. PVC remains the leading polymer for medical tubing, with polyurethane, polyolefins, and blends or alloys such as thermoplastic elastomers also commonly used. For more demanding applications, engineering plastics such as polyamide/imide, polyester, polycarbonate, or various fluoropolymers can be selected. Many resins can be compounded with optical or x-ray opacifiers such as titanium dioxide, barium sulfate, or bismuth subcarbonate, further increasing the number of potential materials and grades. The challenge for manufacturers is to find the optimum processing conditions enabling each grade to produce high-quality, close-tolerance tubing capable of being run in a single operation at acceptable outputs.
Predrying of hygroscopic or moisture-sensitive materials--for example, polyurethanes, polyamides, and polyesters--is essential, particularly if high levels of inorganic filler are present.
When various types of wire are fed via a cross-head die, certain wire-conditioning stages are required to ensure that an accurate and consistent payout rate and tension are maintained on the wire. These may include a tension-controlling dancer, wire cleaner, wire preheater, or wire straightener.
In order for a manufacturer to offer precision medical tube products, the various parts of the extrusion process need to be operated under optimized and integrated conditions. The layout of a typical medical tube extrusion line is shown in Figure 1.
The matching of extruder screw design to the melting and rheological characteristics of the plastic to be processed is fundamental to extruder performance. Screw design is a complex subject, but most screw elements fall within the ranges presented in the box shown below. The key extrusion criteria of output, plasticization, solids conveying, and power consumption are influenced by screw design variables such as channel depth, number of flights, helix angle, compression ratio, flight clearance, and flight geometry.
There is no such thing as a "general-purpose" screw. For medical tube production lines--which demand high levels of quality and performance--it is often sensible to carry a library of screws that suit all of the materials or grades used and to introduce screw changes as a standard procedure at each material change. Since it is rare to find more than four different polymer types used on the same production process, screws designed specifically for the polymer type are normally supplied.
Because medical-grade PVC contains low levels of plasticizer and stabilizer, a different approach is required than that used for cable-grade PVC. The mixing performance of the screw is very important in ensuring sufficient gel reduction to promote high clarity. An amorphous polymer, PVC has a very wide melting range, from 100° to 210°C. As a result, when processed at temperatures below 210°C, gels in the form of unmelts will always be present and must be removed by shear breakdown, higher temperatures, or screen filtration. Conversely, PVC begins to give off HCl gas when the degradation point is reached, which can occur above temperatures as low as 120°C. Unless "mopped up" by heat stabilizers, these "chain-scission" reactions result in discoloration and rapid thermal degradation at around 230°C.
For these reasons, several proprietary multiflighted barrier screws have been developed for PVC. All operate by confining the solid bed to the active side of the barrier flight, while the polymer melt is allowed to flow over the barrier flight into the passive side of the screw channel. This type of screw, if well-designed, ensures complete melting, often over a reduced length of screw, and offers enhanced mixing due to the high levels of shear developed through the barrier clearance. Various designs based on this theme are used, for example, in the Maillefer, Barr, Dray and Lawrence, Kim, and Inger Housz screws.
Fluoropolymers such as FEP need special materials for screw and barrel elements in order to overcome extremely corrosive hydrofluoric acid degradation products. Special corrosion-resistant alloys are often used--for example, Hastelloy for screws, and iron-free nickel/brass/chrome alloy bimetallic lining for barrels. It is important that the iron content be kept to less than 1% so as to eliminate melt contamination caused by iron-based specks that can form in corrosive environments.
A crucial component of the overall extrusion process for medical tube production is the die. Different sets of tooling are often used, with varying pin and bush dimensions, to match the rheological characteristics of the chosen polymer at the defined output rate and line speed. Also, streamlined flow paths are used to prevent holdup within the die, and to minimize degradation and dwell time. Thus, approach angles in the die adapter should be as low as possible, and all changes in section geometry should be radiused.
Dies should be designed for uniform flow of material, producing uniform product with minimal internal stresses. Many postextrusion properties of tubing are related to the viscoelastic nature of the polymer and the level of shear deformation that occurs during die shaping. Elastic recovery causes die swell, and tube reversion or poststerilization shrinkage can result from poorly designed dies.
Given the small dimensions of many intricate multilumen tubes (see Figure 2), high drawdown ratios are often employed to allow die dimensions to be large enough to be practical. With PVC and PUR, however, reversion specifications are critical, and reversion reduces with lower drawdown ratios. Thus, the design and manufacture of small-diameter PVC or PUR tubing becomes more difficult. By contrast, high drawdown ratios can be used with PA and many fluoropolymers, which are therefore more commonly specified for precision microbore or multilumen tubes.
Many tubes incorporate a colored and/or x-ray-opaque stripe down their length to aid in identification or for precision insertion and inspection. The stripes are produced by coextruding another material into the tube die from a second extruder. It is possible to create external or internal surface stripes or to fully encapsulate the stripes in the tube wall to prevent leaking of additives.
The production of precision multilumen tubes or the insertion of forming wires or guidewires requires cross-head die extrusion. In this process, the polymer melt enters the die at right angles to the outlet, which allows lumen characteristics to be controlled by individual, pressurized air supplies fed from the back of a cross-head die and into the tube via precision-bore injector needles. Forming wires are inserted through a cross-head die in a similar way. Because of the very fine gauge of wire used, wire payout systems may include units to control and monitor wire diameter and tension.
Dies are normally stainless steel, which must be hardenable and capable of achieving a good polish. In the case of fluoropolymers, Hastelloy C should be used for all components likely to come into contact with the molten material.
To ensure that a manufacturer's multilumen tubing will sustain precise flow levels, the extrusion process must include some means of maintaining the consistency of all tube dimensions. A typical tolerance range is ±1%, which for a tube with an internal diameter of 1.6 mm translates to accuracies of ±10 µm (the diameter of an average human hair is only 75 µm).
Increasing product accuracy will lead to significant reductions in material usage and resultant cost savings. For example, reducing the tolerance from ±0.08 mm down to ±0.01 mm on a 1.00-mm-ID tube with a 0.225-mm wall thickness yields material savings of 12.5%. Assuming material costs of approximately $10,000/tn, this would represent cost savings of $12.50/hr at a 10 kg/hr production rate.
Outside diameter is controlled by vacuum calibration. Most extruders feature accurate low-level vacuum control, which keeps the outside diameter of the tube stable.
Internal lumens must also be accurately controlled. In a multilumen tube (see, e.g., Figure 3), each lumen has a defined end use, with the cross-sectional area controlling the flow rate, a minimum internal diameter for guidewire insertion, and shape-related draw characteristics for postforming operations. There are two principal methods used for controlling the shape of each lumen. In the first, bore-forming mandrel wires can be inserted temporarily into the tube: as the polymer overlays the mandrels, accurate lumens can be formed by removing the precision-gauge wires after cooling. Alternatively, separate air-pressure control for each lumen can be achieved by using air injection needles. Recent developments in low-pressure regulators along with an increased understanding of such instruments make it possible to accurately adjust and maintain pressure differentials at low pressures. For example, a pressure of 0.017 bar can be maintained to within ±0.002 bar. The relative flow rate required to maintain lumen size at a given die speed can be computed, but care must be taken to ensure that the air supply used for pressure regulation is subject to the same influences as the ambient air surrounding the extrusion line.
POLYMER MASS FLOW
To accurately maintain diameter and wall thickness of intricate polymer tubes, a uniform flow rate of melt from the extruder must be guaranteed. All extruders producing extremely tight tolerances will exhibit some surging as a result of electrical drive control fluctuations, screw design, and the normal rheological variation in the polymer. Clearly, high reject rates and waste levels will result if the process relies solely on the extruder stability. To overcome this, a precision rotary gear pump is used to provide steady pressure and accurate metering of the polymer to the die head in a controlled, surge-free manner.
The melt gear pump consists of a pair of precision-ground, closely intermeshing gears and acts as a positive-displacement pump to supply melt at a set volumetric rate. The pump is driven by a dc motor with tachogenerator feedback and voltage-regulator control, providing speed holding to ±0.01%. A rapid-response, closed-loop microprocessor controller senses the melt pump inlet pressure--or pressure differential across the pump--and automatically adjusts the extruder speed to maintain a constant value.
Placed between the extruder and the die, this pump becomes the main extruder control device, minimizing the inefficiencies inherent in conventional extrusion operations. Discharge pressure, and hence mass-flow variations, can be held to less than 1%, yielding greater dimensional accuracy.
Each extruded tube is pulled through a cooling bath by a precision haul-off unit. For tubes less than 2 mm in diameter, a capstan haul-off gives the best tension control, whereas caterpillar haul-offs are used for larger tubes. Good motor speed control is required, as drawdown ratio and haul-off speed are fundamental for forming accurate small-diameter tubes. Dc motors with tachogenerator feedback and digital speed-loop control can offer speed holding to better than 0.01%. The tube product is then cut to length in-line, or coiled into reels. To retain precision profile and uniform properties, care must be taken to ensure that product collection imparts only low longitudinal tension to the product.
When a manufacturer is working to the accuracies outlined above, all process parameters must be under close control, and constant monitoring is required to ensure compliance with such demanding specifications. Historically, this has involved process data logging and off-line product measurement. However, current trends are toward on-line, real-time monitoring of key parameters so as to achieve "processed-in quality." Automatic control of processing parameters is therefore used to keep the product within specified quality limits.
Precision tube products must be made correctly the first time, every time. This means that the manufacturing process must be stable, and that all personnel involved with the process must seek to improve process performance and reduce variability in the key parameters. However, no process can be controlled until one knows what to measure and how to measure it. Therefore, the first step is to determine how to measure quality, and then identify which process variables can be manipulated to influence that quality. The key quality parameters in medical tube production are dimensional stability and tolerances on all dimensions. The relationships presented in Figure 4 offer the potential for closed-loop control mechanisms, with feedback loops being controlled by high-precision equipment for gauging tube dimensions.
Laser gages offer accurate and rapid measurement of outside diameter by measuring a shadow created when the tube obscures a fine beam of rapidly scanning light. Dual-plane laser gages measure OD in two planes, providing both average OD and ovality with a resolution of 1 µm.
Gamma backscatter probes use gamma-radiation backscatter to determine wall thickness down to 0.05 mm (with a resolution of 1 µm) for tubes with diameters as small as 1 mm. Probes measure wall thickness at a single point around the tube; a number of probes can be used if measurements of multiple points around the diameter are required.
Ultrasonic reflection involves aligning the product in an ultrasonic gage placed in a water bath and arranging transducers (typically four) around the product. Each transducer sends out a transmission pulse that is partially reflected off the outer wall of the tube. While the partial reflection returns to the transducer, the remainder of the initial transmission pulse continues through the product wall. The difference in density between the air and the product creates a second reflection, and the time differential between the two pulses allows wall thickness to be calculated. Enhancing the signal with digital processing can allow measurement to an accuracy of ±5 µm of tubes as small as 1.0 mm OD, with wall thicknesses of 0.13 mm or less.
Statistical process control (SPC) can be achieved by using measuring instruments such as those discussed previously. Data can be gathered (typically at 100 scans/sec) and rapidly converted by a process controller to provide waveform readings or live trend charts. When the data are viewed statistically, deviation trends can be seen, allowing process adjustments to be made by a control feedback loop. The most advanced current technology allows two independent loops to be used (see Figure 5). Typically, one loop controls haul-off or screw speed and the other controls air pressure or vacuum. Any two of the product dimensions may thus be controlled at any one time. SPC control-group data and functions can be used to improve the process capability indices relating to a product's dimensional accuracy (see Figure 6).
Closed-loop control methods have led to major advances in the extrusion of precision tubes for medical and health-care applications. However, the extrusion process is complex and interactive, and attempts at using multiple control loops have invariably led to instability.
Given the power of modern microcomputer systems, it is now possible for extrusion specialists to work in real time with multiple-interaction algorithms. There are signs that, in the near future, this real-time control may allow for "intelligent processing" in the demanding field of precision small-diameter medical tube production.
John Colbert is technical director of Betol UK (Luton, Bedfordshire, UK), where he specializes in all types of extrusion as well as general polymer processing. Betol manufactures twin screws for compounding and complete extrusion lines for the production of fine-tolerance tubing and multilayer film and sheet.