Near-patient in vitro diagnostic (IVD) tests depend on medical devices to perform diagnoses, generally in controlled environments and using non-invasive techniques external to the patient. Rapid availability of IVD results is advantageous to both physicians and patients. Reagent discs are used by physicians in portable point-of-care clinical chemistry systems to analyze minute whole blood samples and perform routine on-site multi-chemistry panels in order to quickly diagnose potential patient illnesses.
Ailments easily detected by the reagent discs — which are designed for patient testing in ambulatory settings — include chronic renal (kidney), bone and metabolic diseases, hyperparathyroidism, adult and juvenile diabetes, hypoglycemia, sepsis (local or generalized infection of the body by pathogenic microorganisms or their toxins), salt poisoning, malnutrition, and much more.
C. Brewer Co. injection molds low-cost, disposable reagent discs at its facilities in Anaheim, CA. The discs are used in blood analysis systems that employ spectrophotometric technology to provide commonly requested panel results for patients in just a few minutes. However, yields — the ratio of usable discs to scrap and the amount of high-quality product obtained from the injection molding process — were being negatively affected by a nearly invisible flaw.
Subtle anomalies detected in the reagent discs’ plastic surfaces were causing the customer, a medical products company, to return unused discs. Irregularities — known as “knit lines” — produced in the molding process could potentially cause test failures by interfering with the light absorbance capacity of tiny optical window “lenses” on the discs through which measurements of blood samples are taken.
The problem called for a fast and effective response. After a thorough review and re-evaluation of all returned discs and the injection molding procedures and processes that made the discs, engineers were able to isolate and fix the problem by developing a polymer mold flow analysis technique: Ultraviolet (UV) Flow Analysis™ — essentially a plastic “angiogram” based on fluorescence.
Examining the Science of Reagent Discs
Each reagent disc, used in a portable point-of-care blood chemistry analyzer, is an 8-cm diameter consumable made of three injection-molded plastic parts ultrasonically welded together. The base and middle layer of the discs are made from polymethyl-methacrylate (PMMA), a thermoplastic resin used in applications such as hard contact lenses. The top layer is made from acrylonitrile butadiene styrene (ABS), a common thermoplastic with good rigidity and resistance to impact, heat, and chemicals.
The disc’s welded base and middle layers form a series of many interlinked internal chambers, passageways, and “cuvettes” that enable fluids to be processed via centrifugal (spinning) and capillary forces within the analyzer. The cuvettes are tiny liquid-holding vessels located on the periphery of the discs and designed to contain all the necessary reagents (chemically reactive substances) to perform a fixed menu of tests on human patients.
Because the reagent cuvettes hold samples for spectroscopic analysis, they act as optical windows with lens-like properties. The lenses must therefore be as clear and transparent as possible, without impurities or flaws that might affect a spectroscopic reading and interfere with obtaining accurate calculations of coefficients of absorption.
A disc’s top layer prevents contamination of the analyzer by any sample spilled on the disc surface, provides imprinted bar-coded, disc-specific calibration information to the analyzer, and protects the cuvette windows from fingerprints or scratches.
The heart of the blood chemistry analyzer is a spectrophotometer, a device that measures absorption of light at various wavelengths coming from the reagent discs. The analyzer’s optical system consists of a stroboscopic lamp, a multiple-wavelength beam-splitter/detector capable of reading multiple wavelengths.
All reactions — including analyte (the substance being analyzed), diluent (diluting substance), reagent, and instrument quality-control testing — occur in solution within the cuvettes. The spectrophotometer monitors the reactions in each cuvette by flashing the lamp synchronously with the spinning disc. The system generates powerful flashes of full-spectrum white light and measures absorption for each reaction at multiple wavelengths, from ultraviolet to near-infrared.
Some sources of error in spectrophotometric measurement of whole blood samples in the reagent discs can be attributable to cuvette lens surface blemishes, impurities, or distortions. This could potentially lead to an aborted test at a customer site.
Pinpointing the Problem
Since the reagent discs were modeled in Autodesk® Moldflow® plastic injection molding simulation software, the engineers started there to attack the problem. They used the software for flow analysis and computational fluid dynamics to analyze any problems involving fluid flows. The engineers ran computer-animated models and performed fluid-flow simulation and thermal analysis so that they could analyze the theoretical flow patterns.
Simulations were performed to validate and optimize the part, the molds, and the molding process in order to find potential part defects resulting from the molding process. They looked for knit lines, air traps, and sink marks, and they optimized the molding process.
Moldflow® was used to predict flow-related anomalies in the cuvette lenses, thereby modeling the melting of knit-line flow fronts. The engineers evaluated multiple materials, processing conditions, and gate and runner designs to improve material flow which, if deficient, could cause the decomposition of a ray of light — a potential source of false readings.
In standard injection molding, the process begins with granular plastic pellets being fed from a hopper into a heated chamber to be mixed and softened. Engineers began altering the process by dropping plastic pellets infused with fluorescent dye into the pellet stream.
In injection molding, a screw forces the material into a mold cavity where it cools to the configuration of the cavity. Pressure is maintained until the mass has solidified sufficiently for removal from the mold.
With the molded parts in hand, the engineers analyzed the finished fluorescent flow of the parts using ultraviolet (UV) light to illuminate the dye in each part to reveal the actual flow characteristics of the polymer.
They developed an Ultraviolet (UV) Flow Analysis™ technique that mimics the process of angiography, the X-ray examination of vessels (arteries, veins, or capillaries through which blood circulates) following injection of a radiation-opaque substance. An angiogram is the X-ray picture produced by angiography.
The flow analysis technique involves using a fluorescent dye infused into plastic to capture and examine a part’s rheological (material flow) behavior, thus mimicking an angiogram.
To create high-resolution images of the fluorescent-colored discs, engineers first used inspection microscopes with USB digital cameras and fiber optics to focus light down to a fine point. The discs were then examined with a black light (UV) lightbox that illuminated the entire part in the blue and ultraviolet portions of the electromagnetic spectrum. The fluorescent dyes in the plastic parts absorb the short-wavelength blue and UV light and re-radiate the energy at longer green and yellow wavelengths that appear in a UV picture in vivid, glowing colors (see Fig. 1).
Under the black light, the “as-molded” fluorescent discs clearly revealed in static state the pattern of the plastic filling the cavity and emphasizing all the flow characteristics, allowing the engineers to identify minute knit lines. These otherwise imperceptible flaws are common on molded plastic parts that form where melted material flows together. The imperfections in the material normally occur around holes or obstructions and are intrinsic to every molded part.
Knit lines occur naturally and unavoidably during the molding process. It is practically impossible to eliminate them once they are formed — but they can be minimized with a mold-flow study when the mold is in design phase. The gate is the channel through which the molten resin flows from the runner feed channel into the mold cavity. Once the mold is made and the gate is placed, knit line flow flaws can be minimized by adding vents and changing pressure, the melt, and the mold temperature.
By making engineering design changes to the parts tools, engineers were able to mitigate shrinkage and warpage while adjusting and altering flow characteristics to effect minute microscopic changes in the plastic disc material. This greatly improved the quality of the cuvette optical window lenses. In addition, by using this technique, the company has completely eliminated knit-line defects in the lenses and the molding of the reagent discs.
This “angiogram” for plastic material allowed engineers to see more clearly than ever before the subtleties of melted synthetic polymer flows. The application of this technology allowed them to detect and fix a nearly invisible but commonplace anomaly that was affecting product quality and impacting yields of reagent discs critical to millions of patients worldwide.