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.