An MD&DI May 1998 Column
Instruments haven't necessarily changed much in what tasks they accomplish, but market and health-care influences have altered their size, consolidated their functions, and forced them to do more with less.
The market for diagnostic and monitoring equipment, including reagents, exceeds $20 billion annually and is growing more than 4% a year despite the negative effects of managed care and hospital consolidation. This continued growth is caused primarily by innovations made by device manufacturers and suppliers. Fluid control component manufacturers that continue to adapt to market changes will be the most successful.
A SYSTEM IN FLUX
Medical fluid control is provided by a wide range of common components, including pumps, valves, manifolds, tubing and connectors, reservoirs, and transducers. Although much could be written on any of these components, the market trends toward systems integration, reduced fluid volumes, and miniaturization affecting these components are of equal or greater significance than individual component details.
Systems Integration. Increased systems integration involves the application of functionally different components in a common packagefor example, pumps, valves, and transducers on a common manifold. OEMs are attempting to consolidate multiple vendors into a smaller, more valuable supplier base, so they can reduce the internal overhead costs of departments such as purchasing, quality assurance, and engineering, which support the supplier base. Miniaturization is a natural consequence of increased systems integration. As more components are integrated onto a common manifold, cabinet space that traditionally had been devoted to strands of spaghetti-like fluid transmission tubing can be eliminated.
Reduced Fluid Volumes. Diagnostic options have increased and physicians are able to take advantage of technological developments to provide patients with more accurate diagnoses. However, the process of pinpointing a diagnosis means subjecting patients to a large number of tests, leading to a corresponding desire on the physician's part to reduce the serum volume required per test. Exotic, expensive reagents also provide an economic incentive to use minimal amounts of fluid. The natural consequence of reducing fluid volumes is to cut back the internal volume of system components.
Miniaturization. In addition to being a consequence of reduced fluid volumes, miniaturization is a market trend in itself. Device manufacturers are continually attempting to offer additional capabilities in increasingly smaller packages. Today's desktop analyzers can outperform the large floor-mounted machines that were common as recently as 10 years ago.
Systems integration, reduction of fluid volumes, and miniaturization all affect the fluid control features in medical devices. But what, really, is fluid control? It's not fluid power, or hydraulics, which in many industries is synonymous with high power in a small, lightweight package. For example, in aerospace flight controls, high-powered actuators must be located within thin wings. The power advantage is also advantageous within automotive hydraulic systems. A driver would notice an increase in a vehicle's weight and a corresponding decrease in braking responsiveness if the hydraulic antilock braking system were replaced with an electromechanical system.
The manufacturers of analytical instruments do not need the weight and power advantages of traditional fluid power systems. Rather, they must use some form of fluid control because the instruments work with fluid samples such as blood, urine, or spinal fluid. Some of the most common medical fields using fluid control systems are clinical chemistry, immunochemistry (immunoassay), hematology, and microbiology.
The term fluids is used here in a broad sense, referring to both liquids and gases. Blood pressure monitors and anesthetic gas monitors are examples of analytical instruments that employ some form of pneumatic fluid control.
LIQUID FLUID CONTROL SYSTEMS
In addition to serum samples, most chemical reagents and assays are liquid. Instrument subsystems that employ some form of fluid control include sample pickup, dilution, and transport; reagent storage; reagent dispense; liquid aspiration; and wash and waste-removal systems. Immunochemistry systems are sensitive and targeted for specific compounds such as drugs, hormones, tumor markers, and other compounds, some of which exist in minute quantities (Figure 1).
Figure 1. Automated immunochemistry systems require a diversity of subcomponents.
Although the instruments mentioned above are very different from one another, their automated systems share similarities. Sample pickup, reagent dispense, aspiration, and waste removal could occur in any automated instrument design measuring assays, chemical concentrations, or microbiologic growth, to name a few examples.
Modern immunoassay systems incorporate dozens of reagents, not just two as shown in Figure 1. Multiple locations are also generally required for aspiration, wash, and waste disposal. The figure is simplified to aid in the illustration of typical fluid control functions, which are numbered and explained below.
Sample Pickup (1). An off-line system is responsible for aspirating and dispensing serum into a disposable cuvette and washing the sample probe with deionized (DI) water prior to dispensing the next serum sample, most likely with a syringe pump similar to step 3 in the schematic. The cuvette (with serum) is then loaded into the instrument's process track.
Figure 2. An inert dispense pump, such as those shown here, introduces antibodies and attached enzymes (in the form of reagents) into the scrum cuvette.
Reagent Dispense (2). An assay reagent (also known as a substrate) is dispensed into the cuvette via a variable displacement, electric motordriven dispense pump (Figure 2) to introduce antibodies and attached enzymes that bond to the antigens in the serum (Figure 3). A three-way valve, separate from the pump, switches from reagent aspiration to reagent dispense and will require varying degrees of inertness depending on reagent chemistry. In an actual instrument, a series of variable displacement pumps is required for reagent dispense. The pumps and three-way valves can be assembled on a single plastic or acrylic manifold. Packaging issues (space constraints) or system internal volumes (fluid passage volume between components) may become primary factors in such a decision.
Figure 3. Immunochemistries rely on antigen/antibody attractions.
Liquid Aspiration (3). After the serum (antigens) and assay reagent (antibodies) have interacted, excess antibodies that failed to bond to the antigens in the serum are aspirated and dispensed to a waste system. After step 3, only solid particles resulting from the antigen/antibody interaction remain. A syringe pump that includes integral valves for the aspiration and dispensation of antibodies and wash fluid complete the process in this step.
Reagent Dispense (4). The schematic for step 4 involves the time-metered dispense of a second pressurized reagent (substrate) through a two-way inert valve; the reagent dispense function can also be satisfied with a variable displacement pump, as used in step 2. Time-metered dispense is simple and inexpensive but has some accuracy limitations, so the system designer must pay attention to regulation of the reagent reservoir pressure and fluidic restriction of the components located hydraulically in series. Time-metered dispense is an ideal means of providing a simple wash system when aspiration is not required.
Analysis (5). The analysis of antigen/antibody interactions can be conducted by a variety of optical techniques; the specific analytical technique illustrated in Figure 1 is luminescence, a by-product of the reaction between the attached enzyme (Figure 3) and the luminescence-enhancing reagent that is dispensed at location 4 in Figure 1.
Cuvette Waste (6). Usually, the individual cuvettes are disposed of after elimination of the liquid assays. In some systems, the cuvettes are incinerated along with the liquid waste.
PNEUMATIC FLUID CONTROL SYSTEMS
Air and anesthetic agents are the typical gases used in pneumatic systems. Air is readily available and there often is no other engineering consideration than filtration. Anesthetic agents, however, may promote swelling of elastomers used as internal valve seals. Materials such as Viton, EPDM, Kalrez, or Chemraz may be required. Noninvasive blood pressure monitors and anesthetic monitors are two of the most common automated instruments that use pneumatic fluid control systems.
Figure 4. A noninvasive system automates blood pressure monitoring.
Noninvasive monitors can duplicate the manual blood pressure measurements performed in a physician's office (Figure 4). The cuff is inflated via a miniature air compressor and deflated in small discrete steps through a normally closed two-way valve as systolic and diastolic blood pressure measurements are recorded. The normally open valve is required for emergency cuff deflation during a power failure.
The primary variation of this scheme is the use of multiple cuffs for patients of all ages and sizes, which obviously increases the number and complexity of the valves. Some manufacturers have also used proportional solenoid valves (rather than the normally closed digital solenoid valve) to create a linear curve of pressure versus time as the cuff is deflated. High-speed digital solenoid valves can be pulse-width modulated during cuff deflation to yield results comparable to those achieved with proportional valves.
Figure 5. Transducer calibration circuits often require three-way solenoid valves.
Many analytical instruments use pressure transducers to verify system pressures in a variety of locations. A common function for three-way solenoid valves is in circuits used to calibrate pressure transducers relative to ambient pressure (Figure 5). The pneumatic system is connected to the pressure transducer (via the normally open flow path of a three-way solenoid) in order to give real-time pressure measurements. The transducer can be connected to ambient air pressure by energizing the valve, which closes the normally open port. In instruments in which system pressure measurement must be accurate, the transducer calibration function is often performed automatically by programming periodic commands into the instrument's software.
Figure 6. Multiple solenoid valves on a manifold. In this example, the valve's design permits eight valves to be packaged on a manifold that measures only 3 x 3/4 in.
Complex instruments may require transducer calibration in several locations, making it necessary to design a large number of three-way valves into the instrument's pneumatic system. As available space becomes an issue, the ability to locate multiple valves in a small space becomes a real advantage (Figure 6).
Diagnostic and monitoring equipment continues to be a hot market segment even while some related areas have been harmed by numerous changes in health-care delivery. Fluid control systems have adapted by becoming smaller, using less fluid volume, and integrating system components. Understanding the various systems' functions will lead to further improvements in numerous medical instruments.
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Jim Klapper is the marketing director at The Lee Co. in Westbrook, CT.