Pictures of the Future      Fall 2008

New Vistas in Diagnostics

Siemens has developed an automated laboratory system that combines a large number of instruments and tests in one machine and greatly accelerates workflows. Every hour, it can analyze 200 samples and perform 1,500 diagnostic measurements.

In medical laboratories, time is of the essence. During peak periods, hundreds of blood and urine samples can arrive each hour at the laboratories of large hospitals. Each sample is tested to determine an average of almost ten different values, which could indicate conditions such as inflammation, cardiac illnesses or abnormal iron metabolism.

The burden on laboratory technicians is enormous. All too often, they have to hurry from one instrument to the next, with a blood sample in hand, measuring value A here and value B there. As a rule, a laboratory contains various pieces of equipment that each analyze only a small number of parameters. Often, the physician must take several vials of blood from a patient at once, because the testing is carried out at several different machines.

In 2007, in the interest of optimizing laboratory workflows, Siemens Healthcare Diagnostics began marketing the Dimension Vista, a multifunctional machine that combines a number of different laboratory analysis instruments in a single appliance. The gray-white machine resembles an oversized photocopier and can automatically conduct up to 1,500 different measurements per hour from 200 patient samples, which saves lab technicians a great deal of running around.

Frank Kraft, product specialist for Dimension Vista in Eschborn, Germany, puts it in a nutshell: "The machine can perform 97 % of the lab tests needed in routine and emergency hospital operations." Currently, 105 different parameters can be processed simultaneously on the Dimension Vista system. These range from routine measurements all the way to very promising methods such as Cystatin C, a new marker of renal function. Over the course of the next year, additional tests will be added, some of them relatively unusual, including markers to facilitate therapeutic drug monitoring in order to prevent rejection reactions in organ transplant patients. There is no other product available that offers this kind of service, says Kraft.

Parallel Approach. The speed of the machine is primarily due to the integration of four analytical processes that run in parallel on it and the way in which these processes are arranged. Under the hood are some sophisticated mechanical components and a sort of miniaturized filling system for samples and reagents. A lab technician simply places patient samples in a holder on a conveyer belt that automatically pulls them into the machine. Inside, a small tube is lowered into each sample, where it draws off a few drops and initially distributes them among storage vessels.

The advantage of this methodology is that, after only a few moments, the machine returns the original sample container to the operator. The sample is therefore available for other tests. In the case of conventional instruments, on the other hand, the original sample often remains in the system for a much longer time until a measurement is completed. Only then can a technician carry out the next measurements at different instruments. But with Dimension Vista, since portions of the sample are siphoned off into storage vessels,  the process is faster and requires a smaller sample volume in the first place, which is easier on the patient and on the hospital’s logistics.

From the storage vessels, the sample is now transferred into measuring cells, also known as "cuvettes." These form the heart of the machine, which is a "cuvette ring"—a rotating disc equipped with holders for 182 cuvettes. Three of the four analysis modules are arranged around this ring. This integrated design is unique and makes it possible to test each sample with multiple analytical systems simultaneously—and not in succession.

The cuvette ring rotates forward every few seconds, advancing its samples to the next measuring point. Of course, the tests themselves take longer than the time it takes to go from one cuvette to another—after all, reagents such as antibodies, which are developed by specialists at Siemens Healthcare Diagnostics, must be pipetted into the samples.

In another automated step, small pipette arms suspended above the cuvette ring draw liquids from cooled storage containers and small glass vessels in the interior of the machine. Here and there, an arm moves and injects reagents into a cuvette, depending on which parameter is being measured. Some reagents must react with the sample volume for a relatively long time before a value can be measured. No problem. A computer maintains a record of what stage each sample is at and when it must be processed.

After the required measurements have been completed, Dimension Vista empties and washes each cuvette, allowing it to be reused. For particularly demanding analyses, however, the system loads a new cuvette from a storage container—this too is unique and combines speed with high quality.

Dimension Vista’s four analytical techniques  measure a wide range of parameters. In combination, their performance is unprecedented. One of the tests uses a method that was developed in-house and is still unrivaled—the LOCI technique, or "luminescent oxygen channeling immunoassay." This test makes it possible to detect the presence of target molecules, such as those that indicate anemia or thyroid illnesses, for examples, in a  patient sample through the binding of antibodies.

Usually, such tests require many steps involving various pipetting and cleaning operations. These steps are not needed in LOCI. The test is therefore up to ten times faster than conventional tests. In addition, it can be used to detect minuscule concentrations of molecules in the blood—substances such as troponin-I, for instance, which is released when a heart attack occurs. To this end, the blood sample is mixed with specific antibodies that bind to the molecule. When illuminated, this antibody-molecule complex releases excited oxygen molecules. The latter cause luminescence in a second substance, which is ultimately measured with a different wavelength. In addition to the LOCI unit, the Dimension Vista contains a photometer that records certain substances by means of characteristic light absorption. It also includes a "V-Lyte-Module," which measures the electrolytes sodium, potassium and chloride as ions.

How Proteins Reveal illnesses. Dimension Vista’s fourth module is its nephelometer. Nephelometry is an optical analytical technique used to determine the concentration of a dilute suspension of small particles, in this case in liquids. The leading developer and user of the technique was the former Dade Behring company, which became part of Siemens in November 2007.

Nephelometry is particularly well suited to detecting plasma proteins in the blood and other body fluids. These proteins are molecules from which a physician can infer the health of a patient. Many illnesses are associated with specific changes in the concentration of characteristic proteins that can be detected in the blood or in other body fluids. Based on this information, a physician can reach conclusions about the risk of a heart attack, for instance, the development of rheumatic illnesses, or dangerous inflammation reactions. "Identifying inflammations is very important before an operation, for example, to determine the extent to which a patient’s immune system may have been weakened," explains Kraft.

In nephelometric tests, proteins react with antibodies. Depending on the protein concentration, a more or less dense protein-antibody network results, which in turn scatters beams of light. Based on the amount of scattering, the instrument can then calculate the concentration of plasma proteins.

Three Thousand Measurements per Hour. Of course, Kraft admits, very large laboratories already have automatic analytical systems—fully automatic lines of equipment that occupy entire rooms. But the majority of private and hospital labs still use a hodgepodge of instruments. "In such case, the Dimension Vista is an ideal supplement," says Kraft. "It’s the golden mean between complete automation and the conventional lab." Those who want to achieve higher processing rates can link Dimension Vista with a second unit. In this way, one laboratory technician can perform over 3,000 measurements per hour.

Daily inspection and quality control are prescribed for laboratory instruments—a sort of quotidian calibration. Are the measurements accurate? Is the instrument working properly? For most labs with a large number of instruments, the answer to such questions entail a huge amount of work. Dimension Vista shortens this process considerably by reducing the number of instruments required and implementing quality control and inspection procedures automatically. Dimension Vista’s developers like to call this ultra-integration.
                                                                                                                  Tim Schröder