Economics, excellent specimen identification, and automatic calibration are among the desired features of today’s lab instruments.
The most important consideration for the purchase of lab instruments is economics. Pressure to reduce operating costs has taken precedence over the previous decade’s focus on accuracy and convenience. While those two factors remain relevant, the drive to cut costs is key.
Autocalibration and specimen ID are two additional considerations that carry weight in the lab today. To learn more about these and other trends in lab-instrument development, IVD Technology editor Richard Park spoke with Peter Wilding, professor emeritus in the Department of Pathology and Laboratory Medicine at University of Pennsylvania Medical Center. In this interview, Wilding discusses what is current and relevant in lab instrumentation, changes in the way instruments are purchased, and the skill set of today’s laboratorian.
IVD Technology: Which factors do clinical laboratories primarily take into account when deciding which instruments should be purchased for their labs?
Peter Wilding: This has changed markedly in the last decade. A decade ago, the factors that were prominent were accuracy and convenience. Today the pressure to reduce operating costs in laboratories has risen to a point where it has become dominant. As a result, I think there’s little doubt that the primary factor currently influencing the selection of lab instruments is economy.
It is not just simply the purchase of the instrument and the cost of consumables; it’s also the cost of staff operating an instrument.
I’ve personally had a situation where we introduced a new instrument that, quite frankly, caused a slight—not great, but slight—decrease in quality. But because of its push-button convenience, it meant that I could use something like a dozen technologists to operate the equipment rather then two highly trained individuals.
So on one hand, it’s not just consumables, it’s also the instrument itself that is a major consideration. Ease of use is important, then, so that it is not only a specialized laboratory technician able to run a test on a certain instrument, but any staff person. What about the importance of multiplexing?
There is little doubt that there are several factors that play a role in the purchase of new instruments today. These include excellent specimen identification and autocalibration. The integrity of the specimen ID is paramount and has always been important, and that importance has increased. New instruments that are purchased today need to provide autocalibration and excellent result presentation, and facilitate connection to an IT system.
All of these things are deemed important, particularly in the high-volume laboratory where QC, calibration, and result presentation, among other things, play a major role.
Are speed and high throughput important factors for labs in considering which instruments to buy for their labs?
That is a difficult question for the simple reason that people can achieve speed in different ways. If you have a very expensive installation, and a single piece of equipment that gives you high throughput, then you are vulnerable. I have learned from experience that it is sometimes better to have built-in redundancy in your laboratory whereby you have perhaps two or three instruments that match the giant one, but it means that you’re less likely to have downtime and to cause problems with the provision of clinical results. This all comes under the headings of Quality and Safety. I believe that these factors are very, very important. The laboratories of 2011 will have an increasing amount of press-button-type instruments in them; therefore, the laboratory is absolutely dependent on the quality of the instrumentation and the reliability of the quality-control results that come out of it. However, the laboratory technologists must still play a major role in maintenance. So the simplicity of maintenance, easy transfer of reagents, and several other factors all sum up to a point where operator convenience and low cost come together.
It is a very complicated question, and it has a very complicated answer.
Laboratory instruments offer a variety of features and are capable of running many different types of tests, as we’ve already discussed a bit. Among the features and capabilities offered by lab instruments, which ones are the most important to clinical labs and laboratorians?
From the laboratory’s point of view, it is really the quality of the results that are being produced that is most important. Nothing is more problematic for a laboratory director then to have serious question marks about the quality of results that his or her laboratory, or a particular instrument, is producing. And it’s not just a case of “switch a result.” We are required now by legislation to be able to explain and document all corrective measures that are taken to ensure that quality is achieved within a laboratory. So I would say that from the laboratory’s point of view, quality has very high priority.
Subsystems and Components
Laboratory instruments are made of different types of subsystems and componentry. Are laboratorians educated and generally knowledgeable about how these subsystems and components work, and the specific roles they play in the lab instruments?
I would say the answer to that is yes and no. What has happened is that some of the laboratory instruments that are available today use very basic chemistry systems, and the older, more experienced technologists who were trained well in chemistry are perfectly aware of the underlying chemistry included in all the assays going on within a particular instrument. However, that same technologist, who is perhaps a good chemist, and understands the chemistry of creatinine, the chemistry of albumin measurement and how ion-specific electrodes work, may not be as knowledgeable in the areas of data transfer, data collection, and specimen identification, and in the way barcode readers work, et cetera. This is inevitable. There’s little doubt at the moment that laboratorians are starting to know less about these subsystems then they did in the past. When we used SMA-1260s and there were 12 chemistries going on one platform with moderate data collection and transfer, every technologist in the laboratory understood the basic chemistry that was going on in the system. Today I think the principles underlying all of the systems are generally known but it’s reaching a point where the technology produced by excellent diagnostic companies uses technology that is sometimes difficult to comprehend. There are now flow-control systems that are using microchemistry and microfluidics, and they are starting to incorporate luminescence or nucleotide amplification. Therefore, today, there are technologists who use instruments without knowing everything about their subsystems.
I can tell you from teaching Pathology residents in clinical chemistry that we have pathologists today who take their board exams in laboratory medicine, and a large number of those people who succeed or become board certified as laboratory directors have little understanding about chemistry subsystems. If asked about the basic chemistry we use to measure calcium, most will not know.
And that’s the way it is. They will know, of course, the clinical significance of elevated or reduced calcium values.
It’s the new world. They look at the chemistry laboratory, and they see something that they associate almost with a factory, with hundreds of different assays being performed. They find it daunting to try and learn about all of the chemistries that are being carried out in that large laboratory. We cut corners today, and I think the average pathologist or clinical chemist, many of whom also became board certified in his or her science, brings to the game varying levels of expertise and understanding of the technical issues. Some lack technical knowledge and some lack a depth of clinical knowledge. Both areas of knowledge are fundamental to the successful direction of a large clinical laboratory.
Despite this lack of knowledge or understanding by certain laboratorians, do laboratorians prefer that certain subsystems and components be included in the lab instruments they use as opposed to others?
I think the answer lies in quality, speed, and convenience. Laboratorians certainly prefer that we have subsystems that ensure quality, such as very good specimen identification. On the other hand, if what you’re asking is about subsystems of the 1960s and 1970s that used continuous-flow technology with pumps, tubes, et cetera-the old AutoAnalyzer technology-that today would worry some laboratorians because it is seen as a technology of a past generation. On the other hand, there are forms of ion-specific electrodes that have been miniaturized and improved to a point where they definitely reflect the latest technology.
The use of “state of the art” technology is important. The classic example is the assay for thyroid stimulating hormone (TSH). Today my former laboratory performs about 400 to 500 TSH assays a day. In the 1990s, many of the laboratories in the United States performing this assay used first- or second-generation TSH assays at a time when clinicians were demanding that they be third-generation. So if you were buying a system and it advertised that it did TSH, then you would want to ensure that the chemistry system was using a third-generation assay. So again, it’s a case of selecting the best, the most sensitive, and the most accurate of chemistry systems possible in the laboratory instruments you buy.
What general trends have recently emerged among subsystems and components and lab instruments?
One is far better specimen-identification systems integrating into modern instruments. Others are the ability to centrifuge and split samples. The so-called ”front ends” of automated chemistry systems are able now to take a specimen of blood, still in the original tube, and automatically centrifuge it, aspirate a sample of the serum or plasma from the cells, and facilitate the generation of “daughter” samples. The daughter samples are perfectly labeled with correct identification. Each of the different samples can then be transferred to another section or instrument. Some of the samples may go off for immunologic-based assays, others may go off for hormone assays, etc. These types of general trends of what I would call automated and efficient front-end systems have emerged, and there is a situation today where there are probably several hundred laboratories around the United States that are using large, automated systems that do multiple chemistries starting with well-identified blood samples. There are even more laboratories around the United States that now appreciate the benefits derived from an “automated front end.” And then once all the sample splitting has been done, those samples can be used or transported to different sections around the laboratory. This is, in my opinion, a trend which is very good. Another trend is the increase in built-in quality control that includes interference compensation.
We are also seeing excellent adaptation of microtechnology into subsystems. The benefit of the microtechnology is that it’s bringing excellent fluid control. Modern microfluidics were not conceivable at the time that instruments like the SMA and SMAC were developed by the Technicon Corporation. In summary, identification, sample splitting, QC, interference compensation, and well-controlled microfluidics are all desirable trends.
Technology and Advancements
Which advancements in lab instrumentation technology during the past couple of years have had the biggest effect on how laboratorians conduct their tests?
Here I would have to say the biggest advancement probably is the provision of press-button operation for many of the instruments so that there is not constant adjustment of calibration, rheostats on amplifiers, or controls on flow cells. Another area that is emerging and where we are starting to see growth is molecular pathology. While it would be difficult to really identify anything that is absolutely brand new in the last couple of years in the chemistry laboratory, there are real and innovative changes occurring in molecular pathology. We only have to go back 10 to 15 years when there were very few instruments that facilitated the detection of genomic-related disease. The net result was that they tended to concentrate on esoteric or rare-disease conditions. That is changing now because new technology is being made available that is rapidly changing the ways in which molecular pathology assays are performed.
In your view, how have molecular diagnostics and molecular pathology influenced clinical labs and clinical laboratorians?
At this moment, that effect is not so great. Examination of many large clinical laboratories will show that the growth in test volume has continued in the general chemistry area. It has also grown, of course, in toxicology with therapeutic drug monitoring and other drug assays. It has grown in endocrinology with improved and more sensitive assays for hormones, et cetera. But in the area of molecular pathology, the growth has been explosive. It is an expensive subdiscipline, but the actual number of results produced by most molecular pathology laboratories is still relatively small compared to the other areas of the laboratory. That is likely to change dramatically. For the last 20 years or so, people have been striving to achieve the isolation, detection, and analysis of circulating fetal cells. If we were able to take a 10- or 20-ml blood sample from a pregnant woman, and easily ascertain the health or potential disease in the fetus—this would not be a small business. This would be a billion-dollar business compared to the invasive technique of amniocentesis. Because of the developments in molecular pathology and the associated use of microtechnology, we are starting to see the real possibility now—not only the possibility, but the proof—that circulating fetal cells or circulating fetal material can be detected and analyzed much more simply than was possible a few years ago. Similarly, close behind this will come the detection, analysis, and interpretation of data related to circulating tumor cells. It is an area in which there is going to be significant growth, and the growth will be exciting. However, whichever manufacturers make the transition over to these new areas, we will still always need basic chemistry systems generating numerous results for liver function, renal function, et cetera, and systems for basic hematology. However, I do believe that molecular pathology will experience some astronomic growth, probably with a very large profit margin not only for the manufacturer but possibly for the clinical laboratory as well.
How have technology advancements in lab instruments, such as press-button operation, improved the sensitivity and specificity of lab tests?
I can pick out a couple of things. I mentioned before the improved immunoassay that’s allowed us to move to third-generation assays for TSH. This is an example of dedication; much of that development work is being done within the diagnostic industry rather than in academia. The results are very good assays for TSH.
There are other areas where we’ve seen the virtual elimination of radio immunoassay. This is because we’ve been able to harness the wonderful sensitivity of luminescence. Also, we have been able to harness the sensitivity and the specificity of PCR, or nucleotide amplification, and they are starting to be incorporated.
One of the things I haven’t mentioned yet is point of care. Certainly the technology advancements in point-of-care diagnostics are absolutely magnificent. Today the multimillion-dollar business of home testing for glucose is really a testament to the fact that the technology has become so simple that most primary care physicians do not hesitate to hand out the instrument and minimal instructions to their patients, then send them home to do that testing. However, we must remember, we only have to go back 10 to 15 years to see companies advocating at-home cholesterol testing, when every airline magazine carried an advertisement for a cholesterol test. Those advertisements have disappeared today. Why? Partly because the technology wasn’t particularly good, and partly because there was very little benefit without clinical consultation or advice from a physician on what to do about the result.
The contrast with diabetes is that, generally speaking, diabetics are are the most informed group of patients that the world has ever seen. They are well organized, and they are well trained.
Coming back to the topic of sensitivity, I would highlight progress deriving from the implementation of new detection systems such as luminescence, nucleotide amplification, better immunoassays, and the use of lateral-flow technology in point-of-care devices. This means that one can get excellent results from a finger stick, on a host of drugs, or various other things. The transfer of all these assay formats that have good sensitivity to environments outside the clinical laboratory is testament to the robust nature of the devices and the underlying chemistries.
The progress is really quite remarkable.
What further improvements would laboratorians like to see made to lab instruments?
I think we still need, if you like, improved systems for the high-volume critical assays that impact turnaround times and can speed up a clinical decision. I have a particular mission about thyroid stimulating hormone. I want to contrast it with blood glucose.
If a potential diabetic attends a clinic, the first thing they do is see the nurse and have their blood sugar assayed - if they haven’t done it themselves. Then they see the physician, who can examine the patient and then make a decision on the implementation, the cessation, or the modification of treatment on that patient because the results were available before examination.
On the other hand, if a patient goes to a thyroid clinic, of which there are thousands all over the country, and a TSH test is requested, then by the time that result is seen by the clinician, it may well be two to three days after contact. The result is often ready within 12 hours. We have excellent results that show that the big delay is often between the results being produced and the clinician getting around to looking at them. Then that clinician will have to remember the patient, decide what to do, call the patient back in, and then implement, cease, or modify, treatment. So a whole social component is involved whereby the cost of medical care and nursing involvement, receptionists, patient travel, and more are adversely affected because we cannot perform a TSH test in the time-frame that we can do a blood glucose test. Yet there are thousands of patients being examined for thyroid function every single day.
So what will further improve it? What would I like to see? I would like to see a speed-up of assays for which the clinical decision can have an impact on the community, and my example is always TSH.
Another thing I would like to see is the move to point of care. I think it can bring real benefit; and again, I emphasize that you have to pick and choose. There are lots of point-of-care tests that are now being done in emergency rooms for cardiac enzymes. Clinicians and technologists or nurses that do that work within an emergency room are doing it without a lot of training, because the assay is simple. And so I think we need more and more of these simple assays. I think they have to be done with quality products to ensure that we don’t mess up someone’s life because the results are not reliable. If we can continue to produce new point-of-care technology that meets an increasing spectrum of assays in a quality manner, then that’s going to be excellent for medical care.
What advice would you give to IVD manufacturers that are beginning to design and manufacture the next generation of their lab instruments?
I think the bulk of their business for the short term is going to come from what I would call the “established spectrum of clinical assays” as operated by all of the laboratories within a hospital; i.e., chemistry, hematology, immunology, microbiology, et cetera.
My advice to IVD manufacturers is to make sure they monitor and engage as early as they can in new technology that’s already showing promise—things such as fetal-cell or fetal-material analysis. If you realize how many pregnancies are now investigated by amniocentesis and the cost of amniocentesis, then whoever is able to provide the same information from a peripheral blood sample in a convenient manner is going to change the world. One of my recommendations is to monitor and look to engage early in that new technology. It will be a billion-dollar business; likewise, the detection and successful analysis of circulating tumor cells is just around the corner. There has been a tendency to develop instruments that are more academically based, and no one is going to make a lot of money in developing instruments for what I would call esoteric or rare diseases, yet these are what often engage a lot of time and money in the molecular pathology laboratories at the moment.
It will probably be the molecular pathologist who will be carrying out fetal material analysis and detecting circulating tumor cells because of the technology that’s involved. It will almost definitely involve some form of PCR or nucleotide amplification.
So my advice to them is to be ready to embrace, or participate in, that new growth area when it comes along. There was a time when it looked as though the technology would be decades away, but it is not decades away now.
Peter Wilding, PhD, is professor emeritus in the Department of Pathology & Laboratory Medicine at University of Pennsylvania Medical Center (Philadelphia). He is a recognized expert in the field of clinical chemistry and the development of microfluidic microchip technology. Wilding can be reached at firstname.lastname@example.org.