'Is the end in sight for the microscope?'

Following on from his recent examination of the white coat, Barry Hill in the second of an occasional series highlighting great laboratory icons turns his focus towards the optical microscope and asks

WITH the possible exception of the white coat itself, no other one single item of equipment summons up the image of the laboratory quite like the microscope does. Based on the Greek words ‘micron’ meaning small and ‘skopein’ meaning to look at, the first useful microscope was developed in the Netherlands in the 1600s although accounts differ as to who by, as three different eyeglass makers have since been credited for the invention. Hans Lippershev, Hans Janssen and his son Zacharias all claim to have been the first to have created what we refer to today as the optical microscope, namely an instrument containing one or more lenses that produce an enlarged image of an object placed in their focal plane.

Janssen and son claim to have invented their microscope while experimenting

with several lenses in a hollow tube, noticing that nearby objects appeared greatly enlarged. The earliest simple microscopes therefore were nothing more than this and provided a magnification less than ten diameters or ten times the actual size. These devices were often used to view fleas or other small insects and so were dubbed ‘flea glasses’ at the time by an excited public. In 1609 however the scientist and astronomer Galileo on hearing of these early experiments worked out the principles of lenses and made an improved version of the instrument incorporating a focusing device, calling it his ‘occhiolino’ or ‘little eye’. Thus began the start of a centuries long love affair between scientist and microscope. It wasn’t until Anton van Leeuwenhoek however, sometimes known as ‘the father of microscopy’ moved the science on some 50 years later, again in the Netherlands. Working as an apprentice in a dry goods store where magnifying glasses were used to count the threads in cloth, Leeuwenhoek discovered new methods for grinding and polishing tiny lenses of great curvature which gave magnifications up to 270 diameters. These led to the building of his microscopes and the biological discoveries for which he is renowned for. He was the first to see and describe bacteria, yeasts and the circulation of red cells in capillaries and along with Joseph Lister in the 1830s was probably responsible for the eventual rise of the simple compound microscope that was to dominate laboratory life ever since.

So today the microscope has become as synonymous with the laboratory as the stethoscope is with a doctor, so much so that hardly any laboratory or pathology investigation used to be possible without the use of one, but is this still strictly as true? In the ever changing landscape of diagnostic testing there are many exciting alternative new techniques in use or on the horizon. As a result we may find that this once indispensable and essential instrument could become obsolete, thereby disappearing from laboratory benches forever.

Most pathology disciplines have always relied heavily on microscopic examinations to aid and assist the diagnosis of a multitude of medical conditions, but this picture is rapidly changing. In transfusion science for instance the basic principle is to observe the antibody and antigen reactions that occur between cells and plasma, signified by agglutination. This agglutination process, whether it is involved in the determination of a blood group, or in the detection of antibodies has historically been observed microscopically by transfusion scientists. Recent introductions however have dramatically altered this situation. The development of powerful monoclonal blood grouping reagents for instance have enabled many reactions to be observed macroscopically with the naked eye for the first time, removing the need for any microscopic analysis.

Equally as important has been the introduction of so called ‘column technology’ which has totally revolutionised transfusion science. These systems use pre-filled cards containing monoclonal reagents in an enclosed column containing gel or beads capable of trapping any agglutination following incubation and centrifugation stages. In some automated systems, these reactions are then captured using digital cameras which are then interfaced directly to computers to interpret blood grouping and antibody screening results without the need of any microscope involvement whatsoever. The combination of these two factors has already led to many blood banks greatly reducing the numbers of traditional microscopes they require, which now are now therefore only really necessary for teaching purposes or for fallback procedures should the automated equipment fail.

Not too long ago you could enter most haematology departments and expect to see perhaps as many as six or more microscopes all being occupied simultaneously by staff, examining stained peripheral blood films and bone marrow slides for cell morphology changes. Those days are gone however, modern haematology analysers are capable of giving highly accurate machine differential counts and these have already dramatically reduced the numbers of stained blood films needed to be examined microscopically and so consequently the numbers of standard microscopes required have fallen. Urine microscopy is an essential part of a typical microbiology department’s routine daily work, and little has changed with this over the years. The most widely used technique uses an inverted microscope to count cells, but this lacks accuracy, is a slow, time-consuming, labour-intensive process often issuing results the following day thus delaying patient treatment. This is why many microbiology departments are now using automated equipment again featuring particle sizing systems to provide a rapid, highly accurate and reproducible same day service. Also, some of the more specialised techniques in microbiology that have traditionally been performed by fluorescent microscopy for instance are starting to be being replaced by serological techniques such as ELISA and other new non-microscopic techniques, all of which could eventually impact on the microscope requirement of the discipline. 

Histology and cytology however by their very nature have always been highly reliant on microscopic examination of stained cellular tissue to diagnose a multitude of conditions, but even this could be changing. In cytology for instance, where cervical screening has traditionally been performed by microscopic examination of stained smears, new technology such as liquid based cytology (LBC) systems are now in use which have already drastically impacted on this. Not only does LBC reduce the numbers of slides needing to be microscopically examined by cytologist due to the better quality of smears produced, but these techniques can also incorporate computerised scanning equipment which may eventually replace the microscope completely. Trials of telepathology systems are already underway using digital imaging techniques of cervical smears, which following a one minute cervical test in the GP surgery, can be videoed and downloaded  to a distant computer for viewing by specialists to allow an immediate diagnosis. In the routine Histology department meanwhile, immunological testing is already aiding the diagnosis of some conditions such as coeliac disease, and the use of biochemical markers are now helping in the investigation of the malignant cells found in cancer and tumours. Although neither of these serological techniques at the moment can replace the need to remove, stain and microscopically examine human tissue itself, when it does become readily available - just as in the other disciplines - the histology department’s microscope requirements will be dramatically reduced.

But it is not only the impact of new technology that is gradually reducing the microscope requirements of pathology laboratories, there are also economic factors at work. As the service struggles to meet the ever increasing demands of today’s clinicians, work patterns in pathology are also changing to meet them.  Many laboratories are now introducing shift patterns to incorporate the continuous processing of routine samples around the clock. These systems allow laboratories to fully maximise the potential of both staff and equipment 24/7, but inevitably this means that there are not as many staff available in the laboratory during core peak hours of the working day. It is therefore no longer necessary, nor is it economically viable to have large numbers of microscopes in the laboratory standing idle, all of which require regular and costly servicing to keep them in working order. As a result, many laboratories have already started to scale down their microscope numbers, sometimes even selling off surplus instruments to reduce their requirements, whilst many other remaining microscopes gather dust as they are quite literally left on the shelf. 

So is the end in sight for the traditional laboratory microscope? It is inevitable that a combination of modern technology and pathology workforce modernisation processes will gradually phase it out from many laboratories. And so with their numbers dwindling and many more lying unused for long periods of time, the once familiar sight of the microscope could soon quite easily become a rarity, perhaps even a curiosity in the pathology laboratories of the future.

By Barry Hill