Hematology laboratories are heading toward reliable automation to achieve faster turnaround time (TAT). Advanced hematology analyzers are well equipped to enumerate clinical utility parameters in addition to the existing ones with good accuracy and precision. Laboratories are, however, increasingly challenged to provide speedy, comprehensive, and accurate information to enhance patient care. Advent of newer technologies in hematology analyzers has succeeded in reducing manual dependency. However, onsite presence of experts for morphological identification continues to be imperative. Thus, laboratories need to integrate middleware systems like WAM (work area manager) and technologies like digital cell morphology with hematology analyzers.

A few modern hematology analyzers are also equipped with the ability to perform hematopoietic stem cell enumeration without usage of monoclonal antibodies. This procedure is performed on a hematology analyzer equipped with a dedicated channel to improve the apheresis workflow in terms of reduction in both time and costs.

Going forward, laboratories would be focusing on automation for standardization of pre-analytical, analytical, and post-analytical stages in order to increase the workflow proficiency. Online test ordering, sample collection, test identification, transportation, and processing would be completely automated thereby eliminating administrative errors.

In the analytical phase, workstations could be operated by a robotic system to supervise and monitor all instruments and reviews to maximize productivity and aid in dramatic reduction in turnaround time.

Post analysis, health informatics can play a major role in integration of imaging, histopathology, pathology, and other clinical data under a common software program with precise algorithms. Such a system would prove instrumental in guiding clinicians for speedy diagnosis and bring down the test costs for patient benefit.

Technology Trends

Indeed, blood cell counters performing a complete blood count (CBC) are becoming more and more sophisticated. With different technological approaches, latest generation instruments perform accurate and reproducible quantitative measurements of peripheral blood cell composition, and have good sensitivity and specificity for flagging the presence of abnormal cells.

Modern analyzers use electrical impedance methods, optical methods, or a mixture of both of these to count and classify white and red blood cells. Vacuum pump fluidic systems deliver perfectly precise volumes of diluents, samples, and reagents to analysis chambers. Fully-automated analyzers have the advantage of being objective, high-throughput, and cost-effective; they can flag up atypical results and have increased measurable parameters such as platelet distribution (PDW), red cell distribution width (RDW), nucleated red cells (NRBCs) and reticulocyte (RET) counts.

Electrical impedance. This technology transformed the clinical laboratory into what it is today, and it would be very difficult to imagine how the modern hematology department would cope without it. One of the problems associated with impedance counting is cell coincidence which in modern hematology analyzers, is usually minimized by the application of hydrodynamic focusing.

Optical technology. The analyzers have only one angle of light and are able to produce only one histogram. However, the current sophisticated analyzers use multi-angle optical scatter analysis (up to five different angles and pulse times), combined with flow cytometry to distinguish different cell populations and identify immature and atypical cells. These analyzers are capable of producing dozens of histograms, giving detailed information about the white cell population.

AIM technology. The newest generations of hematology analyzers incorporate automated intelligent morphology (AIM) technology. This enhanced 3D high-definition cellular analysis solution utilizes flow cytometric technology to help lower manual review rates and increase laboratory efficiency.

VCS technology. Volume, conductivity, and light scatter technology is a multi-angle light scatter technology that provides information on cell volume (forward scatter), internal cell structure (side scatter), and RNA/DNA content (side fluorescence).

Flow cytometry. Some manufacturers have managed to adapt the basic techniques of flow cytometry to enable its incorporation into the automated hematology analyzer. Flow cytometry technology enables analyzers to give more detailed information in the form of flags and messaging.Flow combined with optical and/or impedance methods can be used to create detailed scatter plots, which determine the populations of each cell type.

Cellular interferences. The latest generation of analyzers now offers several additional histograms that are generated by two new angles of light. This additional information can be used to distinguish between the four types of cellular interference, namely nucleated RBCs (nRBCs), giant platelets, intra-cellular parasites, and platelet clumps. Hematology analyzers have traditionally been unable to distinguish between these.

Digital imaging. Advancement in digital imaging, now make it possible to automate the review of blood smears. These instruments review slides at low power, then classify the white blood cells. In some cases, they can also review red cell characteristics and platelet counts. The user is able to share images remotely with other clinicians or laboratory staff, as well as storing images for future review.

Automated slide makers and morphological review. There are numerous analyzers on the market that can automate slide preparation and staining, and several instruments that are capable of actually reviewing the slides themselves. Slide maker strainers are usually sold as part of a hematology solution. These analyzers, however, can either be used alongside the hematology analyzers, or as stand-alone solutions.

Way Forward

The automated hematology analyzer with CBC results has replaced the traditional manual or individual assay methods for hematological parameters and the eye count leukocyte differential as the initial screening and detection system for hematological abnormalities in modern hospitals and clinics. Automation is a growing trend in this market which is shifting from manual testing to fully automated analyzers. In addition, usage of microfluidics technology in hematology analyzers and introduction of digital imaging system in hematology laboratories are also expected to open up opportunities for new players in the market.

Latest generation analyzers are capable of giving detailed cellular information to the operator, such as blast cell differentials. Some are also able to give suggestions of pathological conditions. This level of sophistication in the clinical laboratory has been made possible with advances in instrumentation and technology, going hand in hand with great expectations for doing more for less in a cost-conscious healthcare environment. In addition to achieving previously unachieved levels of accuracy, sensitivity, and specificity, the advancement in technologies will enable real-time results at the bedside and in the clinic. Only time will tell what the role of pathologists and clinical scientists will be as a new generation of blind instruments is deployed in clinical environments where there is an assumption of correctness of all results generated by an instrument.

Sreedharan B.
Industry Speak
Dengue Diagnosis

Dengue is a mosquito borne viral disease; the early signs of dengue may include high fever, joint pains, headache, appetite loss, etc. In rare cases dengue develops into a life threatening disease, which is referred to as dengue hemorrhagic fever (DHF) this is characterized by hemorrhage, blood plasma leakage, and exceptionally low blood platelet count.

It has been observed that since past few years dengue cases are showing an exorbitant increase in numbers year on year. This increase in the cases is directly proportional to the deaths as well. Despite ongoing efforts, there are no sustainable vector control approaches or effective anti-viral drugs to prevent or treat dengue.

Delayed dengue case identification often occurs in areas with limited diagnostics or surveillance resources especially where dengue outbreaks are episodic, especially in areas with minimal laboratory infrastructure this remains a major reason for deaths due to dengue. Though we have varying diagnostic modalities for dengue diagnosis, the dengue rapid diagnostic tests (RDT's) will play a key role in changing this situation. There are rapid diagnostic tests, which can detect dengue from the initial day of symptoms till the late stages, a rapid test with the feasibility to perform the test with whole blood sample can be performed immediately even in the areas with poor lab infrastructure. Thus along with awareness of measures to control the dengue mosquitos among general public, creating awareness on early testing as soon as the individuals see any of the dengue fever symptoms during the monsoon will play a key role in changing the current scenario.

Sreedharan B.
Product Manager- Infectious Diseases,
Alere Medical Pvt. Ltd.

Sanjaymon KR
Industry Speak
Advancements in the IVD Industry

Advancements in the development of electronics, imaging, information technology, microfluidics, and robotics are the key for the new trends in the IVD industry. The innovative products and solutions in automation are changing the way by which diagnosis is made and the IVD industry in India is growing at a faster rate compared to other economies.

In clinical chemistry segment, automation is available with entry level systems ranging from 80 Test/hour throughput. These systems are equipped with most modern operating system and graphical user interface and with facilities, which where once available in the higher end systems. Such innovative products increased the total installation base in the clinical chemistry segment and helped the laboratories to increase the parameters. Grating photometry once seen only in the higher end systems is now available in the lower segment. Most of the common entry level chemistry systems are using universal sample carousel and the introduction of systems with Rack Sampler revolutionised the way of testing.

Hematology segment witnessed a major change with compact systems at affordable price. Most of these systems are with touch screen interface, low volume sampling, and very low maintenance cycle.With the advancement in the flow cytometry techniques, companies are offering differential hematology systems, which can detect immature cells also. The latest entrant in to this segment is hematology analyzer capable of performing CBC and CRP from the same sample. Most of the new generation hematology analyzers are using three reagents there by reducing the cost of test. This was because of the improvement in the electronic and fluidic technology. With the improvement in the electronic – fluidic systems, the systems are becoming more and more compact making it affordable to the laboratories.

Specific protein market is another segment in the IVD that has shown spontaneous growth over the last few years. Nephelometry is considered as the gold standard for the specific protein testing and the major limitation earlier in this segment was the high cost of the instrument and the reagents, which was not affordable to the rural laboratories. The cost in the earlier nephelometer systems was due to the laser technology used along with the robotics.
The new generation laser photometer with compact size made it possible to introduce the semi-automated nephelometer; the game changer in this segment.

One of the major changes in the IVD was the usage of smart card technology for the calibration or programming of the parameter. The major challenge in many specialised tests was the highly sensitive calibration protocol. Any failure in the calibration resulted in repeat tests and calibration and increased the cost of testing and the turnaround time (TAT). In new generation systems, smart cards are used to identify the tests and calibration curve thus minimising the analytical errors. Most of the new generation specific protein analyzers are using this technology.

With the improvement in the microfluidics technology, the IVD segment is now moving toward cartridge based testing systems where single to use cartridge with reagents are used for the testing. Most of these cartridges based systems are equipped with latest IT software system allowing them to communicate within the hospital information systems or laboratory information systems through bluetooth or WiFi. Due to its compact size and easy to use interface, these systems are also used as point-of-care testing analyzer for specific tests like HbA1c.

Lateral flow reader systems were introduced recently in to the industry. The systems are based on Lateral flow technology which allowed performing critical tests like cardiac markers or sepsis markers from whole blood. Introduction of these systems was one of the breakthrough in the ICU where the TAT was of utmost importance.

It is expected that more such innovative systems are going to be introduced in the coming future to make the IVD testing easy and affordable.

Sanjaymon KR
General Manager - Business development,
Agappe

Dr Neeraj Jain
Second Opinion
Upcoming Trends in the Science of Analyzing Blood

In a popular and diverse country like India, our pathologists face distinct and unique challenges in their day-to-day laboratory practice. Hematology is one of the basic specialties that forms the majority of tests performed in a routine medical laboratory operations. Due to increasing work load and ever increasing pressure from the industry under stringent legal and regulatory norms, pathologists are forced to use the best methods with high degree of precision and accuracy to give their final diagnosis. Although, manual counting of blood cells and peripheral smear analysis is considered to be the gold standard, automation is the forced need due to huge population especially during epidemic situations.

Hematology analyzer utilizing diverse methods are available in the market with variety of new parameters and alarms apart from the routine hematology parameters. Market is flooded with various diagnostic companies coming up with the new analyzers, new combination of testing parameters and various cost efficient features. All of these are somewhere provide the reliable results more or less.

Hydrodynamic focusing is one of the basic methods utilized by various analyzers in cell counting. However, the same focusing is now available with double power and thus more reliable and accurate counting, this Japanese technology well known in the market as DHSS i.e. double hydrodynamic sequential system is now being utilized in almost all the reputed laboratories of the country, which are NABL accredited and is giving reliable and better results compared to previous conventional focusing techniques. The technology has a good potential with high resolution and accurate quantification of abnormal cells. Use of DHSS technology has helped the pathologists in utilizing the parameters like atypical lymphocytes (ALY) and large immature cells (LIC), which are helpful in diagnosis and differentiation of various blood pathologies.

Apart from these cell counting and differentiation technologies, automation is now well utilized by the pathologists in making peripheral smears without loss of time and minimum better utilization of laboratory technologists in their laboratory. Smear preparation is one of the most critical processes in diagnosis that requires knowledge of science along with art of making slide as per the pathological need. However, technology has made this also easier for the busy pathologists with resource and space limitations.

Technology may grow to any extent, but the role of pathologist can never be superseded or by passed by any technology and thus, as a pathologist we need to check meticulously what works and what does not as per our population and their physiology.

Dr Neeraj Jain
Director,
Jain Diagnostics, New Delhi


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