Biochemistry, a peek into the future

Using more powerful processing, computer vision, robotics, and AI to drive autonomous operations, labs have the ability to improve throughput and efficiency.

To satisfy the ever-changing demands and needs of patients, global healthcare solutions are always evolving. Clinical laboratories are an essential component of the global healthcare system. Approximately 70 percent of diagnoses are made solely on the basis of test results. The present healthcare crisis has highlighted the need for more advanced, comprehensive, and timely diagnostic tools. To keep up with the shifting terrain of this fiercely competitive diagnostic sector, technological brilliance-based innovation is essential. With the rise in lifestyle problems and infectious diseases, there has been an increase in the demand for diagnostic laboratories. The importance of automated laboratory technology in monitoring chronic diseases and identifying acute illnesses cannot be overstated. Clinical laboratories are no longer restricted to the fields of acute and chronic care. With rising income levels, the sector of preventative care is seeing a surge in expansion. Prevention is becoming increasingly important in healthcare. Tests of higher quality, with more reliability and reproducibility, provide more confidence in initiating early therapies.

Biochemistry, which runs tests on body fluids to assess human health and monitor chronic disorders, is at the heart of most lab activities. Biochemistry labs are becoming increasingly automated, with sophisticated instrumentation capable of completing hundreds to thousands of tests each hour, as is the case in other areas of the laboratory. According to the first Longitudinal Ageing Study in India released by the Union Ministry of Family and Health Welfare, two out of every three older adults in India suffer from a chronic disease, and biochemistry is likely to continue to play an important role in patient care.

Biochemistry analyzers have been evolving at a rapid pace, with fully automated equipment already on the market. These analyzers are capable of recognizing sample and reagent bottles, tube sampling, cap piercing, automatic re-run, and dilution, among other things. One of the primary industry trends is value-based outsourcing, in which laboratory testing is outsourced to clinical reference laboratories. Clinical laboratories have collaborations with small hospitals that lack basic infrastructure for clinical diagnostics. The hospitals outsource the patients to these labs for undergoing various diagnostic tests.

In recent years, the market has shifted from a fee-for-service to a value-based-care paradigm, resulting in the outsourcing of laboratory services to diagnostic vendors. In the future years, the shift from hospital outsourcing to reference laboratories will be a major driver for the biochemistry analyzers market.

The pandemic has led to greater emphasis on diagnosis, and laboratories are looking at ways to increase efficiency and provide cost-effective operations.

Following Covid, there has been a significant increase in CRP, ferritin, LDH, and other blood tests. Diagnostic manufacturers are introducing test kits that have great cross-platform correlation. Biochemistry platforms, on the other hand, remain the chosen option due to their technical supremacy. Therapeutic drug monitoring, a branch of clinical chemistry that focuses on the measurement of medicine in blood, is another rapidly expanding field.

For improved efficiency, labs are routinely implementing automation. Diagnostic companies are now delivering a wide range of capabilities in an automated biochemistry analyzer, which can provide a variety of benefits, such as error-free reporting while improving test volumes and, in turn, improve patient safety. The continuous auto-loading technology reduces the need for manual intervention. Similarly, triple chemistry reagent systems for performing specialty tests are becoming more popular, as they eliminate the requirement for external reagent mixing.

In addition, labs are also expanding their business by expanding menu, opening new branches, and joining hands with existing market leaders, creating good demand for automation. To conclude, from small-size to high-end laboratories, private to public sector hospitals, there is a high demand for automation, and it will be exponentially growing in future. Moreover, as a result of the convergence of system engineering, automation, and IT technology, a significant change has been brought in the biochemistry analyzers market. The use of ELISAs for clinical testing within a laboratory is time consuming and demands more personnel and resources. However, moving from ELISA technique to an automated biochemistry method increases time and personnel efficiency considerably, and this leads to cost effectiveness as well.

Along with analytical automation, there is a growing rise in the integration of laboratory information system (LIS) to evaluate the pre- and post-analytical phases, including reading specimen ID, monitoring the analyzers with respect to predefined algorithms, post-analytical processes, such as re-runs, dilutions, and quality control. Besides, diagnostic manufacturers are upgrading their clinical chemistry instruments through integration of IoT and AI to provide predictive maintenance and remote monitoring.

Multidisciplinary convergence is leading the way to integrated diagnostics, especially in laboratories with high workload. Consolidation and integration aids in gathering and compiling information from different analyzers onto a single platform. This has an immediate positive impact on efficiency, allows access to multiple disciplines at one go, and enhances the overall performance and TAT.

Biochemistry analyzers are utilized for drug monitoring, drug-misuse detection, and a variety of other purposes in addition to pathogen testing. As a result of such breakthroughs in the field of clinical diagnostics, biochemistry analyzer applications that were previously limited to the identification of infectious diseases are now expanding into other fields. Diagnostic tests are seeing an increase in demand as a result of this technological advancement. Initially, biochemistry analyzers were employed for repetitive, reagent-intensive analysis. Low-volume reagents are currently used as a result of the replacement of discrete working systems with discrete working systems. The new equipment can automate routine sample analysis tasks that would typically be performed by a lab staff manually.

The biochemistry industry has undergone a major transformation in favor of automation. Although this tendency is not unique to the scientific community, with the majority of the world preferring modern technology to outdated procedures and processes, automated systems offer a variety of benefits to both laboratories and the people who work in them. As a result of reduced preparation time, faster throughput, and lower human error, testing is now more efficient than ever, generating better results in shorter periods of time and making testing a more profitable undertaking due to increased productivity. While some see robotic assistants as a threat to jobs, it is considered that laboratories will never be able to work completely without human input. As a result, the extra helping hand will reduce fatigue and physiological strain among laboratory workers, allowing them to devote more time to new research, which will lead to new discoveries and future development capabilities.

Research Corner
Researchers identify the genetic causes of three mitochondrial diseases using new approach. Researchers at Washington University School of Medicine in St. Louis and the University of Wisconsin-Madison systematically analyzed dozens of mitochondrial proteins of unknown function and suggested functions for many of them. Using these data as a starting point, they identified the genetic causes of three mitochondrial diseases and proposed another 20 possibilities for further investigation. The findings, published May 25, 2022 in Nature, indicate that understanding how mitochondria’s hundreds of proteins work together to generate power and perform the organelles’ other functions could be a promising path to finding better ways to diagnose and treat such conditions.

Mitochondrial diseases are a group of rare genetic conditions that collectively affect one in every 4300 people. Since mitochondria provide energy for almost all cells, people with defects in their mitochondria can have symptoms in any part of the body, although the symptoms tend to be most pronounced in the tissues that require the most energy, such as the heart, brain, and muscles.

To better understand how mitochondria work, Pagliarini, a professor of cell biology and physiology, of biochemistry & molecular biophysics and of genetics, teamed up with colleagues, including co-senior author Joshua J. Coon, PhD, a UW-Madison professor of biomolecular chemistry & chemistry and an investigator with the Morgridge Institute for Research; and co-first authors Jarred W. Rensvold, PhD, a former staff scientist in Pagliarini’s lab, and Evgenia Shishkova, PhD, a staff scientist in Coon’s lab, to identify the functions of as many mitochondrial proteins as possible.

The researchers used CRISPR-Cas9 technology to remove individual genes from a human cell line. The procedure created a set of related cell lines, each derived from the same original cell line but with a single gene deleted. The missing genes coded for 50 mitochondrial proteins of unknown function and 66 mitochondrial proteins with known functions.

Then, they examined each cell line for clues to the role each missing gene normally plays in keeping the mitochondria running properly. The researchers monitored the cells’ growth rates and quantified the levels of 8433 proteins, 3563 lipids, and 218 metabolites for each cell line. They used the data to build the MITOMICS (mitochondrial orphan protein multi-omics CRISPR screen) app, equipping it with tools to analyze and identify the biological processes that faltered when a specific protein went missing.

After validating the approach with mitochondrial proteins of known function, the researchers proposed possible biological roles for many mitochondrial proteins of unknown function. With further investigation, they were able to tie three proteins to three separate mitochondrial conditions.

One condition is a multisystemic disorder caused by defects in the main energy-producing pathway. Co-author Robert Taylor, PhD, DSc, a professor of mitochondrial pathology at Newcastle University in Newcastle-upon-Tyne, UK, identified a patient with clear signs of the disorder but no mutations in the usual suspect genes. The researchers identified a new gene in the pathway and showed that the patient carried a mutation in it.

Separately, Pagliarini and colleagues noticed that disrupting one gene, RAB5IF, eliminated a protein encoded by a different gene, TMCO1, that has been linked to cerebrofaciothoracic dysplasia. The condition is characterized by distinctive facial features and severe intellectual disability. In collaboration with co-author Nurten Akarsu, PhD, a professor of human genetics at Hacettepe University in Ankara, Turkey, the researchers showed that a mutation in RAB5IF was responsible for one case of cerebrofaciothoracic dysplasia and two cases of cleft lip in one Turkish family.

A third gene, when disrupted, led to problems with sugar storage, contributing to a fatal autoinflammatory syndrome. Data regarding that syndrome were published last year in a paper led by Bruno Reversade, PhD, of A*STAR, Singapore’s Agency for Science, Technology and Research.

“We focused primarily on the three conditions, but we found data connecting about 20 other proteins to biological pathways or processes,” said Pagliarini. “We cannot chase down 20 stories in one paper, but we made hypotheses and put them out there for us and others to test.”

To aid scientific discovery, Pagliarini, Coon, and colleagues have made the MITOMICS app available to public. They built in several user-friendly analysis tools, so anyone can look for patterns and create plots just by clicking around. All of the data can be downloaded for more advanced analysis.

“The hope is that this large dataset becomes one of a number in the field that collectively help us to devise better biomarkers and diagnostics for mitochondrial diseases,” Pagliarini said, “Every time we discover a function of a new protein, it gives us a new opportunity to target a pathway therapeutically. Our long-term goal is to understand mitochondria at sufficient depth to be able to intervene therapeutically, which we cannot do yet.”