Bioprocessing

Shorten Development Cycles and Improve Efficiency

Bioprocessing involves the use of active biological systems like living cells to generate biopharmaceuticals, such as vaccines, cell therapies, bioreactors, recombinant proteins, and antibodies. Bioprocessing aims to minimize variability and ensure a robust and reproducible process that reliably makes a quality product. The development, scale-up, and manufacturing of biopharmaceuticals continue to increase in both complexity and regulatory requirements. All aspects of a bioprocess must be optimized for the highest possible titers with the most cost-effective production. This requires an understanding of all critical process parameters, such as media components, that impact scalability, quality, and control.

Metabolomics is a direct assessment of the active biological system (living cells) and the factors that influence it, making it an ideal tool to improve predictability, quality, and control. Metabolon’s Bioprocessing Insight Assessment is built upon our proprietary metabolomics technology and takes a comprehensive approach to provide specific insight on media/feed optimization, scale-up, cell line selection, batch fingerprinting, and quality predictors to better understand and control your bioprocess.

Comprehensive Understanding of Bioproduct Quality

Many factors can influence the productivity of cell cultures in bioprocessing applications. From choosing the best cellular clone to identifying biomarker predictors of process performance and product quality, understanding the biology of the process is critical to generate high-quality biological products. A deeper understanding of cell culture systems can lead to improvements in the process and the output and enhance the ability to characterize changes in product quality and yield. Metabolomics can provide a comprehensive biochemical view of the cell culture system and enable the interrogation of genetic, environmental, and process design factors to enhance bioprocess understanding and optimization. Metabolomics can be applied across the bioprocess lifecycle, from process development to monitoring, to gain biological insight and facilitate the development, implementation, and execution of robust and reproducible bioprocesses.

Enabling Understanding and Control of Cell Cultures in Bioprocessing

Metabolomics is a direct measure of a system’s active biology, assessing all complex factors that can influence the production process, including genetic, environmental, and nutritional influences. Moreover, metabolomic profiling can be performed to evaluate both cells and media. This increases the assessment of active biology by providing a view of what is happening within the cell as well as what is being released to the media.

Metabolon’s proprietary metabolomics technology provides the broadest coverage of metabolites in the industry, so you can have confidence in your bioprocess monitoring. While traditional technologies focus on a conventional set of 10 to 20 biomarkers, Metabolon can routinely detect 500 to 1500 metabolites in cell culture systems, including amino acids, carbohydrates, cofactors, vitamins, nucleotides, and lipids. Therefore, Metabolon can expand the assessment of biochemical space and provide you with greater understanding and more opportunities for optimization. Our metabolomic approach provides comprehensive coverage of the metabolome and accurate identification of metabolites with high precision. Another challenge of metabolomics profiling is being able to derive actionable knowledge from the data. Our analytical capabilities are supported by informatics research and an extensive knowledge base of metabolism, which enables interpretation of the data and generation of knowledge.

Providing Critical Insight and Value at Every Step of the Bioprocess

Controlling the cost and quality of a bioprocess starts with a quality-by-design approach to process development, which requires a deep understanding of critical process parameters. Metabolon’s Bioprocessing Insight Assessment informs this crucial step with better characterization of cell lines, informing media and feed strategies, and evaluating scale-up stability. Because the bioprocess is dependent on active biology (living cells), metabolomics can be applied across the entire bioprocess life cycle to facilitate understanding and control. Knowledge and insights provided by metabolomics can be used to develop a reproducible final product as well as to evaluate scale-up and transfer of the system. In addition, metabolomics can identify performance and product quality biomarkers that can complement active process monitoring activities.

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Metabolomics Panels for Bioprocessing Applications

Amino Acids Targeted Panel

Amino acids (AA) are the foundational building blocks for peptides and proteins. These small molecules regulate metabolic pathways that are involved in cell maintenance, growth, reproduction, and immunity. Branched chain amino acids play a large role in building muscle tissue and participate in increasing protein synthesis. Amino acids also play a role in cell signaling, gene expression and protein phosphorylation. Maintaining an optimal balance of amino acids is vital to maintaining a stable equilibrium of physiological processes.
Amino Acids Targeted Panel
Beta-Hydroxybutyrate Single Analyte Assay

Beta-Hydroxybutyrate Single Analyte Assay

β-Hydroxybutyrate (BHB, 3-hydroxybutyrate) is an endogenous ketone body that accumulates during periods of fasting, calorie restriction and prolonged exercise. It is created via a multi-step process involving the break-down of fatty acids into acetyl CoA, conversion to acetoacetate and reduction to β-hydroxybutyrate in the liver. BHB is the primary ketone found in the blood and is necessary for brain function especially when glucose is unavailable. It also provides neuroprotective benefits, such as relieving oxidative stress and inhibition of apoptotic pathway in cells.

Bile Acids Targeted Panel

Bile acids are derived from cholesterol and serve an important role in emulsifying and digesting lipids. In addition, their metabolism is intimately involved with the microbiota, and they have been shown to exhibit endocrine and metabolic activity via receptors like FXR and TGR5. The Bile Acids Targeted Panel measures all the major human and rodent primary and secondary bile acids as well as their glycine and taurine conjugates.
Bile Acids Targeted Panel
C4 Single Analyte Assay

C4 Single Analyte Assay

7-α-hydroxy-4-cholesten-3-one (C4) is an intermediate in the biosynthesis of bile acids from cholesterol. The precursor to C4 is 7α-hydroxycholesterol which is produced from cholesterol via the hepatic enzyme, 7α-hydroxylase. 7-α-hydroxylase catalyzes the rate-limiting step in bile acid synthesis and its activity is tightly regulated via the FXR receptor. Measurement of the stable metabolite C4, a product of the next oxidative enzymatic reaction after 7-α-hydroxylase, is reflective of hepatic de-novo bile acid synthesis and FXR receptor activation. Bile acid malabsorption is associated with a variety of gastrointestinal pathologies (eg, irritable bowel syndrome, ileal disease) and is characterized by elevated serum C4 levels.

Central Carbons Targeted Panel

Central carbon metabolism involves the enzymatic conversion of sugars into metabolic precursors that are used to generate the entire biomass of the cell. The metabolites in this panel include key citric acid cycle compounds that connect carbohydrate, fat, and protein metabolism. In addition to supplying key metabolic precursors, central carbon metabolism is used to oxidize simple sugar molecules obtained from food to supply energy to living systems. Measurement of central carbon metabolites has great industrial relevance since it may allow the engineering of selected metabolic steps to optimize carbon flow toward precursors for industrially important metabolites.
Central Carbons Targeted Panel
Free Fatty Acids Targeted Panel

Free Fatty Acids Targeted Panel

Fatty acids play many physiologically important roles in an organism. They are not only key metabolites of energy storage and production but also the basic building blocks of complex lipids that form cellular membranes. A variety of bioactive forms of fatty acid metabolites, known as lipid mediators, act as local hormones and are involved in many physiological systems and pathological processes. Free fatty acids (FFA, non-esterified fatty acids, NEFA) are the nonbound fraction of the total fatty acid pool. The determination of FFAs in plasma (or serum) is of clinical relevance as the association between FFAs and many diseases is well-known (eg, insulin resistance/type 2 diabetes, hypertension, cardiovascular disease).

Salivary Glucose Single Analyte Assay

Daily monitoring of glucose levels is an essential part of managing diabetes. However, blood glucose testing usually involves finger pricks, an invasive procedure that is troublesome to some patients. Therefore, increasing efforts have been made to develop a non-invasive method by self-testing salivary glucose levels, which are two orders of magnitude lower than those in blood.
Salivary Glucose Single Analyte Assay
Impaired Glucose Tolerance Targeted Panel

Impaired Glucose Tolerance Targeted Panel

Impaired Glucose Tolerance is a prediabetic state of hyperglycemia that is associated with insulin resistance and an increased risk of cardiovascular pathology (Barr, 2007). The condition occurs when blood glucose levels remain high for an extended period after oral ingestion of glucose but not high enough to be diagnosed as type 2 diabetes.

Impaired Glucose Tolerance can be assessed with a single fasted blood draw by measuring a panel of selected metabolites comprised of two small organic acids (α-hydroxybutyric acid (AHB) and 4-methyl-2-oxopentanoic acid (4MOP)), 2 lipids (oleic acid and linoleoyl glycerophosphocholine (LGPC)), a ketone body (β-hydroxybutyric acid (BHBA)), an amino acid (serine), a vitamin (pantothenic acid (vitamin B5)), and glucose.

Insulin Resistance Targeted Panel

Insulin resistance is a critical pathophysiological state underlying several chronic conditions, including type-2 diabetes, cardiovascular disease (CVD), hypertension, and polycystic ovarian syndrome. Insulin resistance is evident when glucose builds up in the blood stream instead of being absorbed by the body’s cells. It is a result of a diminished response to the hormone insulin at the whole body, organ, or cellular level.

A panel of biomarkers comprised of a small organic acid (α-hydroxybutyric acid (AHB)), 2 lipids (oleic acid and linoleoylglycero-phosphocholine (LGPC)) and insulin identifies insulin resistance with a single fasting blood sample and may have value as an early indicator of risk for the development of prediabetes and type-2 diabetes.

Insulin Resistance Targeted Panel
Metal Analysis Targeted Panel

Metal Analysis Targeted Panel

Metabolon’s ICP-MS-based Metal Analysis Targeted Panel provides precise measurements of biologically important metal ions in biological samples. In addition to the well-established problems of toxicity associated with several metals, the vital role these ions play in a variety of biological pathways whether by catalyzing enzymatic reactions or stabilizing protein structures is still becoming clear. Intimately intertwined with the proteome and metabolome, metal ions represent an intrinsic piece vital to the holistic understanding of biological phenomena ranging from development through normal functioning to disease. Without an understanding of the role of these metals, a complete understanding of biological processes is not possible. The Metal Analysis Targeted Panel measures a variety of metals ions ranging from the macro level (ppm) including Na, K, and Ca to the micro level (ppb) including Mo, Cu, and Ni.

Metabolon in Action

Increasing Cell Culture Yield with Targeted Metabolomics

In this study, Metabolon’s approach to bioprocess monitoring made it possible to determine the concentration of multiple metabolites in a simple and time-efficient manner. Targeted metabolomics allowed the development of an efficient fed-batch culture media for mAb-producing CHO cell lines.

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Virus Vaccine Optimization with Metabolomics

This study used metabolomics to develop an optimized cell culture medium suitable for infectious bursal disease virus (IBDV) propagation. Therefore, this team of scientists provides a strategy for the efficient production of IBDV vaccines and could potentially be utilized to improve the production of other viral vaccines. In this context, metabolomics provides informative insights into the prevention and treatment of IBDV.

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Improve Bioprocessing Efficiency

This work uncovers meaningful bioprocess markers and targets for genetic engineering, all potentially leading to improved bioprocess productivity. By leveraging metabolomics and lipidomics analyses, this research team deepened their understanding of the CHO biotherapeutic production platform. Metabolomics and lipidomics analyses can thus help pave the way for improved efficiency of bioprocessing and aid the manufacturing of new effective therapies to alleviate patient disease.

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Interested in Further Studies?

Why Metabolon?

Once you see the full value of metabolomics, the only remaining question is who does it best? While many laboratories have metabolite profiling or analytical chemistry capabilities, comprehensive metabolomics technologies are extremely rare. Accurate, unbiased metabolite identification across the entire metabolome introduces signal-to-noise challenges that very few labs are equipped to handle. Also, translating massive quantities of data into actionable information is slow, if not impossible, for most because proper interpretation takes two things that are in short supply: experience and a comprehensive database.

Only Metabolon has all four core metabolomics capabilities

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Coverage

Ability to interrogate thousands of metabolites across diverse biochemical space, revealing new insights and opportunities

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Comparability

Ability to integrate the data from different studies into the same dataset, in different geographies, among different patients over time

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Competency

Ability to inform on proper study design, generate high‐quality data, derive biological insights, and make actionable recommendations

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Capacity

Ability to process hundreds of thousands of samples quickly and cost‐efficiently to service rapidly growing demand

Partner with Metabolon to access:

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A library of 5,400+ known metabolites, 2,000 in human plasma, all referenced in the context of biochemical pathways

  • That’s 5x the metabolites of the closest competitor
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Unparalleled depth and breadth of experience analyzing and interpreting metabolomic data to find meaningful results

  • 10,000+ projects with hundreds of clients
  • 2,000+ publications covering 500 diseases, including numerous peer-reviewed journals such as Cell, Nature and Science
  • Nearly 40 PhDs in data science, molecular biology, and biochemistry

Using our robust platform and visualization tools, our experts are uniquely able to tell you more about your molecule and develop assay panels to help you zero in on the results you need.

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Request a quote for our services, get more information on sample types and handling procedures, request a letter of support, or submit a question about how metabolomics can advance your research.

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