Application

Upstream Bioprocessing

The biopharma upstream process consists of growing microbes or cells to create biopharmaceutical or biotechnological products.

Upstream processing in bioprocess relies on bioreactors, process analytical tools, and single-use technology to enhance efficiency.

By optimizing bioprocess upstream techniques, manufacturers can cost-effectively produce high-quality biological products.

Bioprocess upstream
Hamilton sensors in a bioractor
Cells close up

Whether it involves cell cultures in bioreactors or microbes in fermenters, the upstream process focuses on studying how to synthesize products such as vaccines, enzymes, or monoclonal antibodies. 

By optimizing critical process parameters like pH, DO, and CO₂, cell growth can be maximized, and in turn yield increased.

The produced material is then sent downstream for purification and concentration steps.
 

How Hamilton Supports Your Bioprocess Upstream Workflow

Media is prepared in a tank using sensors and Clean In Place (CIP), It is then transferred to a bioreactor for cell growth, monitored by sensors (VCD, TCD, CO2, DO, pH) with air supplied. The culture is then transferred to a harvest tank, and liquid waste is safely disposed of.

The CIP process ensures that equipment is cleaned and maintained to minimize cross-contamination risks, and improve safety and product quality. To ensure the quality of this process, tight pH and conductivity control is very important. 

Media for cell culture or fermentation are prepared in a sterile environment and monitored carefully in order to get reliable results in the upstream process. To ensure the high quality of these solutions, tight pH and conductivity control is very important. Hamilton’s sensors help maintain consistency across batches and improve confidence in process outcomes.

Aerobic or anaerobic processes are run mainly in stainless steel bioreactors to produce small or large molecules. Process conditions are optimized during pilot-scale, before progressing towards production-scale. To ensure the high quality of the media, pH, Dissolved Oxygen (DO), Viable Cell Density, Total Cell Density and CO2 control is very important. Hamilton sensors enable real-time monitoring of these key variables, helping improve yield and reproducibility.

Once the cell culture or fermentation process is finished the content of several bioreactors are transferred and collected in the harvest tank. At this stage, maintaining the pH and Dissolved Oxygen concentration of the media is imperative. Reliable measurements ensure the integrity of the product as it transitions to downstream processing.

Explore Our Upstream Bioprocessing Solutions and Applications in Detail

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Incyte Arc Expert sensors enable real-time, in-situ measurement of viable cells, making it possible to detect events and respond in real time without increased off-line sampling.

Sensors for Single-Use

Incyte-P SU

Hamilton’s Incyte SU sensor elements are pre-installed as an integral part of a single-use container with a long shelf life. They provide accurate, stable measurements and come ready-to-use and pre-calibrated. They connect to the Arc Module Incyte SU for reliable measurement in single-use applications. Our SU VCD sensors combine the reliability and measurement stability of conventional sensors with the ease of use as an integral part of the bioreactor. Collect real-time viable cell density measurements for deeper insights and data-driven process optimization.

Arc Module and VisiFerm SU

Arc Module Incyte-W SU

The Arc Module Incyte-W, when used with the Incyte-W SU, enables real-time, in-situ measurement of viable cells. This allows for immediate detection of events and real-time responses, reducing the need for increased off-line sampling.
Dencytee Arc RS485 sensors enable real-time, in-situ measurement of total cell density using transmittance and reflectance of near-infrared light in low and high cell density applications. Reduce off-line sampling and increase the reliable optical density measurement range.
EasyFerm Bio pH sensors offer Foodlyte biocompatible electrolyte and EHEDG Certification for pH measurement in processes where non-toxicity is mandatory.
Polilyte Plus pH sensors are engineered for long life and high accuracy in demanding industrial applications. They feature a maintenance-free design with clog-resistant single pore junctions and a stable polymer electrolyte, ensuring reliable pH measurement in diverse conditions.

VisiFerm Dissolved Oxygen Sensors

VisiFerm RS485-ECS

VisiFerm RS485-ECS is an advanced optical dissolved oxygen sensor for biotechnology, biopharmaceutical, and food and beverage industries, offering full measurement functionality, self-diagnostics, and simplified maintenance.

VisiFerm Dissolved Oxygen Sensors

VisiFerm mA

Less frequent calibration and longer lifetime. 2-wire 4-20mA / HART for GMP production environments. Explosive-rated environments.

OxyFerm FDA Dissolved Oxygen Sensors

OxyFerm FDA VP

The OxyFerm FDA VP is an electrochemical oxygen sensor suited for applications with high demands for hygiene.

Arc Module and VisiFerm SU

VisiFerm SU RS485-ECS

The VisiFerm SU RS485-ECS is designed for reliable dissolved oxygen (DO) measurement in single-use applications with the ODO Cap Sx sensor element.

Conducell 4UxF

Conducell 4USF Arc

The Conducell 4USF Arc is a 4-pole conductivity sensor equipped with advanced Arc technology and a VP8 connector. This sensor is designed for hygienic applications, offering features like onboard calibration storage and direct connection to control systems, simplifying integration and maintenance.
Hamilton EasyFerm Plus pH sensors are the most popular product for pharmaceutical applications where autoclave and SIP are frequently performed. They provide accurate and stable pH measurement in demanding biopharma processes.

Lab Syringes

Gastight Syringes

The solution for dispensing both gases and heterogeneous liquids. Hamilton Gastight syringes are equipped with a precision-machined PTFE plunger tip to create a leak-free seal.
Hamilton Microliter syringes are ideal for dispensing homogeneous liquid samples not prone to glass bonding or precipitation. With a hand-fitted stainless steel plunger for frictionless movement and minimal wear, these syringes are designed to last.

Discover our Newest PAT Innovation: GlucoSense

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Glucose is a critical process parameter in cell cultures. Yet, its real-time control remains a significant challenge in bioprocessing R&D. Current methods, such as off-line measurements or complex fiber-optic spectrometers, are often time-consuming, difficult to use, or require specialized expertise.

The solution: GlucoSense

For the first time, a sensor combines real-time, in-situ measurement, high reliability, and true ease of integration, overcoming the limitations of all existing technologies. This innovative solution enables more precise control, higher product quality, and greater process efficiency. 

GlucoSense is not just an evolution; it is a breakthrough designed to transform biopharmaceutical manufacturing.

Are you ready for the future of biopharma?

Good to Know About the Bioprocess Upstream Process

This section provides a selection of additional resources related to the application described on this page. It includes helpful articles, videos, and blogs that offer deeper insights into the topic.

Useful Links

External resources not written by Hamilton but valuable for understanding the topic, such as industry guidelines, explanatory videos, or relevant tools.

Bio-processing overview (Upstream and downstream process)Watch Video
Bioprocessing - Centre for Applied Bioscience ResearchVisit Website

Solutions for Top 3 Challenges of Upstream Bioprocessing

Upstream bioprocessing faces several key challenges in its pursuit of efficient, safe, and compliant manufacturing.
Bioprocess products are complex molecules of biological origin, synthesized by living organisms like mammalian cells or microbes. Maintaining optimal productivity in living organisms used for bioprocessing is a significant challenge, necessitating real-time process control as outlined in regulatory guidelines like the FDA's Process Analytical Technology (PAT) initiative. This demands innovative sensor solutions and a focus on process understanding.

Challenge: Need for reliable and accurate solutions to monitor and control biopharmaceutical processes in real/time.

Solution: Hamilton intelligent sensors measure Critical Process Parameters (CPPs) and Key Performance Indicators (KPIs), enabling a complete view of your bioprocess for smarter, data-driven decisions.

Challenge: Ensuring product quality and meeting stringent regulatory requirements in biopharmaceutical manufacturing.

Solution: Hamilton Intelligent sensors are built to the highest manufacturing standards, helping customers meet or exceed FDA and GMP regulatory requirements.

Challenge: Lack of expertise and experience in implementing process analytics in biopharmaceutical applications.

Solution: With over 30 years of experience, Hamilton offers expert guidance and process analytics know-how tailored for biopharma applications.

Bioprocess Upstream Applications

Benchtop bioractor upstream process

Bioprocess upstream applications focus on optimizing cell growth, media composition, and bioreactor conditions to produce high-quality biological products. Precise control of critical process parameters like oxygen, carbon dioxide, and pH ensures the highest productivity.

Productivity can also be measured in line through KPIS such as viable and total cell density. Advanced technologies, including single-use systems and intelligent sensors, enhance scalability and flexibility.

What Industries Depend on Bioprocessing? 

Bioprocessing is essential to several industries. In biopharmaceuticals, it is the foundation for producing monoclonal antibodies, vaccines, and recombinant proteins. Food and beverage manufacturers utilize upstream processes for fermentation, enzyme production, and probiotic production. In agriculture, it plays a role in developing biofertilizers and pest-resistant crops.

Sustainable energy applications rely on upstream bioprocessing to cultivate microbes for biofuels, while industrial biotechnology utilizes it for the production of biodegradable plastics and specialty chemicals. As advancements in automation and process analytical technology improve efficiency, upstream bioprocessing continues to drive innovation across these sectors.

Upstream bioprocess

Other Upstream Bioprocessing Resources

Browse app notes, user guides, specification documents, and more in our Knowledge Center.

Browse app notes, user guides, specification documents, and more in our Knowledge Center.

Browse app notes, user guides, specification documents, and more in our Knowledge Center.

Browse app notes, user guides, specification documents, and more in our Knowledge Center.

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