Lyophilization, also known as freeze drying, is not a new topic in the field of biology. As early as 1890, Richard Altmann first conducted lyophilization of biological organs. With the development of vacuum equipment, lyophilization technology has been widely applied in modern pharmaceuticals and bioproducts, such as blood products, vaccines, antibiotics, and various applications in the food industry.

With the outbreak of the COVID-19 pandemic, the demand for lyophilization in the in vitro diagnostics (IVD) field has been increasing. In addition to meeting the basic requirements of point-of-care testing (POCT), lyophilized products in the IVD field have several advantages:

• Cost Reduction: Lyophilization can reduce costs on multiple levels. Well-processed lyophilized products can be stored at room temperature for an extended period, reducing the need for cold storage construction costs, corresponding compliance monitoring costs, and the energy consumption costs of the cold storage itself. Additionally, lyophilization can lower the logistics costs of cold chain transportation, including requirements for cold chain packaging, carbon emission regulations, and material degradation costs.
• Convenience of Use: Adopting the form of quantitative lyophilization allows end-users to avoid traditional steps such as thawing and reconstitution of reagents, providing convenience, time savings, and reduced operational errors for customers. Well-processed lyophilized products can achieve rapid reconstitution, enabling instant use.
• Extended Shelf Life: According to literature reports, lyophilized products with good processes can have a shelf life of up to twenty years. In general, well-formulated and well-processed molecular diagnostic reagents can be stored at room temperature for more than two years, meeting the stringent expiration date requirements of end-users.

Regarding the choice between in situ lyophilization and lyophilized beads:

Lyophilization itself is a process issue, and there are many paths from the beginning to the end of lyophilization. The exploration of lyophilization processes (good processes) is not only about ensuring the consistency and stability of product quality but also about minimizing the lyophilization process and energy consumption.

Lyophilization processes are related not only to lyophilization equipment, environment, lyophilized products themselves, and formulation of protective agents but also to the form of lyophilization. In the IVD field, the most common forms of lyophilization are in situ lyophilization and lyophilized beads.

In situ lyophilization involves placing the liquid directly in the packaging container for lyophilization, also known as in-place lyophilization. It is a very mature lyophilization system with a history of over a hundred years in the lyophilization field.

Because lyophilization occurs within the container, there are high requirements for the container. For example, in the pharmaceutical industry, the widely used vials, such as vials for penicillin, have different manufacturing processes—molded vials and tubing vials. However, tubing vials are mainly used for lyophilization. Compared to molded vials, tubing vials have better contact with the bottom and uniform wall thickness. Uniform wall thickness ensures stable and uniform heat exchange during lyophilization, which is crucial for ensuring lyophilization stability and reliability.

In the early stages of the IVD field, many immunoassay, biochemical, and coagulation reagents were also lyophilized using vials. Its characteristic is multi-dose lyophilization, reconstitution before use, effectively solving the problem of cold chain transportation.

As globalization has accelerated the demand for molecular diagnostic reagents among different countries worldwide, the associated transportation costs and environmental pressures have also placed significant demands on lyophilization. The demand for lyophilization in the molecular diagnostic field is particularly urgent, and in situ lyophilization is the most easily thought of solution, with satisfactory results currently.

However, in situ lyophilization cannot escape the requirements for flat-bottom bottles. As a result, people have attempted in situ lyophilization directly using PCR tubes. In this process, there are various issues related to process control, batch-to-batch variation, inter-batch variation, large gaps, and limited production capacity.

Why lyophilized beads?

Looking globally, lyophilized beads are a prominent method in the lyophilization of molecular diagnostics. Essentially, it solves several problems:

• Individual Packaging: Achieves individual packaging for single-dose use.
• Distribution after Lyophilization: Allows for redistribution after lyophilization.
• Mass Production Capability: Solves the issue of mass production capacity.

However, the lyophilization of beads has changed the original form of liquid distribution and mass production for IVD. Currently, there is no particularly professional equipment and skilled operators for matching, which has become a bottleneck limiting the industry's development.

For lyophilized bead production, the process can be roughly divided into the following stages:

• Formula Optimization: Optimizing the formula involves creating stable and well-shaped beads, considering the requirements for moisture desorption during lyophilization, and determining the impact of additives on signal enhancement or attenuation in subsequent experiments. Commonly used sugars, mannitol, etc., all play a role, but whether they can be used in a specific formula and the required concentration are crucial for the entire diagnostic system and require exploration.
• Bead Production Process: The bead production process requires precise control of droplet dosing and continuous production. Currently, some domestic companies are attempting to develop similar equipment, but there is a gap in the understanding of the inspection industry by equipment manufacturers. For practitioners in the biological field, understanding the use and control logic of fluid-related equipment requires a high level of knowledge, and precision fluid control equipment often needs adjustment to adapt to different viscosities, formulations, and surfactants.
• Exploration of Drying Curves: The exploration of drying curves is an operation that combines experience and practice throughout the process. There are many mature lyophilizers on the market that can serve as reference equipment, but to develop equipment that meets or adapts to small beads, the basic framework structure must be understood in the entire process. When necessary, equipment may need to be modified to improve production capacity, energy consumption, and equipment applicability. Low-temperature drying is the best for preserving the activity of the material compared to other drying methods. In the entire equipment, considerations must be given to the shape and arrangement of the drying vacuum chamber, as well as the location, size, and water absorption of the desiccant chamber. Common lyophilizers use a low-temperature cold trap to capture moisture in the material, which places high demands on moisture capture. The drying process is divided into primary drying (MD) and secondary drying (SD), and the conditions for primary drying must match the shape of our formulated liquid. For example, before designing a program, it is necessary to measure eutectic points, melting points, etc. Generally, the drying temperature of the main formulation is kept lower than the eutectic point to effectively control and improve the collapse and surface pitting of beads during the drying process. After MD, there is often some bound water in the bead product that could not be frozen earlier, and it is dried again during the SD process. However, in many tests, it has been found that there is a certain predetermined value for the drying of SD. If this predetermined value is exceeded, it may cause damage to the activity of the product. Experience and necessary means help find the best drying curve.
• Control of Filling Humidity: After drying, the product has a low water content. Taking molecular diagnostics as an example, it can generally maintain long-term stability, with a water content of around 3%. This places high demands on the control of filling humidity. To ensure the stability of the entire process, the environmental humidity during filling generally needs to be controlled below 5%. This places very high demands on the factory's environment and energy consumption. Different means of humidity control place high demands on the rate of dehumidification, final humidity retention, energy consumption, and cost control. The filling speed also affects the stability of the operation. Therefore, automated equipment and related tools become particularly important, but different consumables and bead sizes and characteristics need to be considered during the design of the equipment.

For bead production, quality control after mass production is critical. For well-explored processes and parameters, after producing well-shaped beads, it is necessary to conduct random testing of the water content and functionality of the beads. It may be necessary to retain samples for aging and accelerated testing. For water content testing, mature methods include weight analysis, Karl Fischer titration, thermogravimetric analysis, and infrared spectroscopy. Only by paying attention to all links in the entire chain can we ensure the stability and suitability of our process and the final long-term storage.

In this dynamic field, SBS Genetech offers outstanding lyophilized products and professional lyophilization services. As your trusted partner, we are committed to meeting the growing demands of the global molecular diagnostics industry.

SBS Genetech not only provides high-quality lyophilized products but also boasts an experienced team capable of delivering customized lyophilization services. Our lyophilization techniques and processes are meticulously optimized to ensure the consistency and stability of product quality. Whether it's in situ lyophilization or lyophilized beads, we employ advanced technologies to cater to a variety of customer needs.

By choosing SBS Genetech, you will benefit from:

• Exceptional Product Quality: Our lyophilized products are carefully prepared to guarantee stability and activity during extended storage.
• Customized Lyophilization Services: Our professional team will provide tailored lyophilization services based on your requirements, ensuring optimal product performance.
• Leading Global Technologies: We utilize state-of-the-art lyophilization techniques and processes to meet the evolving demands of the molecular diagnostics market.
• Reliable Partnership: SBS Genetech is built on reliability and professionalism, offering you excellent products and services.

With continuous technological advancements and rapid market changes, choosing SBS Genetech is key to your success. Let's collaborate and shape the exciting future of the molecular diagnostics field together.