Harvesting is a pivotal phase in bioprocessing, involving the isolation and concentration of the target biomolecules/cells from a production/culture medium. It ensures the effective recovery while maintaining high concentration, thus optimizing the downstream purification steps and overall process efficiency. This process significantly influences the overall yield, purity, and quality of the final product, making it a critical determinant of successful biomanufacturing.
Cell harvesting workflows typically involve two key operations: concentration and diafiltration. Concentration is employed to increase the density of the target cells, making it easier to handle and process in subsequent stages. Diafiltration, on the other hand, is used to exchange the buffer environment of the product, which is essential for maintaining cell stability and facilitating downstream applications. Together, these operations streamline the harvesting process, ensuring that the cells remain in the optimal state for subsequent steps.
Harvesting in cell-based workflows
The selection of an appropriate harvesting method is guided by several critical factors. Gentleness is paramount to minimize shear stress and preserve the structural integrity of cells. Yield is another crucial consideration, as maximizing the recovery of the target product directly correlates with the efficiency and cost-effectiveness of the bioprocess. Scalability is essential to ensure that the chosen method can be scaled from laboratory to industrial production without loss of efficiency or product quality. Time efficiency is vital in reducing the overall processing time, thereby enhancing productivity. Cost efficiency is also a key factor, as it ensures that the operational expenses are kept in check while delivering high-quality outputs. These considerations collectively guide the selection of the most suitable harvesting method, balancing performance, and economic viability.
| Considerations | Centrifugation | Dead-End Filtration | Tangential Flow Filtration |
|---|---|---|---|
| Cell Yield | ✔ | ✔ | ✔ |
| Cell Viability | ✔ | ✔ | ✔ |
| Time Efficiency | ✔ | ||
| Scalability | ✔ |
Table. Comparison of techniques used for cell harvesting
On a lab-scale, centrifugation and dead-end filtration (DEF) are the conventional, cost-effective methods for cell harvesting but are often limited by low yields. Achieving higher yields requires high speeds or prolonged centrifugation, which can damage the cells, induce stress, and increase the harvesting time. Comparatively, tangential flow filtration (TFF) provides gentle processing conditions for shear sensitive cells, thus ensuring high cell yield and viability. However, conventional TFF systems come with drawbacks such as large footprints, high hold-up volumes, and labor-intensive operation, making them inefficient for lab-scale workflows.
Therefore, the introduction of a lab-scale TFF system addresses the need for process development and optimization, thus serving as a critical bridge between research and industrial application.
Harvesting Using the µPulse - TFF System
The Formulatrix µPulse® is an automated and miniaturized TFF system explicitly designed for lab-scale applications. It is well suited for harvesting cells, cell lysates, extracellular vesicles, and secretory products while ensuring high product yields and quality. The entire fluid path is miniaturized on the filter chip by combining our patented microfluidic pumping technology with the TFF. This has reduced the hold-up volume to just 0.65 mL, ensuring maximum hold-up recovery.
Its customizable settings, including adjustable pressures and pump parameters, provide a gentle yet highly efficient process for biomolecules and cell harvesting. The filter chips are available with modified polyethersulfone (mPES) and regenerated cellulose (RC) membranes that exhibit low fouling characteristics and are compatible with various sample types. Furthermore, it processes samples 4x faster than the dead-end centrifugal units and in a walk-away approach.
Webinars
Streamline the gentle harvesting of mammalian cells using µPulse while ensuring high yields and cell viability.
Explore the ease of use and cost-effectiveness of µPulse for processing VLPs and other macromolecules compared to dead-end units.
Publications
Therapeutic Potential of Wharton's Jelly Mesenchymal Stem Cells-derived Secretome (S-MSCs) in Psoriasis Vulgaris: A Case Study
Azzahara et al., 2024 | International Journal of Cell and Biomedical Science | Link: https://doi.org/10.59278/cbs.v2i5.37
Background Psoriasis is a chronic immune-mediated skin disease that also has systemic manifestations Case In this report we discuss our findings about a -years old psoriasis suffering male patient with a Psoriasis Area Severity Index PASI score of treated with Wharton s Jelly Mesenchymal Stem Cells-derived Secretome S-MSCs Remarkably complete regression was recorded within a treatment period More.... | Related Solution: µPulse TFF System
Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Ameliorates Hyperglycemia in Type 2 Diabetes Mellitus Rats
Introduction: Type 2 diabetes mellitus (T2DM) is a prevalent form of diabetes that affects 90 - 95 % of all diabetic patients. Insulin sensitizers and insulin exogenous supply could temporarily ameliorate hyperglycaemia; however, they are accompanied by side effects. As a result, new approaches are required to address insulin resistance and regenerate beta cells simultaneously. The secretome of hypoxic mesenchymal stem More.... | Related Solution: µPulse TFF System
Combination Effect of Rotator Cuff Repair with Secretome-hypoxia MSCs Ameliorates TNMD, RUNX2, and Healing Histology Score in Rotator Cuff Tear Rats
Fredianto et al., 2023 | The Archives Of Bone And Joint Surgery | Link: https://doi.org/ 10.22038/ABJS.2023.67933.3218
Objectives: In order to treat a rat model of rotator cuff rupture, this work concentrated on the expression of TNMD and RUNX2, followed by rotator cuff repair and secretome-hMSCs. Methods: A total of thirty 10-weeks-old male Sprague–Dawley rats were separated into five groups randomly, RC on week 0, lesion treated with a rotator cuff repair and saline (RC + NaCl group, n = 6) for 2 and 8 weeks, and lesion More.... | Related Solution: µPulse TFF System
The Effect of Secreted IL-10 from Mesenchymal Stem Cell on Immune Checkpoint Molecules
Background: Immunosuppression in sepsis is hypothesized to result from the increased expression of the immune checkpoint molecules programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). PD-1 and PD-L1 blockade therapies have been reported to increase survival in septic animals. Currently, the interleukin (IL)-10 within mesenchymal stem cell (MSC) secretome is known for its immunomodulatory capacity. More... | Related Solution: µPulse TFF System