Cell-based workflows

Miniaturized cell-based workflows demand precision in automation. From cell culture to assay and screening applications, Hamilton Freiburg´s dispensing technologies guarantee highly reproducible dispensing of living cells. Our solutions ensure elevated survival rates, normal proliferation behavior, and accurate cell differentiation.

Miniaturized cell culture

Enhance throughput and achieve consistent outcomes through standardization in your cell culture processes.

In vitro cell culture studies are crucial for comprehending cellular physiology within an artificial setting. To sustain cells outside living tissue, meticulous control over physio-chemical conditions, including the addition of essential nutrients, is imperative. Hamilton Freiburg´s dispensing technologies facilitate the miniaturization of your experimental setup by precisely delivering ultra-low volumes of growth factors and essential nutrients. This enables increased throughput for co-culture experiments in dense plate formats, fostering more efficient and scalable research.


3D cell culture

Achieve precise cell patterning, whether in low or high densities, across all plate formats for the generation of cell spheroids tailored for advanced investigations.

Cell culture stands as a cornerstone technique in cellular and molecular biology, facilitating a diverse range of studies. From metabolic and cell junction interaction analyses to investigating stem cell behaviors, drug effects, screening, and disease progression in basic research, this technique serves as a fundamental tool. Our advanced printing technologies enable seamless control over cell distribution, empowering your research with reproducible and customizable cell spheroid formations for in-depth exploration.

3D tissue models

Precision-print droplets with variable cell densities to construct intricate 3D tissue models.

Bioprinted tissues emulate natural environments, providing a controlled setting for applied studies. Elevate cell survival rates by adeptly printing on filament layers or utilizing bioinks, enabling in-depth exploration of cell-cell interactions within diseased tissue. Our technology facilitates screening experiments for drug discovery studies, offering a sophisticated platform to advance research in a more controlled and realistic context.

Co-culture of stem cells

Enhance experimental consistency through automated cell printing, minimizing variables in cell culture experiments.

The PIPEJET® excels in dispensing diverse cell densities within nanoliter droplets. Attain outstanding dispensing precision with a remarkable 97% cell survival rate, achieved through gentle cell treatment during the dispensing process. Tailor the transferred energy of the actuation mechanism to the dispensing tip, effectively reducing shear stress. This enables the printing of spheroids across various cell culture dishes or glass slides, providing a versatile platform for cultivating cells with utmost precision.

Tissue engineering

Precision-deposit cells in predefined patterns for the engineering of functional tissue.

Achieve the creation of tissue-engineered biological structures suitable for human studies or transplantation experiments. Leverage the high resolution and rapid printing capabilities, coupled with exceptional cell viability, to seamlessly print polymer or cell droplets in diverse and intricate shapes, providing a versatile and efficient method for crafting functional tissue.

Relevant literature

Bioprinting of high cell‐density constructs leads to controlled lumen formation with self‐assembly of endothelial cells | 2019

Active nutrient supply and waste product removal are key requirements for the fabrication of long‐term viable and functional tissue constructs of considerable size. This work aims to contribute to the fabrication of artificial perfusable networks with a bioprinting process, based on drop‐on‐demand (DoD) printing of primary endothelial cell (EC) suspension bioink.

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Examination of Hydrogels and Mesenchymal Stem Cell Sourcesfor Bioprinting of Artificial Osteogenic Tissues | 2019

Mesenchymal stem cells (MSCs) represent a very important cell source in the field of regenerative medicine and for bone and cartilage tissue engineering applications. Three-dimensional (3D) bioprinting has the potential to improve the classical tissue engineering concept as this technique allows the printing of cells with high spatial control of cell allocation within a 3D construct. In this study, we systematically compared different hydrogel blends for 3D bioprinting of MSCs by testing their cytocompatibility, ability to support osteogenic differentiation and their mechanical properties.

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Assessment of hydrogels for bioprinting of endothelial cells | 2017

In tissue engineering applications, vascularization can be accomplished by coimplantation of tissue forming cells and endothelial cells (ECs), whereby the latter are able to form functional blood vessels. The use of three‐dimensional (3D) bioprinting technologies has the potential to improve the classical tissue engineering approach because these will allow the generation of scaffolds with high spatial control of endothelial cell allocation. This study focuses on a side by side comparison of popular commercially available bioprinting hydrogels (Matrigel, fibrin, collagen, gelatin, agarose, Pluronic F‐127, alginate, and alginate/gelatin) in the context of their physicochemical parameters, their swelling/degradation characteristics, their biological effects on vasculogenesis‐related EC parameters and their printability.

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Contact-Free Dispensing of Living Cells in Nanoliter Droplets

Contact-Free Dispensing of Living Cells in Nanoliter Droplets

We present a novel method for automated dispensing of living cells in nanoliter range droplets using a disposable pipette tip combined with an elastic polymer tube. After introduction of an unmetered suspension of cells into a reservoir connected to the pipette tip, a tuneable volume of 10 - 80 nL of cells suspension is issued in a non-contact procedure. Droplet ejection is enabled by a piezostack driven piston squeezing the tube at a defined position. We achieve a reproducibility of the printed cell culture medium volumes better than 5% and survival rate of the cells of 97% directly after dispensing. In addition we demonstrated good culturability and cell differentiation in order to consider potential long term effects of the dispensing process that could harness the cells.

Revolutionizing Tissue Engineering: The Power of Bioprinting

Bioprinting signifies a significant leap forward from the traditional tissue engineering methods where cells were randomly distributed onto scaffolds. What sets bioprinting apart is its unparalleled precision; it allows cells to be meticulously placed with remarkable spatial accuracy within intricate three-dimensional tissue constructs.

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Scalable fabrication of renal spheroids and nephron-like tubules by bioprinting and controlled self-assembly of epithelial cells

Scalable fabrication concepts of 3D kidney tissue models are required to enable their application in pharmaceutical high-throughput screenings. Yet the reconstruction of complex tissue structures remains technologically challenging. We present a novel concept reducing the fabrication demands, by using controlled cellular self-assembly to achieve higher tissue complexities from significantly simplified construct designs.


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A drop-on-demand bioprinting approach to spatially arrange multiple cell types and monitor their cell-cell interactions towards vascularization based on endothelial cells and mesenchymal stem cells

Spheroids, organoids, or cell-laden droplets are often used as building blocks for bioprinting, but so far little is known about the spatio-temporal cellular interactions subsequent to printing. We used a drop-on-demand bioprinting approach to study the biological interactions of such building blocks in dimensions of micrometers. Highly-density droplets (approximately 700 cells in 10 nL) of multiple cell types were patterned in a 3D hydrogel matrix with a precision of up to 70 μm. The patterns were used to investigate interactions of endothelial cells (HUVECs) and adipose-derived mesenchymal stem cells (ASCs), which are related to vascularization.

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Bioprinting-based automated deposition of single cancer cell spheroids into oxygen sensor microelectrode wells

Three-dimensional (3D) cell agglomerates, such as microtissues, organoids, and spheroids, become increasingly relevant in biomedicine. They can provide in vitro models that recapitulate functions of the original tissue in the body and have applications in cancer research. For example, they are widely used in organ-on-chip systems. Microsensors can provide essential real-time information on cell metabolism as well as the reliability and quality of culture conditions.

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Cytocompatibility testing of hydrogels toward bioprinting of mesenchymal stem cells

Mesenchymal stem cells (MSCs) represent a very attractive cell source for tissue engineering applications aiming at the generation of artificial bone substitutes. The use of three-dimensional bioprinting technologies has the potential to improve the classical tissue engineering approach because bioprinting will allow the generation of hydrogel scaffolds with high spatial control of MSC allocation within the bioprinted construct.


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Large scale production and controlled deposition of single HUVEC spheroids for bioprinting applications

We present (1) a fast and automated method for large scale production of HUVEC spheroids based on the hanging drop method and (2) a novel method for well-controlled lateral deposition of single spheroids by drop-on-demand printing. Large scale spheroid production is achieved via printing 1536 droplets of HUVEC cell suspension having a volume of 1 μl each within 3 min at a pitch of 2.3 mm within an array of 48 × 32 droplets onto a flat substrate.


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