The MBA™ Microbubble Array is a platform featuring spherical compartments with micron-diameter openings molded into a biocompatible polymer. Each array contains hundreds to thousands of individual microbubbles (MBs) per square centimeter. This platform supports static culture and microfluidic flow conditions, serving as a tool for disease modeling, drug discovery, and immunotherapy workflows.
MBA™ Microbubble Array Technical Principles
MBA™ Microbubble Array Structure
MBs are spherical compartments with micron-level openings, arranged in a MBA™ array format. MBA™ arrays are formed using high-precision semiconductor chip fabrication technology combined with the patented gas expansion molding (GEM™) process. The GEM™ process enables precise control to mass-produce arrays with different specifications. Adjustable parameters include opening size and shape (cavity volumes ranging from pico to nanoliter volumes), array density (MBs/cm²), and MB spacing.
Core Advantages
- Scale and Consistency: The patented GEM™ process enables the reliable mass production of consistently dimensioned MBs, making the platform ideal for high-throughput screening (HTS) applications.
- Spherical Geometry and High Aspect Ratio (AR>2): The aspect ratio is defined as the MB maximum diameter divided by its opening diameter. In static cell culture, this structure concentrates cell-secreted factors within the cavity. This creates a niche for cells to rapidly condition the media and serves as a foundation for assay development.
- Stable Cell Retention: The spherical shape hinders the dislodgment of cells within the cavity when fluid flow occurs outside the array. This stable retention is maintained during media changes in static culture or when coupling the array to a microfluidic flow channel.
- Dual Operational Modes: Assays developed using this technology can be performed under both static culture and microfluidic flow conditions.
- Compatible Image Analysis Software: The IMage data Acquisition and Analysis software Tools (IMAAT™) are developed specifically for MBA™ technology and are a key component for HTS applications. Coded in Python, IMAAT™ utilizes convolutional network architectures for the fast and precise segmentation of images to enumerate and report out data from each individual MB in the array.
MBA™ Microbubble Array Plates
MBA™ Microbubble Array 96-Well Plate is a high-throughput spheroid/organoid culture platform in a 96-well format. Each well contains multiple microbubble cavities (microwells) with confined curvature architecture that enable controlled cell compaction into uniform three-dimensional (3D) tissues.
| Product Name | MB Cavity Opening (µm) | MB Cavities/cm² |
|---|---|---|
| MBA™ Microbubble Array 96-Well Plate for 3D Biology | 200 | 156 |
Other opening sizes and array densities are available upon request.
Product Features
By optimizing both biological viability and experimental workflow, the MBA™ Microbubble Array 96-Well Plates provide:
- Rapid 3D Spheroid Formation: Promotes quick and uniform cellular aggregation.
- Enhanced Cell Health: Facilitates enhanced cellular signaling while preventing the formation of a necrotic core.
- Long-Term Stability: Maintains high tissue viability (>90%) for 14+ days.
- Versatile Modeling: Scaffold ECM-ready to support complex tissue microenvironments.
- High-Density Culturing: Supports up to 4,800 microtissues per 96-well plate, enabling high-throughput scalability with strong statistical rigor.
- Spheroid Retention: Cells remain stably confined within the MBs, enabling user-friendly and non-disruptive media exchange.
- Seamless Integration: Fully compatible with laboratory automation and in-situ imaging systems.
MBA™ Microbubble Array Platform Application Cases
Case Study 1: Cancer Cell Screening
The MBA™ Microbubble Array was used to sort tumor-initiating cells (TIC, or cancer stem cells) to study their fate and drug resistance. The array is molded in polydimethylsiloxane (PDMS), which is optically clear for imaging. Its elastic modulus (2 MPa) is more similar to soft tissues (e.g., skin at 0.85 MPa) than hard tissue culture polystyrene (2500 MPa). Additionally, its hydrophobic nature favors anchorage-independent cell growth (anoikis resistance), a characteristic phenotype of TICs.
- Structural Advantages: The unique spherical architecture and nanoliter volumes concentrate cell-secreted factors, allowing for rapid conditioning of the microenvironment and promoting single-cell clonal proliferation.
- Biological Significance: The clonal proliferation of nonadherent aggregates (tumor spheroids) increases the expression of stem cell markers, migratory and invasive characteristics, and resistance to chemotherapeutics.
Figure A demonstrates the clonal expansion of single SCC cells cultured in MB arrays, exhibiting morphologic heterogeneity. Figure B showes cancer cells cultured in the MB array treated with a chemotherapy agent to discover drug-resistant cells.
Figure A. Single SCC cells cultured in MBA™ Microbubble Array (Biomed Microdevices . 2017 Sep;19(3):17)
Figure B. Cancer cells cultured in MBA™ Microbubble Array (Green: live cells; Red: dead cells) (Biomicrofluidics. 2011 Jun;5(2):24110)
Case Study 2: Tissue Chips and Microphysiological Systems (MPS)
The unique spherical architecture of the MBs enables the culture of complex heterogeneous tissues and organoids. Functional salivary gland tissues, lung organoids, and retina organoids have been successfully cultured in the MBA™ Microbubble Array platform for disease modeling, biomarker quantification, and drug discovery.
In a representative study focused on developing salivary gland mimetics (SGm), the platform demonstrated its capability to support hydrogel-based 3D cultures. The study utilized MBs with 200 µm spherical openings, a maximum diameter of ~320 µm, and an array density of 278 MBs/cm². The chips were affixed to the bottom of standard 48-well plates (1 chip/well), yielding ~107 MBs per well.
- Culture Workflow: Acinar cell clusters and intercalated ducts (AIDUCs) isolated from mouse submandibular glands (SMG) were mixed with an MMP-degradable PEG hydrogel precursor solution. The mixture was pipetted onto the MB arrays and incubated for 15 minutes, allowing the AIDUCs and gel precursor to settle into the cavities.
- Microenvironment Formation: Following incubation, the gels were polymerized to create hydrogel-entrapped AIDUCs within the MBs (MB-hydrogels). This specific MB-hydrogel milieu promotes cell aggregation and maintains cell viability. Approximately 20 MB chips were prepared from a single SMG AIDUCs preparation.
By day 7, brightfield imaging demonstrated that the AIDUCs within the MB-hydrogels had successfully reorganized to form SGm.
Figure C. MB-chip (scale bar = 3 mm) and a cross-sectional view of a single MB (a and b). Schematic representation of hydrogel encapsulation of AIDUCs within MB-chips (c). (COMMUNICATIONS BIOLOGY | (2021)4:361)
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