Benchtop and laboratory automation

Scientific Instrumentation Projects

Automated, customizable cell processing

Myocite Cell Isolation System
© Photo Fraunhofer CMI

Myocite Cell Isolation System.

Objective

Obtaining viable myocyte cells is a critical step in performing in vitro cardiac cell assays. Testing new drug candidates in this model heart system requires large numbers of myocytes to be produced quickly for screening. The isolation and production of myocyte cells for this purpose is highly labor intensive and low yielding. Thus, this project sought to automate the manual process and increase throughput.

Methodology

We developed a system that utilizes pressure-based liquid infusion with volumetric feedback control. The pressure-based manifold results in a more affordable, more reliable, and easier-to-use system. The four reaction chamgers feature oscillating mechanical agitators and allow up to four simultaneous cultures to be processed. The housing provides protection from external environmental factors. Customized software permits user-supplied inputs for fluid extraction / replenishment quantities and processing times.

Results

Unique mixing chamber design improves cell survival rate

Setup time less than 20 minutes

Easily customizable protocols

Compact design fits in standard bio-safety cabinet

Each reaction chamber produces 3,000,000 functional cells

Versatile, scalable, and efficient processing of tissue samples

Fraunhofer CMI (USA) and their partners from Fraunhofer IPT (Germany), as part of the ML2 consortium, aim to create portable, low-cost pathogen diagnostics by combining microfluidic and electronic layers into a single device.

Automated Tissue Homogenization
© Photo Fraunhofer CMI

Before and after automated tissue homogenization of a hot dog test sample.

Automated Tissue Homogenization
© Photo Fraunhofer CMI

Human umbilical cord is rapidly homogenized into a single cell suspension in preparation for isolation of mesenchymal stem cells—a critical resource in autologous tissue engineering applications.

Tissue Homogenization System
© Photo Fraunhofer CMI

Tissue Homogenization System

Objective

Tissue homogenization is a critical step for many research and industrial processes.  From grinding down food products to search for microbial contamination or by generating single cell suspensions for downstream immunological assays or ethically sourced mesenchymal stem cells, this labor intensive task slows researchers down.  Although techniques exist for such tissue homogenization, few options are available for processing large sample arrays in parallel.  Standard techniques require skilled users, are often unsuitable for solid tissue samples, or prove too costly and time-intensive.

To address these issues, Fraunhofer CMI developed a prototype instrument capable of quickly homogenizing an array of unique tissue samples directly in a microtiter plate.  No special training was necessary to achieve uniform, repeatable results—the process accommodated semi- or full automation.  The system was easy to clean and sterilize, had configurable speed and force to control shear and to minimize heating, and was useful for a wide range of sample sizes.

The design utilized a novel linkage mechanism that both transmitted torque from the rotary motor to the pestle plate and varied the orbital radius of the pestles.  The multi-function linkage prevented sample smearing against the microtiter plate walls and reduced the risk of dripping and cross-contamination.  By eliminating the need for an independent actuator to control the orbit radius, the machine’s complexity and cost were decreased.

This tissue homogenizer can be flexibly incorporated into existing workflows such as the large automated stem cell factory located at Fraunhofer IPT.  Due to its compact engineering, it can also efficiently function as a stand-alone instrument for on-demand tissue processing.

Results

Designed technique to rapidly homogenize samples in a microtiter plate

Required no special training to achieve uniform, repeatable results

Controlled shear and heating by adjusting motor speed and force

Created multi-function linkage to transmit torque from rotary motor to pestle plate and to vary pestle orbital radius

Achieved low-cost scalability and compatibility with downstream biological analysis

Accommodated wide range of sample sizes and consistencies

Produced more viable cells than manual methods in a fraction of the time (1 min v. 30 min)

Collaborators

Fraunhofer IPT, Aachen, Germany

Funding

Built for two separate biotechnology firms in the U.S.

 

 

 

Development of a microfluidic chip and automated platform

In this prototyping project, Fraunhofer CMI was contracted to design and manufacture microfluidic chips and an associated instrument to automate the gel-based detection of microRNA on-chip.

Objective

MicroRNAs (miRNAs) are small non-coding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression. With greater stability and predictive value than mRNA, this relatively small class of biomolecules has become increasingly important in diagnosing disease. Despite their great promise, clinicians still lack the proper tools to routinely profile miRNA. Together with their collaborators, Fraunhofer CMI sought to develop a point-of-care fluidic chip capable of detecting multiple miRNA biomarkers. Assay validation then warranted the development of a beta prototype.

Deliverables

Plastic microfluidic chips with optimized flow rates and geometries were produced. The microfluidic chips were designed with two identical inlet/outlet ports connected by a single channel. The channel contains evenly spaced cylindrical posts intended to function as anchoring foci for hydrogel material. All chip features were engraved in cyclo olefin polymer (COP) using a computer numerical control (CNC) milling machine, after which the channel was enclosed by bonding a COP coverslip across the engraved surface of the chip.

A prototype instrument was designed and built that automates the assay by controlling fluid flow, temperature, and optics. The instrument consists of LED- and photodiode-based optics, a microfluidic chip interface, and disposable fluid inputs for reagents. The instrument controls are enclosed in housing, and assay conditions are controlled by the researcher using custom-built software.

Academic Collaborators

Patrick Doyle, Department of Chemical Engineering, MIT, Cambridge, MA, USA

Avrum Spira, Boston University School of Medicine, Boston, MA, USA

Catherine Klapperich, Department of Biomedical Engineering, Boston University, Boston, MA, USA

Acknowledgement

This project was funded by the NIBIB Center for Future Technologies in Cancer Care (CFTCC) at Boston University

Fraunhofer CMI designed and built a beta prototype for automated microRNA detection, which includes fluid and temperature control, automated optics, and a microfluidic chip interface.
© Photo Fraunhofer CMI

Fraunhofer CMI designed and built a beta prototype for automated microRNA detection, which includes fluid and temperature control, automated optics, and a microfluidic chip interface.

LED- and photodiode-based optics are incorporated into the prototype for automated microRNA detection.
© Photo Fraunhofer CMI

LED- and photodiode-based optics are incorporated into the prototype for automated microRNA detection.

Photograph showing the microfluidic chip, optics, and interface on the beta prototype designed and built by Fraunhofer CMI. Plastic chips were designed and produced in-house.
© Photo Fraunhofer CMI

Photograph showing the microfluidic chip, optics, and interface on the beta prototype designed and built by Fraunhofer CMI. Plastic chips were designed and produced in-house.