STMicroelectronics (NYSE), one of the world’s leading suppliers of microfluidic devices, has announced that it has designed a complete prototype device able to collect and manipulate specific biological molecules. Combined with ST’s proven laboratory-on-chip technology, ST’s research project is paving the way for the development of low-cost disposable chips that automate the quick preparation, analysis and evaluation of medical and forensic biological samples.
Current state-of-the-art biotechnological platforms such as ST’s In-Check(TM) “lab-on-chip” devices facilitate the diagnosis of specific diseases or the monitoring of food and water for bacterial contaminants by allowing the rapid detection of particular genetic material in liquid biological samples. However, the preparation of the samples is still a relatively time-consuming process performed with large samples in laboratories using techniques that require skilled technicians and are difficult and expensive to implement with smaller samples. The aim of the ST research program is to explore new methods to automate sample preparation, so that the biological molecules of interest could be rapidly extracted from “raw” specimens such as saliva, blood or biopsy tissues and used as the input to the lab-on-chip diagnostic stage.
“The market for diagnostic equipment is evolving towards fully automated, cost-effective devices usable directly at the point of need,” said Maria Teresa Gatti, Director of Research and Innovation, Advanced System Technology, STMicroelectronics.
“Sample preparation technology, integrated with ST’s In-Check lab-on-chip platform, will allow us to build low-cost, easy-to-use systems that will enable diagnostic analyses to be performed outside specialized laboratories, e.g. directly in hospitals or even in the doctor’s office,” noted Anton Hofmeister, Group VP and General Manager, Microfluidics Division, STMicroelectronics.
The technique used by the ST researchers is based on a method called dielectrophoresis, where an electric field is used to separate biological particles contained in a conductive solution. The careful setting of physical and electrical factors allows to precisely control the movement of target particles and the aim of the ST project was to demonstrate that this could be exploited for practical uses. Potential benefits include the ability to isolate cells that are present in low concentrations, to increase the concentration of cells in a solution and to extract DNA from the cell nucleus, as well as allowing sample preparation to be performed in the field by personnel with minimal training on the use of the devices. Importantly, the researchers also successfully showed that by precisely controlling the voltage applied to different electrodes, cells could be collected at one specific region and then moved to other regions in either direction. The ST research project builds on a prior joint research project between ST and Evotec Technologies GmbH.
Details of the research project were unveiled at the NANOMEC06 Symposium on Materials Science & Materials Mechanics at the Nanoscale, held at the Politecnico di Bari, Italy in a paper presented by Marco Bianchessi, Sarah Burgarella and Anna Zocco from ST’s Advanced Systems Technology (AST) organization.
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- Dielectrophoresis is a phenomenon in which a spatially non-uniform electric field exerts a net force on the field-induced dipole of an uncharged particle. Particles with higher polarizability than the suspending medium experience positive dielectrophoresis, and move towards regions of the highest field gradient. Particles less polarized than the surrounding medium experience negative dielectrophoresis, and move towards regions of low electric field concentration.
- The system was built using a technology compatible with the Micro-Electro-Mechanical System (MEMS) technology that ST uses for its In-Check(TM) lab-on-chip devices. The prototype silicon chip contains a tiny channel, measuring about 1mm in length, 0.1mm in width and 50µm in height (a human hair has a diameter of around 100µm) which is filled with a solution containing the molecules of interest. On the bottom of the channel, an array of tiny platinum electrodes (25µm wide, separated by 25µm) provides precise control over the pattern of the electric field in the channel and therefore the forces applied to the biological molecules.
- The operation of the prototype system was tested using a mixture of human white blood cells (B-lymphocytes) and microscopic polystyrene beads of similar size suspended in a Phosphate-Buffered Saline (PBS) solution. Without any applied voltage, the B-lymphocytes and polystyrene beads were randomly distributed in the channel. With an electric signal applied to the electrode array, white blood cells collected at the electrode edges, separating from the polystyrene beads suspended in the same PBS solution. The researchers observed particle motion using a standard direct microscope with a video camera mounted on it.
- The technology is covered by ST-Evotec patent applications 05108445.7 (Europe) and 11/531679 (USA).