Microarray chips enhance clinical diagnostics
AACHEN, Germany — A laser-based benchtop system fabricates protein microarray chips for use in clinical diagnostics, enabling doctors to identify tumor markers in blood samples and to detect pathogens responsible for infectious diseases.
Microarray chips for diagnostic use are produced by depositing small samples of material, biopsied, for example, from a patient's tumor cell, onto a substrate. A small amount of the relevant cell material can be gathered, but this limits the testing that can be carried out, and comprehensive testing is needed if the patient is to receive targeted treatment. For testing to take place, it is crucial to have as many microarray chips as possible to optimize the preparation of the biopsy specimens.
A laser-based benchtop system — called a 'protoprinter' — creates microarray chips preloaded with various proteins for clinical diagnoses. Images courtesy of Fraunhofer Institute for Laser Technology ILT.
Microarrays usually are produced using micro-dispensing systems that work like an ink-jet printer. The major drawback is that the printer head quickly becomes obstructed by many proteins, such as antibodies, that are crucial to the analysis. The process has to be halted and the printer head either cleaned or replaced — making the process costly and time-consuming.
A new 'protoprinter' delivers microscopic amounts of various proteins directly onto substrate materials, producing a functioning test system for cell analysis. The system, developed by a team led by Dominik Riester at Fraunhofer Institute for Laser Technology ILT, is part of the ProtoPrint INNONET project, which is sponsored by the German Federal Ministry of Economics and Technology, in collaboration with GeSiM (Gesellschaft für Silizium-Mikrosysteme mbH).
In the protoprinter process, the microarray is situated beneath a glass slide bearing the biopsy material on its underside, and an intermediate titanium absorber layer is placed between them. A pulsed laser beam focuses on the absorber layer, evaporating the titanium, and the resulting forward impulse transfers the biopsy material onto the microarray. The laser-based process has no need for a printer head, so it can transfer all the relevant proteins with no associated sample or time wastage. Because of this, the amount of biopsy material required to carry out the analysis is significantly smaller.
PDMS — Transfer with the protoprinter.
The protoprinter can produce spot sizes of 10 to 300 µm, which means that up to 500,000 protein spots can fit onto a surface the size of a thumbnail, allowing diagnosis to be performed with a minimal amount of material. Until now, it had not been possible to deposit sample material onto a substrate with the precision and efficiency the technology offers — and in such small amounts.
The protoprinter design is being refined to make it able to produce artificial hematopoietic stem cell niches. The researchers are focusing on integrating an automated camera-assisted recognition process to enable targeted transfer of cells and other biomaterials, providing optimal control of the printing process.
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