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Drop-on-Demand

Printing of Protein Biochip Arrays

Frank G. Zaugg and Peter Wagner Abstract Protein biochips have recently gained a lot of attention as bioanalytical tools in the life sciences. The creation of such biochips has been made possible by the integration of scientific approaches and methodologies in microfabrication, organic interface chemistry, protein engineering, detection physics, and—last but not least—advances in microarrays and microfluidic dispensing technologies. This article reviews some of the current drop-on-demand technologies developed for printing biomolecular arrays, with an emphasis on proteins and the technical challenges associated with them. Keywords: biochips, biocompatibility, biomaterials, biomedical materials, coatings, inkjet printing.

Introduction Biochips, BioMEMS (bio-related microelectromechanical systems), and
TAS (micro total analysis systems) are terms that are now finding a regular place in the scientific literature. These terms all refer to a family of technologies that is bringing biology and chemistry into the realms of the micron world. The miniaturization of bioanalytical processes has become an enabling element in developing tools applied to drug development and clinical diagnosis. For example, the ability to identify hundreds or even thousands of analytes in only a few microliters of a biological sample will aid in determining markers for early disease detection and even understanding the molecular mechanism of biological processes and diseases.1,2 Unlike electronic circuits or chips made of semiconducting layers and other inorganic materials, the active element of a biochip is organic or biological matter. Therefore, the successful fabrication of biochips relies on the development of novel technologies that allow precise and controlled deposition of sensitive reagents on or into the microstructure of the chip. To date, the most common method of generating such devices is based on automated systems that deposit tiny amounts of liquid by contacting a small, solution-wetted metal pin to the substrate (pin printing), MRS BULLETIN/NOVEMBER 2003

thereby forming arrays of microdroplets in two-dimensional patterns. Alternatively, drop-on-demand (DOD) and other microfabricated dispensing systems are becoming important tools in biochip manufacturing. This article emphasizes the more recent development approaches in this area.

Design and Development of Biomolecular Arrays In their simplest form, biological microarrays consist of a number of different biomolecular species (e.g., oligonucleotides, proteins, peptides) used to detect or capture specific analytes from complex mixtures of biological samples such as blood, urine, and cell extracts.3 Monitoring or measuring the interaction of the surface-bound probes with the molecules in the sample provides important information regarding the presence of a specific substance and its concentration. On a given biochip, thousands of such probes can be arranged in a twodimensional array, enabling massively parallel analyses of com