Picoliter Droplets for Single-Particle and Single-Molecule Imaging
Generation of subnanoliter droplets [1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ] is a fundamental technique in modern analytical chemistry. The current methodology of generating droplets can be divided into three types based on
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23.1
Introduction
Generation of subnanoliter droplets [1-16] is a fundamental technique in modern analytical chemistry. The current methodology of generating droplets can be divided into three types based on the generation technique: vibrating orifice, extrusion, and electrospray, as depicted in Fig. 23.1. In the vibrating orifice type, the orifice of a capillary supplied with a liquid stream is vibrated to split the stream into droplets. The performance of this technique is represented by one-by-one generation of droplets smaller than 50pL, typically 1-20pL, at a fast operation rate (10-100 kHz). The smallest volume of the droplets generated is limited by the flow rate of the liquid and by the frequency of the vibrating orifice which determines the operation rate. The higher the frequency, the smaller the volume of droplets. This technique is widely used for preparing gas phase ions in atomic absorption spectroscopy [1], in atomic emission spectroscopy [2]' and in mass spectrometry [3-5]. Also, uniform liquid droplets are produced using this method in spectroscopic and optical research [6], and in single-molecule detection [7-10]. However, this technique is inconvenient for regularly spotting droplets on a surface because its operation rate is too fast and results in less regularly positioning droplets on the surface. In the extrusion type of droplet generation a liquid in a container is pushed or extruded through an orifice, thus generating droplets. The performance of this technique is represented by one-by-one and on-demand generation of droplets smaller than 1 f.lL, typically 30-500 pL, at a moderately fast operation rate (lower than 500Hz) [12-14]. The volume of the droplets generated is limited by the size of the orifice. This technique is widely known as the key technology of inkjet printing [17] and has recently been applied to combinatorial chemistry for drug screening [11], f.l-TAS (micro-total analysis system) [12], preparation of DNA chips [13], and sample preparation in MALDI-TOF (matrix-assisted laser desorption ionization-time-of-flight) mass spectrometry [14]. In the electrospray type of droplet generation, a d.c. voltage is applied to the tip of a capillary supplied with a liquid stream, thus making the stream split into droplets. Performance of this technique is represented by generation of a spray of fine (,,-,submicrometers in diameter) droplets. This technique is H. Masuhara et al. (eds.), Single Organic Nanoparticles © Springer-Verlag Berlin Heidelberg 2003
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M. Ishikawa
a
c
b
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=;··········1. Fig. 23.1. Three current technologies of generating droplets: (a) vibrating orifice, (b) extrusion, (c) electrospray, and (d) our technique. Although isolated droplets are illustrated in (d), the actual way of forming droplets is different from this illustration; see Fig. 23.5
widely used for preparing gas-phase ions in ionization mass spectrometry [15] and for laser-plasma X-ray generation [16]. In the extrusion type of droplet generation, a moderately fast opera
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