Electrospraying for mass fabrication of chips and libraries

Details Electrospraying for mass fabrication of chips and libraries Electrospraying for mass fabrication of chips and libraries

2000-05-08

2002-02-26

Zitomer, Stephanie W. (Department: 1655)

Chemistry: molecular biology and microbiology

Apparatus

C435S287200, C435S006120, C422S050000, C422S068100, C205S158000, C427S002130

Reexamination Certificate

active

06350609

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the deposition of samples of substances, including biological molecules, such as proteins and DNA, into a specified shape or pattern over a substrate surface and to rapid drying and microconcentration of small amounts of substances from their solutions.
2. Description of the Background Art
The method of electrospray is the electrostatic atomization of a liquid or a solution to obtain charged microdroplets, charged clusters and ions. The solution or liquid of the substance to be deposited is placed into a capillary (or array of capillaries), and the application of high voltage results in instability of the liquid or solution, which is then dispersed into small charged droplets 0.3-20 microns in diameter, and typically about 0.5-2 microns in diameter. Electrostatic repulsion rapidly moves these charged microdroplets from the capillary tip, and in their travel toward a substrate surface, the microdroplets evaporate if solvent vapor pressure is low enough, and the size of the droplets reach a Raleigh limit of electrostatic stability. Afterwards, the microdroplets undergo a series of decays, reducing their size to about 10-20 nm and increasing the electrostatic field to a level where evaporation of ionized solvated molecules becomes possible. On further travel through a dry gas, solvent is lost from these solvated ionized molecules. Where evaporation proceeds rapidly, all of the solute content of the microdroplets can be concentrated into small nanoclusters (FIG.
1
).
Electrospray of solutions in solvents with low vapor pressure, such as water, electrospray in atmosphere containing large amount of solvent vapor or where the electrospray source is at a short distance from the substrate surface for deposition, can allow microdroplets to reach the substrate without complete decay and evaporation of all the solvent. This regime is referred to as wet electrospray. The deposition of charged molecules or clusters occurs in a dry electrospray regime where volatile solvents is used and the conditions of low partial vapor pressure of the solvent in gas or a longer distance between the electrospray source and the substrate surface is used.
Accordingly, this electrospray phenomena permits the deposition of substances in the form of charged microdroplets, solvated or dry ionized molecules, or nanoclusters. Nanoclusters or fibers can be produced by electrospray from linear polymers. The form of deposit can be regulated by changing the travel path of the charged species and their speed, by control of vapor pressure in the atmosphere, and by the proper choice of solvent and solution concentration.
One of the earliest applications of electrospraying was in the production of thin sources for radioactivity measurements. In this application, a collimator for providing electrostatic focusing was introduced (Robinson, 1965; van der Eijk et al., 1973). Bruninx et al. (1961) further disclosed a plexiglass disc with a center hole through which the electrospray passes before it reaches the substrate or collector. To obtain thin radioactive sources with a well-defined area, van der Eijk et al. (1973) disclosed that masks can be used, and further disclosed that masks made of Teflon, as first reported by Blumberg et al. (1962), can give rise to the production of thin radioactive sources with diameters appreciably lower than the diameter of the hole in the mask.
Other applications of electrospraying, such as paint spraying, pesticide spraying, and use as a source of ions for mass spectrometry of biological molecules, are reviewed in Michelson (1990). Thus, the electrospraying of biological molecules was developed for use with mass spectrometry to characterize the molecular weight, structural features and non-covalent interactions of biological molecules. The finding that the structural integrity of protein ions was maintained and that non-covalent interactions were preserved was of primary significance for other electrospray applications of biomolecules. For instance, the electrospray mass spectrometry studies stimulated the use of electrosprayed deposits of DNA and protein molecules for imaging by scanning tunneling microscopy (Thundat et al., 1992; Morozov et al., 1993). Whereas Thundat et al. (1992) electrosprayed a solution of DNA molecules directly onto a gold substrate, Morozov et al. (1993) interposed a protective sheet, containing an ion canal, between the electrospray source and the substrate on which protein ions were deposited. Besides the destruction of both protein ions and the impact surface is well documented after collisions of accelerated protein ions with mica and graphite (Reimann et al., 1994; Sullivan et al., 1996).
Methods for patterning proteins and other biological molecules have been developed by adopting either conventional technologies, such as computer controlled robotics pipetting of microdroplets (Shalon et al., 1996), screen printing (Hart et al., 1994) and ink-jet deposition (Newman et al., 1992), or conventional electronic circuit manufacturing technologies, such as those using photo resists and lift-off techniques (Nakamoto et al., 1988). Methods of electrodeposition of protein from solutions onto prefabricated microelectrode arrays in biosensor technologies have also been developed (Strike et al., 1994; Johnson et al., 1994), but the application of electrodeposition is limited mostly to proteins and requires complex procedures of substrate preparation and microelectrode addressing. Furthermore, protein deposition from solution onto microelectrodes may damage protein molecules at the solution-metal interface due to direct oxidation and/or extreme local pH accompanying electrochemical reaction(s) at the electrode. These electrodeposition methods have only a few parameters for controlling the structure and density of a deposited film, and the electrodeposition from solution does not allow for modification of the electrode surface with water soluble polymer in such a way as to readily permit detachment of the sample from the substrate after cross-linking.
Shadow masking technique has been described recently as a method to pattern silicon surface with electrospray produced polypeptide fibers to increase surface adhesiveness to cells (Buchko et al., 1996). However, the conditions of electrospray, namely, use of formic acid as a solvent, are not compatible with preservation of tertiary structure and functional activity of a majority of biological macromolecules. Besides the use of shadow maskings, on the other hand, results in the loss of a large amount of electrosprayed material onto the mask itself. No reliable data were available concerning the retention of functional properties of electrodeposited protein and DNA molecules.
For the deposition of DNA molecules, Cheng et al. (1996) revealed numerous altered DNA molecules in electrophoretic analysis of plasmid DNA electrodeposited on a dry stainless steel electrode. No such alterations were found in experiments where DNA was electrodeposited into a buffer droplet.
Robinson (1966) discloses two copper annular discs around the electrospray tip, designated as a guard ring and a collimator.
Bertolini et al (1965) disclose a hole having an interior surface shaped as a truncated, inverted cone.
Bruninx, et al (1961; see pp. 132-133) disclose a hole in a plexiglass disc laid over a substrate of -aluminum foil so that the substrate is “covered” by the disc. The substrate rotates and the single hole is centered on the axis of rotation.
This arrangement is said to ensure uniform distribution of spray over the uncovered area. From this, two things can be inferred: first, that the spray pattern from the electrospray tip is irregular, because the substrate must be rotated to ensure even distribution; and second, that the plexiglass disc of Bruninx et al acts in the manner of a spray-paint template, merely blocking covered areas of the substrate rather than influencing the paths of the charged particles by electrostatic fields. Bruninx refers to a “well-defin

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