Chemistry: molecular biology and microbiology – Apparatus – Including measuring or testing
Reexamination Certificate
2000-06-27
2002-05-21
Siew, Jeffrey (Department: 1656)
Chemistry: molecular biology and microbiology
Apparatus
Including measuring or testing
C435S006120, C435S007200, C435S091100, C435S091200, C536S063000, C536S023100, C536S024300, C536S024310, C536S024320, C536S024330, C369S275100, C369S275300, C369S275400
Reexamination Certificate
active
06391625
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a biochip, and more particularly, to a biochip including a DNA chip and a protein chip and a method for patterning and measuring biomaterial of the same.
2. Discussion of the Related Art
Generally, a biochip is a hybrid device made of an existing semiconductor chip type by combining bio-organic matters isolated from creatures, such as enzymes, proteins, antibodies, DNA, microbes, animal and plant cells, animal and plant organs and neurons, with inorganic matters such as semiconductors.
The biochip acts to diagnose infectious diseases or analyze genes by using inherent functions of biomolecules and mimicking functions of organisms. The biochip acts as a new function device for processing new information.
It is expected that the biochip will be a core device of a biocomputer which thinks like an organism and responds to external action, because the biochip has characteristics such as high packing density, realization of functions at molecular level, and parallel processing function together with potentials which surpass functions of the existing semiconductor.
According to used biomaterials and systemization, the biochip can be classified into a DNA chip integrated with DNA probes, a protein chip with proteins such as enzymes, antibodies/antigens, and bacteriorhodopsins, and a neuron chip with neurons. Also, in a broad definition, the biochip includes a lab chip having automatic analysis functions including pretreatment of samples, biochemical reaction, detection, and data analysis, and a biosensor having detection and analysis functions of various biochemical materials.
To develop such a biochip, it is necessary to efficiently realize molecular interface between biomaterial and semiconductor such as silicon, thereby optimizing inherent functions of the biomaterials.
Particularly, to produce a biochip such as a DNA chip and a protein chip, it is important that biomaterials are high integrated in a limited area of micrometer scale. The reason why is that highly integrated DNA chip has an improved decoding ability of gene information.
Presently, a DNA chip having 400,000 probes therein can be fabricated.
Although conventional methods for fabricating a DNA chip are different from each other, there are similarities in that DNA samples are hybridized with DNA probes on a surface such as silicon or glass substrate and then hybridization results are compared with known DNA base sequences. The hybridization means that a single-stranded DNA molecule called a probe (base sequence which can hybridize specifically with complementary base sequence) is fixed on a solid, so as to form a double-stranded DNA together with a gene site having complementary base sequences on a target solution.
Accordingly, the conventional methods are similar in that fixed DNA, target DNA or double-stranded DNA is labeled to obtain desired information.
The DNA chip has several advantages. First, it is not necessary to perform complicate steps such as gel electrophoresis and filter hybridization. Second, since a probe having a short length of about 15~30 bases is used, a result of hybridization can be confirmed within relatively short time. Third, if a DNA chip having all possible base sequences is fabricated, hybridization patterns are simply compared to confirm the presence of hereditary disease.
However, several problems still remain in the current DNA chip technology in the following aspects. That is, a DNA array of high density should be fabricated at low cost, hybridization reaction should be optimized, and detection method and pattern comparison method should be improved.
The DNA chip can be fabricated by two methods. That is, the DNA chip can be fabricated in such a manner that synthesized oligonucleotides or peptide nucleic acid (PNA) is laid on a chip. Alternatively, the DNA chip can be fabricated in such a manner that a probe is formed by directly synthesizing oligonucleotides on a chip. These two methods have been utilized most actively in the United States of America, and many results and actual fabrication technologies are being commercially used.
Of the fabrication technologies, there is a method that polypeptides are synthesized in situ on a silicon substrate using photolithography method mainly used in the semiconductor process (U.S. Pat. No. 5,143,854).
However, the fabrication of a DNA chip requires decades of masks which have their own pattern. That is to say, in case where an oligonucleotide probe having a length of 25 bases, four masks are required to form one base layer and total 100 masks are required. Since the fabrication process requires about 100 cycles, complicate process steps and expensive cost are caused in case of mass production of a DNA chip. Furthermore, washing and mask aligning processes are required in each process, and expensive equipment is required.
In other words, since the costs of DNA chip design and oligonucleotide synthesis are expensive, a small quantity of production with various kinds is impossible due to problems related to the required time and costs from order to production.
Besides the above method, there is another method for forming oligonucleotide on a surface of a chip by electrically discharging any one of four bases using piezoelectric printing method of ink jet printer (U.S. Pat. No. 5,474,796).
However, although oligonucleotide of 40~50 bases can be formed, integration is limited by aligning process and pattern size of about 100 &mgr;m. Also, spread occurs when injecting samples and operating a spraying device.
Furthermore, there are a micropipetting method and a spotting method of cDNA (TIBTECH 16; 301~306, 1998).
These methods have problems that a DNA chip cannot be fabricated at high density and mass production is limited. Thus, these methods are applicable to fabrication of a DNA chip for study.
Meanwhile, the DNA chip and the DNA microarray have different fabrication methods but are similar in that different oligonucleotides are aligned on a square spot having a certain size in a check pattern.
Accordingly, to measure a fluorescent material used to confirm hybridization reaction, expensive image scanner is required (U.S. Pat. No. 5,091,652).
In other words, this method has problems that a system having a bidirectional linear translator is required to detect samples, software for processing image data of large capacity is required, and image scan time is long.
The related art biochip has the following disadvantages.
First, when a biochip is fabricated, the process steps are complicate, and a number of masks and expensive equipment are required, thereby preventing mass production.
Second, since the process has limitation in minimizing the size of a pattern material, the biochip of high density cannot be fabricated.
Third, to measure a pattern material of the biochip, expensive equipments and relatively long time are required.
SUMMARY OF THE INVENTION
Accordingly, the present invention is directed to a biochip and a method for patterning and measuring biomaterial of the same, that substantially obviate one or more of the problems due to limitations and disadvantages of the related art.
An object of the present invention is to provide a biochip having reliability and high packing density at low cost and a method for patterning and measuring biomaterial of the same.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the scheme particularly pointed out in the written description and claims hereof as well as the appended drawings.
To achieve these and other advantages and in accordance with the purpose of the present invention, as embodied and broadly described, a biochip according to the present invention includes a substrate, a reflecting layer formed on an entire surface of the substrate, an active layer formed on the reflecting layer
Kim Tae Han
Park Je Kyun
LG Electronics Inc.
Morgan & Lewis & Bockius, LLP
Siew Jeffrey
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