Allow to analyze a huge number of genetic features in a single sample of the source material. In this case, it is desirable that DNA chips have two properties that, in a sense, contradict each other. On the one hand, it is interesting to have as many cells as possible in one DNA chip in order to obtain more information about the sample under study. At the same time, researchers are often forced to work with very small volumes of biological material, so the smaller the size of the DNA chip, the better.

Modern methods(for example, atomic force microscopy, AFM) make it possible to detect a signal in the cells of a DNA chip when their dimensions are several tens of nanometers. Methods for the production of such DNA chips are based on lithography (the most attractive method is dip-pen nanolithography, DPN). Building chips with such small cells is usually quite expensive and time consuming.

A group of scientists from the United States and Korea proposed a method for cheaper, faster and mass production DNA micro- and nanochips. The researchers showed that by taking one DNA chip as a sample, it is possible to print a chip that is complementary to the original one in one step. This method of obtaining DNA chips is called the method of supramolecular nanoprinting (supramolecular nanostamping, SuNS) and is schematically shown in Figure 1.

As a sample, the scientists took an array of single-stranded DNA sutured to gold nanoparticles, in which the cell size was 9 ± 2 nm, and the distance between cells was 77 ± 9 nm. Complementary DNA modified with hexylthiol at the 5' end was added to this DNA chip. After hybridization (i.e., binding of complementary DNA strands), a gold-coated glass substrate was placed on the sample chip. Complementary strands of DNA are attached to this new substrate. Then, at 90 °C, dehybridization was carried out, and as a result, an imprint was obtained that was complementary to the original sample.

After examining the resulting copy, the scientists concluded that the imprint was made successfully: the new DNA chip had cells 14±2 nm in size, separated by 77±10 nm gaps (Figure 2). To show that the arrangement of cells in the array is the same for the sample and print, the radial distribution function was calculated for both cases (Figure 3). It can be seen that the functions turned out to be quite similar.

In the future, it is necessary to show that SuNS is suitable for printing multicomponent chips and for producing many copies from a single sample without loss of accuracy. The researchers believe they will be able to demonstrate this in the near future.

The work "Application of supramolecular nanostamping to the replication of DNA nanoarrays" was published in the journal Nano Letters.

Recently, DNA technologies have been actively developed, which allow not only to determine the trait, but also to simultaneously conduct differential sequencing, i.e. determination of point mutations or polymorphisms in known regions of the genome. These technologies have significant advantages over traditional molecular biological methods, since they make it possible to miniaturize the test sample and the analyzer, which significantly reduces the cost of analysis and the time of its implementation, as well as to simultaneously determine various parameters of the test sample, without losing the sensitivity of amplification methods. The main advantage of methods based on the use of chips with oligonucleotides of all possible nucleotide sequences given length, is their versatility. The presence on the chip of an oligonucleotide of any sequence makes it possible to analyze any sequence under study. The use of microchips is based on the principle of rapid determination of the interactions of certain ligands with many different probes simultaneously. Actually, biological microchips are one or another solid substrate on which certain fragments of nucleic acids, or proteins, or carbohydrates, or any other probe molecules that can be recognized or exhibit biological activity are deposited. The number of different probes on the substrate can reach hundreds of thousands, and the chips of each type are strictly identical and, with existing technologies, can be replicated in hundreds of thousands and millions of copies deposited on the substrate.

DNA microarrays

There are protein, DNA, carbohydrate, tissue chips. special attention deserve DNA chips. They are a unique analytical tool that allows you to determine the presence in the analyzed sample (usually of biological origin) of given DNA sequences (the so-called hybridization analysis). Analysis using DNA chips is several times cheaper than using alternative technologies (electrophoresis, real-time PCR) and allows, in the presence of a detector of simple design, work outside the laboratory.

For the first time DNA chips were used in research in the late 80s of the last century. This now widely used method, which makes it possible to simultaneously analyze the expression of multiple genes, is based on the principle of recognition of mRNA or cDNA targets through their hybridization with single-stranded DNA fragments immobilized on a microarray.

A DNA chip is a solid substrate on which single-stranded DNA fragments of different lengths are immobilized (as a rule, covalently): short - 15-25 nucleotides, long - 25-60 nucleotides, and cDNA fragments - from 100 to 3000 nucleotides. The substrate material used is glass, silicon, various polymers, hydrogels (for example, based on polyacrylamide) and even gold.

Hybridization is the basis of technology

The basis of all modern DNA technologies is hybridization. As a result of hybridization, nucleic acid molecules are able to form stable double-stranded structures due to the bonds between the elements of molecules - nucleotides. Nucleotide adenine (A) is complementary to thymine (T), guanine (G) is complementary to cytosine (C). As a result, a single-stranded ATHC nucleotide sequence will form a stable association, a double-stranded structure, with a single-stranded DNA molecule of the TACG composition.

….. ATHC….

| | | |

….. TACG….

Such complementarity leads to the "sticking" of two DNA molecules, one of which can be immovably fixed on the substrate and be an element of the DNA chip. The more molecules that are complementary to the elements of the chip are contained in the sample, the more of them will bind to the chip, and the higher will be the intensity of the signal perceived from this element. On fig. 1 shows the principle of operation of a DNA cell or an oligonucleotide biochip based on complementary interactions of an adenine base ( A) with thymine ( T) and guanine ( G) with cytosine ( WITH) in two strands of DNA. If the base sequence in one strand of DNA (or oligonucleotide) is completely complementary to the sequence of the other strand, then a stable perfect double-stranded helix is ​​formed - a duplex. However, the presence in the duplex of even one wrong pair, for example G-G, prevents duplex formation. If a specific single-stranded DNA or, say, a 20-mer oligonucleotide (probe) is immobilized in one of the elements of the microchip, then when DNA fragments labeled with fluorescent dyes, for example, the human genome, are added to the microchip, their highly specific interaction will occur. A given oligonucleotide element of the biochip will specifically bind only one complementary sequence out of 4 20 =1.09x10 12 of all possible sequences of this length in DNA. As a result, the fluorescent glow is observed only on this complementary element of the biochip. Thus, one element of the biochip produces one sample from about a trillion possible options, in contrast to the element of an electronic chip, where a binary sample occurs: YES or NO.

Rice. 1. Scheme of the formation of a DNA double helix on a biochip. The oligonucleotide is fixed on one of the elements of the biochip and selectively binds only the complementary one from many fluorescently labeled DNA fragments. As a result, only this element starts to glow. This is due to highly specific interactions of complementary base pairs. A With T And G With WITH. The presence of a non-complementary pair, for example G-G, prevents interaction and leaves the microchip element dark.

The devices used to determine the hybridization parameters make it possible to record not only the final result, but also the kinetics of association and dissociation of complementary chains. These technologies, while enabling multi-parameter analysis of samples, can provide a wealth of information. The results of hybridization depend on the length of the DNA sample, the chemical composition of the labeled DNA target, the temperature at which hybridization is carried out, the composition of the hybridization mixture, and the type of fluorescent label. It should be noted here that passive hybridization is mainly used in DNA chips; the interaction of the target DNA with the immobilized sample is a probabilistic process and depends on various conditions.

The use of DNA chips

Assessment of the state and identification of all genes of the organism under study is one of the critical tasks set before the developers of DNA chips. The solution to this problem can be implemented in the immobilization of all the genes of the organism on a biological chip, which will allow a comprehensive assessment of the state of the genes and the genome as a whole. Biogenetic databases containing all the information (systematized) on the genes and genomes of various organisms provide researchers with great opportunities in the design of DNA chips.

The main reasons for the widespread use of biochip studies include high sensitivity, specificity and reproducibility, simplicity of the procedure, the possibility of simultaneous analysis of many parameters, and relatively low cost of work. The same reasons make us consider biochips as a promising tool in various fields National economy.

Summing up, it should be noted that microarrays are an effective approach for the simultaneous identification of tens to thousands of genes and their structural analysis, to identify specific nucleotide sequences and nucleotide variations in their structure. However, when genes are present in the genome in the amount of one or several copies, which is constantly encountered in clinical practice, their preliminary amplification is required. Most effective method DNA amplification is a polymerase chain reaction, during which there is an exponential increase in the number of DNA molecules from several to millions or more copies, and the main advantage of this type of PCR as Real Time allows even a quantitative assessment of the studied matrix. This is important for solving problems in the development of fundamental and integral sciences, as well as optimizing the conditions of diagnostic methods.

So, two methods that have already become traditional for some areas of science and applied technologies, along with their shortcomings, have completely unique advantages.

RealTime PCR:

makes it possible to estimate the amount of the original matrix;

Does not require additional labor-intensive stages of work;

· the absence of an electrophoresis stage minimizes the risk of contamination and thus reduces the number of false positive results;

· the use of mathematical methods of analysis allows for automatic interpretation of the results obtained and removes the problem of subjective evaluation of electrophoregrams;

provides less stringent requirements for the organization of a PCR laboratory and automatic registration and interpretation of results;

allows you to save time.

Biological microchips:

allow miniaturization of the sample and analyzer;

saves time and cost of analysis;

allows you to simultaneously determine several parameters of the test sample;

· possesses high sensitivity of amplification methods, specificity and reproducibility;

Provides ease of operation.

It is possible that the combination of these methods by converting the polymerase chain reaction into a microchip format will make it possible to create a new generation diagnostic system characterized by the following qualities: higher sensitivity and, mainly, specificity of nucleic acid detection, high productivity at low cost of analysis, general reducing the number of manipulations within each stage of the analysis.



Gene expression- this is the process during which hereditary information from a gene (a sequence of DNA nucleotides) is converted into a functional product - RNA or protein. Regulation of gene expression allows cells to control their own structure and function and is the basis of cell differentiation, morphogenesis, and adaptation.

DNA chips are a unique analytical tool that allows you to determine the presence in the analyzed sample (usually of biological origin) of given DNA sequences (the so-called hybridization analysis). Analysis using DNA chips is several times cheaper than using alternative technologies (electrophoresis, real-time PCR) and allows, in the presence of a detector of simple design, work outside the laboratory.

For the first time DNA chips were used in research in the late 1980s. This now widely used method, which makes it possible to simultaneously analyze the expression of multiple genes, is based on the principle of recognition of mRNA or cDNA targets through their hybridization with single-stranded DNA fragments immobilized on a microarray. Modern DNA microarray consists of thousands of deoxyoligonucleotides (probes, or samples) grouped in the form of microscopic dots and fixed on a solid substrate. Each dot contains several pmols of DNA with a specific nucleotide sequence. The DNA microarray oligonucleotides can be short stretches of genes or other functional elements of DNA and are used for hybridization with cDNA or mRNA (cRNA). Probe-target hybridization is detected and quantified by fluorescence or chemiluminescence, which makes it possible to determine the relative amount of nucleic acid of a given sequence in a sample.

In a conventional DNA microarray, the probes are covalently attached to a solid surface - a glass or silicon chip. Other platforms, such as those made by Illumina, use microscopic balls instead of large hard surfaces.

DNA microarrays are used to analyze changes in gene expression, identify single nucleotide polymorphisms, genotyping or re-sequencing mutant genomes. Microchips vary in design, performance, accuracy, efficiency, and cost.

DNA microarrays:

CDNA microarrays

oligonucleotide

(two-color with fluorescence detection)

oligonucleotide

(Affymetrix, single color with fluorescence detection)

membrane c-DNA microarrays

(with radioactive detection)

Gel c-DNA chips

Protein microarrays

A bit of history

1980s: protein chips

~1991: Supported DNA Synthesis Chemistry (High Density) - Affymetrix Oligonucleotide Chips (Fodor, Stryer, Lockhart)

~1995: Microincision robots - Stanford University cDNA chips (Pat Brown and Dari Shalon)

1990s: IMB gel chips

However, back in 1982 Augenlicht and Kobrin proposed the DNA array ( Cancer Research), and in 1984 they made a chip that included 4,000 elements for the study of cancer cells.

(The article was rejected ScienceAnd Nature)

What can be studied using DNA microarrays?

Gene expression in various tissues

Gene expression in normal and pathological conditions (in normal and cancer cells)

Changes in gene expression over time as a result of external influence (cell interaction with a pathogen, drug)

Expression profiles(patterns) differ between normal and cancerous cells, or between different types of cancer. Curable and incurable types of leukemia produce different patterns. By the type of patterns, it is possible with a high probability to predict the course of the disease at the earliest stage.

Expression microarrays

One of the actively developed areas using microarray technology is the study of transcriptional profiles in complex diseases. Although all cells in our body share the same inherited genomic DNA, each cell expresses different genes as mRNA according to cell type, biological processes, normal or pathological conditions, and so on. This diversity in gene expression profiles is the subject of intense study due to its biological and clinical significance. The ability of microarray technology to analyze the expression of hundreds and thousands of genes has proved to be most in demand in deciphering such a complex disease as cancer. Microarray technology allows simultaneous monitoring of the expression of tens of thousands of genes, creating a molecular portrait of the cell. The most significant implications of the study of gene expression profiles include the diagnosis, stratification, and prognosis of many types of cancer. Although histopathological evaluation, supplemented by cytogenetic examination and analysis of several molecular markers, is still the gold standard in diagnosis and prognosis, recent work shows that in many cases it can be replaced by gene expression profiling. Cancer diagnosis and prognosis require the joint expertise of several practitioners, such as oncologists, pathologists, and cytogeneticists, and the final conclusions may vary depending on the methodological approaches and expertise of the experts. Microchips could completely replace the efforts of many specialists, in addition, improve the accuracy of diagnosis and prognosis, as well as provide a single standardized platform for analysis.

Two types of microarrays are used to analyze gene expression: based on complementary DNA (cDNA) and based on oligonucleotide probes. cDNA-based microarrays are DNA fragments fixed on the surface of standard microscopic glasses or on another solid substrate. Oligonucleotides with a length of 25–60 nucleotide bases (n.b.) are immobilized in oligonucleotide microarrays on the same substrate. The sample preparation procedure for analysis on microarrays is shown in Fig. 1. 2. Total RNA is isolated from the cells (sometimes an mRNA fraction is also isolated), then a reverse transcription reaction is carried out using a combined primer containing a sequence complementary to the polyA-terminal mRNA fragment and a region of the T7 RNA polymerase promoter. The inclusion of the sequence of the T7 RNA polymerase promoter in the cDNA chain being synthesized makes it possible to further carry out the in vitro amplification reaction: the T7 RNA polymerase enzyme produces many copies of RNA from each cDNA molecule in the test tube. This is how linear amplification of the original mRNA occurs. As a rule, labeling of the resulting RNA molecules is carried out simultaneously due to the use of nucleotides containing a fluorescent label in the reaction. In experiments with oligonucleotide microarrays, a fluorescent label of the same type is often used to label a complementary RNA (cRNA) sample, and gene expression levels are determined by comparing the resulting fluorescent signals with the signals from the internal checkpoints of the microarray. When working with cDNA-based microarrays, as a rule, 2 samples are used in the experiment: the control sample is labeled with one fluorescent dye, the test sample with another, then they are mixed and hybridized with one microarray. According to the ratio of two different fluorescent labels in each cell of the microchip, an increase or decrease in the level of expression of a given gene is judged. Regardless of the technological platform, each experiment generates data containing an assessment of the expression level of tens and hundreds of thousands of genes. To process such an amount of data, a rather complex mathematical apparatus is used, primarily cluster analysis. Microarray data can be analyzed in relation to clinical data (hypothesis-oriented analysis, supervised analysis) or without regard to any clinical characteristic of the patient (independent analysis, unsupervised analysis).

Classical methods make it possible to analyze the expression of several genes simultaneously, or require the use of specialized microarray technologies, for example, such as Affymetrix. Affymetrix uses a combination of photolithography and chemical synthesis oligonucleotides for the production of GeneChip® microarrays.

YELLOW- if the gene is expressed in both diseased (Cy5) and normal (Cy3) tissues, then DNA labeled with both red and green colors will hybridize in this spot, and the result will be yellow

RED- if the gene is expressed only in diseased (Cy5) tissue, then only DNA labeled with red dye will hybridize in this spot

GREEN- if the gene is expressed only in healthy (Cy3) tissue, then only DNA labeled with green dye will hybridize in this spot

BLACK- if the gene is not expressed in either diseased or healthy tissue

Thus,

DNA microarrays allow simultaneous analysis of information about the expression of many thousands of genes.

The main types of DNA microarrays currently in use are cDNA microarrays and oligonucleotide chips from Affymetrix.

cDNA microarrays are based on the hybridization of mixed experimental and control samples labeled with various fluorescent dyes to a chip on the surface of which double-stranded c-DNA corresponding to ~10,000-20,000 genes is deposited.

Affimetrix microarrays are based on the hybridization of a biotin-labeled cRNA of an experimental sample with a set of Perfect Match and Mismatch oligonucleotides synthesized on a chip substrate, followed by streptavidin-phycoerythrin staining. GeneChip Human Genome U133 Plus 2.0 allows simultaneous analysis of 47,000 transcripts, including 38,500 characterized genes. The microchip includes 1,300,000 oligonucleotides of various types.

Analysis of the obtained data requires multi-stage mathematical processing using special statistical methods.

In practical terms, the use of microchips already today allows solving the following problems:

accurate diagnosis, identification of new subtypes of the disease, clarification of the classification;

predicting the course of the disease and clinical outcome, identifying genes and signaling pathways involved in the pathogenesis of oncohematological diseases, searching for new targets for directed differentiated therapy;

development and creation of simpler and cheaper diagnostic tests, including those based on microchip technology (microchips containing samples for tens or hundreds of genes instead of tens and hundreds of thousands);

inclusion of microarrays in prospective clinical trials, confirmation of the results of analysis on microarrays for inclusion in clinical treatment protocols, design of clinical protocols taking into account new data on the nature of diseases obtained using microarray technology.

DNA microarray(English DNA microarray) is a complex technology used in molecular biology and medicine. A DNA microchip is a small surface on which fragments of single-stranded synthetic DNA with a known sequence are deposited with a high density in a certain order. These fragments act as probes with which hybridize (form double-stranded molecules) complementary DNA strands from the sample under study, usually labeled with a fluorescent dye. The more DNA molecules with a certain sequence in the sample, the more of them will bind to the complementary probe, and the stronger the optical signal will be at the point of the microchip where the corresponding probe was “planted”. After hybridization, the surface of the microchip is scanned, and as a result, each DNA sequence is associated with one or another signal level proportional to the number of DNA molecules with this sequence present in the mixture.

In a conventional DNA microarray (eg, manufactured by Affymetrix), the probes are attached to a solid surface - a glass or silicone chip. Other platforms, such as those made by Illumina, use microscopic balls instead of large hard surfaces. DNA microarray technology finds a wide variety of applications in modern biology and medicine for the analysis of complex mixtures of DNA - for example, the totality of all transcripts (messenger RNA) in a cell. DNA microarrays are used to analyze changes in gene expression, identify single nucleotide polymorphisms, genotyping, or resequencing mutant genomes. Microchips vary in design, performance, accuracy, efficiency, and cost.

An example of using a DNA microarray

Below is an example of an experiment using a DNA microarray.

1. Biological samples are isolated or grown to be compared. They may correspond to the same individuals before and after any treatment (case of paired comparisons), or to different groups of individuals, e.g. sick and healthy, etc.
2. A purified nucleic acid is isolated from the sample, which is the object of the study: it can be RNA in the study of the gene expression profile, DNA in the study of comparative genomic hybridization, etc. This example corresponds to the first case.
3. Checking the quality and quantity of the received nucleic acid. If the requirements are met, the experiment can be continued.
4. Based on the available RNA samples, complementary DNA sequences (cDNA, English cDNA) are synthesized in the process of reverse transcription.
5. In the process of amplification (synthesis of additional copies of DNA), the number of cDNA sequences in the samples increases many times over.
6. Fluorescent or radioactive labels are attached to the ends of cDNA sequences.
7. The resulting samples, mixed with the necessary chemicals are applied to DNA microarrays through a microscopic hole and the hybridization process begins, during which one of the cDNA chains joins the complementary chain on the microarray.
8. After the end of the hybridization process, the chips are washed to remove residual material.
9. The resulting microchips are scanned using a laser. The output is one- or two-color images (depending on the amount of dyes used).
10. A grid is superimposed on each image, so that each of its cells corresponds to a chip section with samples of the same type. The luminescence intensity of samples in a grid cell is assigned to a certain number, which, in the very first approximation, can serve as a measure of the number of RNA sequences present in the corresponding sample.

Further processing of the results requires a multi-stage involvement of a complex statistical apparatus.

Experiment data preprocessing

The correlation between the intensities of two samples of the same DNA microarray representing the same gene is usually greater than 95%. This fact is often interpreted as confirmation of the good reproducibility of experiments with chips. However, if the same biological material is divided into two parts and made with different microarrays, the correlation between the obtained intensities is likely to be from 60 to 80%. Correlation on chips with samples taken from mice from the same litter can drop to 30%. If experiments are carried out in different laboratories, the correlation between their results can be even lower.

Such low reproducibility of intensities is associated with the cumulative effect of a large number of sources of variation. They can be divided into three large groups. Biological variation includes the inherent features of organisms. The technical variation appears at the stage of sample isolation, staining and hybridization. The measurement error is associated with scanning of finished arrays, the results of which can be affected, for example, by dust inside the scanner.

Neutralization of the effects of technical variation and measurement error is carried out at the stage of DNA microarray preprocessing.

Background correction

The need for a background correction is due to the presence of interfering factors such as noise optical system recognition (intensity data obtained during scanning is not equal to the "real" sample intensities) and non-specific hybridization (attachment of nucleotide sequences to probes of foreign samples).

Normalization

Data normalization makes it possible to make several chips considered in the experiment suitable for comparison with each other. The main goal of the analysis at this stage is to exclude the influence of systematic non-biological differences between microarrays. The sources of such differences are many: variations in reverse transcription efficiency, dye labeling, hybridization, physical differences between chips, small differences in reagent concentrations, variation in laboratory conditions.

It is shown that the choice of the normalization method has a significant impact on the result of the analysis.

Summarization

Generalization of expression level values ​​for all samples corresponding to the same sequences

Quality control

Emission processing

The main stage of statistical processing

Links

• DNA microarray
• DNA microarray experiment - article from the English Wikipedia
• DNA Microarray Virtual Lab - a step-by-step interactive example of an experiment with a two-color DNA microarray
• Ten Pitfalls of Microarray Analysis - common errors in DNA microarray analysis

The young California company Affymetrix (started in 1993) is one of the market leaders in genetic research devices.

The company is known for its revolutionary combination of semiconductor technology, so to speak, "microcircuit" industry and biochemical tests.

DNA chips from Affymetrix are widely used in various laboratories involved in genetic analysis and genetic engineering.

But ordinary people are much more interested in another product of the company. This is a microchip-like device that allows you to identify dozens of DNA from different animals in a sample of human food.

bioMerieux FoodExpert-ID is practically a variation of the so-called GeneChip.

The device can identify biological traces in food from 12 species of mammals, 5 species of poultry and 16 species of fish.

In this way, it allows you to find out whether the goose pate, which causes suspicion in the buyer, really contains goose liver, and not something else.

The DNA chip is created using technologies similar to computer ones, but it is not an electrical, but a bio object (illustration from the affymetrix.com website).

And, for example, Muslims can check whether negligent manufacturers put pork in "beef" cutlets.

All this, however, works, only with the involvement of additional laboratory abilities, so the ordinary consumer will not be able to use the chip in a “naked” form, on the knee.

To understand how FoodExpert-ID works, you need to remember a little bit of genetics: the DNA double helixes that make up their base molecules - adenine, guanine, thymine and cytosine, also that they can only be connected in pairs, like keys and locks.

The DNA chip contains myriads and myriads of "halved" fragments of the DNA code.

A piece of the surface of the chip with key molecules (illustration from the website affymetrix.com).

The surface of a chip the size of a fingernail is divided into 97,000 squares, called "features."

Any "feature" about 26 microns across contains only one DNA code. More precisely, many, many similar molecules.

And they all absolutely refer to one of the 33 animals.

The length of each piece is 17 bases. This is enough for reliable identification, as 17 notes taken in order in any place are enough to find some melody from the available database.

Experimenters extract a whole scattering of broken pieces of DNA from a food standard. What is not there. And what?

"Incorrect" pieces of genetic codes are washed away, and the matching ones are fixed on the chip. The reddish beads are fluorescent molecules (illustration from affymetrix.com).

Let's add molecules of a fluorescent substance to the molecules that make up the genetic code. Apply this mixture to the FoodExpert-ID surface. There is little left to do.

All matching pieces of code will be combined with their "native" sequences in one or another "feature".

Now the chip can be washed with water - all excess will go away. The chip is placed under a laser beam, and the squares containing the captured material will shine brightly. It remains only to check the chip map to find out which DNA has been determined.

And by the intensity of the glow, we can make an indirect conclusion about the proportions of pork and beef in our hypothetical cutlet.

As we see, the implementation of the chip is relatively easy, and allows laboratories with a very conventional set of equipment to do genetic analysis.

But how clever is the creation of the chip. To create such biochemical masterpieces automatically and in bulk, Affymetrix combined the principles of photolithography and combinatorial chemistry.

Colored squares are "features" responsible for identifying one or another DNA code (illustration from the affymetrix.com website).

The initial product - a quartz plate - is coated with a special reagent, silane, which binds tightly to quartz and forms a strictly periodic molecular matrix (with a uniform surface density) ready to accept nucleotides.

In the chains of the upcoming code, the bases go vertically upwards, and they are applied immediately to the entire surface, layer by layer.

Obviously, every time a certain substance is applied to the chip, and in order for it to fix itself exclusively in certain “features”, those micron squares, masks are used, similar to those needed for the production of microcircuits.

A snapshot of a reacted chip with a huge boost. Snow-white, reddish, yellow squares are areas with the highest concentration of a fluorescent substance. Green, blue, black - respectively, with more and more with low (illustration from the website affymetrix.com).

Each time, only those bases that are illuminated through the holes in the mask with ultraviolet light adhere to the base of the chip.

In this process of sequential synthesis, the main thing is to apply the latest mask every time with micron precision, otherwise everything genetic codes mixed on the plate.

So, step by step (there are 17 of them in the food chip, up to 24 in other models of the company) vertical columns of nucleotide chains are formed, which make the keys-analyzers of genes.

This development, of course, serves not only for such ridiculous (perhaps at first glance) areas of application, as the detection of piglet meat in goose pate, but also for completely serious research.

Indeed, on the surface of the chip, on theoretical level, you can apply pieces of any kind of genetic codes.

Affymetrix's work is redundant confirmation that the most noteworthy and promising discoveries occur at the intersection of sciences and disciplines.

It looks like bio abundance in nature, obtained by mixing genes. Is not it?