08 December 2008

Barcode biochip sees dozens of diseases in one drop of blood

Changes in the composition of plasma proteins can tell a lot about the state of the body. Often they report on a particular disease (cancer, heart disease). For doctors, the protein profile is the body's complaint book. But clinical tests on a wide range of these compounds are rarely carried out. Expensive and long. A new biochip can change everything.

Usually doctors in hospitals are limited to a small number of proteins detected in the blood of their wards. To conduct such an analysis, a certain amount of blood is taken from the patient's hand, it is sent to a centrifuge to separate the plasma, which is then tested for the presence of biomarkers of interest to physicians. This laborious process takes hours at best, and the cost of a test kit for one protein is $50.

And if you need to check several dozen of them at once? Easy! And it is ten times cheaper than with traditional methods. All this can be done using a new technology that is currently undergoing the first clinical trials. Moreover, the entire test takes only 10 minutes.

This bright development of a group of scientists from the California Institute of Technology (Caltech) and the Institute For Systems Biology (Institute For Systems Biology) is called "Integrated Blood Barcode Chip" (Integrated Blood-Barcode Chip – IBBC).

Compared to him, even some experienced adjustment laboratories will seem like giants. The IBBC plate is about the size of a microscope slide, and it is also made of glass. Rather, the glass here is the base on which a silicone coating is applied.

Since we want to establish the presence of certain molecules (in our case, proteins), it is necessary that the entire flow passes through an extensive network of specific traps, in which only those molecules to which these traps are tuned would remain. Next, you need to make sure that the reacted traps light up. Then, by looking at the chip under a microscope, you can check the map and find out which proteins are present in the sample.

A drop of blood is fed into a very narrow channel on the surface of the chip and under a little pressure, the blood is forced to go deep. Many side channels, even thinner, depart from the main channel. Blood cells cannot squeeze through them, and plasma passes freely.

Now she finds herself in a corridor that looks like a barcode: across this channel lies a large number of strips 20 micrometers wide. Each strip is covered with specific antibodies that attract only one specific protein.

The general plan of the chip. A drop of blood spreads through a very thin (50 micrometers wide) central channel (here it is shown greatly enlarged), and then falls into even narrower (10 micrometers) lateral branches of the plate, each of which turns into barcodes telling about a particular disease.

It should be noted that IBBC was created at the expense of the American National Cancer Institute (National Cancer Institute) and the Research Department of the US Army (Army Research Office) (illustration by R. Fan, J. Heath).

After the blood has reacted with the strips, the chip is sent for "development". Then the strips that caught the proteins begin to fluoresce red, and the more intensely the more biomarker molecules they have collected.

The whole reacted chip looks like a set of barcodes, unambiguously showing how many and which proteins are present in the plasma. (Details can be found in the IBBC creators' article in Nature Biotechnology.)

Now, to read this barcode of blood, scientists use a laboratory scanner, the same one that is used for genetic research. But, according to the project participants, in the future it will be possible to read IBBC chips using a small device similar in appearance to a manual barcode scanner at supermarket checkout counters.

Here we see the central channel larger. Blood cells run along it, and the plasma separates and goes into three (in this figure) lateral channels. Each of them contains trap strips. The colors of the stripes indicate the different proteins they target. Antibodies fixed on the surface of the strips by DNA hybridization are responsible for the capture of molecules (in the inset).

The "development" of the chip involves the addition of a solution with secondary antibodies labeled with fluorescent markers. The green plane in each code is a reference point, it allows you to accurately determine the position of the illuminated strips for their identification. Each microchannel contains from 30 to 50 complete barcodes targeting a variety of proteins. The concentration of the compound of interest to physicians is determined on average by the results of reading a large number of barcodes on the chip (illustration by J. Heath, R. Fan, H. Amad).

A press release from the California Institute of Technology says that Heath and his colleagues have built several such chips, each of which is capable of simultaneously performing a separate blood test for eight patients, and even for several dozen proteins at once. And over the next year, the researchers intend to bring the capabilities of IBBC to the recognition of 100 different proteins simultaneously.

If the price of one such multitest also turns out (with the mass production of chips) to be identical to the price of the current plasma analysis for a single protein (and scientists are talking about exactly this goal of the project), then IBBC doctors will simply tear off their hands.

In the meantime, Americans are testing their barcode tester in some clinics.

So, with the help of this chip, they were able to track the changing concentration of chorionic gonadotropin in the blood of a pregnant woman, and throughout pregnancy. But in its course, the content of this hormone increases by 100 thousand times. IBBC not only showed the concentration of this protein with good accuracy, but, which is an achievement, was able to easily catch it in both very small and very large "doses". Such a wide range of work is a plus for the method. After all, other tests either do not catch the desired substance, or in the end, on the contrary, they "go off scale".

The authors of the technology also used it to determine breast and prostate cancer in a number of patients. "The types and concentrations of proteins vary from disease to disease, as well as between different individuals. Women with breast cancer, for example, will generate a different set of biomarkers compared to men suffering from prostate cancer, while a woman with an aggressive form of cancer may "show" proteins that differ from a woman with a less deadly form," the researchers report.

And the same concentrations of specific proteins begin to change during treatment, so IBBC is a convenient monitor of positive changes in the patient's condition.

Another high speed of obtaining the result will allow doctors to use a barcode chip to detect a person's reaction to a new drug – after all, what is happening in the body will be visible "without leaving the place." This means that the treatment plan can become more precise and more individual.

Interestingly, one of the key participants in this project is Leroy Hood, president of the Institute of Systems Biology and one of the world's celebrities in the field of biotechnology and DNA sequencing. Four years ago, this scientist said that thanks to biotechnology, over the next 30 years we will witness an increase in the average life expectancy of a person by 10-20 years; and that with new devices we will be able to perform 10,000 different medical tests simultaneously with just one sample of blood from a finger.

As you can see, Dr. Hood's words do not differ from the case: he himself is actively working to realize his forecast.

Membrane

Portal "Eternal youth" www.vechnayamolodost.ru08.12.2008

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