Why is a patient given DNA
The DNA scanner - gene check with terahertz radiation
A short spade, a drop of blood. The doctor pushes the glass slide with the red vital juice into an apparatus the size of a shoe box next to his desk. He smiles relaxed. Short small talk between patient and doctor. 'Ping'. A bright signal tone directs the doctor's gaze to his PC display. The result of the analysis appears in a screen window. The diagnosis: a bacterial infection - not untypical for the cold season. The doctor prescribes a mild antibiotic and recommends bed rest for a week. A few minutes after entering the room, the exhausted patient can start walking home again. Get well!
Is it up to Prof. Dr. Haring Bolívar from the 'Institute for High Frequency Technology and Quantum Electronics' at the University of Siegen, the vision could soon become reality in German medical practices. The electrical engineer is currently working on the development of a DNS scanner with international participation. Disease diagnoses could thus achieve an unprecedented level of precision. The result would be available within a short time.
Precision diagnostics is based on the development of fast and efficient methods for analyzing genetic material. Once the gene sequences have basically been deciphered, every organism can be clearly identified via its DNA; Viruses of all stripes can be proven just as unequivocally as bacteria via their genetic 'fingerprint'. Like a virus program scans the PC for worms and Trojans, the DNS scanner scans the human body for all kinds of pathogens. A drop of blood is enough. Here as there, however, problems can arise as soon as the pathogen changes. Be it through manipulation in the computer world or through mutation in the physical world. Because only what is already known can be found unambiguously.
As useful as the DNS scanner may be for optimizing the diagnosis of diseases, Haring Bolívar sees its actual area of application in a different area: "We envision that the scanner will be used in the future as an effective weapon in the fight against hereditary diseases or cancer." , explains Haring Bolívar when asked about the preferred areas of application. Because not only microorganisms can be determined by DNA analysis; The human genome can also be examined for errors. The DNA scanner recognizes those DNA segments in the human gene pool that are responsible for coding hereditary diseases or susceptibility to cancer. "The individual cancer risk can be determined for each patient with a DNA scan," says the professor. The gene scan would provide information about which organs are more at risk than others or where the likelihood of cancer is highest. In view of the potentially unsettling results, the question immediately arises of what would be gained from such knowledge. In addition Prof. Dr. Haring Bolívar: “Appropriate early detection can significantly lower the cancer-related mortality rate. If the doctor determines a corresponding hereditary predisposition in a patient, targeted efforts can be made in good time to ensure effective cancer prophylaxis; on the one hand through a risk-conscious coordination of the individual lifestyle, on the other hand through appropriately sensitized, regular preventive examinations. In the event of a contingency, the attending physician could also react much sooner and therefore more effectively. "
How does the DNS scanner work?
But how does such a DNS scanner work? The basic principle is actually not that dissimilar to that of a normal scanner, for example a commercially available flatbed scanner. In both cases, the object to be examined is scanned with radiation from the electromagnetic spectrum. Parts of the radiation are absorbed by the scanned object, others are reflected. A sensor measures the corresponding amount of radiation and forwards the data obtained to readout electronics. In the case of a flatbed scanner, the computer (re) constructs the photographic image from this data. A major difference between DNS and flatbed scanners, however, lies in the type of radiation used. While the flatbed scanner uses radiation from the visible range of the electromagnetic spectrum - i.e. 'light' - the DNS scanner uses invisible radiation that is physically located between infrared and microwave radiation: the so-called 'terahertz radiation'. Terahertz radiation is still hardly known to the public. Because it is still difficult to make use of terahertz radiation, engineers and physicists use the term “terahertz gap” for this area of the electromagnetic spectrum. The adjacent frequency ranges, infrared and microwave radiation, have meanwhile been opened up for many everyday applications. In contrast, science has only recently begun to take an interest in terahertz radiation. The Siegen professor explains why: “The main problem with recycling lies in the difficulty of generating radiation. To date it has not been possible to build an efficient and at the same time compact and inexpensive radiation source. "
THz radiation: huge application potential
In contrast to this technological hurdle is the multitude of possible applications: Terahertz radiation makes many optically dense materials transparent. It can be used, for example, to look through clothing to look for weapons or explosives, it can be used for quality control of production processes or for wireless data transmission, which would be many times faster than with conventional W-LAN technologies. “The potential of THz radiation has now been recognized in the professional world, but also in industry. In Siegen we started researching this extremely exciting wave range a few years ago. In the meantime, however, we are competing with universities from all over the world in a race to design the most efficient THz system possible, ”explains Haring Bolívar. And adds with a wink that the early start still ensures a comfortable lead. THz radiation also has great potential for medicine; especially for the analysis of genetic material. Because THz radiation is due to the low energy of THz photons - more precisely: the low energy of the small energy packets that carry this radiation - so-called 'non-ionizing' radiation. Which in plain language means that there is no substance-changing interaction between the exposed object and the radiation. In contrast to X-rays, THz radiation does not trigger any transformations - no “mutations” - of the genetic make-up; THz radiation is harmless to health. It is only possible to use the tiny, several hundred micrometer short waves for the analysis of organic material if the material being examined does not change during observation. THz rays are also suitable for biomedical analyzes for another reason: no other frequency range causes a similarly strong resonance in bio-molecules; No other area of the electromagnetic spectrum provides these modes of vibration that can be used for direct ('resonant') biomolecular identification. The DNA polymers sway in the THz photon stream like a leaf in the wind. “Depending on the structure and the composition of the respective biomolecule, specific wave patterns are created under the influence of the THz rays, which form a well-measurable basis for further material analyzes,” says Haring Bolívar.
Eroticism of genes
Even today there are already methods for the automated analysis of DNA. At the center of this methodology is the 'erotic' attraction between complementary DNA strands. In ancient Greece, the comedy poet Aristophanes referred to 'Eros' as the force that allows man and woman to find each other again as separate halves that were once connected. The genetic material is also a unit made up of two parts. If the genetic material present in the form of a double helix is separated into two individual strands, the parts remain alone until they can join together again with their 'missing half' to form a whole. Biotechnologists take advantage of this property. They place thousands of short single strands of DNA with known base sequences on DNA chips, also known as 'biochips' or 'microarrays'. The fixed nucleotide single chains serve as probes to identify the genetic counterparts in a mixture of innumerable DNA molecules in a patient sample. As soon as a DNA fragment comes into contact with its missing partner, the isolated single strands reconnect to form a double helix. All methods for high-throughput analysis of genetic material are based on this natural property of DNA building blocks to combine with their missing partner particles. As in a puzzle, the carrier substrate and the sought-after target DNA fit together according to the 'lock and key principle'. The approaches differ only in the way this 'docking' is detected.
A widely used technique is the marking of DNA strands with fluorescent dye molecules. If a labeled molecule binds to a suitable DNA probe, a grid of light signals is created after illumination with a suitable laser. The fluorescent dots signal the presence of a certain gene or a certain gene defect. The information about the gene activities in diseased or healthy cells can finally be recorded with the individual light signals. However, this method has certain disadvantages. It is time-consuming and costly to provide the DNA samples with the appropriate fluorescent markers. In addition, the dye molecules can interfere with the detection of genes, since the light signals sometimes vary. A clear quantification of the presence of a gene is then not possible. In many cases, especially in cancer research, it is of crucial importance to be able to make quantitative statements about the presence of genes or genetic defects.
The color-based detection method is problematic for the construction of a powerful DNS scanner. All in all, this detection technique turns out to be too labor-intensive, too expensive and, in some applications, too imprecise. In preliminary experiments, the team led by Prof. Dr. Peter Haring Bolívar discovered that with electromagnetic waves of a few trillion Hertz - the THz rays - one can find out without detour whether two complementary DNA strands are coupled or not. The terahertz waves (one THz corresponds to 1012 Hz) stimulate a number of characteristic vibrations in the DNA molecules that are only possible in bound gene sequences. The binding state between known and unknown DNA sequences can be determined directly via the THz resonances, which can be measured as THz absorption or THz refraction. This makes it possible to build THz biochips that can directly quantitatively detect and identify gene sequences without any marking.
One chip, one sensor, one THz emitter
The DNA scanner of the research team led by Prof. Dr. Haring Bolívar consists of three components. Firstly from the THz radiation source, secondly from a DNA chip, which can be equipped with numerous different DNA sequences - depending on the analysis interest (detection of tumor cells, viruses or bacteria) with different single strands - and thirdly from a detector that detects the Measures radiation resonance. The work on the radiation source and on substrates that intensify the interaction of DNA and THz radiation is currently particularly research-intensive; The aim behind this is to enable more sensitive analyzes as well as to be able to further reduce the amount of DNA required for this. When designing the radiation source, the scientists use existing optical or electronic methods to generate THz radiation, which they refine and make usable for the analyzes. At the Institute for High Frequency Technology and Quantum Electronics, Haring Bolívar's employees are experimenting with a quantum cascade laser, for example. This currently still has to be cooled in a complex manner, but can provide the required high THz radiation intensities. On the sensor side, the team is developing substrates, so-called 'frequency-selective surfaces', on which the DNA query molecules can be fixed. With the help of the substrates, the THz fields are concentrated precisely on the point at which the interaction of THz radiation and DNA molecules leads to a strong change in the THz signals. Such sensor approaches have meanwhile increased the sensitivity for DNA analyzes by more than six orders of magnitude, i.e. by more than a million times, compared to the first investigation methods. This means that the THz DNS query technology, the process prototype of the future 'DNS scanner', has for the first time achieved the sensitivity that users want.
Author: Hellermann / Haring Bolívar
Text and images are free to reprint
Prof. Dr. Ing.Peter Haring Bolívar
University of Siegen
Interdisciplinary Center for Sensor Systems (ZESS) /
FB12 - Electrical Engineering and Computer Science
Phone: +49 271 740 4428
Fax: +49 271 740 2648
Interdisciplinary Center for Sensor Systems (ZESS)
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