DE10164432A1 - Diagnostic method especially for animals, comprises extracting extrudate from specific tissue layers (e.g. skin) or organs using vacuum system into syringe for further processing - Google Patents

Abstract

Diagnostic method, especially for animals comprises extracting extrudate from specific tissue layers (e.g. skin) or organs using a vacuum system into a syringe for further processing. An Independent claim is included for apparatus for carrying out the method comprising a transparent vacuum cup fitted with a valve through which a vacuum can be applied and a syringe connected to the cup to receive extrudate.

Description

An innovative method and a device for diagnostic removal of liquid and cellular Fabric components using a special vacuum element, the is placed over the perforated or deliberately injured skin.

The normal laboratory analyzes are based on blood samples taken from the Veins performed. These blood samples from the so-called peripheral blood, however, can only detect laboratory parameters that are systemic, that is, play in the whole body or in the whole body be distributed and not only remain local. A Herd diagnosis of liquid (humoral) components as usual morphologically in the case of biopsies or cytologically in the case of punctures possible, does not currently exist. With such a humoral Local diagnostics would then be possible to use all previously used Laboratory parameters of peripheral laboratory diagnostics also for local or To make focus diagnosis accessible.

However, many diseases only exist locally. Especially with the well-observed diseases of dermatology, in which often no pathological laboratory parameters found in peripheral blood but clear morphological changes in the skin. That is why there are so many diseases in this medical field secured by biopsies.

But also these biopsies, which are only morphological, structural Showing changes to the skin often fail because they have no information about the fluid space or the interstitial space, the Can give changes. Also targeted tapping could specific humoral analyzes of certain tissue layers Tissue layers or certain organs or organ layers be performed.

The human body consists of over 70% liquid components. In the interstitial tissue, the connective tissue, the largest organ at all, 50-60 liters of liquids are exchanged per minute. This is a multiple of the cardiac output. In this All cells are embedded in the fluid space, since the entire cell is located above it Substance and gas transport from the capillary to the cell must take place. Changes take place very early in it, which take place much earlier show as morphological-structural changes.

Large suction cups are used in obstetrics The child's head can be put on the child from the birth canal to draw. Large suction bells are also available in erotic retailers  with which the genitals can be sucked in. With these large suction cups, no diagnostic Measures carried out.

In recent years, the so-called microdialysis z. B. also antibiotic determinations in the skin or the Subcutaneous adipose tissue performed. These microdialyses are invasive, Medical intervention in the skin, with tubing in the tissue are inserted, which are rinsed with solutions and the osmotic Draw tissue water from the tissue.

There is nothing in the relevant patent literature that the Vacuum diagnostics would be comparable. It is the example here Publication at the German Patent Office DT 26 11 721 A1 dated Filing date March 19, 1966 discussed. The inventor describes one Vacuum serum-vacuum device. The first claim discloses that a concave vacuum chamber placed on the skin Aspirates tissue serum. The inventor expressly points out that the skin and mucous membranes are not injured beforehand should and describes the application to inner mucous membranes. The vacuum stamp explained on a drawing is elongated and connected to a vacuum motor. The disadvantages of such Apparatus are on hand. For physical reasons it is e.g. B. only possible with considerably high vacuum pressures from the to suck out uninjured skin serum. It arises forced bruising because the vessels must be destroyed for this. In addition, due to the high vacuum pressure, the suctioned out Ingredients that are also sucked through the skin layers must be traumatized in such a way that especially sensitive Proteins and cellular components are damaged. The one shown Vacuum stamp is designed for and for endoscopic removal the application on the skin too unstable and too small from the suction surface.

Therapeutic, bloody cupping is from naturopathy known in which after needling the skin over a cupping glass Blood-lymphatic mixture is extracted. The cupping glass contains one Vacuum and sucks the blood-lymphatic mixture through the little ones Skin injuries to the skin surface. The extracted mixture is discarded after cupping.

In this blood-lymphatic mixture, however, apart from the humoral, liquid components also diagnostically valuable cellular components contain.

Diagnostics in naturopathy is increasingly used Dark field microscopy according to Prof. Enderlein applied the Endobionts in their various forms and growth stages  in the blood. These endobionts are in the whole body and in distributed to the tissues. So far, dark field microscopy has not been used used for analysis of tissue fluids.

In recent times, molecular biological or molecular genetic diagnostic methods used, the smallest Detect and identify amounts of protein or nucleic acids capital. This is especially true for the so-called extracellular protein - and nucleic acid analysis too. Such analytics can be used as recently shown a certain BSE diagnosis in animals or Detect micrometastases in humans.

Also, it would often be useful if you didn't just have access could determine laboratory parameters for vessels, but also as before described about the removal through the skin. You needed this no special anatomical knowledge, it would be easier and harmless and hygienic matters are not so important Importance. Any layperson would be able to do this after brief instructions.

The task of a procedure and arises from the above To develop instruments with which a hearth diagnosis of all humoral and cellular components becomes possible. A procedure and instruments that allow it, all previous ones Laboratory parameters of the usual blood analyzes also locally and not only to be able to carry out systemically.

The innovation described solves this task.

This is achieved according to the invention in that a special Vacuum element with suitable accessories according to the previous one Perforation or targeted injury to the skin, the humoral and cellular components of the underlying tissue in the usual syringe containers of the blood collection instruments can be raised.

This diagnostic procedure is vacuum diagnostics by me called. The extracted cell and liquid mixture is I called it an extrudate.

This has the advantage that you can be local, in or at the hearth of the action, for the first time simple and comprehensive laboratory diagnostics conventional medicine and naturopathic type. In addition, many laboratory parameters that were previously only about venous or arterial vascular puncture diagnostics were also accessible can be removed through the targeted perforated or damaged skin.  

The extracted blood-lymph mixture, the extrudate, can after the aspirated withdrawal tapped and into the laboratory analyzers be introduced like the usual blood draw. But you have that The advantage of having all relevant skin or tissue components hereby recorded. In addition, such removal can always take place because even with unfavorable vein conditions and in infants and toddlers can access easily accessible skin areas. So a new, always existing alternative is requested diagnostic access route.

To carry out such vacuum diagnostics correctly however, special suction devices are used that do the job are specially adapted. For hygienic reasons only to use vacuum elements to be used once, their Skin contact area is large and airtight or adhesive to the to maintain the required vacuum well.

A particular advantage of this diagnostic procedure is that that the skin in different ways for each Purpose of diagnostic vacuum removal can be prepared. So ointments and creams can be applied to the skin before diagnosis and be removed again that numb the skin or the skin hyperaemisieren.

Another benefit is that after defined preparation diagnostic slices can be placed on the skin, their content (e.g. allergens, antibodies, markers, fluorescence markers etc.) react directly with the extrudate and after removing the Vacuum elements prepared for the examinations and then analyzed can be.

For allergy tests, this would e.g. B. mean that if the Disc-defined allergens would not contain the allergen in the skin would have to be introduced, but the absorbed Extradat from the Skin penetrates into the pane, reacts there and is then analyzed could. The patient is not at risk since nothing gets into the skin is introduced.

An important advantage for dermatologists would result from the fact that these vacuum analyzes of course also on the skin-sick areas can be carried out. This is how exact tests of Psoriasis, eczema, contact allergies etc. possible because here without local, invasive anesthesia and sampling exact, two- and three-dimensional samples of liquid and cellular, extractable substances of the herd can take place. These analyzes  could in the future be used for routine diagnosis of skin changes belong.

For example, if work-related contact dermatitis is suspected, from the Eczema skin extracted and inflammatory mediators and T lymphocytes to be analyzed. T lymphocytes in the contact area are much more sensitive than that T-lymphocytes of the peripheral blood. You can also use this Remove much more sensitized T lymphocytes that focus then specifically z. B. with the lymphocyte transformation test many allergens in their reaction could be checked. This would significantly improve eczema diagnosis and make it safer. It can also be used to measure drug levels in the skin and Determine tissue layers such as B. of antibiotics.

This diagnostic vacuum removal is defined under Conditions and is carried out with special instruments, supplements several established diagnostic procedures and closes previous ones analytical gaps. It also enables safe diagnostics, since nothing is brought into the skin, but gently sucked out becomes. This is how dermatological herd histology (biopsy) is performed this dermatological vacuum diagnostics expanded, which naturally can perform other analyzes that focus on general histology completely withdraw.

Allergologically, non-hazardous analyzes can be liquid and cellular skin components using the methods of established In-vitro analyzes can be meaningfully combined and supplemented and thus the Make allergological diagnostics better and less dangerous.

Vacuum diagnostics are fundamentally different from those hitherto established morphological and laboratory chemistry Diagnostic procedures.

During the biopsy, cellular and connective tissue structures in the Association and in connection with a suspicious change taken. There remains a defect that is closed by a scar becomes. Local anesthesia and some suturing of the biopsy hole are usually carried out. At the punctures fluid-filled cavities, i.e. delimited structures like the bladder or punctured the belly water (ascites) and immediately the aspirate won. Or the punctures are long, thin Needle punch biopsies performed (e.g. liver or kidney). When blood is drawn normally through the veins or arteries specifically punctured a vessel and immediately obtained the blood. In the  Capillary blood collection, which is often used in pediatrics, are at defined points such as the fingertips or the Earlobes after perforation of the skin a very small amount of blood (25-200 microliters) by massaging or gently squeezing the blood removed and sucked into a thin capillary tube.

However, vacuum diagnostics is a procedure for under the long, constant vacuum pull Tissue fluid along with its cellular proportions from the Tissue is sucked out and then analyzed. Here arise no tissue defects. The analysis can be repeated as often as necessary become; Pain-free long-term analyzes are also possible. With these Long-term analyzes can be carried out with the vacuum element in continuous amounts of extrudate can be obtained at different times.

Such an innovative diagnostic procedure and the handling of the vacuum element are described below using the example of a skin analysis:
The area of the skin to be analyzed is pretreated with an analgesic cream and possibly cold pads. Then, after sterilizing the skin surface, the skin is perforated with a lancet. The skin area is now stretched and the vacuum element is placed on this area. Then a vacuum is created with the attached syringe under slight pressure, which guarantees that the vacuum element is firmly attached to the skin. In contrast to the analyzed skin area, the air-containing interior of the vacuum elements should have a small volume so that a vacuum can be created quickly and easily. The task of the vacuum element is only to seal the element airtight on the skin and not to form the reservoir for the extrudate. The extrudate should be sucked into the attached analytical syringe as quickly as possible so as not to trigger coagulation processes or other disruptive effects in the vacuum volume space. The less time and space in between, the better. The diameter of the contact surface of the vacuum element should, however, be several centimeters, the edge of the contact surface should be widened in order to ensure a good air seal. Possibly. it would also be helpful to have double-sided adhesive rings that are glued to the skin beforehand, that improve this air seal to the skin and at the same time better mark the area and fix the vacuum element.

The vacuum element can also have a bulge in which the Extrudate flow and from where it can be drawn into a syringe. This bulge should be connected to the syringe through a thin tube be connected what the fiddling with the suction of the extrudate  much simplified. All usual can be used as syringes Disposable syringes with the different interior wall coatings or Additives can be used. Of course you could also at the Make a small circle that can be punctured, through which the extrudate is aspirated through a cannula and a syringe can. At the top pole of the vacuum element, that is at the part lying at the top of the skin surface is a Connection for a syringe available, with which one can use a thin one Hose can generate the required vacuum. Of course this can also done with the analysis syringe in the bulge, or you could first use a syringe to connect the vacuum generate and then suck in the extrudate. However, it is easiest via 2 syringe connections, which are provided with valves that Handling very easy and safe to make not that Stressing the vacuum element mechanically unnecessarily and thereby Endangerment and negative pressure. If no valves are used, the thin hoses can then be clamped airtight with clamps become. The use of 2 syringe accesses also has the advantage that with the vacuum syringe, if necessary, liquids (for rinsing, Coagulation and other) can be entered in vacuum elements can without disturbing the suction of the extrudate. Is the Analysis syringe full, so the vacuum in the vacuum element be lifted off and the vacuum element disposed of. in this connection due to hygiene only the usual caution as with normal Blood collection may be required.

Special cases

If deeper layers like the skin are analyzed, one may have to be Local anesthesia of the layer is done. You can also use targeted Diagnostics e.g. B. the fat layer used special perforation needles become. These needles can also be capillary tubes have a firm stop, which exactly limits their penetration depth. This Needles should define the penetration depth and the puncture holes should be open hold to enable extraction of the deeper extrudate. The perforation holes created by sole, brief puncturing would collapse quickly and thus win the Prevent extrudates. The needles only have that sense Extrudate what you want and not all layers. That would be over the small needle ends protruding from the skin Vacuum element put on and fixed. Then that would Extrudate be removed exactly as described above. To the Special skin tensioners could also be used to keep the pores open become.  

The vacuum element could also be used to poison or other substances found in a small wound (e.g. in Snake bites) are to be pulled out.

Humoral tissue diagnostics could also be used for organ biopsies combine elegantly with the punch biopsies by following Aspiration of the biopsy to the lying punch needle slowly building vacuum connects. This could possibly be more specific Biopsy needles are developed.

The vacuum device could be offered as a set together with the syringes become. Possibly. could be a simple one in the set Diagnostic disks can be integrated, which can be used as required relevant diagnostics would be equipped. Or it could be in the syringe even the diagnostics are done. So could be important investigations can be carried out inexpensively by laypeople and without visiting a doctor. This would be interesting for the private sector (AIDS diagnostics) and development aid would also have useful applications Find. The same would apply to veterinary medicine.

The innovative vacuum diagnostics is now based on the following Drawings explained.

Fig. 1 shows a variant of the vacuum element in a hemispherical design in cross section.

Fig. 2 shows the ideal variant of the vacuum element as a flat shell with spacers in cross section.

Fig. 3 shows the ideal variant of the vacuum element in supervision.

Fig. 4 shows the ideal variant of the vacuum element consisting of several chambers or of coordinated arrangements of several vacuum elements in the plan.

In Fig. 1 adheres to the skin ( 1 ) the hemispherical vacuum element ( 2 ), which has been dotted for a better overview. It could also be bulged at one point in order to promote blood accumulation there, i.e. to serve as a reservoir. However, since the blood should expediently be drawn up immediately into the analysis syringe ( 9 ), such a variant was dispensed with. A vacuum was generated inside ( 3 ) of the vacuum element via the syringe ( 10 ) and the connecting hose ( 11 ), the syringe attachment piece ( 17 ) and the valve device ( 13 ) by moving the piston of the syringe ( 10 ) in the direction of the arrow. The vacuum element ( 2 ) has a broad support ( 7 ) on the skin, which ensures that there is no air. This contact surface could also be self-adhesive.

Due to the negative pressure, the extrudate ( 5 , 6 ) is sucked out through the perforations ( 4 ) into the interior ( 3 ) of the vacuum element. The extrudate ( 6 and 18 ) can be sucked into the analysis syringe ( 9 ) via the thin tube ( 12 ) by moving the piston of this syringe in the direction of the arrow. The analysis syringe is connected to the vacuum element via the deep-seated connection ( 14 ). The skin ( 15 ) is sucked into the interior ( 3 ) of the vacuum element in a hump-like manner by the vacuum. The height of the vacuum element must therefore be so great that the skin hump does not hit the roof of the vacuum element and thus does not hinder the extrudate from escaping. The vacuum element itself should be built as flat as possible, since it only serves to generate the vacuum and not as a collecting container for the extrudate. The extrudate should be fed into the analysis syringe ( 9 ) as quickly and easily as possible. Depending on the analysis, the inner wall of the vacuum element can be coated with different materials, such as the inner wall of the analytical syringe. B. be wetted with silicone or with heparin. The approach ( 13 ) of the suction syringe ( 10 ) should be established so that it does not come into contact with the extrudate. Of course, it would also be possible to work with just one syringe connection, to which the suction syringe and then the analysis syringe are connected. However, the use of 2 syringes is more practical and hygienic, since the vacuum has to be readjusted again and again during removal. A simple clamp ( 16 ) is attached to the hose of the analysis syringe, which closes the hose completely so that the syringe ( 9 ) can be removed cleanly or several syringes can be filled. The diameter of the vacuum element should be several centimeters (over 4 cm), otherwise too little extrudate will be obtained.

You can also clearly see the advantage of vacuum diagnostics here versus capillary blood sampling at the fingertip or the earlobe.

In the case of capillary removal, the fingertip or the blood from the skin of the earlobe is squeezed or massaged pressed. This leads to known artifacts and malfunctions of the Blood cells. Such errors are caused by the use of negative pressure avoided. With the capillary blood collection only very small Blood amounts up to a maximum of 300 microliters analyzed, while in the Vacuum diagnostics easily several milliliters of extrudate to let win.

Another advantage of the innovative process is that any layperson can carry out such extrudate extraction.

He does not need any anatomical knowledge for this, he does not need any vessels dot; the withdrawal process is completely safe and the  Skin surface easily accessible. This should also be an important advantage be with extrudate withdrawals in veterinary medicine. The fur of the animals will shaved in a small place, the skin perforated, the vacuum element prepared and the extrudate removed. The farmer can do all of this do it yourself without having to call the vet.

This alternative method could be used nowadays Blood sampling Save time and money. In addition, the Vacuum diagnosis of the usual blood collection via the puncture of the be superior to animal blood vessels.

Fig. 2 shows an ideal, flat design of the vacuum element ( 20 ). It can be kept so flat because spacers ( 21 , 25 ) prevent the skin ( 15 ) from being sucked upwards. This flat vacuum element also has a wide edge seal ( 22 ) for effective air sealing. The extrudate ( 27 ) is drawn out of the skin through the perforations ( 26 ) of the skin ( 15 ). The vacuum is generated via the syringe ( 23 ), which is connected to the interior ( 3 ) of the vacuum element via the hose ( 24 ). As in Fig. 1, this hose ( 24 ) can also be connected to a valve mechanism that has been firmly integrated on the roof of the vacuum element. The spacers ( 21 , 25 ) allow the vacuum element to be kept so flat that even very small amounts of the extrudate ( 27 ) can be sucked up at several points of the vacuum element via hoses ( 29 , 28 ) in analysis syringes ( 32 ). These tubes can be brought very close to the surface of the skin due to the predetermined skin distance. Because several syringes can be attached to this vacuum element, it is also possible to introduce anticoagulant substances or other substances into the interior of the vacuum element. The analysis tubes can in turn be sealed with clamp closures ( 30 ) and carry syringe adapters or other closures ( 31 ). The spacers also serve to hold resorbing filter papers etc. on the skin surface that could be used for diagnostics.

Fig. 3 shows the flat, round vacuum element ( 20 ) in the plan. Because of the low extrudate yield per square centimeter of skin area, the vacuum elements must cover larger areas of the skin or have a larger diameter, ideally over 4 cm, optimally 6-8 cm. Due to the possibility of removing the extrudate at various points on the vacuum element ( 24 , 29 , 28 ), the local extrudate formation can be optimally dealt with. The extrudate can also be removed at several points with a single analysis syringe. In this view, the extradate is drawn up at point ( 28 ) via the analysis syringe ( 32 ). The spacers ( 25 , 21 ) prevent the skin ( 1 ) from being lifted up. The vacuum element has the wide edge ( 22 ).

In the top view Fig. 4a shows a flat vacuum element (33), which is composed of a plurality of vacuum chambers (34) and has the shape of a dog bone. The spacers ( 35 ) are installed centrally. The analysis holes for the hoses were not shown. The flat, large vacuum element is flexible and transparent. FIG. 4b and 4c show honeycomb (36) and window-like (37) arrays of individual, flat vacuum elements. This guarantees that the configuration of the vacuum elements can be adapted to the purpose or size of the area to be analyzed. This could be of concern for the micrometastasis search.

Fig. 4d shows an elongated design of a flat vacuum element, which in turn consists of several chambers ( 38 ), each containing spacers ( 39 ) and analysis tubes ( 40 ). Again, the wide edge ( 41 ) for air sealing is marked here.

Claims (17)

1. Diagnostic method for humans and animals, characterized in that after defined injuries to the tissue layers (skin layer, fat layer, muscle layer) or organs or organ layers, humoral and cellular tissue components (extrudate) are extracted via a special vacuum element placed on the skin and immediately drawn into a syringe for further diagnosis. 2. The method according to claim 1, characterized in that all Appropriate laboratory analyzes of the usual blood samples are used are including the determination of drug levels in tissue as well as analyzes of localized tissue or Organ changes (focus diagnosis) herewith carried out become. 3. The method according to claim 1-2, characterized in that the Procedure is used as an alternative blood collection procedure. 4. The method according to claim 1-3, characterized in that hereby determinations of extracellular proteins and nucleic acids c be performed. 5. The method according to claim 1-4, characterized in that the Tissue or organ layer with a defined perforations, Milling, removal, peeling, punching, curettage, Scratches, punctures are pretreated and the special Means are used to help the organs or tissues in their Spread and depth or their different depth layers to hit exactly and keep the injuries open. 6. The method according to claim 1-5, characterized in that Means for tensioning or pulling apart the tissue or Organ layer are provided. 7. Diagnostic device for use on humans and on Animal, characterized in that after defined injuries of tissue layers or organs or organ layers on the Skin surfaces or organ surface a transparent Vacuum element is placed, which has a wide edge approach has and in its stable wall holes for the inlet of Hoses and valves are provided, from which one Syringe or a motor air from the vacuum element attached can be evacuated and what that through the vacuum ascending extrudate immediately into a standard blood collection syringe can absorb and integrated spacers in the wall that prevent bulging of the skin or organ surface and those positioned on the skin surface and organ surface diagnostic media to the skin or organ surface  press it. 8. The device according to claim 7, characterized in that transparent vacuum elements of defined, useful sizes, Forms and vacuum developments and materials for single use and multiple use, but especially flat, round shapes with an inner diameter of 4-8 centimeters. 9. The device according to claim 7-8, characterized in that Vacuum elements with special bulges and connections for collecting the extrudate and connecting at least 2 Syringes used and one-way valves for air evacuation in the Vacuum element to be installed as well as permanent markings can be attached to the vacuum element. 10. The device according to claim 7-9, characterized in that for an airtight seal on the skin or organ surface the wide support edge of the vacuum element on both sides adhesive rings can be attached. 11. The device according to claim 1-10, characterized in that for targeted injury to the tissue and organ layers special perforation needles or capillary tubes are used, which have a defined inner diameter and a defined penetration depth by guaranteeing that they are in a have a defined height and if necessary in skin or organ surface for the duration of the extraction can remain. 12. The device according to claim 1-11, characterized in that at the bottom of the vacuum element over the skin or Organ surface suction pads can be installed as serve diagnostic slices and defined markers, allergens, Contain antibodies, etc., which react immediately with the extrudate and can be further analyzed for diagnostic purposes. 13. The apparatus according to claim 1-12, characterized in that multiple suction devices are used, their extrudate ultimately via a common hose directly to a diagnostic Laboratory device is connected. 14. The apparatus according to claims 1-13, characterized in that several, separately evacuable in a large vacuum element and separately extractable vacuum chambers are included. 15. The apparatus according to claim 1-14, characterized in that these large vacuum elements have any convenient shape and Can be large and flexible. 16. The apparatus according to claim 1-15, characterized in that the vacuum element together with the associated syringes and additives (needles etc.) in a sterile packed set for Single use is offered.   17. The apparatus according to claim 1-16, characterized in that the set is offered as a single use diagnostic set, which besides the vacuum element, syringes and accessories Appropriate diagnostics, such as test strips, test sticks, etc. include.