Method for detection and quantification of cell free DNA in biological sample

Abstract

The invention relates to a method for detection and / or quantification of cell free DNA in biological sample, use of such measurements for the detection and diagnosis of disease, and monitoring disease. In particular, the present invention provides for precise cost and labor- efficient methods of cfDNA (total cfDNA) quantification in biofluids.

Description

[0001]METHOD FOR DETECTION AND QUANTIFICATION OF CELL FREE DNA IN BIOLOGICAL SAMPLE SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on August 19, 2024, is named Sequence Listing_3541-1PCT.txt and is 5,08 KB in size. FIELD OF THE INVENTION The invention relates to a method for detection and / or quantification of cell free DNA in biological sample, use of such measurements for the detection and diagnosis of disease, and monitoring disease. BACKGROUND OF THE INVENTION Cell free DNA (cfDNA), also called extracellular DNA (eDNA), is present in small amounts in the biofluids of healthy individuals. An increased level of cfDNA in biofluids (mainly in the blood) is now a widely accepted as a marker for a number of diseases and pathological conditions including but not limited to cancer, metastatic cancer, acute organ failure, organ infarct (including myocardial infarction and ischemic stroke), hemorrhagic stroke, autoimmune disorders, graft-versus-host-disease (GVHD), graft rejection, sepsis, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), graft-versus-host-disease (GVHD), traumatic injury, proinflammatory status in aged individuals, diabetes, atherosclerosis, neurodegenerative disease, autoimmune disease, eclampsia, infertility, coagulation disorder, pregnancy- associated complications and infection. [See, for example, Kustanovich A. et al.1] cfDNA originates from various source and may be packaged in the form of mono- or oligonucleosomes, exosomes, other extacellular vesicles. Apart from apoptotic and necrotic cell death, there are other DNA release mechanisms, including oncosis, pyroptosis, phagocytosis, active secretion, and excision repair. Also, activated blood cells types such as neutrophils, macrophages, eosinophils, basophils, mast cells, plasmacytoid dentritic cells, and monocytes release extracellular traps (ETs), which comprise nuclear cfDNA strands bind anti-bacterial proteins (myeloperoxidase, pentraxin 3, neutrophil elastase, MMP9, histones and others). [Nija,R.J. et al.2] The concentration of cfDNA and its change in biofluids (mainly in the blood, blood plasma or serum) are used as prognostic marker, marker for monitoring the disease dynamic as well as criterion for selection of treatment options or for therapeutic decision. For example, level of plasma cfDNA has much better prognostic utility than MODS or APACHE II scores, or the biomarkers measured for patient outcome in ICU including patients with sepsis, trauma, major surgery [Dwivedi D.J. et al.3],[ Ahmed, A.I. et al.4]; [Liu, J.P. et al.5],[Merkle J et al.6]. Level of cfDNA in the circulation is good prognostic marker that is negatively correlated with survival for patients with aggressive non-Hodgkin lymphoma (NHL) [Hur JY, et al.7], metastatic melanoma [Valpione S, et al.8] and positively correlated, for example, with diabetic kidney disease progression in patients with type 2 diabetes [Li X, et al.9]. Plasma cfDNA measurement result is used to predict radiation therapy (RT) toxicity in personalized care (i.e. to make a clinical decision) for patients underwent radiotherapy [Lockney NA et al.10]. But, cell free DNA are considered as not only biomarker but as the potent danger-associated molecular pattern (DAMP) [Műzes, G et al.11]. Cell free fDNA may causally contribute to multiple aging-related diseases, such as cancer, diabetes, and Alzheimer’s disease [Gravina S, et al.12]. Some research works showed that tumor cell-free DNA promotes malignant transformation in non-tumor cells [Souza A.G., et al.13]. Excess of neutrophil extracellular traps (NETs) leading to tissue hyper-inflammation and organ injury. NETs are known as the drivers of vascular damage and venous thrombosis [von Brühl, M.L. et al.14] The compounds that specifically disrupt or bind this target (cell free DNA) in the blood circulation are considered as therapeutic agents for treatment of some diseases and conditions associated with excess of cell free DNA [Dawulieti J, et al.15], [ Liu F16] The extracorporeal methods for removal of cell free DNA from patient body for treatment various diseases associated with cell free DNA excess, are proposed also in [US2020026163917], and [Gocho, T., et al.18]. As was shown, the extracorporeal removal of cfDNA from blood of septic patients lead to clinical improvement and reducing septic complication rate [Abramovsky, S. V. et al.19] The cell free DNA is measured in biofluids with various methods, most of which are considered the extraction of the cfDNA from the biofluids sample with consequent measure of more or less purified cfDNA using (as a rule) DNA- binding fluorescent dyes or PCR. The selection of the source (i.e., plasma, serum, urine, cerebral fluid etc.), the method of sample collection (e.g., EDTA-containing tubes, etc.), the parameters of centrifugation (i.e., speed, temperature, time), variant of extraction and purification, cfDNA storage conditions influence the measurement results [Martignano, F20], [Devonshire, A.S. et al.21] Polymerase chain reaction (PCR) method is broadly used for plasma cfDNA quantification. This method usually requires pre-analytical step of the extraction of DNA from the liquid sample. It also requires complex equipment, it is laborious and multi-step process, and its results depend on the correct selection of primers, since differences in the primers used lead to the big difference in cfDNA quantification results [Shi, H. et al.22]. Also, the quantification of cfDNA in human biofluids with qPCR using Alu [Lou X. et al.23] or L1PA2 [Neuberger, E.W.I. et al.24] is suitable for primate biofluids only as Alu and L1PA2 elements are primate-specific and cannot be used for cfDNA quantification in biofluids of non-primate mammalians such as dogs, cats and, as example, farm animals. For cfDNA quantification in dog biofluids with qPCR canine specific elements (most abundant repeat sequence present in the canine genome), like LINE-1 retroposon can be used as a qPCR target. The choice of a pair of primer is important to quantify short and long cfDNA fragments. Some investigators explored the potential of droplet digital PCR (ddPCR) when multiplex assay targets three fragment size ranges (73–165 bp; 166–253 bp; > 253 bp) from several olfactory receptor (OR) genes, together with the co-amplification of a customizable diploid locus (STAT6) for the estimation of absolute cfDNA concentrations without the need of reference samples and calibration curves [Alcaide, M. et al.25]. But cfDNA quantification with any type of PCR required preliminary DNA extraction from the sample as enzymatic inhibitors can indeed be common in biofluids. The loss of cfDNA during the DNA extraction is common, inevitable and amount and type (at least, high and low molecular-weight cfDNA fractions) of lost cfDNA is unpredictable [Sorber, L. et al.26], [Warton, K. at al.27], [Pérez- Barrios, C. et al.28]; and again, enzymatic inhibitors are present in some of the chemical solutions used during cfDNA extraction. For the methods of the cfDNA quantification of the present invention no preliminary DNA extraction is needed and this prevent the loss of cfDNA to be quantified. Since, as cfDNA extraction / isolation steps are time consuming and labor intensive and not always acceptable in a clinical setting, some clinical researchers have used the direct (i.e., without a preliminary DNA extraction step from a biological sample) fluorescent method for determining cfDNA concentration [Goldshtein, H. et al.29], [Shoham, Y. et al.30], [von Meijenfeldt, F.A. et al.31]; [Zhang, S. et al.32]. As was shown, the unspecific bind of the fluorescent dye with plasma / serum proteins presented in more than 105-fold excess as compared to cfDNA lead to prominent background fluorescence and cfDNA packed in nucleosomes resulted in a markedly lower fluorescence signal compared with purified protein-free cfDNA [Chen, J.A. et al.33]. As considered, the cfDNA detectable in plasma is present (1) predominantly within mono- nucleosomes or (2) transcription factor complexes circulating in the blood of healthy individuals. [Sanchez, C et al.34] ELISA methods routinely used for nucleosome quantification [Zeerleder, S. et al.35]. ELISA methods are developed and broadly used for measurement of total cell free nucleosome concentration (as a biomarker for some pathological conditions) in plasma of mammals including humans and dogs [Verhoeven, J.G.H.P. et al.36]; [Dolan, C. et al.37] In some case circulating cell-free DNA assayed by quantitative PCR is a better biomarker than nucleosomes assayed by ELISA [Seefeld, M. et al.38]. As was shown, circulating nucleosomes contain nuclear-derived cfDNA, but the plasma contains approximately 50,000-fold more copies of the mitochondrial genome than that of the nuclear genome, while accounting for 10 to 25% of the total blood plasma cfDNA mass content and this circulating mithochondrial DNA (mtDNA) originates mainly from circulating cell-free mitochondria [Roch, B. et al.39]. Moreover, as recently reported, pool of plasma cfDNA contains the unique class of non- nucleosomal ultrashort single-stranded cfDNA of nuclear origin with a modal size of 50nt [Cheng, J. et al.40] Thus, no surprisingly that in some case researchers find no correlation between total nucleosome concentration measured with ELISA and total cfDNA concentration measured using a fluorimeter in mammalian plasma [Letendre, J.A. et al.41]. Also, the sandwich nucleic acid hybridization assay provides an approach for cfDNA quantification by amplifying the reporter signal using branched DNA (bDNA) technology [Lockney, N.A. et al.42]. Branched DNA technology allows quantification of cfDNA comprising Alu sequences directly from a variety of sample types without cfDNA purification or target PCR amplification. This assay is proposed for quantification of plasma cfDNA to predict the level of damage to cells in a mammal [US Pat. No.8,404,44443]. But again, this laborious and multi-step process takes about 24 hours, and, of course, this method cannot be used when quick cfDNA quantification and therapeutic decision making is required. The methods for quantification of single stranded DNA in not only pure DNA samples, but also in samples containing significant amounts of protein, are known: any single-stranded DNA (ssDNA) is non-diffusively bound to a solid support where the ssDNA is brought into contact with a single-stranded binding protein (BP), which is either bound non-diffusively to the solid support, or added in soluble form. The ssDNA binds to the BP forming ssDNA-BP complexes, which may be detected by means of a label on either the BP or the ssDNA. The single-stranded DNA binding protein may be from any source, either eukaryotic or prokaryotic, and may include single-stranded DNA binding proteins, topoisomerases, and DNA unwinding proteins. Of particular interest are single-stranded DNA binding protein from E. coli, T4 gene 32 protein and topoisomerase I from Micrococcus luteus and E. coli. [US Pat. No.4,978,60844]. Also, the method for the detection and immunological determination of nucleic acids present in biological media is proposed when nucleic acid to be assayed is immobilized on an appropriate support and then contacted with anti-nucleic acid monoclonal antibodies; the complex between nucleic acid with the anti-nucleic acid monoclonal antibodies may be revealed with immunoenzymatic method. The immobilization of the nucleic to be assayed is carried out by a specific ligand, which consists in immobilizing by active or passive route on a solid support such as a microtitration plate, an antibody or mixture of anti-nucleic acid antibodies or specific molecules affine for the nucleic acids (histones, etc.). The anti-nucleic acid monoclonal antibodies are produced by generic hybridoma technic with immunization of “common” Balb / C line mice with DNA of salmon sperm, or with immunogens preliminary prepared by conjugation of nucleosides with proteins with periodic oxidation method; naïve NZB mice NZB mice which spontaneously develop an autoimmune disease characterized by production of anti-RBC, - lymphocyte, and -ssDNA Abs, may be used [Patent FR 260615445]. Again, as all other total cfDNA immunoassays (ELISA and others), this one required preliminary obtaining anti- nucleic acid monoclonal antibodies with laborious hybridoma technology; the specificity / affinity / avidity of such of antibodies in relation of all types of cfDNA could not be confirmed / checked. As s clearly shown recently DNA structures in chromatin express distinct DNA functions, and each structure is a unique antigen. As is known in relation to the reverse situation (the measurement of the level of antibodies against DNA), it is necessary to carefully select the immunological pair "DNA-antibody to be measured by ELISA”): antibodies to elongated linear B DNA, cruciform dsDNA, ssDNA in transcriptionally active chromatin [Rekvig, O.P.46]. Indeed, to measure total (i.e. of all type) cfDNA with ELISA or other immunologic method the mix of the monoclonal capture antibodies of different specificity to different epitopes of cfDNA (alone or bind with proteins), is required. Also, as was shown signals for isotype control and even for uncoated microwells on ELISA tests for plasma, were similar to those for the specific anti-ds DNA coating (capturing) antibody [Hayden, H. et al.47]. Thus, there is an unmet need for precise cost and labor-efficient method or methods of cfDNA (total cfDNA) quantification in biofluids. SUMMARY OF THE INVENTION According to a first aspect of the invention there is provided a method for detection and / or quantification of cell free DNA (cfDNA) in a biological sample, the method comprising: (i) contacting a first linker histone immobilized on a solid surface with the biological sample to provide the immobilized first linker histone - cfDNA complex; (ii) contacting immobilized first linker histone - cfDNA complex with a second linker histone, which binds to the first linker histone - cfDNA complex; (iii) freeing said solid surface from unbound second linker histone; (iv) detecting or quantitating the binding of said second linker histone to the first linker histone - cfDNA complex; and (v) using the degree of such binding as a measure of amount of cfDNA in the sample. In some embodiments, this method further comprises the freeing said solid surface from unbound biological sample after step (i). According to a second aspect of the invention there is provided a method for detection and / or quantification of cell free DNA (cfDNA) in a biological sample, the method comprising: (i) contacting a first linker histone conjugated with a detectable marker with the biological sample to provide first linker histone-cfDNA complex; (ii) contacting the first linker histone - cfDNA complex with a second linker histone, said second linker histone immobilized on a solid surface binds to the first linker histone - cfDNA complex; (iii) detecting or quantitating the binding of said second linker histone to the first linker histone-cfDNA complex; and (iv) using the degree of such binding as a measure of amount of cfDNA in the sample. In some embodiments, this method further comprises the freeing said solid surface from unbound biological sample after step (i). In some embodiments, this method further comprises the freeing said solid surface from unbound the first linker histone - cfDNA complex after step (ii). In some embodiments, the linker histone is immobilized on a solid surface via linker. In some embodiments, the linker histone of the method is a linker histone H1 or a linker histone H5. In some embodiments, the linker histone of the method is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments, the linker histone H1 of the method is a human H1.0 linker histone. In some embodiments of the method of the invention, the linker histone of the method comprises an amino acid sequence which is at least 70% identical (e.g., at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 98% identical, or at least 99% identical) to the amino acid sequence: MSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSG VSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAA SGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGT KKVAKS AKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:1) In some embodiments, the linker histone H1 of the method of the invention is a human bis- met H1.3 linker histone having amino acid sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: TENSTSAPAAKPKRAKASKKSTDHPKYSDMIVAAIQAEKNRAGSSRQSIQKYIKSHY KVGENADSQIKLSIKRLVTTGVLKQTKGVGASGSFRLAKSDEPKKSVAFKKTKKEIK KVATPKKASKPKKAASKAPTKKPKATPVKKAKKKLAATPKKAKKPKTVKAKPVKA SKPKKA KPVKPKAKSSAKRAGKKK (SEQ ID NO:2). In some embodiment, any of the linker histone is a human bis-met H1.3 linker histone having amino acid sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO: 5). In some embodiments, the linker histone of the method comprises an amino acid sequence, which is at least 70% identical to the sequence: TDSPIPAPAPAAKPKRARAPRKPASHPTYSEMIAAAIRADKSRGGSSRQSIQKYVKSH YKVGQHADLQIKLAIRRLLTTGVLKQTKGVGASGSFRLAKGDKAKRSPAGRKKKKK AARKSTSPKKAARPRKARSPAKKPKAAARKARKKSRASPKKAKKPKTVKAKSLKTS KPKKAR RSKPRAKSGARKSPKKK (SEQ ID NO:3). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: MTESLVLSPAPAKPKRVKASRRSASHPTYSEMIAAAIRAEKSRGGSSRQSIQKYIKSH YK VGHNADLQIKLSIRRLLAAGVLKQTKGVGASGSFRLAKSDKAKRSPGKKKKA VRRSTSPKKAARPRKARSPAKKPKATARKARKKSRASPKKAKKPKTVKAKSRKASK AKKVKRSK PRAKSGARKSPKKK (SEQ ID NO:4). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: MSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSV SLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAAS GEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGTK KVAKS AKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:6). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: SETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVA ASKERSGVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSF KLNKKAASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKK PATAAGTKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKA APKKK (SEQ ID NO:7). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: HHHHHHTENSTSAPAAKPKRAKASKKSTDHPKYSDMIVAAIQAEKNRAGSSRQSIQ KYIKSHYKVGENADSQIKLSIKRLVTTGVLKQTKGVGASGSFRLAKSDEPKKSVAFK KTKKEIKKVATPKKASKPKKAASKAPTKKPKATPVKKAKKKLAATPKKAKKPKTV KAKPVKASKPKKAKPVKPKAKSSAKRAGKKK (SEQ ID NO:8). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: MSETAPAAPAAPAPAEKTPVKKKARKSAGAAKRKASGPPVSELITKAVAASKERSG VSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAA SGEAKPKAKKAGAAKAKKPAGAAKKPKKATGAATPKKSAKKTPKKAKKPAAAAG AKKAKSPKKAKAAKPKKAPKSPAKAKAVKPKAAKPKTAKPKAAKPKKAAAKKK (SEQ ID NO:9). In some embodiments, the second linker histone is conjugated to a horseradish peroxidase. In some embodiments, the linker histone is conjugated to an alkaline phosphatase. In some embodiments, the solid surface is an inner surface of a compartment of polymeric plate having a plurality of such compartments or an inner surface of polymeric tube. According to the invention the linker histone - cfDNA complex containing detectable marker may be detected or quantified with use of the substrate selected from 3, 3', 5, 5'- tetramethylbenzidine (TMB); o-phenylenediamine dihydrochloride (OPD); 2,2'-azinobis [3- ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS); p-Nitrophenyl phosphate (PNPP). In some embodiments the biological sample where cell free DNA (cfDNA) to be detected or quantified by claimed methods is a blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, an endometrial fluid sample, a urine sample, a saliva sample, a lymph sample, a tear fluid sample, a synovial fluid sample, or a sputum sample. In some embodiments, the solid surface any of the claimed methods for detection and / or quantification of cell free DNA (cfDNA) in a biological sample is a surface of porous material or membrane. According to further aspect of the invention there is provided a kit for detecting or quantifying cell free DNA (cfDNA) in a sample, the kit comprising: a first linker histone immobilized on solid surface and a second linker histone conjugated to a detectable marker. In some embodiments, any of the linker histone of the kit is linker histone H1 or a linker histone H5. In some embodiments, any of the linker histone of the kit is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments, any of the linker histone H1 of the kit is a human H1.3 linker histone. In some embodiments, any of the linker histone of the kit comprises the amino acid sequence, which is at least 70% identical (e.g., at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 98% identical, or at least 99% identical) to the sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9. In some embodiments, any of the linker histone of the kit is bis-met histone H1.3 having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5). In some embodiments, this kit further comprises a plastic plate having a plurality of compartments. In some embodiments, the plurality of compartments of the kit comprise a reaction chamber and one or more of the plurality of compartments further comprises at least one of linker histone immobilized on solid surface of inner wall of the reaction chamber. In some embodiments, a solid surface where the first linker histone immobilized is the surface of on magnetic beads. According to further aspect of the invention there is provided a method for detection and / or quantification of cell free DNA (cfDNA) in a biological sample, the method comprising: (i) contacting a first linker histone conjugated with a detectable marker with the biological sample to provide first linker histone-cfDNA complex; (ii) contacting the first linker histone - cfDNA complex with a second linker histone, said second linker histone immobilized on a solid surface binds to the first linker histone - cfDNA complex; (iii) detecting or quantitating the binding of said second linker histone to the first linker histone-cfDNA complex; and (iv) using the presence of such binding as a measure of presence cfDNA in the sample or using the degree of such binding as a measure of amount of cfDNA in the sample, wherein the contacting of the first linker histone conjugated with detectable marker with a biological sample is carried out (a) at sample application site disposed on or in a porous substrate of a lateral flow device or (b) prior to applying a biological sample to sample application site disposed on or in a porous substrate of a lateral flow device, and the second linker histone immobilized on a solid surface of the said porous substrate at detection site, wherein said porous substrate defines a flow path through the sample application site flows under capillary action away from said sample application site into said detection site where the contacting the first linker histone - cfDNA complex with a second linker histone immobilized on a solid surface, is carrier out; detecting the binding of the second linker histone to the first linker histone-cfDNA complex is carried out visually or instrumentally at the detection site where the accumulation of detectable marker produces a indicative of the presence or of the presence at not less than of defined level of the cfDNA in the biological sample. In some embodiments, the detectable marker is colored particle. In some embodiments, the detectable marker is fluorescent moiety and the visualization of such marker accumulation at the detection site is carried out with use of ultraviolet light. According to further aspect of the invention there is provided a lateral flow device for quantification of cell-free DNA (cfDNA) in a biological sample, where said lateral flow device comprises: a porous substrate; a sample application site disposed on or in said porous substrate; a detection site disposed on or in said porous substrate where said detection site comprises at least a first test line (L1) and a second test line (L2) each test line comprising linker histone, said linker histone immobilized on a solid surface of the porous substrate and bind a complex formed between cfDNA and free linker histone conjugated to a detectable marker; wherein said porous substrate defines a flow path through which a sample applied to the sample application site flows under capillary action away from said sample application site into said detection site; and wherein: said first test line (L1) and said second test line (L2) are configured so that either no test line signal or just a signal at the first test line (L1) is detectable when cfDNA level in a biological sample applied to said device is lower than a certain predefined cfDNA level; and said second test line (L2) is configured so that a signal is detectable at said second test line when cfDNA level in a biological sample applied to said device is greater than a certain predefined cfDNA level. In some embodiments, in the lateral flow device for quantification of cell-free DNA (cfDNA) in a biological sample, the certain predefined cfDNA detected is the indicative level of need of cfDNA-scavenging therapy of a cfDNA-associated disease or a pathological condition. In some embodiments, the lateral flow device further comprises a control line downstream from said first test line and said second test line, wherein said control line comprises binding moiety that can capture the said free linker histone conjugated to the detectable marker, in the presence or absence of cfDNA in the biological sample. In some embodiments, the lateral flow device further comprises a complex-forming site comprising a linker histone conjugated with a detectable marker, where this complex-forming site is disposed in sample application site and / or between sample application site and the detection site. In some embodiments, the detectable marker of the lateral flow device is selected from the group consisting of a colorimetric marker, a fluorescent marker, a radioactive marker, and a magnetic marker. In some embodiments, any of the linker histones of the lateral flow device is a linker histone H1 or a linker histone H5. In some embodiments, any of the linker histones of the lateral flow device is the linker histone selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments, any of the linker histones of the lateral flow device is the linker histone comprises the amino acid sequence which is at least 70% identical (e.g., at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 98% identical, or at least 99% identical) to the sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9. In some embodiments, the linker of the lateral flow device is a human bis-met H1.3 linker histone having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5). According to further aspect of the invention there is provided a method for determination of a status of cfDNA-associated disease in а subject, which comprises the steps of: (i) detecting or quantification a сfDNA in a biological sample of a body fluid of a subject according to the methods of the invention; and (ii) using the cfDNA level measured to determine the cfDNA-associated disease status of the subject. According to further aspect of the invention there is provided a method for assessment of a subject for suitability for cfDNA-scavenging therapy of a cfDNA-associated disease which comprises the steps of: (i) detecting or quantification a cfDNA in a biological sample of the subject according to the methods of the invention; and (ii) using the cfDNA level measured as a parameter of assessment of suitability of a subject for cfDNA-scavenging therapy. In some embodiments of a method for assessment of a subject for suitability for cfDNA- scavenging therapy of a cfDNA-associated disease, the suitability of a subject for cfDNA- scavenging therapy of a cfDNA-associated disease is considered as blood plasma level of cfDNA at least 500 ng / mL, at least 700 ng / mL, at least 800 ng / mL, at least 900 ng / mL, at least 1000 ng / mL, at least 1100 ng / mL, at least 1200 ng / mL, at least 1300 ng / mL, at least 1400 ng / mL, at least 1500 ng / mL, at least 1600 ng / mL, at least 1700 ng / mL, at least 1800 ng / mL, at least 1900 ng / mL, at least 2000 ng / mL, at least 2100 ng / mL, at least 2200 ng / mL, at least 2300 ng / mL), at least 2500 ng / mL, at least 2600 ng / mL, at least 2700 ng / mL, at least 2800 ng / mL, at least 2900 ng / mL, at least 3000 ng / mL, at least 3100 ng / mL, at least 3200 ng / mL, at least 3300 ng / mL, at least 3400 ng / mL, at least 3500 ng / mL, at least 3600 ng / mL, at least 3700 ng / mL, at least 3800 ng / mL, at least 3900 ng / mL, at least 4000 ng / mL, at least 4100 ng / mL, at least 4200 ng / mL, at least 4300 ng / mL, at least 4400 ng / mL, at least 4500 ng / mL, at least 4600 ng / mL, at least 4700 ng / mL, at least 4800 ng / mL, or at least 5000 ng / mL in blood plasma when the subject is considered to be suitable for cfDNA-scavenging therapy of a cfDNA-associated disease. According to further aspect of the invention there is provided a method for monitoring a treatment of cfDNA-associated disease in a subject which comprises the steps of: (i) detecting or quantification a cfDNA in a biological sample of a biofluid of the subject according to the methods of the invention; (ii) repeating the detection or quantification of a cfDNA in a biological sample of a body fluid of the subject at least one other occasion; (iii) using any changes in the cfDNA level detected as a parameter for any changes in the course of cfDNA-associated disease of the subject. In some embodiments cfDNA-associated disease is selected from the group of cancer, metastatic cancer, acute organ failure, organ infarct (including myocardial infarction and ischemic stroke), hemorrhagic stroke, autoimmune disorders, graft-versus-host-disease (GVHD), graft rejection, sepsis, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), graft- versus-host-disease (GVHD), traumatic injury, crush syndrome, proinflammatory status in aged individuals, diabetes, atherosclerosis, neurodegenerative disease, autoimmune disease, eclampsia, infertility, coagulation disorder, pregnancy-associated complications and infection (bacterial, fungal or viral, including COVID-19). In some embodiments cfDNA-scavenging therapy is selected from the group: therapy with compound destroying cfDNA in biofluids; therapy with compound binding or deactivate cfDNA in biofluids. In some embodiments, cfDNA-scavenging therapy is extracorporeal therapy removing cfDNA from biofluids wherein the biofluid is first removed from the subject then passed over columns with specific cfDNA-binding ligand to remove cfDNA and returned into the subject. In a further embodiment cfDNA-binding ligand is a protein of linker histone H 1 family. In a further embodiment the linker histone H1 is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments the biofluid is blood. In some embodiments the subject is an animal or a human. According to further aspect of the invention there is provided a method of assessment of effectivity of an extracorporeal column to remove cfDNA from a biofluid wherein the biofluid is first removed from the subject then passed over the column with specific cfDNA binding ligand to remove cfDNA and returned into the subject, which comprises the steps of: (iii) quantification a сfDNA in biofluid removed from the subject and sampling before passing over the column according to the methods of the invention; (iv) quantification a сfDNA in the sample biofluid returned into the subject and sampling after passing over the column according to the methods of the invention; and (v) using the difference between cfDNA level measured at step (i) and cfDNA level measured at step (ii) to determine effectivity of the extracorporeal column to remove cfDNA from the biofluid. In some embodiments cfDNA-binding ligand is a protein of linker histone H1 family and is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments biofluid is blood or plasma or lymph or cerebrospinal fluid. According to further aspect of the invention there is provided a method of assessment of effectivity of an extracorporeal column to remove cfDNA from a biofluid, wherein the biofluid is first removed from the perfused organ then passed over the column filled with cfDNA-affinity matrix to remove cfDNA and returned into the perfused organ, which comprises the steps of: (i) quantification a сfDNA in biofluid removed from the perfused organ and sampling before passing over the column according to the methods of the invention; (ii) quantification a сfDNA in the sample biofluid returned into the subject and sampling after passing over the column according to the methods of the invention; and (iii) using the difference between cfDNA level measured at step (i) and cfDNA level measured at step (ii) to determine effectivity of the extracorporeal column to remove cfDNA from the biofluid. In some embodiments cfDNA-affinity matrix contains a protein of linker histone H1 family and is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments biofluid is blood or plasma or lymph or cerebrospinal fluid. In some embodiments of a method of the invention of assessment of effectivity of an extracorporeal column (containing cfDNA-affinity matrix) to remove cfDNA from a biofluid wherein the biofluid is first removed from the perfused organ then passed over the column filled with а cfDNA-affinity matrix to remove cfDNA and returned into the perfused organ cfDNA-binding ligand is a protein of linker histone H1 family and is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone, biofluid is selected from blood, red blood cells (RBCs) suspension, fresh frozen plasma (i.e thawed immediately before use), colloid solution with hemoglobin‐based oxygen carrier (HBOC). BRIEF DESCRIPTION OF THE DRAWINGS FIG.1 shows the standard calibration curve specified in Example 2. FIG.2 shows the scheme of typical lateral flow device configured to detect or quantitate an analyte (for example, cfDNA). FIG.3 illustrates the principle of a quantitation of cfDNA in biofluid having varying concentrations cfDNA using a lateral flow assay (LFA) device. FIG.4 shows distribution of cfDNA concentrations in healthy volunteers. FIG.5 shows cfDNA values in healthy volunteers, ST-ACS patients on admission and 24 hours after percutaneous coronary intervention (PCI) FIG.6 shows ROC curves for cfDNA concentration before and after PCI in relation to the risk of implantation of ≥2 stents (a) and the risk of ≥2 or more zones of local contractility impairment (b) in ST-ACS patients DETAILED DESCRIPTION OF THE INVENTION Definitions As used herein, the terms “cell free DNA (cfDNA)”, “extracellular DNA (eDNA)”, are used interchangeably to refer to DNA present in a biofluid located outside of cells whether in naked-form, protein-bound (including DNA of neutrophil extracellular traps (NETs)), or associated with extracellular vesicles (EVs). [See, for example, Bronkhorst, A.J. et al.48]. As used herein, the terms “circulating DNA”, “circulating cell free DNA (cfDNA)”, and“circulating extracellular DNA (eDNA)” are used interchangeably to refer to DNA present in blood or plasma located outside of circulating cells of hematopoietic and non- hematopoietic origin. As used herein, the term “linker histone” is used herein to refer to the primary protein components of chromatin which bind to the nucleosome core particle at the linker (internucleosomal) DNA entry and exit points, provide an interaction region between adjacent nucleosomes and generate second- order chromatin structure (i.e., nucleosomal filament) by drawing adjacent nucleosomes together. Linker histones typically comprise approximately 200 amino acids and typically possess a tripartite structure conserved across all eukaryotes, including a short and flexible N-terminal tail, a structured globular domain (GH1) which interacts with a nucleosome dyad, and a structurally disordered, lysine-rich C- terminal tail. Linker histones and exist as variants with varying sequences. The linker histones H1 and H5 are the most divergent group of the histone proteins. Histone H1 protein family comprises 12 subtypes [Parseghian M.H. et al.49] The individual subtypes can be grouped into 3 distinct groups: (i) the somatic replication-dependent subtypes (H1.1–H1.5) that are expressed mainly in the S-phase, (ii) the somatic replication-independent variants (H1.0 and H1.10) expressed during the complete cell cycle and (iii) the germ line-specific (testis or oocyte) subtypes (H1.6 (TS), H1.7 (TS), two splice variants of H1.8 (OO) and H1.9 (TS)). [See, e.g., Brockers, K. et al Schneider, R.50; Hergeth, S.P., Schneider, R.51]. Linker histone H5 from chicken erythrocytes was known at its discovery to be an equivalent of H1 and has long been known to be a specific ortholog of H1.0, as H5 does not form a separate high-level structural class of histones [Talbert P.B. et al52]. As used herein, the terms "polypeptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non- naturally occurring amino acid polymer. Unless otherwise indicated, a particular polypeptide sequence also implicitly encompasses conservatively modified variants thereof. As used herein, the term “detectable marker” refers to enzymes, gold nanoparticles, fluorescent dyes and other markers, which can be used in colorimetric, chemiluminescent or fluorescence detection methods. As used herein, the term “solid surface” refers to a solid surface used in the assay as described in the invention for coating linker histone in order to capture an cfDNA in a biological sample. The solid surface thus provides a solid phase for reactions to take place between components of the biological sample and various reagents during various steps in the methods, device and kits claimed, and it serves to isolate and concentrate reacting species from a fluid sample. The solid surface may be in various configuration such as a test tube, a well (a microtiter well), a bead (a magnetic bead), a particles (magnetic particles) a rod, or a strip (a sheet), a porous substrate, a membrane (f.e. a porous membrane), The solid surface may be composed of inorganic material (such as glass), a metal (such as gold) or metal oxide (such as magnetite Fe3O4, maghemite γFe2O3, ferrites), an alloy, or a composite such as for example indium-tin oxide or mica, an organic polymer such as polystyrene, cellulose (diazotized cellulose), agarose ( cross-linked agarose), cross-linked dextrane, nitrocellulose, polyvinylchloride, polyvinylidine fluoride. The solid surface may be composed of a material consisting of parts of both organic and inorganic components (e.g. some hybrid silicates, such as compounds of the structure R—Si—O—). As used herein, the term "lateral flow" refers to liquid flow along the plane of the porous substrate. As the assay devices are "lateral flow" assay devices or “lateral flow” devices, they are configured: (a) - to receive a diluted or undiluted biological sample at a sample application site and, then - to provide for the sample through a complex-forming site to a detection site, such that the sample is wicked laterally along the device from the sample application site through a complex forming site to the detection site by capillary action. or (b) - to receive a diluted or undiluted a biological sample preliminary contacted to a complex- forming agent to form a complex of “an analyte - complex-forming agent” at a sample application site and, then - to provide the sample with the complex to move laterally to the detection site by capillary action. or (c) - to receive a diluted or undiluted a biological sample a sample application site to contact to a complex-forming agent to form a complex of “an analyte - complex-forming agent” directly in a sample application site and, then - to provide the sample with the complex to move laterally to the detection site by capillary action. As used herein, the terms “subject” and “patient” are used interchangeably and refer to animals, including mammals such as humans, veterinary animals (e.g., cats, dogs, cows, horses, sheep, pigs, etc.). By “sequence identity” is intended the same amino acid residues are found within the variant (candidate) sequence and a reference sequence when a specified, contiguous segment of the amino acid sequence of the variant (candidate) is aligned and compared to the amino acid sequence of the reference sequence. As used herein, "percent (%) sequence identity" with respect to the amino acid sequences identified is defined as the percentage of amino acid residues in a variant (candidate) sequence that are identical with the amino acid residues in a reference sequence. Methods for comparing the identity of two or more sequences are well known in the art. For example, programs available in the Wisconsin Sequence Analysis Package, version 9.1, for example the programs BESTFIT and GAP, may be used to determine the % identity between two polypeptide sequences. BESTFIT uses the “local homology” algorithm of Smith and Waterman and finds the best single region of similarity between two sequences. Other programs for determining identity between sequences are also known in the art, for instance the Needle program, which is based on the Needleman and Wunsch algorithm, described by Needleman and Wunsch53.Peptides consisting of an amino acid sequence “at least 70%, 75%, 80%, 85%, or 90% identical” to a reference sequence may comprise mutations, such as deletions, insertions and / or substitutions compared to the reference sequence. As used herein, the term "disease" refers to any alteration in state of the body or of some of the organs, interrupting or disturbing the performance of the functions and / or causing symptoms such as discomfort, dysfunction, distress. A disease can also include a distemper, ailing, ailment, malady, disorder, sickness, illness, complain, interdisposition and / or affectation. A “cfDNA-associated disease,” as used herein, is intended to include any disease associated with the high level of cfDNA in systemic circulation. Such a disease may be caused or promoted by excess circulating cfDNA in the blood. A “cfDNA-associated disease” include, at least, cancer, metastatic cancer, acute organ failure, organ infarct (including myocardial infarction and ischemic stroke), hemorrhagic stroke, autoimmune disorders, graft-versus- host-disease (GVHD), graft rejection, sepsis, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), graft- versus-host-disease (GVHD), traumatic injury, crush syndrome, proinflammatory status in aged individuals, diabetes, atherosclerosis, neurodegenerative disease, autoimmune disease, eclampsia, infertility, coagulation disorder, pregnancy-associated complications and infection, (including COVID- 19). High circulating cfDNA level predict worse outcomes and worse prognosis for these conditions. In the context of the present invention insofar as it relates to any of the disease conditions recited herein, the terms “treat”, “treatment”, and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression of such condition. Within the meaning of the present invention, the term “treat” also denotes to arrest, delay the onset (i.e., the period prior to clinical manifestation of a disease) and / or reduce the risk of developing or worsening a disease. The terms “treat”, “treatment”, and the like regarding a state, disorder or condition may also include (1) preventing or delaying the appearance of at least one clinical or sub-clinical symptom of the state, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition; or (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or sub-clinical symptom thereof; or (3) relieving the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or sub-clinical symptoms. The term "extracorporeal device" as used herein refers to any assembly known in the art to enable the purification of liquid solutions, such as, without limitation, e.g., any hollow-ware, a column, a column matrix, a filter, a membrane, a semi-permeable material, a bead (e.g., a microbead or a nanobead, including magnetic beads), or a tubing. The terms “extracorporeal column”, “column”, “cartridge” and “extracorporeal cartridge” are used interchangeably herein in the context of an apheresis device. The term “cfDNA-affinity matrix” as used herein refers to (i) a solid support onto which a ligand (cfDNA-binding ligand) is immobilized or to (ii) a solid support formed by the cfDNA-binding ligand itself (e.g., a water-insoluble oligomer, polymer or co-polymer comprising any of the cfDNA-binding molecules). As used herein "cfDNA-scavenging therapy" is defined to include all the type of therapy specifically lowers circulating cfDNA through, for example, its specific binding or specific destroying or specific removal. Methods and kit of the invention. The specific reaction between biomolecules are widely used for detection and / or quantification of the various high molecular analytes according to the equilibrium reaction scheme type A + B → AB. This principle commonly used in immunometric methods are based on specific reactions between the antigen and the antibody. Both, the course and the result of the reaction depend on the structure of these components and the way they are combined. The enzyme-linked immunosorbent assay (ELISA) technic is most commonly employed indirect immunometric method. ELISA belongs to the group of solid-phase tests and is an enzyme immunoassay that uses a color reaction of the enzyme coupled to the antibody. Usually, the ELISA test is performed on micro-plates, where the antigen-antibody reactions takes place on the surface walls (i.e. solid phase) of the microwells. ELISA used two types of antibodies are used: primary antibody which (a) is not labeled and (b) recognizes a given antigen, and secondary, which (a) is labeled with enzyme and (b) recognizes primary antibody. The secondary antibody attaches to a given primary antibody and fact of attachment may be detected and / or amount of attached secondary antibody proportional of quantity of the antigen of interest, may be quantified. [McCarthy, J54]. The standard ELISA technique commonly does not show high sensitivity and, therefore, it was refined by developing so-called “sandwich”-type ELISA, which differs in that the antigen is not immobilized directly on the solid phase surface but is bound to the coat antibody introduced on the solid phase surface first. ELISA technic has some disadvantages: commonly, a limited number of commercially available specific antibodies for specific antigen and reduced specificity of antibodies labeled with enzymes, and particularly, in the relation of total cfDNA quantification as was mentioned above, the first of all, a priory lack of primary (monoclonal or polyclonal) antibodies with “universal” specificity to all types of cfDNA. For example, the ELISA used the primary antibody specifically recognized one type of histone H3.1 in nucleosomes (containing cfDNA) cannot recognize other variant of nucleosomes with another histone H3.1 variant [Rahier, J.F. et al 55 ]. Also, secondary antibody might cross-react with the endogenous immunoglobulins or other proteins of the sample. Also, the major disadvantages of this type of ELISA are the time and expense and the necessary use of “matched pair” [Shah, K., Maghsoudlou, P.56], i.e. antibodies must not share an epitope or have steric hinderance. Matched pairs are the basis of sandwich ELISAs as they should be capable of detecting different epitopes on the same antigen, so they can be used together in a sandwich ELISA: on the one hand, the formation of steric hindrance after an antibody binds to an antigen will prevent most of other antibodies binding to the antigen again, and the antibodies that can be successfully paired with each other have stringent requirements on the antibody binding angle and the distance between the identified antigen determinants; on the other hand, each detection system has different requirements on antibody pairs since the solid phases and labels adopted are different, for example, not all antibody pairs that can be used in ELISA can be used in chemiluminescent immunoassay (CLIA), which puts forward more requirements on antibody pairs. The inventors surprisingly found that for cfDNA detection or cfDNA quantification purposes a linker histone protein (a first linker histone) may be used in role of the moiety which specifically recognizes (specifically binds) cfDNA and creates complex “cfDNA-linker histone” (like the first / capture antibody in classic sandwich immunometric methods) , and, then, a linker histone protein (a second linker histone) may be used in role of a molecule recognizes (specifically binds) this “cfDNA- (first) linker histone H1” pre-formed complex (like the second / detecting antibody in classic sandwich immunometric methods). As was surprisingly found by the inventors, the first linker histone does not interfere with the second linker histone from recognizing cfDNA and depending on which of the two histones (the first or the second) the detectable marker is pre-attached, the present invention provides different particular variants of solid-surface method for the detection and / or quantification of cfDNA in biofluids. The method of the present invention comprises: (i) contacting a first linker histone immobilized on a solid surface with the biological sample to provide the immobilized first linker histone - cfDNA complex; (ii) contacting immobilized first linker histone - cfDNA complex with a second linker histone conjugated to a detectable marker and which bind to the first linker histone - cfDNA complex; (iii) freeing said solid surface from unbound second linker histone conjugated to a detectable marker; (iv) detecting or quantitating the binding of said second linker histone conjugated to a detectable marker to the first linker histone - cfDNA complex; and (v) quantification of the detectable marker as a measure of amount of cfDNA in the sample. In some embodiments, this method further comprises the freeing said solid surface from unbound biological sample after step (i). The role of a detectable label may play the enzymes: to quantify the number of labeled linker histone H1 in the complex “cfDNA-the first histone H1” with the second histone H1, the activity of the enzyme should be detected. Enzymes may be attached to first histone by means of glutaraldehyde or sodium periodate or enzyme–antienzyme complex (e.g., peroxidase–antiperoxidase (PAP), alkaline phosphatase–alkaline antiphosphatase (APAAP)). According to further aspect of the invention there is provided a method for detection and / or quantification of cell free DNA (cfDNA) in a biological sample, the method comprising: (i) contacting a first linker histone conjugated with a detectable marker with the biological sample to provide first linker histone-cfDNA complex; (ii) contacting the first linker histone - cfDNA complex with a second linker histone, said second linker histone immobilized on a solid surface binds to the first linker histone - cfDNA complex; (iii) detecting or quantitating the binding of said second linker histone to the first linker histone-cfDNA complex; and (iv) using the presence of such binding as a measure of presence cfDNA in the sample or using the degree of such binding as a measure of amount of cfDNA in the sample. In some embodiments, this method further comprises freeing said solid surface from unbound biological sample after step (i). In some embodiments, this method further comprises the freeing said solid surface from unbound the first linker histone - cfDNA complex after step (ii). In some embodiments, a linker histone is immobilized on a solid surface via linker. In some embodiments, this linker is antibody targeting to the respective linker histone. In some embodiments, the linker histone of the method of the cfDNA detection or quantification is a linker histone H1 or a linker histone H5. In some embodiments, the linker histone of the method of the cfDNA detection or quantification is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments, the linker histone of the method of the cfDNA detection or quantification is H1 is a H1.3 linker histone. In some embodiments, the linker histone of the method of the cfDNA detection or quantification is H1 is a bis-met H1.3 linker histone having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5). In some embodiments, the linker histone H1 of the method of the cfDNA detection or quantification is a H1.0 linker histone. In some embodiments, the linker histone of the method comprises an amino acid sequence which is at least 70% identical (e.g., at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 98% identical, or at least 99% identical) to the sequence: MSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSV SLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAAS GEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGTK KVAKS AKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:6). In some embodiments, the linker histone of the method comprises an amino acid sequence which is at least 70% identical to the sequence: TENSTSAPAAKPKRAKASKKSTDHPKYSDMIVAAIQAEKNRAGSSRQSIQKYIKSHY KVGENADSQIKLSIKRLVTTGVLKQTKGVGASGSFRLAKSDEPKKSVAFKKTKKEIK KVATPKKASKPKKAASKAPTKKPKATPVKKAKKKLAATPKKAKKPKTVKAKPVKA SKPKKA KPVKPKAKSSAKRAGKKK (SEQ ID NO:2). In some embodiments, the linker histone of the method comprises an amino acid sequence which is at least 70% identical to the sequence: TDSPIPAPAPAAKPKRARAPRKPASHPTYSEMIAAAIRADKSRGGSSRQSIQKYVKSH YKVGQHADLQIKLAIRRLLTTGVLKQTKGVGASGSFRLAKGDKAKRSPAGRKKKKK AARKSTSPKKAARPRKARSPAKKPKAAARKARKKSRASPKKAKKPKTVKAKSLKTS KPKKAR RSKPRAKSGARKSPKKK (SEQ ID NO:3). In some embodiments, the linker histone of the method comprises an amino acid sequence which is at least 70% identical to the sequence: MTESLVLSPAPAKPKRVKASRRSASHPTYSEMIAAAIRAEKSRGGSSRQSIQKYIKSH YK VGHNADLQIKLSIRRLLAAGVLKQTKGVGASGSFRLAKSDKAKRSPGKKKKA VRRSTSPKKAARPRKARSPAKKPKATARKARKKSRASPKKAKKPKTVKAKSRKASK AKKVKRSK PRAKSGARKSPKKK (SEQ ID NO:4). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: SETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVA ASKERSGVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSF KLNKKAASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKK PATAAGTKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKA APKKK (SEQ ID NO:7). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: HHHHHHTENSTSAPAAKPKRAKASKKSTDHPKYSDMIVAAIQAEKNRAGSSRQSIQ KYIKSHYKVGENADSQIKLSIKRLVTTGVLKQTKGVGASGSFRLAKSDEPKKSVAFK KTKKEIKKVATPKKASKPKKAASKAPTKKPKATPVKKAKKKLAATPKKAKKPKTV KAKPVKASKPKKAKPVKPKAKSSAKRAGKKK (SEQ ID NO:8). In some embodiments, the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: MSETAPAAPAAPAPAEKTPVKKKARKSAGAAKRKASGPPVSELITKAVAASKERSG VSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAA SGEAKPKAKKAGAAKAKKPAGAAKKPKKATGAATPKKSAKKTPKKAKKPAAAAG AKKAKSPKKAKAAKPKKAPKSPAKAKAVKPKAAKPKTAKPKAAKPKKAAAKKK (SEQ ID NO:9). In some embodiments, the detectable marker of the method of the invention is horseradish peroxidase (HRP). In some embodiments, the detectable marker of the method of the invention is alkaline phosphatase (AP). Other examples of enzymes, useful in methods, kit and device of the invention include: β-D- galactosidase, glucose oxidase. In some embodiments, the solid surface is an inner surface of a compartment of polymeric plate having a plurality of such compartments or an inner surface of polymeric tube. According to the invention the linker histone - cfDNA complex containing detectable marker may be detected or quantified with use of the substrate selected from 3, 3', 5, 5'- tetramethylbenzidine (TMB); o-phenylenediamine dihydrochloride (OPD); 2,2'-azinobis [3- ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS); p-Nitrophenyl phosphate (PNPP). In some embodiment the presence of other substrates (also called as chromogens) is necessary also for the enzymatic reaction to occur: for HRP, for example, 3,3- diaminobenzidine (DAB), 3-amino-9-ethylcarbazole, dimethylformamide (AEC), 2,2′-azino- bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS); for Alkaline phosphatase (AP), for example, naphthol phosphate AS-MX + Fast blue BB, naphthol phosphate AS-TR + hexazonium fuchsine, 5-bromo-4-chloro-3-indolyl phosphate + nitrotetrazolium blue; for β- D-galactosidase, for example, 6-bromo-2-naphthyl + Fast blue BB, 5-bromo-4-chloro indolyl + Fast blue BB; for Glucose oxidase, for example, phenazine methosulphate + nitrotetrazolium blue. [See, as example, Zabel, M.57]. In some embodiments the biological sample where cell free DNA (cfDNA) to be detected or quantified by claimed methods is a blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, an endometrial fluid sample, a urine sample, a saliva sample, a lymph sample, a tear fluid sample, a synovial fluid sample, or a sputum sample. In some embodiments, the solid surface any of the methods of the invention for detection and / or quantification of cell free DNA (cfDNA) in a biological sample is a surface of porous material or membrane. According to further aspect of the invention there is provided a kit for detecting or quantifying cell free DNA (cfDNA) in a sample, the kit comprising: a first linker histone immobilized on solid surface and a second linker histone conjugated to a detectable marker. In some embodiments, any of the linker histone of the kit of the invention is linker histone H1 or a linker histone H5. In some embodiments, any of the linker histone of the kit of the invention is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments, any of the linker histone H1 of the kit is a H1.3 linker histone. In some embodiment, any of the linker histone H1 of the kit of the invention is a bis-met H1.3 linker histone having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5). In some embodiments, any of the linker histone H1 of the kit is a H1.0 linker histone. In some embodiments, any of the linker histone of the kit of the invention comprises the amino acid sequence which is at least 70% identical (e.g., at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 98% identical, or at least 99% identical) to the sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9. In some embodiments, this kit further comprises a plastic plate having a plurality of compartments. In some embodiments, the plurality of compartments of the kit comprise a reaction chamber and one or more of the plurality of compartments further comprises at least one of linker histone immobilized on solid surface of inner wall of the reaction chamber. The most frequently used a reaction chamber is made of polymer (plastic) and plurality of compartments is plurality of wells (i.e. microwells, holes) configured into a microtiter plate or assembled strip(s). Usually, the microtiter plate wells (i.e. microwells, holes) for coating with proteins have a modified inner surface, i.e. highly charged polystyrene surface with high affinity to molecules with polar or hydrophilic groups. Such kind of surface has a high binding capacity for proteins. [Minic, R., Zivkovic, I.58]. According to further aspect of the invention, a solid surface wherein a first linker histone immobilized is the surface of magnetic beads or particles. The most common examples of magnetic beads or particles have magnetic iron oxide cores and non-magnetic polymer shells featuring surface chemical functionality for attachment of biomolecules. The magnetic core can also consist of a collection of magnetic nanoparticles embedded in a polymer core. Usually magnetic beads or particles have sizes in the range 50 nm to 100 μm in diameter. In some embodiments the magnetic beads (MB) or particles are conjugated with a first linker histone and are held onto a sensor surface by a magnetic field; cfDNA is then captured onto the magnetic beads or particles followed by adding labeled (for example, enzyme-labeled) a second linker histone. According the invention, in case of use an enzyme as the label, a current proportional to cfDNA concentration is generated by injecting a solution containing a substrate for the enzyme label and using a potential to electrolyze the enzyme product, or by using a mediator that exchanges electrons with the enzyme. [See for example review of Mani, V. et al.59]. Such coupling electrochemical sensors with magnetic beads hold significant promise for clinical diagnostic devices. In some embodiments of the invention of the methods of cfDNA quantification, these magnetic beads (MB) or particles are gold-coated ones used as a solid phase for developing a sandwich-type (i.e. sandwich of “a first linker histone – cfDNA- a second linker histone labeled with a detectable marker”) assay to detect or quantify cfDNA using horseradish peroxidase as the enzyme label. Analogous methods of using gold-coated is described for sandwich ELISA [Zhang, H., Meyerhoff, M.E.60]. In some embodiments of the of the invention of the method of cfDNA quantification, electrochemiluminescence (ECL) detection is used where a second linker histone is labeled by electrogenerated chemiluminescence (ECL) label, for example, tris (2,2′-bipyridyl) ruthenium(II), (RuBPY), and the RuBPY-labeled second histone is added to bind to a first histone-cfDNA complex which initiates ECL when its oxidized form reacts with a suitable sacrificial reductant such as, for example, tri-n-propylamine. In some embodiments of the of the invention of the method of cfDNA quantification with use of ECL -detectable marker, magnetic beads with immobilized a first linker histone that capture cfDNA from sample of diluted or undiluted biofluids, are used; RuBPY-labeled second histone is added to bind to the first linker histone-cfDNA complex, and the beads with the sandwich “the first linker histone-cfDNA-the second linker histone” on their surfaces are washed and magnetically captured onto an electrode for ECL measurement. In some embodiments of the of the invention of the method of cfDNA quantification with use of ECL-detectable marker, a first linker histone is attached to the surface magnetic beads (MB) and a second linker histone-coated polymeric beads (PB) entrapping a number of electrogenerated chemiluminescence (ECL) labels to form “the first linker-histone immobilized on the MB solid surface” and “the second linker histone conjugated to PB / ECL detectable label”, respectively; sandwich-type aggregates “MB-the first linker histone- cfDNA-second linker histone- PB / ECL detectable label” is formed when “the first linker- histone immobilized on the MB solid surface” is mixed with “the second linker histone conjugated to PB / ECL detectable label” in the presence of cfDNA to be quantified in the sample of the biofluid, undiluted or preliminary diluted. These newly formed sandwich-type aggregates, along with any unbound “the first linker- histone immobilized on the MB solid surface”, are magnetically separated from the free unbound “second linker histone conjugated to PB / ECL detectable label” and dissolved in аcetonitrile containing tri-n-propylamine as an ECL co-reactant; The ECL signal is obtained by cyclic voltammetry scanning (i.e. instrumentally), and the ECL intensity is proportional to the analyte сfDNA concentration. According to further aspect of the invention there is provided a method for detection and / or quantification of cell free DNA (cfDNA) in a biological sample, the method comprising: (i) contacting a first linker histone conjugated with a detectable marker with the biological sample to provide first linker histone-cfDNA complex; (ii) contacting the first linker histone - cfDNA complex with a second linker histone, said second linker histone immobilized on a solid surface binds to the first linker histone - cfDNA complex; (iii) detecting or quantitating the binding of said second linker histone to the first linker histone-cfDNA complex; and (iv) using the presence of such binding as a measure of presence cfDNA in the sample or using the degree of such binding as a measure of amount of cfDNA in the sample, wherein the contacting of the first linker histone conjugated with detectable marker with a biological sample is carried out (a) at sample application site disposed on or in a porous substrate of a lateral flow device or (b) prior to applying a biological sample to sample application site disposed on or in a porous substrate of a lateral flow device, and the second linker histone immobilized on a solid surface of the said porous substrate at detection site, wherein said porous substrate defines a flow path through the sample application site flows under capillary action away from said sample application site into said detection site where the contacting the first linker histone - cfDNA complex with a second linker histone immobilized on a solid surface, is carrier out; detecting the binding of the second linker histone to the first linker histone-cfDNA complex is carried out visually at the detection site where the accumulation of detectable marker produces a indicative of the presence or of the presence at not less than of defined level of the cfDNA in the biological sample. In some embodiments, the detectable marker is colored particle. In some embodiments, the detectable marker is fluorescent moiety and the visualization of such marker accumulation at the detection site is carried out with use of ultraviolet light. In some embodiments, the detectable marker is enzyme and the visualization of such marker accumulation at the detection site is carried out with use of a substrate (chromogen) for the enzyme. This enzyme, for example, may be HRP, for example, in a manner described by Zhang C., et al61for lateral flow assay device. According to further aspect of the invention there is provided a lateral flow device for quantification of cell-free DNA (cfDNA) in a biological sample, where said lateral flow device comprises: a porous substrate; a sample application site disposed on or in said porous substrate; a detection site disposed on or in said porous substrate where said detection site comprises at least: (1) a first test line (L1) and (2) a second test line (L2), each test line comprising linker histone, said linker histone immobilized on a solid surface of the porous substrate and bind a complex formed between cfDNA and free linker histone conjugated to a detectable marker; wherein said porous substrate defines a flow path through which a sample applied to the sample application site flows under capillary action away from said sample application site into said detection site; and wherein: said first test line (L1) and said second test line (L2) are configured so that either no test line signal or just a signal at the first test line (L1) is detectable when cfDNA level in a biological sample applied to said device is lower than a certain predefined cfDNA level; and said second test line (L2) is configured so that a signal is detectable at said second test line when cfDNA level in a biological sample applied to said device is greater than a certain predefined cfDNA level. The sample application site, conjugate region and detection region may be part of a capillary flow member that is made up of a porous substrate that supports capillary flow from the sample application site to the detection site. The capillary flow member may be fabricated from any convenient material. Examples of suitable materials include highly absorbent or bibulous materials, where bibulous materials of interest include, but are not limited to: organic or inorganic polymers, and natural and synthetic polymers. More specific examples of suitable highly absorbent or bibulous materials include, without limitation, glass, glass fiber, cellulose, nylon, crosslinked dextran, untreated paper, porous paper, various chromatographic papers, nitrocellulose, nitrocellulose blends with polyester or cellulose, rayon, acrylonitrile copolymer and plastic. While the capillary flow member and overall configuration of the lateral flow assay device may vary, in certain embodiments the capillary flow member has a strip configuration. Where the highly absorbent or bibulous material is configured as a strip, the capillary flow member has a length that is longer than its width. While any practical configuration may be employed, in some instances the length is longer than the width by 1.5-fold or more, such as 2-fold or more, e.g., 10-fold or more, including 20-fold or more. In some instances, the length of the bibulous member ranges from 0.5 to 20 cm, such as 1.0 to 15 cm, e.g., 2.0 to 10 cm, while the width ranges 0.1 to 5.0 cm, such as 0.5 to 2.5 cm, e.g., 1 to 2 cm. The thickness of the capillary flow member may also vary, ranging in some instances from 0.01 to .05 cm, such as 0.1 to 0.4 cm, e.g., 0.1 to 0.25 cm. As indicated above, the capillary flow member includes a sample application site, a complex- forming site (in case if a sample contacting a linker histone conjugated to detectable marker immediately at the porous substrate of the device), detection site, where these sites are arranged such that liquid sample added to the sample application site flows or wicks through the (optionally) complex-forming to the detection site and in some instances, e.g., as further described below, to further downstream sites, e.g., control sites, wicking sites / absorbent pads, etc. The sample application site may simply be a first site of the capillary flow member, e.g., a site positioned closer to one end, which may be viewed as the proximal end, of the capillary flow member. Alternatively, the sample application site may be distinct from the capillary flow member but configured to provide for fluid communication of sample into the capillary flow member upon application of sample to the sample application site. The sample application site and a complex-forming site may be located in the same place of the porous substrate, i.e. sample application site may consist linker histone conjugated to detectable marker. The sample application site may be configured to receive samples of varying volumes, where in some instances the sample application site is configured to receive a sample having a volume ranging from 0.1 to 5000 pL. The detectable marker stably associated with a linker histone which specifically bind to cfDNA. The stable association of the linker histone with the detectable marker may be achieved via covalent or non-covalent binding, as desired. Thus, the detectable marker is stably associated with the linker histone in the complex of cfDNA - linker histone conjugated to the detectable marker; they do not disassociate from the detectable marker under the assay conditions of the LFA devices of the invention. The detectable marker may be a particle or particles. They may vary, as desired. The particles are optically detectable particles that may be manufactured from a variety of materials, such as metals, e.g., gold, or colored glass or plastic (e.g., polystyrene, polypropylene, latex beads). The label particles may vary in diameter, where label particle diameter in some instances may range from 1 to 5000 nm, such as 1 to 2500 nm. In some instances, the label particles are reflective nanoparticles, e.g., metallic, reflective nanoparticles, such as gold reflective nanoparticles. The term "nanoparticle" as used herein, refers to particles having one dimension in the range of 1 to 1000 nanometers ("nm"). The nanoparticles of the invention may be of any shape. In certain embodiments the nanoparticles are spherical. The detection site is a site that includes an immobilized linker histone that specifically binds to the complex of “cfDNA - linker histone conjugated to the detectable marker”. The detection site includes an amount of linker stably associated with (immobilized on) the porous substrate in the detection site. The dimensions of the detection site may vary, and in some embodiments the detection site has an area ranging from 0.01 to 0.5 sq. cm, such as 0.05 to 0.1 sq. cm and including 0.1 to 0.2 sq.cm. The detection site may have a variety of different configurations, where the configuration may be a line, circle, star, square, or more complex shape, as desired. In some instances, the detection site is configured as a line of immobilized linker histone, where the dimensions of the line may vary, where in some instances the line ranges in length from 2 to 10 mm, such as 3 to 7 mm, e.g., 4 to 6 mm. As indicated above, the detection site includes a linker histone stably associated with the absorbent material. By "stably associated with" is meant that the linker histone and porous substrate maintain their position relative to each other in space under the conditions of use, e.g., under the assay conditions. As such, the linker histone and the porous substrate can be non-covalently or covalently stably associated with each other. In some embodiments, in the lateral flow device for quantification of cell-free DNA (cfDNA) in a biological sample, the certain predefined cfDNA detected is the indicative level of need of cfDNA-scavenging therapy of a cfDNA-associated disease or a pathological condition. In some embodiment the diluted or undiluted biosample is applied to the sample pad (sample application site), where it begins to flow through the LFA strip. Any cfDNA in the sample binds to the first linker histone conjugated to detectable marker to form the first linker histone-cfDNA complexes in conjugation site; when these first linker histone-cfDNA complexes cross the detection zone (detection sites), they will first bind to second linker histone immobilized in first test line (L1); the first linker histone-cfDNA complexes that do not bind to L1 will be able to bind to L2. The first linker histone-cfDNA complexes that do not bind to L1 or L2 will then be able to bind to L3; finally, the unbound cfDNA and any remaining first linker histone-cfDNA complexes will bind to the control line to indicate a valid test; after, e.g., 20 minutes, the number of labeled (e.g. colored) test lines i.e. corresponding cfDNA concentration is counted (recorded). FIG [3] illustrate a variant of this embodiment of the present invention: so-called barcode format of LFA is based on the formation of several test lines (bars), which contain the agent / agents [inker histone(s)] capturing an analyte (cfDNA). In this case, the principle of the method consists in the consumption of the labeled (with a detectable marker) linker histone - cfDNA complexes as the sample moves along the strip and reacts (binds) with another / or same but immobilized (and unlabeled) agent or agents [linker histone(s)]. I.e immobilization of the linker histone on the membrane implemented in the form of several zones with a consistently increasing concentration. The intensity and the number of colored (in case of the use of colored particles as detectable marker) bars in the test zone are directly proportional to the concentration of analyte (cfDNA) in the biofluid sample. Gradient LFA principle is realized by the stepwise binding of complex “cfDNA-linker histone labeled by detectable marker” over multiple test lines with increasing (gradient) concentration of an immobilized linker histone [Linker Histone amount / Concentration (LHC)] from line to line. To implement gradient LFA for cfDNA quantification, a linker histone (or mix of linker histones) with an increasing concentration are immobilized on the analytical membrane of the test strip in the form of parallel test lines (detection sites). After applying the sample to the sample pad (sample application site), the cfDNA moves along the strip under capillary forces and interacts with the labeled (for example, by colored particles, for example, particularly, by gold nanoparticles) linker histone in the complex-forming site. In some variants of the LFA strip / device does not comprise linker histone labeled by detectable marker (i.e. no CFS needed) and the formation of “cfDNA-linker histone labeled by detectable marker” is preformed preliminary and separately (in a tube, a hole, or a flack) and then complex “cfDNA-linker histone labeled by detectable marker” is applicated on sample application site. Due to the excess of the linker histone associated with the surface of the colored particles (marker), cfDNA forms a complex with this labeled linker histone that is characterized by the equilibrium association constant. As the complex “cfDNA-linker histone labeled by detectable marker” passes through all the test lines where the same or another (unlabeled) linker histone is preliminary immobilized in increasing (gradient) concentration from line to line, the sandwich complex is formed and marked (colored) test lines develop. The intensity of test lines color increases gradiently from the nearest to the sample application site (with lowest amount of immobilized linker histone) to the farthest (with highest amount of immobilized linker histone). The result of analysis is read as the number of colored test lines, which corresponds to defined (particular) concentration of cfDNA. (The calibration of each line of test zone are performed with solutions of known concentration of the analyte, i.e. DNA standard / cfDNA standard). One of variant of claimed "lateral flow" assay device has porous substrate of a star-shaped or other two-dimensional geometry (taken in plan view) having a liquid sample application site in a central region and multiple arms that extend or radiate out from the central region in a manner described in US9518985 B262. In this variant these arms each include one or more detection sites located at different locations relative to the central region in a manner that the cfDNA in a biological sample placed on the central region resides in different quantities at least some, or all, of the detection sites of the arms in a manner to produce a gradual variation of detection sites color, grayscale or other characteristic from arm to arm and that can be analyzed to yield quantitative data from the lateral flow assay. In some embodiments, the lateral flow device further comprises a control line downstream from said first test line and said second test line, wherein said control line comprises binding moiety that can capture the said free linker histone conjugated to the detectable marker, in the presence or absence of cfDNA in the biological sample. In some embodiments, the lateral flow device further comprises a complex-forming site comprising a linker histone conjugated with a detectable marker, where this complex-forming site is disposed in sample application site and / or between sample application site and the detection site. Other words, in addition to the sample application site, lateral flow assay devices of present invention further may include a complex-forming site. The a complex-forming site is a site that includes a linker histone conjugated to detectable marker that specifically bind to cfDNA to be determined or quantitated. The linker histone conjugated to detectable marker are non- stably associated with the porous substrate in the complex-forming site. By "non-stably associated" is meant that while the linker histone conjugated to detectable marker may be stationary relative to the porous substrate prior to sample application, upon sample application and sample wicking through the complex-forming site, the linker histone conjugated to detectable marker are free to specifically bind cfDNA, present in the sample and to move with the sample through the porous substrate of the capillary flow member by capillary action. As such, the complex of cfDNA and linker histone conjugated to detectable marker move laterally through the porous substrate under the bulk fluid flow forces. In some embodiment the diluted or undiluted biosample is applied to the sample pad (sample application site), where it begins to flow through the LFA strip. Any cfDNA in the sample binds to the first linker histone conjugated to detectable marker to form the first linker histone-cfDNA complexes in conjugation site; when these first linker histone-cfDNA complexes cross the detection zone (detection sites), they will first bind to second linker histone immobilized in first test line (L1) ; the first linker histone-cfDNA complexes that do not bind to L1 will be able to bind to L2. The first linker histone-cfDNA complexes that do not bind to L1 or L2 will then be able to bind to L3; finally, the unbound cfDNA and any remaining first linker histone-cfDNA complexes will bind to the control line to indicate a valid test; after, e.g., 20 minutes, the number of labeled (e.g. colored) test lines i.e. corresponding cfDNA concentration is counted (recorded). In some embodiments, the detectable marker of the lateral flow device is selected from the group consisting of a colorimetric marker, a fluorescent marker, a radioactive marker, and a magnetic marker, an electrochemiluminescent marker. In some embodiments, the any of the linker histones of the lateral flow device is a linker histone H1 or a linker histone H5. In some embodiments, the any of the linker histones of the lateral flow device is the linker histone selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments, the linker histone H1.3 of the lateral flow device is a human H1.3 linker histone. In some embodiments, the linker histone H1 of the lateral flow device is a bis-met H1.3 linker histone consisting of having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5). In some embodiment, the any of the linker histones of the lateral flow device is the linker histone comprises the amino acid sequence which is at least 70% identical (e.g., at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 98% identical, or at least 99% identical) to the sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9. In some embodiments a first or second linker histone is linked to a detectable marker via linker, and wherein said linker is selected from the group consisting of a cleavable linker, a non-cleavable linker, a hydrophilic linker, a procharged linker and a dicarboxylic acid based linker. In some embodiments, the linker is derived from a cross-linking reagent selected from the group consisting of: N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), N- succinimidyl 4-(2- pyridyldithio)pentanoate (SPP), N-succinimidyl 4-(2- pyridyldithio)butanoate (SPDB), N- succinimidyl-4-(2-pyridyldithio)-2-sulfo-butanoate (sulfo-SPDB) , Ν-succinimidyl iodoacetate (SIA), N-succinimidyl(4- iodoacetyl)aminobenzoate (SIAB), maleimide PEG NHS, N- succinimidyl 4- (maleimidomethyl) cyclohexanecarboxylate (SMCC), N- sulfosuccinimidyl 4- (maleimido methyl) cyclohexanecarboxylate (sulfo-SMCC) or 2,5-dioxopyrrolidin-l-yl 17-(2,5- dioxo- 2,5-dihydro- 1 H-pyrrol- 1 -yl)-5,8, 11 , 14-tetraoxo-4,7, 10, 13-tetraazaheptadecan- 1 -oate (CX 1 - 1). In a specific embodiment, the linker is derived from the cross-linking reagent N- succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC). According to further aspect of the invention there is provided a method for determination of a status of cfDNA-associated disease in а subject which comprises the steps of: (vi) detecting or quantification a сfDNA in a biological sample of a body fluid of a subject according to the methods of the invention; and (vii) using the cfDNA level measured to determine the cfDNA-associated disease status of the subject. According to further aspect of the invention there is provided a method for assessment of a subject for suitability for cfDNA-scavenging therapy of a cfDNA-associated disease which comprises the steps of: (i) detecting or quantification a cfDNA in a biological sample of the subject according to the methods of the invention; and (ii) using the cfDNA level measured as a parameter of assessment of suitability of a subject for cfDNA-scavenging therapy. In some embodiments of a method for assessment of a subject for suitability for cfDNA- scavenging therapy of a cfDNA-associated disease, the suitability of a subject for cfDNA- scavenging therapy of a cfDNA-associated disease is considered as blood plasma level of cfDNA at least 500 ng / mL, at least 600 ng / mL, at least 700 ng / mL, at least 800 ng / mL, at least 900 ng / mL, at least 1000 ng / mL, at least 1100 ng / mL, at least 1200 ng / mL, at least 1300 ng / mL, at least 1400 ng / mL, at least 1500 ng / mL, at least 1600 ng / mL, at least 1700 ng / mL, at least 1800 ng / mL, at least 1900 ng / mL, at least 2000 ng / mL, at least 2100 ng / mL, at least 2200 ng / mL, at least 2300 ng / mL, at least 2500 ng / mL, at least 2600 ng / mL, at least 2700 ng / mL, at least 2800 ng / mL, at least 2900 ng / mL, at least 3000 ng / mL, at least 3100 ng / mL, at least 3200 ng / mL, at least 3300 ng / mL, at least 3400 ng / mL, at least 3500 ng / mL, at least 3600 ng / mL, at least 3700 ng / mL, at least 3800 ng / mL, at least 3900 ng / mL, at least 4000 ng / mL, at least 4100 ng / mL, at least 4200 ng / mL, at least 4300 ng / mL, at least 4400 ng / mL, at least 4500 ng / mL, at least 4600 ng / mL, at least 4700 ng / mL, at least 4800 ng / mL, at least 4900 ng / mL or at least 5000 ng / mL in blood plasma when the subject is considered to be suitable for cfDNA-scavenging therapy of a cfDNA-associated disease. According to further aspect of the invention there is provided a method for monitoring a treatment of cfDNA-associated disease a subject undergoing the treatment which comprises the steps of: (i) detecting or quantification a cfDNA in a biological sample of a biofluid of the subject according to the methods of the invention; (ii) repeating the detection or quantification of a cfDNA in a biological sample of a body fluid of the subject at least one other occasion; (iii) using any changes in the cfDNA level detected as a parameter for any changes in the course of cfDNA-associated disease of the subject. In some embodiments cfDNA-associated disease is selected from the group of cancer, metastatic cancer, acute organ failure, organ infarct (including myocardial infarction and ischemic stroke), hemorrhagic stroke, autoimmune disorders, graft-versus-host-disease (GVHD), graft rejection, sepsis, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), graft- versus-host-disease (GVHD), traumatic injury, crush syndrome, proinflammatory status in aged individuals, diabetes, atherosclerosis, neurodegenerative disease, autoimmune disease, eclampsia, infertility, coagulation disorder, pregnancy-associated complications and infection, including bacterial, fungal and viral (for example, COVID-19). In some embodiments, cfDNA-scavenging therapy is selected from the group: therapy with compound destroying cfDNA in biofluids; therapy with compound binding or deactivate cfDNA in biofluids. In some embodiments the biofluid is first removed from the subject then passed over columns filled with cfDNA-affinity matrix to remove cfDNA and returned into the subject. In some embodiments, cfDNA-affinity matrix contains a protein of linker histone H 1 family. In some embodiments, cfDNA-affinity matrix contains a protein of linker histone H 1 family, the linker histone H1 is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone. In some embodiments, the biofluid is blood. In some embodiments, the subject is an animal or a human. According to further aspect of the invention there is provided a method of assessment of effectivity of an extracorporeal column to remove cfDNA from a biofluid wherein the biofluid is first removed from the subject then passed over the column filled with cfDNA- affinity matrix to remove cfDNA and returned into the subject, which comprises the steps of: (viii) quantification a сfDNA in biofluid removed from the subject and sampling before passing over the column according to the methods of the invention; (ix) quantification a сfDNA in the sample biofluid returned into the subject and sampling after passing over the column according to the methods of the invention; and (x) using the difference between cfDNA level measured at step (i) and cfDNA level measured at step (ii) to determine effectivity of the extracorporeal column to remove cfDNA from the biofluid. Thus, this invention proposes to use the detection and / or quantification of the "linker histone- cfDNA" complex using the same or a different linker histone, while the detectable marker used for detection and / or quantification of cfDNA is pre-attached to either the linker histone forming the "linker histone-cfDNA complex " or to a linker histone interacting with the "linker histone-cfDNA complex”. This approach leads not only to adequate and fast detection or quantification of cfDNA, which is unattainable using known methods, but, as it turned out, unexpectedly, it provides a diagnostic tool to determine whether it is necessary to start or continue therapy DNA-scavenging therapy in the treatment of cfDNA- associated diseases. In one embodiment, the method of the invention is repeated on multiple occasions. This embodiment provides the advantage of allowing the detection results to be monitored over a time period. Such an arrangement will provide the benefit of monitoring or assessing the efficacy of treatment of a disease state. Such monitoring methods of the invention can be used to monitor onset, progression, stabilisation, amelioration, relapse and / or remission. According to further aspect of the invention there is provided a method of assessment of effectivity of an extracorporeal column to remove cfDNA from a biofluid wherein the biofluid is first removed from the perfused organ then passed over the column with cfDNA- affinity matrix to remove cfDNA and returned into the perfused organ, which comprises the steps of: (iv) quantification a сfDNA in biofluid removed from the perfused organ and sampling before passing over the column according to the methods of the invention; (v) quantification a сfDNA in the sample biofluid returned into the subject and sampling after passing over the column according to the methods of the invention; and (vi) using the difference between cfDNA level measured at step (i) and cfDNA level measured at step (ii) to determine effectivity of the extracorporeal column to remove cfDNA from the biofluid. In some embodiments, cfDNA-binding ligand is a protein of linker histone H1 family and is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone, In some embodiments biofluid is blood or plasma or lymph or cerebrospinal fluid. In some embodiments cfDNA-binding ligand is a protein of linker histone H1 family and is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone, biofluid is selected from blood, red blood cells (RBCs) suspension, fresh frozen plasma (i.e thawed immediately before use) , colloid solution with hemoglobin‐based oxygen carrier (HBOC). Normothermic machine perfusion of donor organ is widely used for transportation of donor organ. The red blood cells (RBCs) suspension, fresh frozen plasma, hemoglobin‐based oxygen carrier (HBOC), a gelatin‐based colloid solution may be used as media for the perfusion [Matton, A.P.M., et al63]. The selective removal of cfDNA (including cfDNA of NETs) with column / device incorporated to organ perfusion circuit leads to improvement of function of damaged organ and this technology increase the donor organ pull for organ transplantation, for example, the column containing specific cfDNA absorber, - human histone H1.3 protein conjugated to polymer beads was used [Mittendorfer, M. et al.64]. As the perfusion usually lasts 4-6 hours, the column is saturated with adsorbed cfDNA, the cf- DNA sorption effectivity is lowered, if so, the assessment of effectivity of such extracorporeal column to remove cfDNA during the organ perfusion, is needed and this assessment is performed with the method of the invention. Thus, the invention further provides assessment of effectivity of an extracorporeal column to remove cfDNA from a biofluid wherein the biofluid is first removed from the perfused organ then passed over the column filled with а cfDNA-affinity matrix to remove cfDNA and returned into the perfused organ, the cfDNA in the biosamples of the removed biofluid and the returned biofluid quantitates with the method of the invention and difference is used for the assessment of effectivity of the extracorporeal column. EXAMPLE 1. Preparation of a linker histone conjugated with a detectable marker. Horseradish peroxidase (HRP) was used as a detectable marker. Activation of HRP with sodium periodate (P1) was performed as follows: HRP (BBI Enzymes, UK), was dissolved in bi-distilled water (100 mg / mL). Then sodium meta-periodate (Sigma) was added to final concentration of 1.3%. The reaction was stopped after 30 min by separation on a Sephadex G-25 column (10 x 1 cm) equilibrated with acetate buffer (рН 4.0) which was used as elution buffer. The sample volume was 160 ^L. The fractions containing brown colored HRP were pooled (2-3 mL) and 0.2M NaOH was added to pH 9,5-10. (approx.1-2 drops of 0.2M NaOH solution per 1 mL of pooled fractions. Bis-met histone H1.3 having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5), i.e. N-Met-Met-H1.3, (see EP198562865); N,N-bismethionylhistone H1.3. (see RU263440866), was used: 1 mL of 50 mg / mL solution of the recombinant histone H 1.3 in bi-distilled water was added with 1 mL of 0.1 M bicarbonate buffer (pH 9.5). This histone H 1.3 solution was mixed with activated HRP solution (ratio HRP / histone H 1.3 was 1:3) and the mixture was incubated at room temperature. The conjugation reaction continued for 2 hr, then sodium borohydride (Sigma) was added to final concentration of 0.04%. After further sodium borohydride treatment at room temperature for 2 hr the mixture was dialyzed 16 hr against the phosphate buffer (pH 7.4- 7.6) at 4 °C (SEVAPOR, dialysis tubing, Cat N 44144, pore diameter ca.25 Å. Before storage at −20 °C, glycerol was added to the preparation to final concentration of 60% to prevent freezing.The conjugate was stored for a maximum two weeks prior to further experiments. EXAMPLE 2. Quantification of cfDNA in the biological sample with use a first linker histone immobilized on a solid surface and a second linker histone conjugated with a detectable marker and the kit comprising: a first linker histone immobilized on solid surface and a second linker histone conjugated to a detectable marker. Bis-met histone H1.3 having the sequence MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5), i.e. N-Met-Met-H1.3, (see EP198562867); N,N-bismethionylhistone H1.3. (see RU263440868), provided by Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the RAS (Moscow) was used as the first linker histone. Ten lanes of an Nunc™ MaxiSorp™ flat-bottom 96 well plate (Thermo Fisher Scientific, USA) were coated with 100 ^L per well of 1:50 dilution of 1 mg / mL bis-met histone H1.3, (manufactured by Shemyakin–Ovchinnikov Institute of bioorganic chemistry RAS, Russia), 98,5% purity, in coating buffer (0.1М Na2CO3, 0,1 NaHCO3, рН 9,5-9,6) for 18 hours at 4°C. Edge lanes 1 and 12 were left empty. Wells were thrice washed with bi-distilled water and blocked with 2% bovine serum albumin solution (BSA) in PBS (0,2М NaCl, 8 мМ Na2HPO4, 2,7 мМ KCl, 1,5 мМ KH2PO4, рН 7,4-7,6) for 30 min at room temperature on an orbital shaker set to 90rpm. Then the wells were washed 3 three times with bi-distilled water. 1Kb DNA Ladder (Eurogen, Russia, NL001) was used as DNA standard. The standard curve lane was generated with 5 two-fold serial dilutions beginning at 625 ng / mL in 2% BSA (with the last well in standard curve lane left with incubation buffer only as a blank). Remaining wells were incubated in duplicate with 100 microliters of biological sample of interest (plasma sample) serially diluted with 2% BSA in PBS; at least 7 serial plasma dilutions beginning at 1:2, were used. Incubation was completed for 2 hours at room temperature. After this each well was washed (added and aspirated) 3 times with bi-distilled water. The same linker histone (bis-met histone H1.3) was used as a second linker histone according the method of the invention. The conjugate of bis-met histone H1.3 to HRP was prepared as described in Example 1 and diluted 1 : 5000 from a stock concentration in PBS with 2% BSA.100 ^L of the conjugate was added to each well and incubated for 30 min at room temperature. After this each well was washed (added and aspirated) 3 times with bi-distilled water. Following final washes, 100 ^L of mixture of 3,3´,5,5´-tetramethylbenzidine (TMB) (final concentration of 0.025 %) and hydrogen peroxide (final concentration of 0.013%) in citric acid buffer (0.15 M sodium citrate, pH 7.8 –8.0) was added to each microplate well. The enzymatic reaction was allowed to continue for 15 minutes, protected from light, and stopped by addition of 100 ^L of 10% sulfuric acid. The plate was immediately read at 450nm. Testing data (standard curve) is presented on Fig.1. Duplicate standard and sample wells were averaged, and background-subtracted based on blank wells. The concentration of cfDNA in the biological sample was calculated using a quadratic curve equation calculated in Microsoft Office Excel 2016. Final cfDNA values shown were presented as ng / mL. EXAMPLE 3. The kit for quantifying cell free DNA (cfDNA) comprising a first linker histone immobilized on solid surface and a second linker histone conjugated to a detectable marker. As described in the Example 2 the plate coated with the first linker histone, or the first linker histone separately, the conjugate of the second linker histone with a detectable marker (enzyme, as an example), and, optionally: uncoated plate, standard cfDNA, substrate, chromogen and buffers, packed together, with instruction for use present the kit according of the invention. EXAMPLE 4. Quantification of cfDNA in plasma of patient undergoing selective cfDNA plasmasorption: the assessment of effectivity of an extracorporeal column / device to remove cfDNA from a biofluid wherein the biofluid is first removed from the subject then biofuids (or its part) passed over the column filled with cfDNA-affinity matrix to remove cfDNA and returned into the subject. The cfDNA-scavenging extracorporeal therapy (the selective cfDNA plasmasorption or cfDNA-apheresis) was performed with single use, disposable extracorporeal column packed with 100 mL of crosslinked agarose beads which have been modified to contain coupled N,N-bismethionylhistone H 1.3 human recombinant protein on the beads surface (NucleoCorTM / NucleoCaptureTMdevice). To provide specific cfDNA sorbent (i.e. cfDNA- affinity matrix) for the column, cross-linked agarose beads (Sepharose 4FF, GE Healthcare Bio-Sciences AB) are activated with 0,4% sodium metaperiodate for 2 hrs. After washing with water for injection and a 0,2 M borate buffer, the suspension activated agarose beads are incubated with ligand solution for 2,5 hours. Once the immobilization is completed the solution with unbound ligand is removed and the suspension of the beads is washed with a 0,2 M borate buffer. The remaining activity of the beads is blocked for 15 min with 0,3% sodium borohydride. The suspension of the agarose beads bind with recombinant human N,N-bismethyonyl-histone Н1.3 protein which is then washed with water for injection and a 0.9% sodium chloride injection several times. The prepared sterile suspension of beads with immobilized ligand is used for filling the column plastic body by aseptic processing. The volume of the column is 150 ±2 ml and the volume of the matrix is 100 ± 10 ml. The housing has two filters that provide free flow of fluid (e.g. plasma) through the column and keep the cfDNA-affinity matrix inside. The threaded caps on both sides of the housing have fittings with standard Luer-Lock connectors for connection to the extracorporeal lines. This column is intended for elimination of cell free DNA (cfDNA) during an extracorporeal procedure from patient's blood plasma. Column operates in conjunction with any plasma separation device: a centrifuge type plasma separator during the extracorporeal cfDNA- scavenging therapy session, which includes regional citrate anticoagulation. The column is integrated into the plasma extracorporeal circuit of a commercial plasmaseparator, i.e. downstream from where the plasma is separated. A patient had retroperitoneal abscess (RA) and sepsis, and the extracorporeal session of this cfDNA-scavenging therapy was performed after his informed consent. After assembling the inlet and outlet lines to the plasma separation extracorporeal circuit, plasma filtration run: the session was started at a plasma flow rate of 15–20 mL / min. Then, the plasma flow rate through the column was 30–60 mL / min; the average plasma flow rate during the extracorporeal cfDNA-scavenging therapy session was 40 mL / min. The total volume of plasma passed through the column was from 3 to 4 volume of circulating blood plasma (CPV). The level of cfDNA in the samples of plasma taken from plasma extracorporeal contour before plasma enters to the cfDNA- apheresis column (pre-column sample) and after the plasma passed through column (post-column sample) was measured with the method of the invention as described in the Example 2. As shown in the Table 1 the extracorporeal column / device effectively removed cfDNA from the plasma passed through the sorbent during entire cfDNA-scavenging extracorporeal therapy session. There was no evidence of saturation of column with adsorbed cfDNA. Otherwise, that is, with a significant decrease in cfDNA-scavenging effectivity (for example, at least to 30%), it would be necessary to replace the column with a new one in order to continue effective extracorporeal removal of cfDNA from biofluids passed through cfDNA-affinity matrix of the column. Table 1. Quantification of cfDNA in plasma of patients undergoing selective cfDNA plasmasorption: the level of cfDNA in the samples of plasma taken from plasma extracorporeal contour before plasma enters to the cfDNA- apheresis column (pre- column sample) and after the plasma passed through column (post-column sample) quantified with the method of the invention. Thus, the methods of invention of quantitation of cfDNA is successfully used for assessment of effectivity of an extracorporeal column / device to remove cfDNA from a biofluid, wherein the biofluid is first removed from the subject then passed over the column with specific cfDNA binding ligand to remove cfDNA and returned into the subject. EXAMPLE 5. The assessment of a subject for suitability for cfDNA-scavenging therapy of a cfDNA-associated disease and monitoring a treatment of cfDNA-associated disease using the method of invention for quantification of cfDNA in biofluids. The patients with various cfDNA-associated disease were treated with cfDNA-scavenging extracorporeal therapy using single use, disposable extracorporeal column packed with 100 mL of crosslinked agarose beads which have been modified to contain coupled N,N- bismethionylhistone H 1.3 human recombinant protein on the beads surface (NucleoCaptureTMdevice) as described in Example 4. The total volume of plasma passed through the column during one session was from 3 to 4 volume of circulating blood plasma (CPV) for each patient. The venous blood was sampled before start and immediately after end of the session of cfDNA-scavenging extracorporeal therapy. The cfDNA was quantified in venous blood plasma with an embodiment method of the invention described in the Example 2, but the purified cfDNA from human plasma (UltraPure cfDNA, PlasmaLab International, USA) was used as cfDNA standard. Also, the level of cfDNA was measured with “sandwich” ELISA with use (Cell Death Detection ELISA plus, Roche Diagnostics): the assay is based on a quantitative sandwich enzyme immunoassay principle: two monoclonal mouse antibodies directed against DNA (single stranded (ss) - DNA and double stranded(ds)-DNA) and histones (H1, H2A, H2B, H3 and H4) catch specifically mono- and oligonucleosomes which originate from the nucleus of eukaryotic cells, and whereas the anti-DNA antibody labeled with peroxidase reacts with substrate [2,2’-azino- bis(3-ethylbenzothiazoline sulfonate)], [see Holdenrieder S, et al69]. (ELISA Method 1) Also, additionally, the second alternative ELISA method was used, namely Nu.Q H3.1 ELISA Assay, Volition Rx, This assay uses anti-histone H3.1 as capture (primary) antibody with an anti-nucleosome detection antibody to ensure only histones within intact nucleosomes are quantified 70. Details on analytical performance of the Nu.Q H3.1 assay can be found in the Instruction for Use 71(ELISA Method 2). The results of the cfDNA quantifications are presented in the Table 2. Table 2. Quantification of cfDNA in plasma of patients undergoing selective cfDNA plasmasorption: the results of venous blood plasma cfDNA quantifications with the methods of the invention and some “common” / commercial ELISA methods in the patients treated with cfDNA-scavenging extracorporeal therapy. *CBI - Clinical and Biochemical Improvement after the session (i.e positive therapeutic effect of cfDNA-scavenging extracorporeal therapy sessions) The presented data of the concentration of blood plasma cfDNA measured with method of the invention shows that (1) the method of invention was successfully used for quantification of cfDNA in biological fluid samples (2) cfDNA is diminished during cfDNA-scavenging therapy; (3) most prominent absolute and relative decreasing of cfDNA was noted in the patients with high initial level of the cfDNA and (4) clinical and biochemical improvement was noted in the patients with the cfDNA level not less than 500 ng / mL, i.e. the patients with cfDNA level which is more than some definite level (threshold). Thus, the method of the invention for quantification of cfDNA is used successfully (a) for selection of the subject for their suitability for cfDNA-scavenging therapy; (b) for monitoring of the efficacy of cfDNA- scavenging therapy. The immunogenic method, particularly, cfDNA ELISA methods did not “recognizes” a cfDNA of all type and could not be used as tools for all abovementioned purposes. Moreover, paradoxically the level of cfDNA measured with ELISA Method 1 and ELISA Method 2 was increased in one patient, possibly, as a result of change of ratio between different types of cfDNA, having different specificity to the primary antibodies used. EXAMPLE 6. Preparation of linker histone gold nanoparticle conjugate. All reagents for gold nanoparticles production were purchased from Sigma-Aldrich (USA). To obtain gold seeds, 2.7 mL 1% sodium citrate solution was added to 100 mL boiling solution of 0.01% HAuCl4and stirred for 15 min. Further, to prepare gold nanoparticles (colloidal gold solution), 0.5 mL gold seeds, 220 μL 1% sodium citrate, and 1 mL 0.03 M hydroquinone were added dropwise to 0.01% HAuCl4solution. The mixed solution quickly turned blue and was stirred for 30 min. Histone H1.3 (CusaBio, Cat. No. CSB-YP010379HU, Tag-Free, > 85% purity, SEQ: SETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVA ASKERSGVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSF KLNKKAASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKK PATAAGTKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKA APKKK (SEQ ID NO:7)) was used for production of gold nanoparticle-histone H 1.3 conjugate. For that 1.0 mL of histone H1.3 at concentration of 20 µg / mL in phosphate- buffered saline (pH 8.0) was added dropwise to 10.0 mL colloidal gold solution at pH 7.5. The resulting mixture was incubated for 30 min at 20-22 Coand treated with bovine serum albumin (BSA) (BSA final concentration was 0.2%) for 40 min under constant stirring. The conjugate obtained was separated by centrifugation (9,000 g for 10 minutes), resuspended in 10 mM phosphate-buffered saline (PBS, pH 7.8) with 0.1% BSA, 6% trehalose, and 0.01% sodium azide. The conjugate was stored at 4 °C. EXAMPLE 7. Preparation of LFA device and quantification of cfDNA. Nitrocellulose membrane (CNPF-SS10), sample pad (GFB-R7L), conjugate pad (PT-R5) and absorbent pad (AP045) materials for lateral flow assay (LFA) were all purchased from MDI Technologies, India. LFA strips were assembled with absorbent pad, sample pad, conjugate pad, analytical nitrocellulose membrane. Conjugate pad was soaked with histone H 1.3 - gold nanoparticle conjugate solution prepared as described in the Example 6 (with concentration corresponded to optical density of 2.0) and dried at room temperature, i.e. histone H 1.3 was used as first linker histone, of the variant of method of invention where this first linker histone conjugated with a detectable marker contacts with the biological sample to provide first linker histone-cfDNA complex. Recombinant protein of linker histone H1 (H1.0, NP_005309.1, UniProt P07305, Histone family, member 0 (H1F0),with N-terminal 6xHIS tag OriGene Technologies, Inc. , Cat. No TP761539, having full length amino acid sequence: HHHHHHTENSTSAPAAKPKRAKASKKSTDHPKYSDMIVAAIQAEKNRAGSSRQSIQ KYIKSHYKVGENADSQIKLSIKRLVTTGVLKQTKGVGASGSFRLAKSDEPKKSVAFK KTKKEIKKVATPKKASKPKKAASKAPTKKPKATPVKKAKKKLAATPKKAKKPKTV KAKPVKASKPKKAKPVKPKAKSSAKRAGKKK (SEQ ID NO:8)) was used as a second linker histone of this variant of the method of invention, where this second linker histone immobilized on a solid surface binds to the first linker histone-cfDNA complex. The test lines (detection sites) on the analytical nitrocellulose membrane (NC) was formed by spreading the solutions of this protein in PBS (pH 8.0) using the automatic Lateral-Flow Reagent Dispenser (Claremont BioSolutions, Upland, CA) equipped with an external syringe pump. Linker histone H1 protein solutions were deposited in the form of four parallel lines with a distance between them of 4 mm at amounts of 0.02; 0.05; 0.1; 0.2 μg / cm, correspondingly. These amounts of the second linker histone was selected by experimental (empiric) way to quantify 100 ng / mL, 250 ng / mL, 500 ng / mL, 1000 ng / mL, correspondingly, see below). UltraPure cfDNA obtained from human plasma (PlasmaLab International, USA) was used as DNA-standard for calibration purpose (see below). The NC membrane was then cut into 4 mm wide strips using a paper cutter and the strips were stored with desiccant at temperature 22-24 CO. To obtain assembled test strip (i.e. LFA device), the nitrocellulose membrane strip (length 40 mm) was additionally adhered to a plastic backing card, and PT- R5 conjugate pad (length 20 mm) was applied as a conjugate pad and AP045 absorbent materials was used as the absorbent / waste pad. The standard solutions at different concentration in PBS (for the calibration purposes) or biofluids to be tested were applied to sample pad (sample application site) of the test strip placed horizontally. In 20 min one or more colored test lines on the strip was detected visually: while the first linker histone-cfDNA complex is flow through all the test lines (detections sites) where the second linker histone immobilized in gradiently increased concentration, the “sandwich” complex ( the first liker histone-cfDNA-the second linker histone) is formed and colored test lines appeared. The intensity of test lines increases gradiently from the nearest to the sample pad (sample application site) to the farthest. The result of cfDNA quantification is recorded as the number of colored test lines, which corresponds to concentration range of cfDNA. EXAMPLE 8. Preparation of LFA device and quantification of cfDNA. The LFA strip (device) was prepared as described in Example 7 but LFA strip had 5 lines (detection sites) containing different amounts of Histone H1.4 (HIST1H1E), UniProt P10412, (NM_005321), having the sequence MSETAPAAPAAPAPAEKTPVKKKARKSAGAAKRKASGPPVSELITKAVAASKERSG VSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAA SGEAKPKAKKAGAAKAKKPAGAAKKPKKATGAATPKKSAKKTPKKAKKPAAAAG AKKAKSPKKAKAAKPKKAPKSPAKAKAVKPKAAKPKTAKPKAAKPKKAAAKKK (SEQ ID NO:9) (OriGene Technologies, Inc., USA no: TP761832): the lines L1, L2, L3, L4, L5 (detection sites) were calibrated with DNA standard (Calf Thymus Sonicated DNA Cytiva 27-4563-0, Merck, no GE27-4563-01) for quantification of 200 ng / mL; 400; ng / mL; 600 ng / mL; 800 ng / mL, and 1000 ng / mL, accordingly. EXAMPLE 9. The assessment of a subject for suitability for cfDNA-scavenging therapy of a cfDNA-associated disease and monitoring a treatment of cfDNA-associated disease using the method of invention. Canine distemper virus is a single-stranded negative-sense RNA virus which belongs to the Paramyxoviridae family in the Morbillivirus genus. 1-year-old non-vaccinated mixed-breed male dog was taken to the veterinary clinic with severe diarrhea, difficulty breathing, a cough that worsened despite antibiotic treatment. Complementary examinations in the hospital revealed a stress leucogram, thrombocytopenia and diffuse alveolar interstitial opacification on radiographs of the thorax. As febrile condition with multisystemic clinical signs involving the respiratory, gastrointestinal, and neurologic systems, hyperkeratosis of footpads and dehydration, canine distemper was considered in the diagnosis. Laboratory 9 9 examination revealed leukopenia (4.19 x 10 / L; ref. range, 5.4-17.4 x 10 / L), 9 9 9 thrombocytopenia (50.2 x 10 / L; ref. range, 102-395 x 10 / L), lymphopenia (0.7 x 10 / L; ref. 9 9 9 range, 1-5.4 x 10 / l), and neutropenia (1.9 x 10 / L; ref. range, 2.9-13.8 x 10 / l). Abnormalities were also observed within the population of red blood cells (RBC); having 12 12 reduced values of total RBCs (3.21 x 10 / L; ref. range, 5.3-8 x 10 / L), hematocrit (25.3%; ref. range, 37-35%), and hemoglobin concentration. As there is no specific treatment for canine distemper, the treatment included ketoprofen 2mg / kg, ceftriaxone sodium as bacterial infection prophylaxis, 25mg / kg b.w. To manage diarrhea and dehydration metronidazole, 10 mg / kg b.w and infusion of Ringer lactate solution, 15ml / kg b.w was given respectively. From 2nd day to onward, ketoprofen, per os 2mg / kg b.w once daily, Cephalexin, 15mg / kg 2 times per day after feeding was recommended. Three days later dog was returned to the hospital, where the packed cell volume (PCV) was 24%. Eight days later, the dog re-presented to his veterinarian due to lethargy, and the PCV was 15%. The blood serum level of cfDNA measured with the one embodiment method and device of the invention (as described in this Example 8) was found between 600 and 800 ng / mL. The dog was discharged home with clindamycin, 75 mg per os every 12 hrs and recombinant deoxyribonuclease as systemic cfDNA-scavenging therapy (Pulmozyme, Roch, 2500 U / 2,5 mL / 2.5 mg), at dose of 2,5 mg each 4 hrs, i.m. On the next three days, the respiratory rate and coughing had decreased, and the dog was able to eat a small amount of food. Thoracic radiographs were repeated and showed a slight reduction in the intensity of alveolar abnormalities. The serum blood level decreased to level of between 100 and 200 ng / mL and the injection of deoxyribonuclease were discontinued. Over the next 48 h, the dog's condition rapidly worsened. He suddenly became severely dyspneic and too weak to stand. Body temperature decreased to 35,5°C. He was tachycardic (145 beats / min.) and tachypneic (55 breaths / min.). A analysis venous blood gas showed a pH of 7.41 (reference range, 7.32 to 7.38), decreased PО2(17.5 mmHg; ref. range, 40 to 54 mmHg), increased HCO3- (26.8 mmol / L; ref. range, 18.4 to 22.8 mmol / L), and decreased pCO2 (34.2 mmHg; ref. range, 36 to 52 mmHg). Thoracic radiographs showed a bilateral mixed pulmonary interstitial and alveolar lung pattern which was worse in the right lung lobes. Repeat ultrasound showed confluent B-lines bilaterally with no evidence of left atrial enlargement as determined by the LA:Ao ratio. Acute respiratory distress syndrome (ARDS) was diagnosed. The dog was treated with 100% (cage with 100% FiO2) and started on enteral doxycycline (10 mg / kg each 24 hrs) via nasogastric tube. N-acetylcysteine as a mucolytic agent was administered intravenously at a dose of 70 mg / kg every 6 hours. No evidence of noted clinical and biochemical improvement was registered in next 12 hrs. The blood serum level of cfDNA measured with the one embodiment method of the invention (as described in Example 2) was found as 1345 ng / mL and measured with another embodiment method of the invention (as described in Example 8) was found as equal or more than 1000 ng / mL. According to this finding, the veterinarian decided to restart the systemic cfDNA-scavenging therapy with Pulmozyme at doses of 5 mg each 4 hrs, i.v. The dog's PCV improved and remained stable (24%–25%) through-out the first day of Pulmozyme therapy restarting; thedog's SpO2mildly improved, but significant tachypnea was continued. In 24h, SpO2 wasmore than 93% and the dog was placed to an oxygen cage with 30% FiO2. Five hours later,oxygen supplementation was discontinued. The blood serum concentration of cfDNA was measured as less than 200 ng / mL with LFA device described in Example 8) and as 184 ng / mL with method described in Exaple 2. Accordingly the this finding the cfDNA- scavenging therapy (deoxyribonuclease administrations) was discontinued. Thus, the method of invention of detection and / or quantification of cfDNA was successfully used for assessment the dynamic of cfDNA level; the cfDNA values obtained by the method reflect the clinical status; the method allows to assess subject suitability for cfDNA- scavenging therapy of a cfDNA-associated disease and to monitor a treatment of cfDNA- associated disease. EXAMPLE 10. Assessment of cfDNA concentration in biofluid and monitoring a treatment of cfDNA-associated disease using the LFA method of invention for quantification of cfDNA in biofluids The LFA strip (device) as one of embodiment of method of the invention was prepared as described in Example 8 using LFA strip with 5 lines (detection sites) and containing different amounts of another linker histone: bis-met histone H1.3 having the sequence MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERS GVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKA ASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAG TKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5) (see Example 2 for reference). The lines L1, L2, L3, L4, L5 (detection sites) were calibrated with cfDNA standard (cfDNA Reference Standard Set, Horison UK, cat.no HD780) for quantification of 200 ng / mL; 400; ng / mL; 600 ng / mL; 800 ng / mL, and 1000 ng / mL, accordingly. A 56-year-old man with acute myeloblastic leukemia (AML) underwent allo-HSCT from a 10 / 10 HLA-matched younger nonrelative donor. The donor and recipient were CMV IgG (+) and EBV IgG (+) IgM (-). The conditioning regimen consisted of infused Fludarabine (30 mg / m2 / day −7 to −2) and Busulfan (2 mg / kg, day -5; 4 mg / kg day -4 to -3). GVHD prophylaxis was performed with tacrolimus, sirolimus, and cyclophosphamide. On day 37, post-transplantation, the post-transplant period was complicated with erosive cystitis, and the patient was hospitalized. At the admission the patient had decreased RBC 2.4 x 10*6 / mcL [normal value from 4.7 to 6.1 x 10*6 / mcL]; Ht: 22.3 % [normal values 40.0 - 48.0%]; Hb: 7.5 g / dl [normal values 13.2 – 16.4 g / dl];; Hp 28 [normal values 41 to 165 mg / dL], platelets 14 x 10e9 / l [normal values 150 – 400 x 10e9 / l]. The blood smear showed a significant number of schistocytes (5%). A white blood cell (WBC) count revealed a decreased neutrophils of 1.27 x 10*9 / L [normal values 2.2-4.8 x 10*9 / L] and an increased lymphocyte level of 2.6 x 10*9 / L. The level of С-reactive protein 50.21 mg / L [normal value up to 5.0 mg / L] and serum lactate dehydrogenase (LDH) was increased by 473 U / L[normal values up to 280 U / L). The urine analysis exhibits proteinuria 2.960 g / L [normal values up to 0.015 g / l]. PCR for CMV, herpes virus types 1, 2, 6, and Epstein Barr virus was negative. Together, the laboratory findings confirmed diagnostic criteria proposed by an International Working Group for TA-TMA: (1) > 4% schistocytes on blood smear; (2) thrombocytopenia < 50 × 109 / L; (3) increased LDH; (4) decrease of Hb and (5) haptoglobin (15). The patient received fentanyl 50 ^ / mL to manage the pain syndrome. Therapy with eculizumab, sirolimus, platelets infusion (15 procedures), and RBC infusion (8 procedures) led to partial improvement. The patient was readmitted on post-transplant day 71 with diarrhea (black 200-300 mL / daily). The endoscopy revealed total hemorrhagic gastritis and confirmed the existence of acute GVHD grade III. At the admission the analysis showed decreased RBC 2.2 x 1012 / L, Ht: 20.7 %; Hb: 7.4 g / dl; platelets 12 x 109 / L. A white blood cell count revealed a decrease of neutrophils 1.36 x 109L. After the diagnosis of GVHD, the patient sequentially received various lines of treatment (corticosteroids and sirolimus) without any response. During the next 27 days, the patient was treated with eltrombopag and received plasma infusion (6 procedures, 1.8 L total), RBC infusion (45 procedures, 12.3 L total), and platelets infusions (11 procedures, 1.6 L total). The sites of stomach mucosa bleeding were electro coagulated, but the overall appearance of stomach mucosa was not improving since hospitalization. On day 30 post-hospitalization (101 post-transplant day), the patient noted increased weakness and the appearance of hemorrhagic rashes on the upper limbs. The blood analysis revealed continuous reduction of the RBC 1.8 x 1012 / L, Ht: 16.5 %; Hb: 5.6 g / dL; platelets 18 x 109 / L. During the next three days, the patient received plasma infusion (10 procedures, 3 L total), RBC infusion (16 procedures, 4.3 L total), and platelets infusions (3 procedures, 0.4 L total). However, despite this therapy, his blood analysis continued to deteriorate, and endoscopic analysis of his stomach showed progression of hemorrhagic gastritis with confluent defects, ulcerations, and complete denudation of the mucosa typical for GVHD grade IV. On 100-day post transplantation the blood serum level of cfDNA measured with LFA according the invention (as described in Example 7) was found to be more than 1000 ng / mL. On 105-day post-transplantation, treatment was initiated with cfDNA-scavenging therapy (human recombinant DNase I provided by CLS Therapeutics, USA) with a dosage of 6,750 Kunitz units / ml) x 2 times a day for four days. By the end of cfDNA-scavenging therapy, the patient ceased requiring plasma and thrombocyte transfusions and received only one erythrocyte transfusion on the 9th-day post initiation of DNase I. The blood serum level of cfDNA measured with LFA according invention in same day was found to be substantially decreased to level of between 100 and 250 ng / mL. The patient showed progressive improvement by day 12 post-initiation of cfDNA-scavenging therapy with improved the analytical parameters of anemia: RBC 3.0 x 1012 / L, Ht: 28 %; Hb: 9.2 g / dl; platelets 42 x 109 / L and disappearance of hemorrhagic rush. Thus, the method of invention of quantification of cfDNA was successfully used for assessment the dynamic of cfDNA level; the cfDNA values obtained by the method reflect the clinical status; the method has cfDNA-associated disease monitoring value. EXAMPLE 11: Quantification of cfDNA in cohorts of healthy volunteers and patients with acute coronary syndrome with ST segment elevation (ST-ACS). Quantification of cfDNA was performed as specified in the Example 2. The cfDNA level was first quantified in 26 healthy volunteers to determine the reference limits of normal values, which was 78.0 (59.7-106.0) ng / ml. Fig.4. shows distribution of cfDNA concentrations in healthy volunteers. Further, cfDNA level was quantified in 44 patients with acute coronary syndrome with ST segment elevation (ST-ACS) admitted to cardiac intensive care unit of the Yudin Clinical Hospital (Moscow) and received percutaneous coronary intervention (PCI). Blood for cfDNA quantification was sampled immediately upon admission and 24 hours after PCI. Fig.5 shows cfDNA values in healthy volunteers and in ST-ACS patients on admission and 24 hours after PCI. Fuhrer analysis show statistically significant associations of cfDNA concentration before PCI with implantation of 2 or more stents (0.71 (0.56-0.86), p = 0.039) per procedure (Fig.6A). Pre-PCI cfDNA >90 ng / ml increased the risk of implantation of 2 or more stents by 5.4 times (OR 5.495% CI 5.80-28.93, p=0.044). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 82%, 52%, 37.5% and 90.0%, respectively. In addition, the association of cfDNA before PCI with the number of affected coronary arteries ≥2 approached statistical significance (0.67 with 95% CI (0.51-0.83), p = 0.052). A statistically significant association of cfDNA was found for stented segment length >24 mm (0.73 with 95% CI (0.58-0.89), p=0.009 For the level of cfDNA after PCI, an association was found with impaired local contractility in 2 or more segments of the LV myocardium (0.73 with 95% CI 0.57-0.89, p = 0.014) (Fig.6B). The risk of detecting a violation of local contractility of LV segments in ≥2 segments with a cfDNA cut-off point >105 ng / ml. increased 5 times (OR 5.0, 95% CI 1.23- 20.3, p=0.014). Sensitivity, specificity, PCR and PCR for cfDNA >105 ng / ml were 79%, 57%, 26.5% and 75%, respectively. Thus, quantification of cfDNA using method according the invention has useful clinical prognostic / monitoring value. The present invention is not to be limited in scope by the specific embodiments described herein. 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Claims

CLAIMS 1. A method for detection and / or quantification of cell free DNA (cfDNA) in a biological sample, the method comprising: (i) contacting a first linker histone immobilized on a solid surface with the biological sample to provide the immobilized first linker histone - cfDNA complex; (ii) freeing said solid surface from unbound biological sample; (iii) contacting immobilized first linker histone - cfDNA complex with a second linker histone conjugated to a detectable marker and which bind to the first linker histone - cfDNA complex; (iv) freeing said solid surface from unbound second linker histone conjugated to a detectable marker; (v) detecting or quantitating the binding of said second linker histone conjugated to a detectable marker to the first linker histone - cfDNA complex; and (vi) using the degree of such binding as a measure of amount of cfDNA in the sample.

2. A method for detection and / or quantification of cell free DNA (cfDNA) in a biological sample, the method comprising: (i) contacting a first linker histone conjugated with a detectable marker with the biological sample to provide first linker histone-cfDNA complex; (ii) contacting the first linker histone - cfDNA complex with a second linker histone, said second linker histone immobilized on a solid surface binds to the first linker histone - cfDNA complex; (iii) detecting or quantitating the binding of said second linker histone to the first linker histone- cfDNA complex; and (iv) using the degree of such binding as a measure of amount of cfDNA in the sample.

3. The method of claim 1 or 2, further comprising the freeing said solid surface from unbound biological sample after step (i).

4. The method of claim 2, further comprising the freeing said solid surface from unbound the first linker histone - cfDNA complex after step (ii).

5. The method of claim 1, wherein said second linker histone immobilized on a solid surface via a linker.

6. The method of claim 2, wherein said first linker histone immobilized on a solid surface via a linker.

7. The method of any one of claims 1 to 6, wherein the linker histone is a linker histone H1 or a linker histone H5.

8. The method of claim 7, wherein the linker histone H1 is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone.

9. The method of claim 8, wherein the linker histone H1 is H1.3 linker histone.

10. The method of any one of claims 1 to 6, wherein the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: MSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSGVS LAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGEG KPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGTKKVAKS AKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:1),or to the sequence: TENSTSAPAAKPKRAKASKKSTDHPKYSDMIVAAIQAEKNRAGSSRQSIQKYIKSHYKV GENADSQIKLSIKRLVTTGVLKQTKGVGASGSFRLAKSDEPKKSVAFKKTKKEIKKVAT PKKASKPKKAASKAPTKKPKATPVKKAKKKLAATPKKAKKPKTVKAKPVKASKPKKA KPVKPKAKSSAKRAGKKK (SEQ ID NO:2).

11. The method of claim 10, wherein the linker histone is bis-met H1.3 linker histone having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSGV SLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGE GKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGTKKVAK SAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5).

12. The method of any one of claims 1 to 6, wherein the linker histone comprises an amino acid sequence, which is at least 70% identical to the sequence: TDSPIPAPAPAAKPKRARAPRKPASHPTYSEMIAAAIRADKSRGGSSRQSIQKYVKSHYK VGQHADLQIKLAIRRLLTTGVLKQTKGVGASGSFRLAKGDKAKRSPAGRKKKKKAARK STSPKKAARPRKARSPAKKPKAAARKARKKSRASPKKAKKPKTVKAKSLKTSKPKKAR RSKPRAKSGARKSPKKK (SEQ ID NO:3), or to the sequence: MTESLVLSPAPAKPKRVKASRRSASHPTYSEMIAAAIRAEKSRGGSSRQSIQKYIKSHYK VGHNADLQIKLSIRRLLAAGVLKQTKGVGASGSFRLAKSDKAKRSPGKKKKA VRRSTSPKKAARPRKARSPAKKPKATARKARKKSRASPKKAKKPKTVKAKSRKASKAK KVKRSK PRAKSGARKSPKKK (SEQ ID NO:4), or to the sequence: MSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSVSL AALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGEGK PKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGTKKVAKS AKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:6), or to the sequence: SETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVA ASKERSGVSLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKL NKKAASGEGKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATA AGTKKVAKSAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:7), or to the sequence: HHHHHHTENSTSAPAAKPKRAKASKKSTDHPKYSDMIVAAIQAEKNRAGSSRQSIQ KYIKSHYKVGENADSQIKLSIKRLVTTGVLKQTKGVGASGSFRLAKSDEPKKSVAFKKT KKEIKKVATPKKASKPKKAASKAPTKKPKATPVKKAKKKLAATPKKAKKPKTVKAKP VKASKPKKAKPVKPKAKSSAKRAGKKK (SEQ ID NO:8), or to the sequence: MSETAPAAPAAPAPAEKTPVKKKARKSAGAAKRKASGPPVSELITKAVAASKERSGVSL AALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGEAK PKAKKAGAAKAKKPAGAAKKPKKATGAATPKKSAKKTPKKAKKPAAAAGAKKAKSP KKAKAAKPKKAPKSPAKAKAVKPKAAKPKTAKPKAAKPKKAAAKKK (SEQ ID NO:9).

13. The method of any one of claims 1 to 12, wherein the detectable marker is horseradish peroxidase.

14. The method of any one of claims 1 to 12, wherein the detectable marker is alkaline phosphatase.

15. The method of any one of claims 1 to 12, wherein the detectable marker is a colored particle.

16. The method of any one of claims 1 to 15, wherein the biological sample is a blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, an endometrial fluid sample, a urine sample, a saliva sample, a lymph sample, a tear fluid sample, a synovial fluid sample, or a sputum sample.

17. The method of any one of claims 1 to 16, wherein the solid surface is an inner surface of a compartment of polymeric plate having a plurality of such compartments or an inner surface of polymeric tube.

18. The method of any one of claims 1 to 16, wherein the solid surface is a surface of porous material or membrane.

19. A kit for detecting and / or quantifying cell free DNA (cfDNA) in a sample, the kit comprising: a first linker histone immobilized on solid surface and a second linker histone conjugated to a detectable marker together with instructions for use of the kit.

20. The kit of claim 19, wherein the any of the linker histone is a linker histone H1 or a linker histone H5.

21. The kit of claim 20, wherein the any of the linker histones is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone.

22. The kit of claim 21, wherein any of the linker histone H1 is a H1.3 linker histone.

23. The kit of claim 21, wherein the any of the linker histones comprises the amino acid sequence, which is at least 70% identical to any of the sequences selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO:

9.

24. The kit of claim 23, wherein any linker histone is bis-met histone H1.3 having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSGV SLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGE GKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGTKKVAK SAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5).

25. The kit of any one of claims 20 to 24, further comprising a plastic plate having a plurality of compartments.

26. The kit of claim 25, wherein the plurality of compartments comprises a reaction chamber and one or more of the plurality of compartments further comprises at least one of linker histone immobilized on solid surface of the inner wall of the reaction chamber.

27. The kit of any one of claims 20 to 26, wherein linker histone immobilized on magnetic beads.

28. The method of claim 2, wherein the contacting of the first linker histone conjugated with detectable marker with a biological sample is carried out: (a) at sample application site disposed on or in a porous substrate of a lateral flow device, or (b) prior to applying a biological sample to sample application site disposed on or in a porous substrate of a lateral flow device, and the second linker histone immobilized on a solid surface of the said porous substrate at detectionsite, wherein said porous substrate defines a flow path through the sample application site flows under capillary action away from said sample application site into said detection site where the contacting the first linker histone - cfDNA complex with a second linker histone immobilized on a solid surface, is carried out; detecting the binding of the second linker histone to the first linker histone-cfDNA complex is carried out visually or instrumentally at the detection site where the accumulation of detectable marker produces a indicative of the presence or of the presence at not less than of defined level of the cfDNA in the biological sample.

29. The method of claim 28, wherein detectable marker is colored particle.

30. The method of claim 28, wherein detectable marker is fluorescent moiety and the visualization of such marker accumulation at the detection site is carried out using ultraviolet light.

31. The method of claim 28, wherein detectable marker is enzyme and the visualization of such marker accumulation at the detection site is carried out using a substrate (chromogen) for the enzyme.

32. A lateral flow device for quantification of cell-free DNA (cfDNA) in a biological sample, wherein said lateral flow device comprises: a porous substrate; a sample application site disposed on or in said porous substrate; a detection site disposed on or in said porous substrate, wherein said detection site comprises at least (1) a first test line (L1) and (2) a second test line (L2), each test line comprising linker histone, said linker histone immobilized on a solid surface of the porous substrate and bind a complex formed between cfDNA and free linker histone conjugated to a detectable marker; wherein said porous substrate defines a flow path, through which a sample applied to the sample application site flows under capillary action away from said sample application site into said detection site; and wherein: said first test line (L1) and said second test line (L2) are configured so that either no test line signal or just a signal at the first test line (L1) is detectable when cfDNA level in a biological sample applied to said device is lower than a certain predefined cfDNA level; and said second test line (L2) is configured so that a signal is detectable at said second test line when cfDNA level in a biological sample applied to said device is greater than a certain predefined cfDNA level.

33. The lateral flow device for quantification of claim 32, wherein a certain predefined cfDNA level is the indicative level of need of cfDNA-scavenging therapy of a cfDNA-associated disease.

34. The lateral flow device of claim 32, wherein said lateral flow device comprises a control line downstream from said first test line and said second test line, wherein said control line comprises binding moiety that can capture the said free linker histone conjugated to the detectable marker, in the presence or absence of cfDNA in the biological sample.

35. The lateral flow device of any one of claims 32 to 34, wherein said lateral flow device further comprises a complex-forming site comprising a linker histone conjugated with a detectable marker, where said complex-forming site is disposed in said sample application site and / or between sample application site and said detection site.

36. The lateral flow device of any one of claims 32 to 36, wherein said detectable marker is selected from the group consisting of a colorimetric marker, a fluorescent marker, a radioactive marker, and a magnetic marker.

37. The lateral flow device of any one of claims 32 to 38, wherein the any of the linker histones is a linker histone H1 or a linker histone H5.

38. The lateral flow device of claim 37, wherein the any of the linker histones is selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone.

39. The lateral flow device of any claims 32 to 38, wherein the any of the linker histones comprises the amino acid sequence, which is at least 70% identical to the sequence selected from the groupconsisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO:

9.

40. The lateral flow device of claim 39, wherein the any of the linker histone is human bis-met linker histone H1.3 having the sequence: MMSETAPLAPTIPAPAEKTPVKKKAKKAGATAGKRKASGPPVSELITKAVAASKERSGV SLAALKKALAAAGYDVEKNNSRIKLGLKSLVSKGTLVQTKGTGASGSFKLNKKAASGE GKPKAKKAGAAKPRKPAGAAKKPKKVAGAATPKKSIKKTPKKVKKPATAAGTKKVAK SAKKVKTPQPKKAAKSPAKAKAPKPKAAKPKSGKPKVTKAKKAAPKKK (SEQ ID NO:5).

41. A method for determination of a status of cfDNA-associated disease in а subject, which comprises the steps of: (i) detecting or quantification of a сfDNA in a biological sample of a subject as defined in the method of claim 1 or 2; and (ii) using the cfDNA level measured to determine the cfDNA-associated disease status of the subject.

42. A method for assessment of a subject for suitability for cfDNA-scavenging therapy of a cfDNA- associated disease, which comprises the steps of: (i) detecting or quantification of a cfDNA in a biological sample of the subject as defined in the method of claim 1 or 2; and (ii) using the cfDNA level measured as a parameter of assessment of suitability of a subject for cfDNA-scavenging therapy.

43. The method of claim 45, wherein the suitability of a subject for cfDNA-scavenging therapy of a cfDNA-associated disease is considered as blood plasma level of cfDNA at least 500 ng / mL.

44. A method for monitoring a treatment of cfDNA-associated disease of a subject undergoing a treatment, which comprises the steps of: (i) detecting or quantification of a cfDNA in a biological sample of a biofluid of the subject as defined in the method of claim 1 or 2; (ii) repeating the detection or quantification of a cfDNA in a biological sample of a biofluid of the subject at least one other occasion; (iii) using any changes in the cfDNA level detected as a parameter for any changes in the course of cfDNA-associated disease of the subject.

45. A method of any one of claims 42 to 43, wherein cfDNA-associated disease is selected from the group of cancer, metastatic cancer, acute organ failure, organ infarct (including myocardial infarction and ischemic stroke), hemorrhagic stroke, autoimmune disorders, graft-versus-host- disease (GVHD), graft rejection, sepsis, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), graft-versus-host-disease (GVHD), traumatic injury, crush syndrome, proinflammatory status in aged individuals, diabetes, atherosclerosis, neurodegenerative disease, autoimmune disease, eclampsia, infertility, coagulation disorder, pregnancy-associated complications and infection.

46. A method of any one of claims 44 to 47, wherein cfDNA-scavenging therapy is selected from the following group: therapy with compound destroying cfDNA in biofluids; therapy with compound binding or deactivate cfDNA in biofluids.

47. A method of claim 46, wherein cfDNA-scavenging therapy is extracorporeal therapy removing cfDNA from biofluid, wherein the biofluid is first removed from the subject, then passed over column filled with cfDNA affinity matrix to remove cfDNA and returned into the patient.

48. A method of assessment of effectivity of an extracorporeal column to remove cfDNA from a biofluid, wherein the biofluid is first removed from the subject, then passed over the column filled with cfDNA-affinity matrix to remove cfDNA and returned into the subject, which comprises the steps of: (i) quantification of a сfDNA in biofluid removed from the subject and sampling before passing over the column according to the methods of the invention; (ii) quantification of a сfDNA in the sample biofluid returned into the subject and sampling after passing over the column according to the methods of the invention; and (iii) using the difference between cfDNA level measured at step (i) and cfDNA level measured at step (ii) to determine effectivity of the extracorporeal column to remove cfDNA from the biofluid.

49. A method of claim 48, wherein cfDNA-affinity matrix contains a protein of linker histone H1 family.

50. A method of claim 49, wherein the protein of linker histone H1 family is the linker histone H1 selected from an H1.0 linker histone, an H1.1 linker histone, an H1.2 linker histone, an H1.3 linker histone, an H1.4 linker histone, and an H1.5 linker histone.

51. A method of any one of claims 46 to 48, wherein the biofluid is blood or plasma.

52. A method of any one of claims 46 to 48, wherein the biofluid is lymph.

53. A method of any one of claims 46 to 48, wherein the biofluid is cerebrospinal fluid.

54. The method of any one of claims 46 to 48, wherein the subject is an animal or a human.

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