BACKGROUND OF THE INVENTION
Apparatus and methods currently used for carrying out patient fluid management require whole blood to be removed from the patient and processed in two ex-vivo stages. In a first stage the blood is processed to separate plasma, and in a second stage the plasma is processed in an ultrafiltration apparatus to remove plasma water and toxins. Although such procedure reduces the blood volume to normality, thereby treating fluid overload, the procedure causes massive change in blood hemodynamics in a short period of time including producing heavy stress on the human system with severe fluctuations and blood pressure and trauma to other body organs. Moreover, whole blood removal results in the necessity to heparinize or anticoagulate the patient to minimize clotting in the ex-vivo circuit and apparatus. Such treatment is counter-indicated in most surgical patients and deleterious to others due to consequential damage to blood components and the removal of vital blood components unrelated to the therapy. Removing and treating whole blood ex-vivo dictates that the procedure be a “batch” or intermittent process with attendant loss of efficiency and confinement of the patient to a clinical setting where support systems and machinery are available. Removal of whole blood also exposes the patient to contamination by viral and/or bacterial infection from nosocomial sources, and removal of erythrocytes, platelets and other large cellular blood components exposes them to risk of damage due to mechanical and chemical exposure to non-biocompatible surfaces of ex-vivo apparatus.
SUMMARY OF THE INVENTION
The present invention relates to a method and apparatus for carrying out patient fluid management including acute and chronic fluid overload without removing whole blood from the patient. The apparatus includes a filter device for being implanted in a blood vessel for carrying out in-vivo plasma separation using a plurality of elongated hollow fibers having an asymmetrical fiber wall morphology in which the inner wall surface along the interior fiber lumen has a lower mass density and the fiber wall adjacent to the outer wall surface has a higher mass density. Plasma is separated from whole blood in-vivo by passing through the fiber wall from the outer wall surface to the interior fiber lumen. The filter device comprises one or more elongated hollow conduits or tubes to which opposite ends of each of the fibers are secured so that the interior of the one or more hollow tubes communicates with the interior lumen of each of the elongated hollow fibers. The fluid management apparatus includes a multiple lumen catheter, secured to the proximal end of the one or more hollow tubes, for directing the in-vivo separated blood plasma from the filter device to an ultrafiltration apparatus in which plasma water and selected plasma components are separated and removed from the plasma. The treated plasma is returned to the patient. A preferred ultrafiltration apparatus has a sieving coefficient cutoff below about 6×104 daltons. The apparatus also includes piping and cooperating pumps for directing plasma between system components as well as backflush components comprising piping, backflush pump and source of backflush fluid selectively directed to the filter device for a duration and flow rate sufficient to substantially cleanse filter pores. In a preferred embodiment, operation of the apparatus is controlled by a microprocessor/controller.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic illustration of a preferred embodiment of an apparatus for carrying out patient fluid management;
FIG. 2 is a top view of a preferred embodiment of a filter device shown in FIG. 1 for separating plasma from blood in-vivo having a pair of elongated hollow tubes joined together along their length, showing distal and proximal end segments;
FIG. 3 is an enlarged sectional view of the filter device of FIG. 2 along the lines A-A showing a single elongated hollow fiber secured to the hollow tubes;
FIG. 4 is an enlarged view of a portion of the filter device shown in FIG. 2;
FIGS. 5-7 are sectional views of other filter device embodiments;
FIG. 8 is a sectional view of a triple lumen catheter of the apparatus shown in FIG. 1 illustrating the catheter interior; and
FIG. 9 is a scanning electron microscopy (SEM) image of a cross-section of a preferred elongated hollow fiber wall used in a filter device shown in FIG. 2 at 400 μm magnification.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The preferred embodiment of an apparatus for carrying out patient fluid management according to the invention schematically illustrated in FIG. 1 includes a filter device 10, a multiple lumen catheter 20, an ultrafiltration apparatus 40, a fluid control assembly including tubing and pumps, and a microprocessor/controller 30. The filter device 10, which will be described in more detail hereinafter, is implantable in the vasculature of a patient or animal in which in-vivo plasma separation is to be carried out. Examples of veins suitable for implanting the filter include the superior or inferior vena cava or the subclavian vein. In the drawing, the filter device 10 is shown implanted in a blood vessel 50.
The filter device 10 is used in combination with a multiple lumen catheter, preferably a triple lumen catheter 20 as illustrated in FIG. 8. The catheter is of a suitable length to provide for implanting or installing the filter device into the appropriate vessel of the patient, e.g., the inferior vena cava, between the diaphragm and the iliac junction via the femoral vein, jugular vein or subclavian vein. The catheter 20 may be secured to the proximal end 17 of the filter device 10 by a suitable method, e.g., using a suitable adhesive and an injection-molded connector 19. The catheter 20 has an access lumen 26 which is in open fluid communication with the interior of elongated hollow tubes 14 and 16 of the filter device. Return lumen 22 is occluded or blocked off at the distal end of the catheter 20, and is provided with one or more ports through the catheter wall near the distal end of the catheter whereby treated plasma may be returned to the patient. Backflush lumen 24 is also in open fluid communication with the interior of the hollow tubes 14 and 16 through which periodic backflush fluid is directed for preventing occlusion of the hollow fiber membrane caused by blood components. Plasma is separated from whole blood within the blood vessel in which the filter device is inserted using trans-membrane pressure (TMP) supplied by access pump or first pump 34, a positive displacement volumetric pump that operates to regulate pressure and control trans-membrane pressure and plasma volume removal rate.
Plasma separated from whole blood through the microporous fibers 12 of the filter device is directed through access lumen 26 and first tubing 31 to ultrafiltration apparatus 40 for separating and removing plasma water and selected plasma components from the plasma. Plasma water and plasma components removed from the treated plasma may be directed to a container 44. An effluent pump 42 is optional and may be advantageously used for assisting in controlling the rate of plasma water removed by providing controlled trans-membrane pressure across filter membranes of the ultrafiltration apparatus. Plasma is returned to the patient via tubing 43 at a rate controlled by pump 36. The tubing 43 is in fluid communication with plasma return tube 32 which is connected to plasma return lumen 22 of triple lumen catheter 20 (FIG. 4).
The ultrafiltration apparatus 40 for treating the plasma removed in vivo by the previously described filter apparatus and filter device may be a conventional ultrafiltration apparatus used for separating plasma water from blood utilizing conventional hemodialysis apparatus and procedures. Such apparatus is known to those skilled in the art and is described, for example, in U.S. Pat. No. 5,605,627, the description of which is incorporated herein by reference. A commercial example of such ultrafiltration apparatus is MINNTECH HEMOCOR HPH 400TS®. The ultrafiltration apparatus is capable of and configured for removal of metabolic toxic waste including plasma water to carry out the desired patient fluid management. The make-up of blood and plasma components by molecular weight in daltons is shown in Table 1. A preferred ultrafiltration apparatus is configured to remove and separate plasma components having a molecular weight below the molecular weight of albumin (6.9×104). Removal of substantial or excessive amounts of albumin is to be avoided to prevent hypoalbuminemia. Albumin replacement is expensive as is removal of other important immune system proteins, as will be understood by those skilled in the art. Thus, although an ultrafiltration sieving coefficient cutoff between about 1×104 and about 1×105 daltons could be used, it is preferred that the ultrafiltration sieving coefficient cutoff is less than about 6.9×104, and more preferably less than about 6×104 daltons. Any ultrafiltration apparatus capable of separating and removing plasma water and components within the aforesaid ranges may be used. Preferred plasma separation filter cutoff (sieving coefficient cutoff) is above ultrafiltration cutoff and below about 5×106 daltons, and preferably between about 6×104 and about 2×105 daltons.
The preferred apparatus shown in FIG. 1 includes backflush fluid reservoir 37, backflush pump 38 and backflush tube 33 communicating with a backflush lumen of the multiple lumen catheter. Such backflush components and method are disclosed in U.S. Pat. No. 6,659,972, the description of which is incorporated herein by reference in its entirety. Backflush pump 38 is selectively and periodically operated to provide backflush fluid flow for substantially cleansing the pores of the fiber membrane of the filter device. Such a backflush cycle is preferably operated at high trans-membrane pressure and low volume and at relatively short injection times for backflushing whereby the membrane pores of the filter device are temporarily expanded and flushed to dislodge adhered proteins, thereby restoring pore integrity and density of the virtual filter area for improved plasma separation performance after each backflush cycle.
Fluid control of plasma within the apparatus may be controlled using a microprocessor/controller operatively communicating with the positive displacement volumetric pumps for controlling trans-membrane pressure in the filter device, plasma removal rate, plasma return rate and backflush pressure and rate. Such fluid control and management may be selected, tailored or designed for slow, continuous acute fluid removal. For example, operation of the system may be used for controlling plasma extraction rate from blood to achieve removal of 1-2 L, or more, of plasma water over a 24-hour period. The fluid control assembly may also include volume sensors, pressure sensors, blood leak detectors and air detectors connected to the piping and reservoirs as desired. As illustrated in FIG. 1, the microprocessor/controller 30 is operatively connected to the pumps. Similarly, the microprocessor/controller operates for controlling backflush pump 38 and plasma is returned at a selected rate by controlling pump 36. The microprocessor/controller may be programmed for flow rates designed to a the prescribed patient therapy. Plasma fluid control may also require the infusion or addition of fresh plasma fluid to compensate for excess plasma water loss. In the embodiment shown in FIG. 1, a source of fresh plasma fluid 41 provides such fluid which may be introduced via the ultrafiltration apparatus or the plasma return line.
In a preferred embodiment illustrated in FIGS. 2 and 3, a pair of elongated hollow tubes are joined side-by-side lengthwise to form the core of the filter device. The two elongated hollow core tubes 14 and 16 terminate at a distal end with a distal end plug or cap 13 formed of a material that seals the open tube ends. The tubes and end cap may be made of any suitable biocompatible material, for example, medical grade extruded urethane tubes. Other biocompatible materials include synthetic rubbers, polycarbonate, polyethylene, polypropylene, nylon, etc. The elongated hollow tubes may be secured together using suitable bonding material 18, adhesive compositions, etc., for example, a UV curable adhesive applied along the length between the two tubes. The length and diameter of the filter device may be selected to accommodate the vessel or vein in which it is to be implanted. Accordingly, the diameter and length of the one or more elongated hollow tubes forming the central core of the filter device are selected. A suitable tube length is between about 15 cm and about 25 cm, and preferably between about 18 cm and about 22 cm. Where a pair of core tubes is used as shown in the preferred embodiment, an outer diameter of each tube of between about 1 mm and about 3 mm is suitable. A detectable marker component 31, e.g., a radio opaque material may also be bonded to the device, for example, in bonding material 18 extending along the length of the tubes to assist in implanting and/or monitoring the device especially during insertion and removal.
The elongated hollow microporous fibers used in the filter device are the asymmetrical wall fibers disclosed in U.S. Pat. No. 6,802,971, the description of which is incorporated herein by reference in its entirety. The morphology of the fiber walls is asymmetrical between the inner fiber lumen and the outer fiber wall which is in direct contact with the blood flowing in the vasculature in which the device is implanted. The filtration performance of such a device is a function of the filter surface of the exposed fibers whereby consideration is given to use larger diameter fibers and to maximize the number of fibers. Thus, it may be desirable to use as many individual fibers along the hollow core tubes of the filter device as is practical while maintaining separation of the individual fibers to provide for fluid flow therebetween, and to maximize the amount of outer fiber surface exposed to blood flowing along the length of the filter device. Moreover, the fibers are secured along the length of the hollow tubes in such a manner as to form a fluid flow space between the fibers and the tubes. Again, however, the length of the filter device as well as the overall cross-sectional dimension are tailored or dictated by the blood vessel in which the device is to be used so as to avoid substantial interference with blood flow through the vessel while at the same time be efficient to achieve the intended flow rate of separated plasma.
In a preferred embodiment, the ends of each of the fibers are offset longitudinally relative to one another as illustrated in FIGS. 2 and 3. As shown, elongated hollow fiber 12 has a first end 21 secured in first elongated hollow tube 14 and second end 23 secured in second hollow tube 16. In the specific device illustrated, the longitudinal spacing between the first and second ends of each fiber is a three-hole or three-fiber offset, e.g., about 0.5 cm. However, with intervals between the adjacent fiber ends of between about 0.1 cm and about 1.0 cm, offsets between first and second fiber ends may be between about 0.3 cm and about 3.0 cm, by way of example. With such offsets between first and second fiber ends, a straight line extending between the ends of a fiber forms an acute angle with an elongated axis of either or both of the elongated hollow tubes, and whereby the fibers also extend lengthwise between their ends along an angle other than 90° relative to the axes of the elongated hollow tubes. The acute angle preferably is between about 45° and about 85°. However, other fiber angles including 90° are not precluded and may be used where desired. In another preferred embodiment shown in FIG. 2, the proximal and distal fibers 11 and 15 located at each end of the filter device are filled with polyurethane or other biocompatible synthetic resin composition. These solid fibers at the ends of the row of fibers protect the adjacent hollow fibers from potential damage caused by mechanical stress during catheter insertion and removal.
In an example of assembly of a filter device, the elongated hollow core tubes 14 and 16 are joined as previously described and holes are drilled at the desired spacing along each of the two tubes. The holes may be drilled along opposite sides of the two tubes, and preferably are spaced at regular intervals of between about 0.1 cm and about 1.0 cm, and more preferably between 0.1 cm and about 0.3 cm. In a device as illustrated in FIGS. 1-3, 6 fibers/cm are used and the interval or spacing between fiber ends along each of the tubes is approximately 1.66 mm. However, other practicable fiber spacing may be used, for example, between about 4 and about 8 fibers/cm and preferably between 5 and 7 fibers/cm of the length of the hollow tubes. The fibers may be secured in the spaced holes by any suitable method. For example, a first fiber end is inserted in a first hole in one of the tubes, the tubes are rotated 180°, and a second end of the fiber inserted in a first hole in the other tube. The procedure is repeated until all fiber ends are inserted in the holes along the two joined tubes. A wire or other elongated member may be inserted along the interior of each of the core tubes during assembly to provide a uniform limit or stop for the fiber ends along the respective hollow tube interior passageways. The fibers are bonded to the tubes and the joints between the fibers and the tubes sealed using a suitable adhesive or potting compound and the wires are removed. In the specific example of a filter device shown in FIG. 1, 118 active hollow fibers and 2 filled end fibers are spaced at 6 fibers/cm along 20.4 cm of the tubes. Each fiber is about 1.5 mm long.
FIG. 5 illustrates an alternative embodiment in which fibers are positioned on two sides of the filter device. Fibers 62 and 64 extend at opposite sides of the device whereby first and second ends of each of the fibers are secured along two rows along each of the tubes. As shown in FIGS. 3-5, the fibers are arched to form a space between the fibers and the elongated tubes. In FIGS. 3 and 4, a space 25 is formed by the arched fibers, and in FIG. 5, two spaces 27 and 29 are formed by the arched fibers on both sides of the filter device. The length of the fibers may be selected to accommodate the desired filter surface, as well as the desired cross-sectional dimension of the filter device as previously discussed. Suitable fiber lengths are between about 1 mm and about 4 mm to provide sufficient space between the arched fibers and the hollow tubes without distorting the fibers which could cause undesirable strains along the fiber walls or otherwise compromise fiber performance.
FIGS. 6 and 7 illustrate alternative filter device design embodiments. In FIG. 6, a single tube 51 having a divider wall or septum 53 extending the length of the tube separates two elongated chambers 52 and 54. Another plasma separation filter design is illustrated in FIG. 7 utilizing a single tube 36 having one elongated hollow passageway 58 extending along the tube. Such alternative filter devices are produced, assembled and function substantially as previously described for the two-tube embodiment.
As previously stated, the plasma separation filter device utilizes elongated microporous fibers having asymmetrical fiber wall structure between the inner wall surface extending along the interior fiber lumen and the outer fiber wall surface exposed to blood in the vessel in which the filter device is implanted. The fiber wall at or adjacent to the outer wall surface has a higher mass density than the mass density adjacent to or at the inner wall surface. The mass density is a function of the average nominal pore size. Such asymmetric fiber wall morphology is illustrated in FIG. 9 showing a scanning electron microscopy (SEM) image of a cross-section of the fiber at 400 μm magnification. It will be observed that the structure of the fiber from the outer surface to the lumen is a continuous change in mass density whereby the pore size gradually changes between these fiber wall surfaces. The fiber walls are also characterized by a substantially uniform wall thickness between the inner and outer wall surfaces and comprises a continuum of voids bounded by solid frames and substantially without macrovoids other than the pores, as shown. It may be convenient to describe the continuum of different mass density as sections or zones of the wall area having an average nominal pore size or average pore diameter, each zone having a different average nominal pore size. Thus, the walls may be characterized by two or more zones, for example 2, 3, or 4 or more mass density zones. Again, such fibers are more fully described in U.S. Pat. No. 6,802,971.
The advantages of using the methods and apparatus described above for patient fluid management over conventional procedures include elimination of the disadvantages of the removal of whole blood from the body and subsequent ex-vivo plasma separation and ultrafiltration. The in-vivo plasma extraction technique permits a new approach to extracorporeal therapies especially useful and beneficial for the treatment of chronic fluid overload as well as for acute conditions such as patients having congestive heart failure. The in-vivo separation of plasma may reduce blood damage and loss, simplify the extracorporeal circuit and permit operation with lower pressures and less heparinization in the extracorporeal circuit. The absence of red cells in the extracorporeal circuit will eliminate thrombosis and may result in a better and longer utilization of the external filter and potential reduction in cost. In-vivo plasma separation permits continuous real time therapy in most applications with resultant improvement in effectiveness, and in many applications would result in the ability to perform the therapy in a home setting or ambulatory mode which could be a major improvement in patient lifestyle as well as economy for the medical care system. Moreover, the use of the methods and apparatus described herein would increase the capacity of most caregiver organizations which are now limited by patient load capacity including the number of centrifuge machines available in the facility.
TABLE 1
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BLOOD AND PLASMA COMPONENTS
SIZE BY MOLECULAR WEIGHT (DALTONS)
COMPONENT≦103 DAL.≦104 DAL.≦105 DAL.≦106 DAL.≧106 DAL.
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ELECTROLYTES
H2O18
Sodium22.89
Magnesium24.3
Chloride35.4
Potassium39.1
Calcium40.0
NaCl58.5
Urea60.0
Glysine (smallest amino acid)75.0
Creatinine113.1
Uric Acid168.1
Glucose180
Dextrose180.1
Triptophane (largest amino acid)204.2
Sucrose342
Billirubin584.6
Haptens<1 × 103
PROTEINS (74 g/L mean-adults)
Low flux Dialyzer cut-off
Inulin5 × 103
Amyloid A protein8 × 103
β2-Microglobulin1.18 × 104
Lisophospholipase1.3 × 104
IL-2 Interleukin1.55 × 104
CD 3 (T3ξ) membrane complex1.6 × 104
Myoglobin1.76 × 103
J-chain1.76 × 104
IL-5 Interleukin1.8 × 104
M-CSF1.8 × 104
Serum amyloid A component2.0 × 104
IL-4 Interleukin2.0 × 104
CD3 (T3δ, ε) membrane complex2.0 × 104
IL-6 Interleukin2.1 × 104
Retinol binding protein2.12 × 104
C8 γ complement protein2.2 × 104
IL-3 Interleukin-32.2 × 104
Factor D2.4 × 104
Flagellin2.5-6 × 104
CD3 (Tγ) membrane complex2.5 × 104
α1-Microglobulin2.5-3.3 × 104
C1s Complement protein2.7 × 104
Class II histocompatibility molecules2.7-3.4 × 104
CD3 (T3 ω) membrane complex2.8 × 104
G-CFS3.0 × 104
9.5 S-α Glycoprotein3.08 × 104
Li Invariant chain3.1 × 104
IL-1 Interleukin-a3.1 × 104
Urokinase Low H form3.3 × 104
Thrombin3.3 × 104
C3d complement protein3.3 × 104
Apolipoprotein E3.3 × 104
Erythropoietin3.4 × 104
β2-Glycoprotein III3.5 × 104
Transcobalamin II3.8 × 104
Factor I β3.8 × 104
Interferon γ4.0 × 104
Zn.α2-Glycoprotein4.1 × 104
Actin filaments4.2 × 104
Protein A4.2 × 104
Class 1 histocompatibility moleule4.4 × 104
α1-Acid glyoprotein4.41 × 104
M-CSF4.5 × 104
α1-Antitrypsin4.5 × 104
CD1 Membrane glycoprotein4.6 × 104
Fab Fragment4.7 × 104
High flux Dialyzer cut-off
FactorVII Proconvertin5.0 × 104
β2-Glycoprotein I5.0 × 104
α1B Glycoprotein5.0 × 104
Factor I α5.0 × 104
Transcortin5.07 × 104
CD 2 membrane glycoprotein T lymph.5.0-5.8 × 104
LMK kininogen5.0-6.8 × 104
Ge-Globulin5.2 × 104
Urokinase high M form5.4 × 104
Thromboplastin FactorIII5.6 × 104
Properdin5.6 × 104
Factor X Stuart-Prower factor5.6 × 104
Factor IX Plasma thromboplastin5.7 × 104
Factor AtIII Heparin cofactor5.8 × 104
Hemopexin5.7 × 104
C1s Complement protein α5.8 × 104
α-Antichymotrypsin5.8 × 104
3.8S-α-glycoprotein5.8 × 104
Hemofilter cut-off
α2HS-Glycoprotein5.9 × 104
α1 T-Glycoprotein6.0 × 104
Proalbumin6.1 × 104
Prothrombin6.27 × 104
α2-Antiplasmin6.3 × 104
Thiroxine-binding globulin6.3 × 104
C8 α,β complement protein6.4 × 104
CD 5 membrane glycoprotein6.5 × 104
Klenow fragment6.8 × 104
Hemoglobin6.8 × 104
α1X-Glycoprotein6.8 × 104
Protein S6.9 × 104
Albumin6.9 × 104
DAF decay accelerator7.0 × 104
α2-Aniti plasmin7.0 × 104
C9 Complement component7.1 × 104
t_PA Tissue plasminogen activator7.2 × 104
Dextran7.5 × 104
C5, C4, C3 Complement component β7.5 × 104
Factor XII Hageman factor8.0 × 104
Hemepoxin8.0 × 104
C1r complement protein8.3 × 104
Kallikrein8.8 × 104
Interferon gamma receptor9.0 × 104
Transferrin9.0 × 104
Hmk kininogen8-11.4 × 104
β2-Glycoprotein II9.3 × 104
C4 Complement component α9.3 × 104
Sex binding Globulin9.4 × 104
Fab2 fragment9.5 × 104
CR4 Complement receptor9.5-15 × 104
Factor B 1 × 105
CALLA glycoprotein 1 × 105
Haptoglobin 1 × 105
DNA polymerase 11.03 × 105
C1Inh glycoprotein 1 × 105
HMWK Kininogen1.1 × 105
C7 Complement component1.04 × 105
C1 inhibitor1.05 × 105
C4 binding protein1.07 × 105
C2 Complement1.08 × 105
C-reactive protein1.1 × 105
Integrins1.1-1.3 × 105
E-LAM I adhesion molecule 11.15 × 105
C5 Complement component α1.15 × 105
C3 α1.17 × 105
C6 complement protein1.24 × 105
Globulins (average)1.4 × 105
CR2 Complement receptor1.45 × 105
Factor H1.5 × 105
IgG Immuneoglobulin1.5 × 105
CR3 α Complement receptor1.55 × 105
Factor XI (PTA)1.6 × 105
Cefuloplasmin1.6 × 105
IgA Immuneoglobulin1.6 × 105
γG-Immuneoglobulin1.6 × 105
IgD Immuneogloblin1.75 × 105
Clathrin1.8 × 105
lnter-α-trypsin inhibitor1.8 × 105
IgE Immuneogloblin1.9 × 105
Plasma filter cut-off
Carcinoembryonic antigen2.0 × 105
P complement (properdin)2.2 × 105
CR1 Complement receptor2.5 × 105
Fibronectin2.5 × 105
Factor XIII Fibrin stabalizing factor3.2 × 105
Factor V Proaccelerin3.3 × 105
Cholinesterase3.4 × 105
Fibrinogen4.0 × 105
Cold insoluble globulin4.5 × 105
α-1 LipoproteinHDL31.9 × 105
HDL24.5 × 105
RNA polymerase4.5-5 × 105
α2-Macroglobulin8.2 × 105
C1 complex
IgM Immuneogloblulin 9 × 105
β-Lipoprotein (LDL)9.55 × 105
α2-Lippoprotein (LDL) 3.2 × 106
Factor VIII antihemophilic globulin5-20 × 106
Lymphocyte 8.3 × 106
Megakaryocyte>106 d = 8-12 μm
>106 d = 35-160 μm
Lymphoid NK cellsd = 15 μm
Plasma cellsd = 14 μm
Plateletd = 2-4 μm
Polymorphonuclear leukocyted = 13 μm
Erythrocytesd = 7.5 μm
HIV virus Retroviridaed = 80-130 nm
HBV virus Hepadnaviridaed = 40 nm
CMV virus Herpesviridaed = 150-200 nm
HCV virus Flaviridaed = 40-50 nm
MuLV virusd = 80-120 nm
Polio virusd = 23-30 nm
Herpes Simplex virusd = 120-150 nm
Aadenovirusd = 70-90 nm
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Patent Application
20050215936
