Biomarker panel for dose assessment of radiation injury and micro plasma filter

Abstract

Materials, systems and methods are provided for qualitative assessment of exposure of a person to ionizing radiation by measuring amounts of the biomarkers, wherein a change compared with corresponding un-irradiated control reference ranges of the biomarkers, provides the assessment, wherein the biomarkers include (i) alpha-1-Antichymotrypsin (ACT), (ii) Fms-related tyrosine kinase 3 ligand (Flt3L), and (iii) one or more additional proteins.

What is claimed is: 
     
         1 . A blood filter cartridge comprising a cylindrical housing, a chamber, an inlet, a plurality of elongate hollow apheresis fibers, each comprising a lumen and wall having pore size sufficient to pass plasma but not blood cells, and an outlet, wherein the inlet is in bulk fluid connection with the lumens, the housing confines the chamber, the fibers are contained within the chamber, and the chamber is in bulk fluid connection with the outlet, configured such that in operation, blood enters the lumens from the inlet, plasma passes though the walls of the fibers into the chamber and then out the outlet. 
     
     
         2 . The blood filter cartridge of  claim 1  wherein the fibers are affixed at one end to a cylindrical manifold, in a grid pattern, and aligned lengthwise with the chamber. 
     
     
         3 . The blood filter cartridge of  claim 1  comprising 4-100 of the elongate, parallel fibers; having a dead volume of less than 100 ul; and requiring an operating pressure of less than 2 PSI. 
     
     
         4 . The blood filter cartridge of  claim 2  comprising 4-100 of the elongate, parallel fibers; having a dead volume of less than 100 ul; and requiring an operating pressure of less than 2 PSI. 
     
     
         5 . A blood filter comprising an integrated cartridge of  claim 1 , a running buffer contained in a running buffer reservoir, an actuator plunger, and a seal separating the running buffer from the cartridge inlet, configured so that depressing the plunger breaks the seal and urges the running buffer into the cartridge inlet. 
     
     
         6 . A blood filter comprising an integrated cartridge of  claim 2 , a running buffer contained in a running buffer reservoir, an actuator plunger, and a seal separating the running buffer from the cartridge inlet, configured so that depressing the plunger breaks the seal and urges the running buffer into the cartridge inlet. 
     
     
         7 . A blood filter comprising an integrated cartridge of  claim 1 , a running buffer contained in a running buffer reservoir, an actuator plunger, and a seal separating the running buffer from the cartridge inlet, configured so that depressing the plunger breaks the seal and urges the running buffer into the cartridge inlet, wherein the filter is operably connected to a lateral flow strip. 
     
     
         8 . A blood filter comprising an integrated cartridge of  claim 2 , a running buffer contained in a running buffer reservoir, an actuator plunger, and a seal separating the running buffer from the cartridge inlet, configured so that depressing the plunger breaks the seal and urges the running buffer into the cartridge inlet, wherein the filter is operably connected to a lateral flow strip. 
     
     
         9 . A blood filter comprising an integrated cartridge of  claim 1 , a running buffer contained in a running buffer reservoir, an actuator plunger, and a seal separating the running buffer from the cartridge inlet, configured so that depressing the plunger breaks the seal and urges the running buffer into the cartridge inlet, wherein the filter is operably connected to a plurality of lateral flow strips, each comprising affinity capture molecules specific to predetermined biomarkers. 
     
     
         10 . A blood filter comprising an integrated cartridge of  claim 1 , a running buffer contained in a running buffer reservoir, an actuator plunger, and a seal separating the running buffer from the cartridge inlet, configured so that depressing the plunger breaks the seal and urges the running buffer into the cartridge inlet, wherein the filter is operably connected to a plurality of lateral flow strips, each comprising affinity capture molecules specific to predetermined biomarkers of exposure of a person to ionizing radiation. 
     
     
         11 . A blood filter comprising an integrated cartridge of  claim 1 , a running buffer contained in a running buffer reservoir, an actuator plunger, and a seal separating the running buffer from the cartridge inlet, configured so that depressing the plunger breaks the seal and urges the running buffer into the cartridge inlet, wherein the filter is operably connected to a plurality of lateral flow strips, each comprising affinity capture molecules specific to predetermined biomarkers of exposure of a person to ionizing radiation, wherein the biomarkers comprise (i) alpha-1-Antichymotrypsin (ACT), (ii) Fms-related tyrosine kinase 3 ligand (F1t3L), and (iii) one or more additional proteins selected from the group consisting of: Serum amyloid A isoform 1 or 2 (SAA1 or SAA2), C-reactive protein (CRP), Salivary alpha amylase (AMY1A), Alpha-1-antitrypsin isoform 4 (SERPINA1), Neutrophil gelatinase-associated lipocalin (NGAL), Alpha-1-acid glycoprotein 1 or 2, Leucine-rich alpha-2-glycoprotein (LRG1), Tenascin-C (TNC), Clusterin (CLU), Hemopexin (HPX), Haptoglobin (HP), Apolipoprotein A-IV (APOA4), Interleukin 15 (IL15), Interleukin 18 (IL18), and Monocyte chemotactic protein 1 (MCP1). 
     
     
         12 . The blood filter of  claim 11  wherein the additional proteins are selected from the group consisting of: AMY1A, NGAL, APOA4, IL15, IL18, MCP1 and HPX. 
     
     
         13 . The blood filter of  claim 11  where the biomarkers comprise:
 (i) ACT, F1t3L, AMY1A and IL15; 
 (ii) ACT, F1t3L, NGAL and AMY1A; or 
 (iii) ACT, F1t3L, NGAL and MCP1. 
 
     
     
         14 . A method of using the blood filter of  claim 9  comprising the steps of:
 (a) separating with the filter biomarkers of a blood sample of the person; and 
 (a) detecting the separated biomarkers. 
 
     
     
         15 . A method for qualitative assessment of exposure of a person to ionizing radiation, comprising the steps of:
 (a) separating biomarkers of a blood sample of the person; and   (a) measuring amounts of the separated biomarkers, wherein a change in the amounts, compared with corresponding un-irradiated control reference ranges of the biomarkers, provides the assessment,   wherein the biomarkers comprise (i) alpha-1-Antichymotrypsin (ACT), (ii) Fms-related tyrosine kinase 3 ligand (F1t3L), and (iii) one or more additional proteins selected from the group consisting of: Serum amyloid A isoform 1 or 2 (SAA1 or SAA2), C-reactive protein (CRP), Salivary alpha amylase (AMY1A), Alpha-1-antitrypsin isoform 4 (SERPINA1), Neutrophil gelatinase-associated lipocalin (NGAL), Alpha-1-acid glycoprotein 1 or 2, Leucine-rich alpha-2-glycoprotein (LRG1), Tenascin-C (TNC), Clusterin (CLU), Hemopexin (HPX), Haptoglobin (HP), Apolipoprotein A-IV (APOA4), Interleukin 15 (IL15), Interleukin 18 (IL18), and Monocyte chemotactic protein 1 (MCP1).   
     
     
         16 . The method of  claim 15  wherein the measuring step is comprises a lateral flow immunoassay, ELISA, microsphere-based immunoassay, Western blot, immune-dot blot, or quantitative mass spectroscopy. 
     
     
         17 . The method of  claim 15  wherein the radiation exposure is >2 Gy. 
     
     
         18 . The method of  claim 15  wherein the measuring step occurs 1-14 days after the radiation exposure. 
     
     
         19 . The method of  claim 15  wherein the method further comprises the step of: classifying the person as either irradiation exposed or unexposed, based on the assessment, above or below a predetermined exposure threshold. 
     
     
         20 . The method of  claim 15  further comprising the step of treating the person for the radiation exposure, wherein the treating is therapy, monitoring or prescribing further assessments.