Methods and systems for biological sample collection and analysis
Filtration devices for collection and filtration of biological samples are disclosed. Devices having a filtration element oriented in a generally vertical orientation are provided, as well as filtration devices that incorporate a cooling mechanism to reduce the temperature of collected solids. Tissue collection devices, such as aspiration assemblies, tissue sampling devices, and the like incorporating filtration devices are disclosed. Methods of collecting biological samples and separating biological solids from a liquid/solids mixture are also disclosed, together with analytical techniques and protocols for analyzing biological samples.
1. A cooled filtration assembly for filtering biological materials comprising a housing having a liquid/solids input chamber and a liquid output chamber; a liquid/solids input port communicating with the liquid/solids input chamber, a liquid output port communicating with the liquid output chamber, and a filtration member interposed between the liquid/solids input chamber and the liquid output chamber, wherein the filtration member comprises a thermoelectric cooling surface that is actively cooled during operation and filtrate comprising biological materials residing in the filtration assembly during a filtration operation is cooled to a temperature at least 20° F. cooler than the temperature of biological materials entering the liquid/solids input port.
2. The cooled filtration assembly of claim 1 , wherein the filtration member is oriented in a generally vertical orientation during operation of the cooled filtration assembly.
3. The cooled filtration assembly of claim 1 , additionally comprising a jacket mountable on the filtration assembly and comprising an active or passive cooling system.
4. The cooled filtration assembly of claim 1 , additionally comprising an insulating jacket mountable on the filtration assembly.
5. The cooled filtration assembly of claim 1 , wherein the filtration member comprises a size exclusion filtration member.
6. The cooled filtration assembly of claim 1 , wherein the cooled filtration assembly comprises an additional port in proximity to the liquid/solids input chamber for introduction of a cooled fluid during the filtration operation.
7. The cooled filtration assembly of claim 1 , wherein at least one of the liquid/solids input chamber and the liquid output chamber additionally incorporates an active cooling element.
8. A cooled filtration assembly for filtering biological materials comprising a liquid/solids input port communicating with a liquid/solids input chamber, a liquid output chamber and a liquid output port communicating with the liquid output chamber, and a filtration member interposed between the liquid/solids input chamber and the liquid output chamber, wherein at least one of the liquid/solids input chamber, the liquid output chamber and the filtration member is actively cooled during operation and filtrate comprising biological materials residing in the filtration assembly during a filtration operation is cooled to a temperature at least 20° F. cooler than the temperature of biological materials entering the liquid/solids input port, wherein the filtration member is oriented in a generally vertical orientation during operation of the cooled filtration assembly and extends less than the full height of the liquid/solids input chamber and liquid output chamber, leaving a gap permitting material to flow between the liquid/solids input chamber and the liquid output chamber.
9. The cooled filtration assembly of claim 8 , wherein at least one of the liquid/solids input chamber, the liquid output chamber and the filtration member comprises a thermoelectric cooling surface.
10. The cooled filtration assembly of claim 8 , additionally comprising a jacket mountable on the filtration assembly and comprising an active or passive cooling system.
11. The cooled filtration assembly of claim 8 , additionally comprising an insulating jacket mountable on the filtration assembly.
12. The cooled filtration assembly of claim 8 , wherein the filtration member comprises a size exclusion filtration member.
13. The cooled filtration assembly of claim 8 , wherein the cooled filtration assembly comprises an additional port in proximity to the liquid/solids input chamber for introduction of a cooled fluid during a filtration operation.
14. An aspirating system for withdrawal of biological materials from a subject comprising a distal operating head for withdrawing a biological liquid/solids mixture sample from a target interventional site in the subject, a catheter having a lumen for transporting the biological liquid/solids mixture sample in a proximal direction, and a cooled filtration assembly comprising a liquid/solids input port communicating with a liquid/solids input chamber, a liquid output chamber and a liquid output port communicating with the liquid output chamber, and a filtration member interposed between the liquid/solids input chamber and the liquid output chamber, wherein the filtration member comprises a thermoelectric cooling surface, whereby the filtration member is actively cooled during operation and filtrate comprising biological materials residing in the filtration assembly during a filtration operation is cooled to a temperature at least 20° F. cooler than the temperature of biological materials entering the liquid/solids input port.
15. An aspirating system of claim 14 , additionally comprising a reservoir for collecting the biological liquid/solids mixture sample prior to passage of the biological liquid/solids mixture sample to the cooled filtration assembly.
16. A filtration device for filtering biological materials comprising a liquid/solids input port communicating with a liquid/solids input chamber, a liquid output chamber and a liquid output port communicating with the liquid output chamber, and a filtration member interposed between the liquid/solids input chamber and the liquid output chamber, wherein at least one of the liquid/solids input chamber, the liquid output chamber and the filtration member is actively cooled during operation and the filtration member is adapted to be oriented in a substantially vertical orientation during a filtration operation, wherein the filtration member extends less than the full height of the liquid/solids input chamber and liquid output chamber, leaving a gap permitting material to flow between the iquid/solids input chamber and the liquid output chamber.
17. A method for processing a biological sample comprising:
(a) withdrawing a liquid/solids mixture comprising a target tissue sample from a target site in a subject;
(b) conveying the liquid/solids mixture to a filtration device comprising a liquid/solids input port communicating with a liquid/solids input chamber, a liquid output chamber and a liquid output port communicating with the liquid output chamber, and a filtration member interposed between the liquid/solids input chamber and the liquid output chamber, wherein at least one of the liquid/solids input chamber, the liquid output chamber and the filtration member is actively cooled during operation for separation of at least a fraction of the solids from liquids, and wherein the filtration member extends less than the full height of the liquid/solids input chamber and the liquid output chamber, leaving a gap permitting material to flow between the input and output chambers and is adapted to be oriented in a substantially vertical orientation during a filtration operation, whereby the solids reside in the filtration device and the liquids are withdrawn from the filtration device;
(c) actively cooling the solids residing in the filtration device to produce cooled solids; and
(d) analyzing the cooled solids.
18. A method of claim 17 , wherein the target tissue sample comprises solids removed from blood vessels.
19. A method of claim 17 , additionally comprising removing the cooled solids from the filtration device and washing them with cold, sterile water to provide washed solids; pelleting and freezing the washed solids.
20. A method of claim 17 , additionally comprising assaying the cooled solids for expression of at least one gene encoding a protein selected from the group consisting of: ATP-binding cassette, sub-family A (ABC1), member 1: Angiotesin I converting enzyme (peptidyl-dipeptidase A) 1; Adipose differentiation-related protein; Apolipoprotein A-I; Apolipoprotein B (including Ag(x) antigen); Apolipoprotein E; BCL2-associated X protein; B-cell CLL/lymphoma 2; BCL2-related protein A1; BCL2-like 1; BH3 interacting domain death agonist; Baculoviral IAP repeat-containing 3; Chemokine (C-C motif) ligand 2; Chemokine (C-C motif) ligand 5; Chemokine (C-C motif) receptor 1; Chemokine (C-C motif receptor 2; CD44 antigen (Indian blood group); Cadherin 5, type 2, VE-cadherin (vascular epithelium); CASP8 and FADD-like apoptosis regulator; Collagen, type III, alpha I (Ehlers-Danlos syndrome type IV, autosomal dominant); Colony stimulating factor 1 (macrophage); Colony stimulating factor 2 (granulocyte-macrophage); Connective tissue growth factor; Early growth response 1; Elastin (supravalvular aortic stenosis, Williams-Beuren syndrome); Endoglin (Osler-Rendu-Weber syndrome 1); Fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor); Fas (TNF receptor superfamily, member 6); Fibrinogen alpha chain; Fibroblast growth factor 2 (basic); Fibronectin 1; Heparin-binding EGF-like growth factor; Intercellular adhesion molecule 1 (CD54), human rhinovirus receptor; Interferon (alpha, beta and omega) receptor 2; Interferon, gamma; Interleukin 1, alpha; Interleukin 1 receptor, type I; Interleukin 1 receptor, type II; Interleukin 2; Interleukin 3 (colony-stimulating factor multiple); Interleukin 3; Interleukin 5 (colony-stimulating factor, eosinphil); Intergin, alpha 2 (CD49B), alpha 2 subunit of VLA-2 receptor); Intergin, alpha 5 (fibronectin receptor, alpha polypeptide); Intergrin, alpha X (antigen CD11C (p150), alpha polypeptide); Intergrin, beta 2 (antigen CD18 (p95), lymphocyte function-associated antigen 1; macrophage antigen 1 (mac-1) beta subunit); Kinase insert domain receptor (a type III receptor tyrosine kinase); Kruppel-like receptor 2 (lung); Laminin, alpha 1; Low density lipoprotein receptor (familial hypercholesterolemia); Leukemia inhibitory factor (cholinergic differentiation factor); Lipoprotein, Lp(a); Lipoprotein lipase; Matrix metallipeptidase 1 (interstitial collagenase); Matrix metallopeptidase 3 (stromelysin 1, progelatinase); Macrophage scavenger receptor 1; Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105); Nitric oxide synthase 3 (endothelial cell); Neuropeptide Y; Nuclear receptor subfamily 1, group H, member 3; Platelet-derived growth factor alpha polypeptide; Platelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog); Platelet-derived growth factor receptor, beta polypeptide; Peroxisome proliferative activated receptor, alpha; Peroxisome proliferative activated receptor, delta; Peroxisome proliferative activated receptor, gamma; Prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase and cyclooxygenase); Retinoid X receptor, alpha; Selectin E (endothelial adhesion molecule 1); Selectin L (lymphocyte adhesion molecule 1); Selectin P ligand; Serpin peptidase inhibitor, clade B (ovalbumin), member 2; Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type I), member 1; Superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)); Secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1); Transforming growth factor, beta 1 (Camurati-Engelmann disease); Transforming growth factor, beta 2; Thrombospondin 4; Tenasein C (hexabrachion); Tumor necrosis factor (TNF superfamily, member 2); Tumor necrosis factor, alpha-induced protein 3; Vascular cell adhesion molecule 1; Vascular endothelial growth factor; Von Willebrand factor; Human 18S ribosomal RNA; Hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome); Ribosomal protein L13a; Glyceraldehyde-3-phosphate dehyrogenase; and Actin, beta.
21. A tissue sampling assembly for withdrawal of biological materials from a subject comprising a sample removal device for removing a biological sample and a cooled filtration assembly comprising a liquid/solids input port communicating with a liquid/solids input chamber, a liquid output chamber and a liquid output port communicating with the liquid output chamber, and a filtration member interposed between the liquid/solids input chamber and the liquid output chamber, wherein the filtration member comprises a thermoelectric cooling surface, whereby the filtration member is actively cooled during operation and filtrate comprising biological materials residing in the filtration assembly during a filtration operating is cooled to a temperature at least 20° F. cooler than the temperature of biological materials entering the liquid/solids input port.