WO2019021258A1

WO2019021258A1 - Labware with low protein and/or dna binding properties

Info

Publication number: WO2019021258A1
Application number: PCT/IB2018/055648
Authority: WO
Inventors: Ed KUNG; Alexander Van Goudswaard; Manish Nandi; Ranjan Dash
Original assignee: Sabic Global Technologies B.V.
Priority date: 2017-07-28
Filing date: 2018-07-27
Publication date: 2019-01-31

Abstract

A labware having a reduced polypeptide or polynucleotide binding capacity is disclosed. The labware can include 80 wt. % to 99.99 wt. % of a base polymeric matrix and 0.01 wt. % to 20 wt. % of a surface modifying macromolecule (SMM) having a fluoro-oligomeric compound comprised within the polymeric matrix. At least a portion of the labware's surface can include the SMM and can have a polypeptide or a polynucleotide binding capacity of less than 80 nanograms (ng)/cm2.

Description

LABWARE WITH LOW PROTEIN AND/OR DNA BINDING PROPERTIES

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority of U. S. Provisional Patent Application No. 62/538,061 filed July 28, 2017, which is hereby incorporated by reference in its entirety. BACKGROUND OF THE INVENTION

A. Field of the Invention

[0002] The invention generally concerns labware having reduced binding or affinity for biological materials. In particular, the labware includes an article made from a base polymer and a surface modifying molecule such that at least a portion of the surface of the resulting article has a reduced ability to bind to biological materials, such as polypeptides and/or polynucleotides.

B. Description of Related Art

[0003] Biological materials such as peptides, proteins, nucleic acids, and cells are often stored or transferred in plastic containers such as centrifuge tubes and pipettes made of plastic or other hydrophobic materials. It is a common observation that these biological materials bind to the surfaces of such containers.

[0004] For many applications, such binding is undesirable. For example, the binding can result in the loss of valuable materials (e.g., enzymes, antibodies, etc.) during removal of the materials from the containers. In particular, the materials remain attached to the surface of the containers rather than being transferred to other containers or administered to patients. This can be problematic especially when small volumes of such materials are used. By way of example, in certain applications such as polymerase chain reaction (PCR) and next generation sequencing (NGS), the decrease in concentration can result in a decrease in accuracy and sensitivity of analysis. In another example, variations in the amount of materials administered to a patient can result in decreased efficacy of the administered material (e.g., monoclonal antibodies such as HUMIRA® (adalimumab)).

[0005] Attempts have been made to solve this surface binding problem. For example, surface coatings using poly(ethylene glycol) (PEG), polysaccharides, polyamides, polybetaines and polyampholytes are reported in literature. PEG is considered most effective in reducing adsorption of biological materials due to its strong hydrogen-bonding and dipole-dipole interactions with water (Weikart et al, SLAS Technology 2017, 22(1):98-105). The tightly bound water molecules cover the plastic surface thereby providing little space for biological molecule to adsorb. However, PEG-modified materials in aqueous solutions have been reported to be unstable due to oxidation leading to hydroperoxides, which over time can damage dissolved biological solutions. Another issue related to coatings is the extractable and leachable components originating from the coating surface. Leachable and extractable materials can contaminate, interact with, and damage the biological molecules. Coatings also suffer from issues related to temperature stability. Labware may be stored/used at temperatures ranging from dry ice temperature (-80 °C) to about 100 °C. Sometimes, the labware may have to undergo thermal cycling. The coating has to be stable in these temperatures and under thermal cycling conditions. The coating may decrease the transparency of the labware, which may be required in certain applications.

[0006] Another proposed solution is surface treating plastic containers to reduce binding affinity with biological materials. By way of example, WO 2016/176561 discloses the use of surface plasma treatment to chemically modify the surface of plastic container with predominantly hydrogen-bond-acceptor uncharged polar groups. While this technology works for decreasing the binding of certain types of proteins, it does not work for decreasing the binding of nucleic acid molecules. Also, the binding properties of plasma treated parts depends on the type of resin used in fabricating the parts. Still further, such surface treatment introduces an additional processing step in the manufacture of the plastic container, which can increase the costs and/or complexity of the producing the container.

[0007] In a further attempt, U.S. Patents 6,319,664 and 7,312,057 each disclose the use of non-ionic surfactants extending from the surface of containers to reduce surface adsorption of biological materials. One of the potential issues with surfactants is that they could potentially denature nucleic acid molecules as well as polypeptides and proteins. [0008] Although various attempts have been made to address the surface adhesion issues with biological materials vis-a-vis plastic containers, the resulting containers are oftentimes modified in a manner that can negatively affect the structure of the biological materials and/or be cost prohibitive to implement for commercial manufacturing purposes.

SUMMARY OF THE INVENTION [0009] A discovery has been made that provides a solution to the aforementioned problems associated with biological materials adhering to the surface of lab ware-related containers, devices, and/or equipment. The solution is premised on producing polymeric items or articles from blends that include a base polymer and a surface modifying macromolecule (SMM) having a fluoro-oligomeric compound. In certain aspects, the polymeric items are labware- related items. The blends can be cast or molded into labware such that at least a portion of the surface of the labware has reduced binding capacity for polynucleotides and/or polypeptides (the terms polypeptides and proteins can be used interchangeably throughout this specification). In particular, at least a portion of the labware's surface can have a polynucleotide or polypeptide binding capacity of less than 80 nanograms (ng)/cm². A labware of the present invention can be prepared by molding or casting a base polymer/fluoro-oligomeric compound (i.e., a surface modifying macromolecule (SMM)) blend or mixture). During molding or casting the SMM can migrate to the air/polymer interface. This migration can be provoked through sheer force during said molding or casting process. Consequently, at least a portion of the surface layer can have the SMM molecule present at its surface or extending outwards from its surface. Without wishing to be bound by theory, it is believed that the fluoro-oligomeric compound imparts hydrophobic properties to the surface, thereby reducing the binding capabilities of the surface vis-a-vis biological materials such as polynucleotides and/or polypeptides. In certain aspects, the labware can be made from a material that includes 80, 81, 82, 83, 84, 85, 86, 87, 88, 89 wt. % to 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.99 wt. % of a base polymeric matrix, including all values and ranges there between, and 0.01, 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9 wt. % to 10, 11, 12, 13, 1, 15, 16, 17, 18, 19, 20 wt. % of a surface modifying macromolecule (SMM), including all values and ranges there between. At least a portion of the labware's surface can have a polypeptide or a polynucleotide binding capacity of less than 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 nanograms (ng)/cm² including all values and ranges there between. In certain aspects, the concentration of the SMM is greater at the labware's surface than in its interior volume, which can be caused by the migration of the SMM to the surface of the labware item during the molding or casting processing step.

[0010] In certain aspects of the invention, the base polymeric matrix can be a thermoplastic polymer matrix or a thermoset polymer matrix. In a further aspect, the thermoplastic polymer is polyester, polyethylene, polypropylene, polystyrene, polysulfone, polyetherimide, polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), polycarbonate, polyamide, or a blend or copolymer thereof. In a particular aspect, the copolymer is a polypropylene/polyethylene copolymer. In another aspect the polymer is a BPA-free copolyester (e.g., TRITAN™ from Eastman). In yet a further aspect, the polymer can be a cyclic olefin copolymer (COC) or a cyclic olefin polymer (COP). [0011] A surface modifying macromolecule (SMM) in the context of the present invention includes a hydrophobic macromolecular having a fluoro-oligomeric compound (see for example, Rana et al. J. Mater. Chem A2: 10059, 2014; Suk, Daniel Eumine. Development of surface modifying macromolecule blended polyethersulfone membranes for vacuum membrane distillation. Diss. University of Ottawa (Canada), 2006). The molecular weight (MW) of the SMM can be at least 50 Daltons to 5,000 Daltons, preferably 100 Daltons to 4,000 Daltons, or more preferably from 300 Daltons to 3,000 Daltons or 100 Daltons to 1,500 Daltons. In certain aspects, the SMM is a fluorinated macromolecule or a fluoro-oligomeric molecule. In some embodiments, the fluoro-oligomeric compound has a structure according to Formula I or Formula II:

(F_T)-(oligo)-(F_T)

Formula I,

(F_T)-[(L)](oligo)[(L)]-(F_T)

Formula II where (FT) is a polyfluoroorgano group and (oligo) is an oligomeric segment.

[0012] The oligomeric segment can have a molecular weight of 500 to 3,000 Daltons. The oligomeric segment can be a branched or non-branched oligomeric segment of at least, at most, or equal to 3 to 10, 2 to 15, or 3 to 15 repeating units. In certain aspects the oligomeric segment is at least, at most, or equal to 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 repeating units. In certain aspects, the oligomeric segment is a polyurethane, polyurea, polyamide, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl derivative, polypeptide, polysaccharide, polysiloxane, polydimethylsiloxane, polyethylene-butylene, polyisobutylene, polybutadiene, polypropylene oxide, polyethylene oxide, polytetramethylene oxide, or polyethylenebutylene. The SMM can be, for example, a poly(urethane propylene glycol) or poly(urea dimethylsiloxane urethane). The polyfluoroorgano group (FT), e.g., polyfluoroalkyl, can have a molecular weight between 100 to 1,500 Da. The polyfluoroalkyl can be selected from the group consisting of CF3(CF₂)rCH₂CH2- wherein r is 2-20, and CF3(CF₂)_s(CH₂CH₂0)_y wherein y is 1-10 and s is 1- 20. In certain aspects the polyfluoroalkyl is lH, lH,2H,2H-perfluoro-l-decanol; lH,lH,2H,2H-perfluoro-l-octanol; lH,lH,5H-perfluoro-l-pentanol; or ΙΗ,ΙΗ, perfluoro-1- butanol. In a further aspect, the polyfluoroalkyl is (CF3)(CF₂)5CH₂CH₂0-, (CF3)(CF2)2CH₂CH₂0-, (CF₃)(CF₂)₅CH₂CH₂0-, CHF₂(CF₂)₃CH₂0-, or (CF₃)(CF₂)₂CH₂0-. [(L)] is an optional linker. L can be urethane, carboxylic acid, anhydride, epoxy, acyl halide etc. The oligomeric segment can be a branched or non-branched oligomeric segment of at least, at most, or equal to 3 to 10, 2 to 15, or 3 to 15 repeating units. In certain aspects, the oligomeric segment is at least, at most, or equal to 10, 1 1, 12, 13, 14, 15, 16, 17, 18, 19, or 20 repeating units. In other aspects, the SMM can be any one of formulas I to XV described below.

[0013] In certain aspects, the labware has a polypeptide or polynucleotide binding capacity of less than 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 ng/cm², including all values and ranges there between. In some embodiments, the labware has a polypeptide or polynucleotide recovery percentage of at least 80, 85, 90, 95, 98, 99%. As used herein a "recovery percentage" is the amount of polypeptide or polynucleotide recovered from labware relative the total amount of polypeptide or polynucleotide placed in contact with a labware article. In particular aspects, at least a portion of the labware' s surface has not been coated or plasma treated to reduce its polypeptide or polynucleotide binding capacity. Certain aspects explicitly exclude an article or surface that has been coated or plasma treated to reduce its polypeptide or polynucleotide binding capacity. In particular, certain aspects explicitly exclude a post-molding or casting treatment (a secondary treatment of the labware) that alters the labware surface after molding or casting. In yet other embodiments, the labware of the present invention does not include a surfactant and/or its surface has not been modified with a surfactant (e.g., non-ionic, cationic, anionic, or zwitterionic surfactant).

[0014] In certain aspects, at least a portion of the labware' s surface is hydrophilic. In another aspect, at least a portion of the labware' s surface is hydrophobic.

[0015] Certain embodiments of the invention are directed to methods for reducing the loss of polypeptides and/or polynucleotides in an aqueous solution due to surface binding of polypeptides and/or polynucleotides to a labware. The method can include: (a) providing the labware described herein for use in processing the aqueous solution; and (b) contacting the labware with the aqueous solution containing a polypeptide or polynucleotide.

[0016] Some embodiments of the invention are directed to methods of making the labware described herein, including one or more of the following steps: (a) adding a surface modifying macromolecule (SMM) having a fluoro-oligomeric compound with a base polymer to form a blend, wherein the blend comprises 80 wt. % to 99.99 wt. % of the base polymer and 0.01 wt. % to 20 wt. % of the SMM; and (b) casting or molding the blend into the labware having a polypeptide or a polynucleotide binding capacity of less than 80 nanograms (ng)/cm², wherein the SMM in the blend migrates to the surface of the casted or molded labware during the casting or molding step (b) such that the concentration of the SMM in the casted or molded labware is greater at its surface than in its interior volume. [0017] Embodiment 1 is labware having a reduced polypeptide or polynucleotide binding capacity, the labware comprising 80 wt. % to 99.99 wt. % of a base polymeric matrix and 0.01 wt. % to 20 wt. % of a surface modifying macromolecule (SMM) having a fluoro-oligomeric component comprised within the polymeric matrix, wherein at least a portion of the labware' s surface includes the SMM and has a polypeptide or a polynucleotide binding capacity of less than 80 nanograms (ng)/cm². Embodiment 2 is the labware of embodiment 1, wherein the polypeptide or polynucleotide binding capacity is less than 50 ng/cm², less than 20 ng/cm², or less than 10 ng/cm². Embodiment 3 is the labware of any one of embodiment 1 to 2, wherein the SMM has a structure according to Formula I or Formula II: FT-(oligo)-FT (Formula I) or FT-[(L)](oligo)[(L)]-FT (Formula II), wherein (oligo) is an oligomeric segment having a molecular weight of 500 to 3,000 Daltons, FT is a polyfluoroorgano group, and L is a linker molecule. Embodiment 4 is the labware of embodiment 3, wherein the oligomeric segment is a branched or non-branched oligomeric segment of fewer than 20 repeating units, preferably about 2 to 15 units, to 10 units, 3 to 15 units, or 3 to 10 units. Embodiment 5 is the labware of embodiment 4, wherein the oligomeric segment is selected from polyurethane, polyurea, polyamide, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl derivative, polypeptide, polysaccharide, polysiloxane, polydimethylsiloxane, polyethylene-butylene, polyisobutylene, polybutadiene, polypropylene oxide, polyethylene oxide, polytetramethylene oxide, or polyethylenebutylene. Embodiment 6 is the labware of any one of embodiments 3 to 5, wherein FT is a polyfluoroalkyl having a molecular weight between 100-1,500 Da. Embodiment 7 is the labware of embodiment 6, wherein FT is selected from the group consisting of CF3(CF2)rCH2CH2- wherein r is 2-20, and CF3(CF2)s(CH2CH20)y wherein y is 1-10 and s is 1-20. Embodiment 8 is the labware of any one of embodiments 3 to 5, wherein FT is selected from lH, lH,2H,2H-perfluoro-l-decanol; lH,lH,2H,2H-perfluoro-l-octanol; lH,lH,5H-perfluoro-l-pentanol; or ΙΗ,ΙΗ, perfluoro-1- butanol, and mixtures thereof. Embodiment 9 is the labware of any one of embodiments 3 to 5, wherein FT is selected from (CF3)(CF2)₅CH2CH₂0-, (CF3)(CF2)2CH₂CH₂0-, (CF3)(CF2)₅CH2CH₂0-, CHF₂(CF2)3CH₂0-, or (CF3)(CF₂)2CH₂0-. Embodiment 10 is the labware of any one of embodiments 1 to 9, wherein the base polymeric matrix is a thermoplastic polymer matrix or a thermoset polymer matrix. Embodiment 11 is the labware of embodiment 10, wherein the base polymeric matrix is a thermoplastic polymer matrix comprising polyethylene, polypropylene, polystyrene, polysulfone, polyetherimide, polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), polycarbonate, polyamide, a polyethylene/polypropylene copolymer, or a blend thereof. Embodiment 12 is the labware of any one of embodiments 1 to 10, wherein the at least a portion of the labware' s surface has not been coated or plasma treated to reduce its polypeptide or polynucleotide binding capacity. Embodiment 13 is the labware of any one of embodiments 1 to 11, wherein the labware is a tube, a microcentrifuge tube, a microtiter plate, a cartridge, a pipette tip, a filter cartridge, or a microfluidic device. Embodiment 14 is the labware of any one of embodiment 13, wherein the microtiter plate is a polystyrene plate, a polypropylene plate, a polymethyl methacrylate plate, a 24-well plate, or a 96-well plate. Embodiment 15 is the labware of any one of embodiments 1 to 14, wherein the at least a portion of the labware's surface is hydrophilic. Embodiment 16 is the labware of any one of embodiments 1 to 14, wherein the at least a portion of the labware' s surface is hydrophobic. Embodiment 17 is the labware of any one of embodiments 1 to 16, wherein the labware comprises at least one containment portion configured to hold a material and having a volume of less than 1 mL. Embodiment 18 is the labware of any one of embodiments 1 to 17, wherein the labware has a polypeptide or polynucleotide recovery percentage of at least 80, 85, 90, 95, 98, 99% and/or wherein the concentration of the SMM is greater at the labware's surface than in its interior volume. Embodiment 19 is labware having a reduced polypeptide or polynucleotide binding capacity, the labware comprising 80 wt. % to 99.99 wt. % of a base polymeric matrix and 0.01 wt. % to 20 wt. % of a surface modifying macromolecule (SMM) having a fluoro-oligomeric component comprised within the polymeric matrix, wherein the labware has not been subjected to a post-molding or post-casting treatment or modification. Embodiment 20 is a method for reducing the loss of polypeptides and/or polynucleotides in an aqueous solution due to surface binding of polypeptides and/or polynucleotides to a labware, the method comprising: (a) providing the labware of any one of embodiments 1 to 18 for use in processing the aqueous solution; and (b) contacting the labware with the aqueous solution containing a polypeptide or polynucleotide. Embodiment 21 is a method of making the labware of any one of embodiments 1 to 18, the method comprising: (a) adding a surface modifying macromolecule (SMM) having a fluoro-oligomeric compound with a base polymer to form a blend, wherein the blend comprises 80 wt. % to 99.99 wt. % of the base polymer and 0.01 wt. % to 20 wt. % of the SMM; and (b) casting or molding the blend into the labware having a polypeptide or a polynucleotide binding capacity of less than 80 nanograms (ng)/cm², wherein the SMM in the blend migrates to the surface of the casted or molded labware during the casting or molding step (b) such that the concentration of the SMM in the casted or molded labware is greater at its surface than in its interior volume.

[0018] Other embodiments of the invention are discussed throughout this application. Any embodiment discussed with respect to one aspect of the invention applies to other aspects of the invention as well and vice versa. Each embodiment described herein is understood to be embodiments of the invention that are applicable to all aspects of the invention. It is contemplated that any embodiment discussed herein can be implemented with respect to any method or composition of the invention, and vice versa. [0019] The following includes definitions of various terms and phrases used throughout this specification.

[0020] "Bind" or 'binding" refers to the ability of a biological molecule such as a polynucleotide or polypeptide to attach to the surface of a labware item of the present invention. The attachment can be surface adsorption or absorption onto or into, respectively, the polymeric matrix of the labware item. The attachment mechanism can be through covalent bonds, ionic bonds, hydrogen bonds, or Van der Walls forces between the surface of the labware item and a given biological material.

[0021] "Laboratory consumable" or "labware" or "labware item" refers to equipment that comes into contact with reagents or samples in the course of normal laboratory use, including use for example in medical environments such as hospitals and research laboratories. Generally these will be single use disposable devices, although some may be used repeatedly (e.g. , they can be washed or cleaned and reused) or for extended periods of time (e.g. , as storage containers). Examples of labware or laboratory consumables include, but are not limited to, pipette tips; microplates (including 96 well plates); microfluidic devices, immunoassay products (such as lateral flow devices); centrifuge tubes (including microcentrifuge tubes); microtubes; specimen tubes; test tubes; blood collection tubes; flat based tubes; aseptically produced containers; blister packs, trays, general labware; burettes; cuvettes; nucleic acid, polypeptide, or protein-based drug delivery devices (e.g., needles, syringes, etc.); IV. bags; sample vials/bottles; screw cap containers; or weighing bottles. These can be made from a wide variety of thermosetting resins or thermoplastic resins. In certain aspects both the inside surface and the outside surface have reduced binding surfaces as described herein. Some embodiments are directed to laboratory consumables configured to handle small volumes (less than 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 or 1 mL, including all values and ranges there between) of sample or reagent, such as microtitre plates, microplates (including 96 well plates), centrifuge tubes (including microcentrifuge tubes), or microtubes. In certain aspects, the volume is a stream or a discreet volume. In some additional embodiments, the labware is a drug delivery device (e.g., needles, syringes, etc.) that can administer therapeutic drugs having polynucleotides or proteins (e.g., antibodies, vaccines, etc.). In certain aspects, labware can include, or in certain instance exclude, wearables such as masks, aprons, gloves, safety glasses, shoe covers (e.g., boots or over-shoes), head covers (e.g., surgical caps), gowns, and the like. In a particular aspect, labware specifically excludes tubing and membranes. [0022] The use of the word "a" or "an" when used in conjunction with the term "comprising" in the claims and/or the specification may mean "one," but it is also consistent with the meaning of "one or more," "at least one," and "one or more than one."

[0023] The term "about" or "approximately" are defined as being close to as understood by one of ordinary skill in the art. In one non-limiting embodiment the terms are defined to be within 10%, preferably within 5%, more preferably within 1%, and most preferably within 0.5%.

[0024] The term "substantially" and its variations are defined to include ranges within 10%, within 5%, within 1%, or within 0.5%.

[0025] The terms "inhibiting" or "reducing" or "preventing" or any variation of these terms includes any measurable decrease or complete inhibition to achieve a desired result.

[0026] The term "effective," as that term is used in the specification and/or claims, means adequate to accomplish a desired, expected, or intended result.

[0027] The terms "wt. %," "vol. %," or "mol. %" refers to a weight, volume, or molar percentage of a component, respectively, based on the total weight, the total volume, or the total moles of material that includes the component. In a non-limiting example, 10 moles of component in 100 moles of the material is 10 mol. % of component.

[0028] As used in this specification and claim(s), the words "comprising" (and any form of comprising, such as "comprise" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include") or "containing" (and any form of containing, such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. [0029] The compositions and methods of making and using the same of the present invention can "comprise," "consist essentially of," or "consist of particular ingredients, components, blends, method steps, etc., disclosed throughout the specification. With respect to the transitional phase "consisting essentially of," in one non-limiting aspect, a basic and novel characteristic of the labware items of the present invention are their ability to have reduced polypeptide or polynucleotide binding capacity such as a polynucleotide binding capacity of less than 100 nanograms (ng)/cm², preferably less than 10, 20, 30, 40, 50, 60, 70, or 80 ng/ cm², including all values and ranges there between.

[0030] Other obj ects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. DETAILED DESCRIPTION OF THE INVENTION

[0031] There is a need for labware to be as non-binding as possible to reagents, samples, drugs, and other materials that include polynucleotides and/or polypeptides so as to avoid retention of these materials on the labware surface. By way of example, the reactions needed for conducting assays for detecting, measuring, or characterizing polypeptides or polynucleotides or both for research or analysis, and in particular medical or forensic diagnostics, often use very small volumes of samples or reagents. Retention of samples or reagents in any significant proportion on the surface of laboratory equipment can affect the results significantly. Furthermore, since many of the reagents are extremely costly, there are economic implications as a result of reagent loss. Even further, administration of biological drugs such as therapeutically effective polynucleotides or polypeptides/proteins can be negatively affected if the drugs remain attached to the syringe surface during administration.

[0032] As discussed herein, a solution to at least some of the binding affinity problems associated with biological materials to labware items has been discovered. The solution is premised on preparing thermoplastic or thermoset labware or laboratory supplies having a fluoro-oligomeric compound present on the surface or extending from the surface of the labware. This fluoro-oligomeric compound (or SMM) can impart hydrophobic characteristics to the surface of the labware and thereby reduce polypeptide or polynucleotide binding capacity to the surface.

[0033] These and other non-limiting aspects of the present invention are discussed in further detail in the following sections. A. Materials Used to Prepare Labware

[0034] The materials used to prepare labware of the present invention can include base- polymers and surface modifying macromolecule (SMM) having a fluoro-oligomeric compound. Still further, additives can also be incorporated into the labware of the present invention.

1. Base Polymers [0035] The base polymer can be a polymer or a blend of polymers that form a polymeric matrix. Examples of base polymers that can be used in the context of the present invention include thermoplastic and thermoset polymers. Non-limiting examples of thermoplastic polymers include polyethylene terephthalate (PET), polycarbonates (PC), polybutylene terephthalate (PBT), poly(l,4-cyclohexylidene cyclohexane-l,4-dicarboxylate) (PCCD), glycol modified polycyclohexyl terephthalate (PCTG), poly(phenylene oxide) (PPO), polypropylene (PP), polyethylene (PE), polyvinyl chloride (PVC), polystyrene (PS), polymethyl methacrylate (PMMA), polyethyleneimine or polyetherimide (PEI) or derivatives thereof, thermoplastic elastomers (TPE), terephthalic acid (TPA) elastomers, poly(cyclohexanedimethylene terephthalate) (PCT), polyethylene naphthalate (PEN), polyamides (PA), polysulfone sulfonate (PSS), polyether ether ketone (PEEK), polyether ketone ketone (PEKK), acrylonitrile butyldiene styrene (ABS), polyphenylene sulfide (PPS), co-polymers thereof, or blends thereof. More preferred thermoplastic polymers include polypropylene, polyamides, polyethylene terephthalate, polycarbonates (PC), polybutylene terephthalate, poly(phenylene oxide) (PPO), polyetherimide, polyethylene, co-polymers thereof, or blends thereof. Even more preferred thermoplastic polymers include polypropylene, polyethylene, polyamides, polycarbonates (PC), co-polymers thereof, or blends thereof, such as polyethylene/polypropylene copolymers.

[0036] Non-limiting examples of thermoset polymers suitable for use in the context of the present invention include unsaturated polyester resins, polyurethanes, bakelite, duroplast, urea- formaldehyde, diallyl-phthalate, epoxy resin, epoxy vinylesters, polyimides, cyanate esters of polycyanurates, dicyclopentadiene, phenolics, benzoxazines, co-polymers thereof, or blends thereof. [0037] In another aspect the polymer can be a bisphenol A (BPA)-free copolyester (e.g., TRITAN™ (Eastman Chemical Company, Kingsport, Tenn.). The presence of BP A in resins used for medical devices and drug delivery is significant because BPA is linked to serious health and environmental concerns. According to certain aspects of the present invention, the synthetic polymeric material can be a polyester or copolyester. In one aspect, the synthetic polymeric material can comprise glycol units derived from 2,2,4,4-tetram ethyl- 1,3- cyclobutanediol and/or 1,4-cyclohexanedimethanol. In a particular aspect, the synthetic polymeric material can be a polyester having a dicarboxylic acid component and a glycol component, where the dicarboxylic component comprises at least 70, 80, 90, 95, or 100 mole percent of terephthalic acid residues and the glycol component comprises at least 10, 15, 20, or 25 mole percent and/or not more than 80, 60, 40, 35, or 30 mole percent of 2,2,4,4-tetramethyl- 1,3-cyclobutanediol and at least 20, 40, 60, 65, or 70 mole percent and/or not more than 90, 85, 80, or 75 mole percent of 2,2,4,4-tetram ethyl- 1, 3 -cyclobutanediol. In one aspect, the synthetic polymeric material can include TRITAN™ WX500 or TRITAN™ WX510 (Eastman Chemical Company, Kingsport, Tenn.).

[0038] In yet a further aspect, the polymer can be a cyclic olefin polymer (COP) or a cyclic olefin copolymer (COC). A cyclic olefin polymer (COP) is an olefin polymer that comprise a saturated hydrocarbon ring. Certain COPs comprise at least 25 wt % cyclic units, which weight percentage is calculated based on the weight percentage of the olefin monomer units containing, including functionalized to contain, the cyclic moiety ("MCCM") that is polymerized into the COP as a percentage of the total weight of monomers polymerized to form the final COP. Preferably the COPs comprise at least 40 wt %, more preferably at least 50 wt % and more preferably at least 75 wt % MCCM. The cyclic moiety can be incorporated in the backbone of the polymer chain (such as from a norbornene ring-opening type of polymerization) and/or pendant from the polymer backbone (such as by polymerizing styrene (which is eventually hydrogenated to a cyclic olefin) or other vinyl-containing cyclic monomer). COPs can be homopolymers based on a single type of cyclic unit; copolymers (COCs) that can include more than one cyclic unit type; or copolymers comprising one or more cyclic unit type and other incorporated monomer units that are not cyclic, such as units provided by or based on ethylene monomer, as described in more detail below. Within copolymers, the cyclic units and other units can be distributed in any way including randomly, alternately, in blocks or some combination of these. The cyclic moiety in the COP need not result from polymerization of a monomer comprising the cyclic moiety per se but may result from cyclically functionalizing a polymer or other reaction to provide the cyclic moiety units or to form the cyclic moiety from a cyclic moiety precursor. As an example, styrene (which is a cyclic moiety precursor but not a cyclic unit for purposes of this invention) can be polymerized to a styrene polymer (not a cyclic olefin polymer) and then later be completely or partially hydrogenated to result in a COP. [0039] COCs include copolymers of unsaturated cyclic monomers, and may be obtained by either chain polymerization of one or more unsaturated cyclic monomers with one or more unsaturated linear monomer, such as ethylene, or may be obtained by ring-opening metathesis of one or more unsaturated cyclic monomers and subsequent hydrogenation. Examples of unsaturated cyclic monomers may be chosen from, without limitation, norbornene and derivatives thereof such as for example 2-norbornene, 5-methyl-2-norbornene, 5,5-dimethyl- 2-norbornene, 5-butyl-2-norbornene, 5-ethylidene-2-norbornene, 5-methoxycarbonyl-2- norbornene, 5-cyano-2-norbornene, 5-methyl-5-methoxycarbonyl-2-norbornene, and 5- phenyl-2-norbornene; cyclopentadiene and derivatives thereof such as for example dicyclopentadiene and 2,3-dihydrocyclopentadiene; and combinations of two or more thereof. Examples of unsaturated linear monomer may be chosen, without limitation, from alkenes having 1 to 20, preferably from 1 to 12 carbon atoms, most preferably from 1 to 6 carbon atoms, such as for example alpha-olefins, for example ethylene, propylene, and butylene. Other unsaturated linear monomers may be chosen from 1-butene, 4-methyl-l-pentene, 1-hexene, 1- octene, 1-decene, 1-dodecene, 1-tetradecene, 1-hexadecene, 1-octadecene and 1-eicocene, cyclopentene, cyclohexane, 3-methylcyclohexene, cyclooctene, 1,4-hexadiene, 4-methyl-l,4- hexadiene, 5-methyl-l,4-hexadiene, 1,7-octadiene, dicyclopentadiene, 5-ethylidene-2- norbornene, 5-vinyl-2-norbornene, tetracyclododecene, 2-methyltetracyclododecene, and 2- ethyltetracyclododecene; or combinations of two or more thereof. Preferably the unsaturated linear monomer is ethylene. Analogous to COC, the olefin portion of COP can be composed of aliphatic cyclic or bicylic hydrocarbons with 5 to 7 membered ring or rings and the above- defined optional minor proportions of ethylene or propylene.

[0040] Suitable cycloolefin polymers are the products sold under the trademark TOPAS® by Ticona, or ZEONOA™ by Zeon Corporation.

2. Surface Modifying Macromolecule

[0041] A surface modifying macromolecule (SMM) of the present invention is a hydrophobic macromolecular polymer having a fluoro-oligomeric component. In some embodiments the fluoro-oligomeric component has a structure according to the formula polyfluoroorgano(FT)-(oligo)-polyfluoroorgano(FT) (Formula I), wherein (oligo) is an oligomeric segment having a molecular weight of 500 to 3,000 Daltons. The fluoro-oligomeric compound can also include a linker (L) between the oligomeric segment and one or both polyfluoroorgano group, resulting in a structure according to the formula polyfluoroorgano(FT)-[(L)] (oligo) [(L)]-polyfluoroorgano(FT) (Formula II), wherein [(L)] indicates the linker is optional. L can be urethane, carboxylic acid, anhydride, epoxy, acyl halide etc. The oligomeric segment can be a branched or non-branched oligomeric segment of at least, at most, or about 3 to 10, 2 to 15, or 3 to 15 repeating units. In certain aspects the oligomeric segment is at least, at most, or about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 repeating units. In certain aspects the oligomeric segment is a polyurethane, polyurea, polyamide, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl derivative, polypeptide, polysaccharide, polysiloxane, polydimethylsiloxane, polyethylene-butylene, polyisobutylene, polybutadiene, polypropylene oxide, polyethylene oxide, polytetramethylene oxide, or polyethylenebutylene. The SMM can be a poly(urethane propylene glycol) or poly(urea dimethylsiloxane urethane). The polyfluoroalkyl can have a molecular weight between 100 to 1,500 Da. The polyfluoroalkyl can be selected from the group consisting of CF3(CF2)rCH2CH2- wherein r is 2-20, and CF3(CF2)s(CH2CH20)y wherein y is 1-10 and s is 1-20. In certain aspects the polyfluoroalkyl is lH, lH,2H,2H-perfluoro-l-decanol; lH,lH,2H,2H-perfluoro-l-octanol; 1H,1H,5H- perfluoro-l-pentanol; or 1H, 1H, perfluoro-l-butanol. In a further aspect the polyfluoroalkyl is (CF3)(CF2)₅CH2CH₂0-, (CF3)(CF2)2CH₂CH₂0-, (CF3)(CF2)₅CH2CH₂0-, CHF₂(CF2)3CH₂0-,

[0042] As used herein, a linker (L) refers to a coupling segment capable of covalently linking two oligo moieties and a surface active group. Typically, linker molecules have molecular weights ranging from 40 to 700. Linker molecules can be functionalized diamines, diisocyanates, disulfonic acids, dicarboxylic acids, diacid chlorides and dialdehydes, where the functionalized component has secondary functional chemistry that is accessed for chemical attachment of a surface active group. Such secondary groups include, for example, esters, carboxylic acid salts, sulfonic acid salts, phosphonic acid salts, thiols, vinyls and secondary amines. Terminal hydroxyls, amines or carboxylic acids on the oligo intermediates can react with diamines to form oligo-amides; react with diisocyanates to form oligo-urethanes, oligo- ureas, oligo-amides; react with disulfonic acids to form oligo-sulfonates, oligo-sulfonamides; react with dicarboxylic acids to form oligo-esters, oligo-amides; react with diacid chlorides to form oligo-esters, oligo-amides; and react with dialdehydes to form oligo-acetal, oligo-imines.

[0043] The term "oligo" refers to a relatively short length of a repeating unit or units, generally less than about 50 monomelic units and theoretical molecular weights less than 10,000 Daltons, but preferably <7,000 Daltons and in some examples, <5,000 Daltons. In certain embodiments, oligo is selected from the group consisting of polyurethane, polyurea, polyimide, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl, polypeptide, polysaccharide, and ether and amine linked segments thereof.

[0044] Additional SMMs include molecules of the general structural formulas described below (see U.S. Patent 8,877,062, which is incorporated herein by reference in its entirety).

[0045] Formula I has the general structure of:

(FT)-(oligo)-(FT) Formula I, where FT is a polyfluoroorgano group and oligo is an oligomeric segment.

[0046] Formula II has the general structure of:

(Fx)-[(L)](oligo)[(L)]-(F_T) Formula II where FT is a polyfluoroorgano group, oligo is an oligomeric segment (oligo), and (L) is an optional linker.

[0047] Formula III has the general structure of:

( oligo)— | ( L) -†oligo)|

Formula III where (i) FT is a polyfluoroorgano group covalently attached to linker (L); (ii) C is a chain terminating group; (iii) oligo is an oligomeric segment; (iv) (L) the linker is a coupling segment; and (v) "a" is an integer greater than 0.

[0048] Formula IV has the general structure of:

FT-[B-(oligo)]n-B-FT Formula IV where (i) B is a hard segment and includes a urethane; (ii) oligo includes polypropylene oxide, polyethylene oxide, or polytetramethylene oxide; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 1 to 10. [0049] Formula V has the general structure of:

FT-[B-A]N-B-FT Formula V where (i) A is a soft segment including hydrogenated polybutadiene, poly(2,2 dimethyl-1-3- propylcarbonate), polybutadiene, poly(diethylene glycol)adipate, poly(hexamethylene carbonate), poly(ethylene-co-butylene), neopentyl glycol-ortho phthalic anhydride polyester, di ethylene glycol-ortho phthalic anhydride polyester, 1,6-hexanediol-ortho phthalic anhydride polyester, or bisphenol A ethoxylate; (ii) B is a hard segment including a urethane; and (iii) FT is a polyfluoroorgano group, and (iv) n is an integer from 1 to 10.

[0050] Formula VI and VII have the general structure of:

Formula VI

Formula VII where (i) A is a soft segment; (ii) B is a hard segment including a isocyanurate trimer or biuret trimer; (iii) each FT is a polyfluoro-organo group; and (iv) n is an integer between 0 to 10.

[0051] Formula VIII has the general structure of:

F_T-[B-(oligo)]n-B-F_T Formula VIII where (i) oligo is an oligomeric segment including polypropylene oxide, polyethylene oxide, or polytetramethyleneoxide and having a theoretical molecular weight of from 500 to 3,000 Daltons (e.g., from 500 to 2,000 Daltons, from 1,000 to 2,000 Daltons, or from 1,000 to 3,000 Dal tons); (ii) B is a hard segment formed from an isocyanate dimer; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 1 to 10.

[0052] Formula IX has the general structure of:

Formula IX where (i) A is an oligomeric segment including polypropylene oxide, polyethylene oxide, polytetramethyleneoxide, or mixtures thereof, and having a theoretical molecular weight of from 500 to 3,000 Daltons (e.g., from 500 to 2,000 Daltons, from 1 ,000 to 2,000 Daltons, or from 1 ,000 to 3,000 Daltons); (ii) B is a hard segment including an isocyanurate trimer or biuret trimer; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 0 to 10.

[0053] Formula X has the general structure of: FT-[B-(oligo)]N-B-FT Formula X where (i) oligo is a polycarbonate polyol having a theoretical molecular weight of from 500 to 3,000 Daltons (e.g., from 500 to 2,000 Daltons, from 1 ,000 to 2,000 Daltons, or from 1 ,000 to 3,000 Daltons); (ii) B is a hard segment formed from an isocyanate dimer; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 1 to 10. [0054] Formula XI has the general structure of:

Formula XI where (i) A is an oligomeric segment including a polycarbonate polyol having a theoretical molecular weight of from 500 to 3,000 Daltons (e.g., from 500 to 2,000 Daltons, from 1 ,000 to 2,000 Daltons, or from 1 ,000 to 3,000 Daltons); (ii) B is a hard segment including an isocyanurate trimer or biuret trimer; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 0 to 10.

[0055] Formula XII has the general structure of:

Formula XII where (i) A includes a first block segment selected from polypropylene oxide, polyethylene oxide, polytetramethyleneoxide, or mixtures thereof, and a second block segment including a polysiloxane or polydimethylsiloxane, wherein A has a theoretical molecular weight of from 1 ,000 to 5,000 Daltons (e.g., from 1 ,000 to 3,000 Daltons, from 2,000 to 5,000 Daltons, or from 2,500 to 5,000 Daltons); (ii) B is a hard segment including an isocyanurate trimer or biuret trimer; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 0 to 10. [0056] Formula XIII has the general structure of: FT-[B-A)]N-B-FT Formula XIII where (i) A is a soft segment selected from hydrogenated polybutadiene (HLBH) diol (e.g., HLBH diol), polybutadiene (LBHP) diol (e.g., LBHP diol), hydrogenated polyisoprene (HHTPI) diol (e.g., HHTPI diol), and polystyrene and has a theoretical molecular weight of from 750 to 3,500 Daltons (e.g., from 750 to 2,000 Daltons, from 1 ,000 to 2,500 Daltons, or from 1 ,000 to 3,500 Daltons); (ii) B is a hard segment formed from an isocyanate dimer; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 1 to 10.

[0057] Formula XIV has the general structure of:

Formula XIV where (i) A is a soft segment selected from hydrogenated polybutadiene (HLBH) diol (e.g., HLBH diol), polybutadiene (LBHP) diol (e.g., LBHP diol), hydrogenated polyisoprene (HHTPI) diol (e.g., HHTPI diol), and polystyrene and has a theoretical molecular weight of from 750 to 3,500 Daltons (e.g., from 750 to 2,000 Daltons, from 1 ,000 to 2,500 Daltons, or from 1 ,000 to 3,500 Daltons); (ii) B is a hard segment including an isocyanurate trimer or biuret trimer; (iii) FT is a polyfluoro-organo group; and (iv) n is an integer from 0 to 10.

[0058] Formula XV has the general structure of:

Formula XV where (i) A is a polyester having a theoretical molecular weight of from 500 to 3,500 Daltons (e.g., from 500 to 2,000 Daltons, from 1 ,000 to 2,000 Daltons, or from 1 ,000 to 3,000 Daltons); (ii) B is a hard segment including an isocyanurate trimer or biuret trimer; (iii) FT is a polyfluoroorgano group; and (iv) n is an integer from 0 to 10.

[0059] In certain embodiments, the surface modifying macromolecule of formulas I and III can include an oligo segment that is a branched or non-branched oligomeric segment of fewer than 20 repeating units (e.g., from 2 to 15 units, from 2 to 10 units, from 3 to 15 units, and from 3 to 10 units). In another embodiment, the surface modifying macromolecule can include an oligomeric segment selected from polyurethane, polyurea, polyamide, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl derivative, polypeptide, polysaccharide, polysiloxane, polydimethylsiloxane, polyethylene- butylene, polyisobutylene, polybutadiene, polypropylene oxide, polyethylene oxide, polytetramethylene oxide, or polyethylenebutylene segments.

[0060] In certain embodiments, the surface modifying macromolecule of formula V can include a hard segment formed from a diisocyanate selected from 3-isocyanatomethyl, 3,5,5- trimethyl cyclohexylisocyanate; 4,4 '-methylene bis(cyclohexyl isocyanate); 4,4 '-methylene bis(phenyl)isocyanate; toluene-2,4 diisocyanate); m-tetramethylxylene diisocyanate; and hexamethylene diisocyanate; and n is 1 or 2.

[0061] In certain embodiments, the surface modifying macromolecule of formulas VI and VII can include a soft segment having a theoretical molecular weight of 500 to 3,500 Daltons (e.g., from 500 to 2,000 Daltons, from 1,000 to 2,000 Daltons, or from 1,000 to 3,000 Daltons) and/or the soft segment includes hydrogenated polybutadiene (HLBH), poly(2,2 dimethyl-1-3- propylcarbonate) (PCN), polybutadiene (LBHP), polytetramethylene oxide (PTMO), (propylene)oxide (PPO), diethyleneglycol-orthophthalic anhydride polyester (PDP), hydrogenated polyisoprene (HHTPI), poly(hexamethylene carbonate), poly(2-butyl-2-ethyl- 1,3-propyl carbonate), or hydroxylterminated polydimethylsiloxane (C22). In other embodiments the hard segment can be formed by reacting a triisocyanate with a diol including the soft segment, wherein the triisocyanate is selected from hexamethylene diisocyanate (HDI) biuret trimer, isophorone diisocyanate (IPDI) trimer, or hexamethylene diisocyanate (HDI) trimer.

[0062] In some embodiments of the surface modifying macromolecule of formula VIII, B can be a hard segment formed from 3-isocyanatomethyl, 3,5,5-trimethyl cyclohexylisocyanate; 4,4'-methylene bis(cyclohexyl isocyanate); 4,4'-methylene bis(phenyl) isocyanate; toluene-2,4 diisocyanate); m-tetramethylxylene diisocyanate; and hexamethylene diisocyanate; and n is an integer from 1 to 3. The surface modifying macromolecules can be used in labware of the invention, or a component thereof, and in conjunction with any methods, systems, and kits of the invention described herein.

[0063] In certain embodiments of the surface modifying macromolecule of formula IX, B is a hard segment formed by reacting a triisocyanate with a diol of A (e.g., the oligomeric segment), wherein the triisocyanate is selected from hexamethylene diisocyanate (HDI) biuret trimer, isophorone diisocyanate (IPDI) trimer, and hexamethylene diisocyanate (HDI) trimer; and n is 0, 1, 2, or 3. [0064] In certain embodiments of the surface modifying macromolecule of formula X, "oligo" includes poly (2,2 dimethyl- 1 -3 -propyl carbonate) (PCN) polyol (e.g., PCN diol); B is a hard segment formed from 3-isocyanatomethyl, 3,5,5-trimethyl cyclohexylisocyanate; 4,4'- methylene bis(cyclohexyl isocyanate); 4,4'-methylene bis(phenyl) isocyanate; toluene-2,4 diisocyanate); m-tetramethylxylene diisocyanate; and hexamethylene diisocyanate; and n is 1, 2, or 3.

[0065] In certain embodiments of the surface modifying macromolecule of formula XI can include A poly (2,2 dimethyl- 1 -3 -propyl carbonate) (PCN) polyol (e.g., PCN diol) or poly(hexamethylene carbonate) (PHCN) polyol; B is a hard segment formed by reacting a tnisocyanate with a diol of A (e.g., the oligomenc segment), where the triisocyanate is selected from hexamethylene diisocyanate (HDI) biuret trimer, isophorone diisocyanate (IPDI) trimer, and hexamethylene diisocyanate (HDI) trimer; and n is 0, 1, 2, or 3.

[0066] In certain embodiments of the surface modifying macromolecule of formula XII, A includes polypropylene oxide and poly dimethyl siloxane; B is a hard segment formed by reacting a triisocyanate with a diol of A, wherein the triisocyanate is selected from hexamethylene diisocyanate (HDI) biuret trimer, isophorone diisocyanate (IPDI) trimer, and hexamethylene diisocyanate (HDI) trimer; and n is 0, 1, 2, or 3.

[0067] In certain embodiments of the surface modifying macromolecule of formula XIII, A includes hydrogenated polybutadiene diol; B is a hard segment formed from 3- isocyanatom ethyl, 3,5,5-trimethyl cyclohexylisocyanate; 4,4 '-methylene bis(cyclohexyl isocyanate); 4,4'-methylene bis(phenyl) isocyanate; toluene-2,4 diisocyanate); m- tetramethylxylene diisocyanate; and hexamethylene diisocyanate; and n is 1, 2, or 3.

[0068] In certain embodiments of the surface modifying macromolecule of formula XIV, A is selected from hydrogenated polybutadiene (HLBH) diol (e.g., HLBH diol), and hydrogenated polyisoprene (HHTPI) diol (e.g., HHTPI diol); B is a hard segment formed by reacting a triisocyanate with a diol of A (e.g., the oligomeric segment), wherein the triisocyanate is selected from hexamethylene diisocyanate (HDI) biuret trimer, isophorone diisocyanate (IPDI) trimer, and hexamethylene diisocyanate (HDI) trimer; and n is 0, 1, 2, or 3. [0069] In certain embodiments of the surface modifying macromolecule of formula XV, A is selected from poly (diethylene glycol)adipate, neopentyl glycol-ortho phthalic anhydride polyester, diethylene glycol-ortho phthalic anhydride polyester, and 1,6-hexanediol-ortho phthalic anhydride polyester; B is a hard segment formed by reacting a triisocyanate with a diol of A (e.g., the polyester segment), wherein the triisocyanate is selected from hexamethylene diisocyanate (HDI) biuret trimer, isophorone diisocyanate (IPDI) trimer, and hexamethylene diisocyanate (HDI) trimer; and n is 0, 1, 2, or 3. [0070] For any of the surface modifying macromolecules formed from an isocyanate dimer, the isocyanate dimers can be selected from 3-isocyanatomethyl, 3,5,5-trimethyl cyclohexylisocyanate; 4,4'-methylene bis(cyclohexyl isocyanate) (HMDI); 2,2'-, 2,4'-, and 4,4'-methylene bis(phenyl) isocyanate (MDI); toluene-2,4 diisocyanate; aromatic aliphatic isocyanate, such 1,2-, 1,3-, and 1,4-xylene diisocyanate; meta-tetramethylxylene diisocyanate (m-TMXDI); para-tetramethylxylene diisocyanate (p-TMXDI); hexamethylene diisocyanate (HDI); ethylene diisocyanate; propylene-l,2-diisocyanate; tetramethylene diisocyanate; tetramethylene-l ,4-diisocyanate; octamethylene diisocyanate; decamethylene diisocyanate; 2,2,4-trimethylhexamethylene diisocyanate; 2,4,4-trimethylhexamethylene diisocyanate; dodecane-l, 12-diisocyanate; dicyclohexylmethane diisocyanate; cyclobutane-1,3- diisocyanate; cyclohexane-l,2-diisocyanate; cyclohexane-l,3-diisocyanate; cyclohexane-1,4- diisocyanate; methyl-cyclohexylene diisocyanate (HTDI); 2,4-methylcyclohexane diisocyanate; 2,6-methylcyclohexane diisocyanate; 4,4'-dicyclohexyl diisocyanate; 2,4'- dicyclohexyl diisocyanate; 1,3,5-cyclohexane triisocyanate; isocyanatomethylcyclohexane isocyanate; l-isocyanato-3,3-5-trimethyl-5-isocyanatomethylcyclohexane; isocyanatoethylcyclohexane isocyanate; bis(isocyanatomethyl)-cyclohexane diisocyanate; 4,4'-bis(isocyanatomethyl)dicyclohexane; 2,4'-bis(isocyanatomethyl)dicyclohexane; i sophoronediisocyanate (IPDI); 2,4-hexahydrotoluene diisocyanate; 2,6-hexahydrotoluene diisocyanate;3,3 '-dimethyl-4,4'-biphenylene diisocyanate (TODI); polymeric MDI; carbodiimide-modified liquid 4,4'-diphenylmethane diisocyanate; para-phenylene diisocyanate (PPDI); meta-phenylene diisocyanate (MPDI); triphenyl methane-4,4'-, and triphenyl methane-4,4"-triisocyanate; naphthylene-l,5-diisocyanate; 2,4'-, 4,4'-, and 2,2- biphenyl diisocyanate; polyphenyl polymethylene polyisocyanate (PMDI); mixtures of MDI and PMDI; mixtures of PMDI and TDI; dimerized uredione of any isocyanate described herein, such as uredione of toluene diisocyanate, uredione of hexamethylene diisocyanate, and mixtures thereof; and substituted and isomeric mixtures thereof.

[0071] For any of the surface modifying macromolecules formed from an isocyanate trimer, the isocyanate trimer can be selected from hexamethylene diisocyanate (HDI) biuret trimer, isophorone diisocyanate (IPDI) trimer, hexamethylene diisocyanate (HDI) trimer; triisocyanate of 2,2,4-trimethyl-l,6-hexane diisocyanate (TMDI); a trimerized isocyanurate of any isocyanates described herein, such as isocyanurate of toluene diisocyanate, trimer of diphenylmethane diisocyanate, trimer of tetramethylxylene diisocyanate, and mixtures thereof; a trimerized biuret of any isocyanates described herein; modified isocyanates derived from the above diisocyanates; and substituted and isomeric mixtures thereof.

[0072] In any of the formulas, the surface modifying macromolecule can include the group FT that is a polyfluoroalkyl having a theoretical molecular weight of between 100-1,500 Da. For example, FT may be selected from the group consisting of radicals of the general formula CF3(CF₂)rCH₂CH2 - wherein r is 2-20, and CF₃(CF₂)_s(CH₂CH₂0)x wherein x is 1-10 and s is 1-20. Alternatively, FT may be selected from the group consisting of the general formula CHmF(3-m)(CF₂)rCH₂CH₂ and CH_mF₍₃-m)(CF₂)_s(CH₂CH₂0)x, wherein m is 0, 1, 2, or 3; x is an integer between 1-10; r is an integer between 2-20; and s is an integer between 1-20. In certain embodiments, FT is selected from lH, lH,2H,2H-perfluoro-l-decanol; 1H, 1H,2H,2H- perfluoro-l-octanol; lH, lH,5H-perfluoro-l-pentanol; and ΙΗ, ΙΗ, perfluoro-l-butanol, and mixtures thereof. In still other embodiments, FT is selected from (CF₃)(CF₂)5CH₂CH₂0, (CF₃)(CF₂)₂CH₂CH₂0, (CF₃)(CF₂)₅CH₂CH₂0, CHF₂(CF₂)₃CH₂0, and (CF₃)(CF₂)₂CH₂0.

[0073] In some embodiments, the above surface modifying macromolecule can have a theoretical molecular weight of less than 10,000 Daltons (e.g., from 500 to 10,000 Daltons, from 500 to 9,000 Daltons, from 500 to 5,000 Daltons, from 1,000 to 10,000 Daltons, from 1,000 to 6,000 Daltons, or from 1,500 to 8,000 Daltons).

[0074] In certain aspects, the above surface modifying macromolecule includes from 5% to 40% (w/w) of the hard segment (e.g., from 5% to 35% (w/w), from 5% to 30% (w/w), and from 10% to 40% (w/w)), from 20% to 90% (w/w) of the soft segment (e.g., from 20% to 80% (w/w), from 30% to 90% (w/w), and from 40% to 90% (w/w)), and from 5% to 50% (w/w) of the polyfluoro-organo group (e.g., from 5% to 40% (w/w), from 5% to 30% (w/w), and from 10% to 40% (w/w)).

[0075] In certain aspects, the above surface modifying macromolecule can have a ratio of hard segment to soft segment of from 0.15 to 2.0 (e.g., from 0.15 to 1.8, from 0.15 to 1.5, and from 0.2 to 2.0). 3. Additives

[0076] Additives can be incorporated into the labware items of the present invention. Non- limiting examples of such additives include impact modifiers, fillers, colorants including dyes and pigments, antioxidants, heat stabilizers, light and/or UV light stabilizers, reinforcing agents, light reflecting agents, surface effect additives, plasticizers, lubricants, mold release agents, flame retardants, antistatic agents, anti-drip agents, radiation (gamma) stabilizers, and the like, or a combination comprising at least one of the foregoing additives. A combination of additives can be used, for example a combination of a heat stabilizer, mold release agent, and ultraviolet light stabilizer. Specifically, a combination of additives can be used comprising one or more of an antioxidant such as IRGAPHOS®, pentaerythritol stearate, a compatibilizer such as JONCRYL® epoxy, a quaternary ammonium compound such as tetramethyl ammonium hydroxide or tetrabutyl ammonium hydroxide, and a quaternary phosphonium compound such as tetrabutyl phosphonium hydroxide or tetrabutyl phosphonium acetate. In general, the additives are used in the amounts generally known to be effective. The total amount of additives (other than any impact modifier, filler, or reinforcing agents) is generally 0.01 to 5 weight %, based on the total weight of the composition.

B. Process Used to Prepare Labware [0077] The labware of the present invention can be made by obtaining a blend of a base polymer and a surface modifying macromolecule. Once the blend is obtained, it can be further processed into a labware item via casting or molding techniques.

[0078] With respect to preparing the blend, a desired amount of a base polymer along with a surface modifying macromolecule and optionally additives can be mixed in a HENSCHEL MIXER high speed mixer. In preferred instances, at least 80 wt. % of the base polymer and up to 20 wt. % of the SMM can be used. If additives are added, then they can be present in a desired amount, and generally 0.01 to 5 wt. %. Other low shear processes including but not limited to hand mixing can also accomplish this blending step. The blend can then fed into the throat of an extruder via a hopper. Alternatively, one or more of the components can be incorporated into the blend by feeding directly into the extruder at the throat and/or downstream through a sidestuffer. In certain instances, the SMM and, optionally the additives, can also be compounded into a masterbatch with a desired base polymer polymeric resin and fed into the extruder. The extruder is generally operated at a temperature higher than that necessary to cause the composition to flow, but at which temperature components of the thermoplastic composition do not decompose so as to significantly adversely affect the composition. In some specific instances, a twin-screw extruder can be used, which is typically operated at a temperature of 180 °C to 385 °C, preferably 200 °C to 330° C, or more preferably 220 °C to 300° C. The extrudate is subsequently quenched in a water bath and pelletized. The pellets, so prepared when cutting the extrudate, can be one-fourth inch long or less as desired. Such pellets can be used for subsequent molding, shaping, or forming.

[0079] The prepared blend can then be used to cast or mold a labware item of the present invention. Illustrative, but not limiting examples of the molding/casting methods that can be used in the context of the present invention include injection molding, compression molding, thermoforming, injection blow molding, injection stretch blow molding, extrusion blow molding, and extrusion. For articles, the shapes of which permit, and which require a high degree of dimensional accuracy the most preferred method of forming of the plastic is injection molding. [0080] The molding conditions generally include, but are not limited to injection pressure, back pressure, melt temperature, and mold temperature. The processing conditions for injection molding of lab ware depends on numerous factors including the properties and process-ability of base polymer, design of the lab ware, wall thickness, transparency and other requirements of the finished parts. During the molding process the SMMs present in the blend tend to migrate to the surface of the molded/casted labware item such that the surface of the labware item can include SMMs present on and/or extending outward/away from the surface. Without wishing to be bound by theory, it is believed that the SMMs migrate to the polymer matrix/air interface, thus allowing the surface to become increasing populated with SMMs. Once migrated, the SMMs present on or extending from the surface impart the low binding properties of the labware vis-a-vis biological molecules such as polynucleotides and/or polypeptides.

[0081] In certain aspects, an injection apparatus can be used to mold labware of the invention. The injection apparatus can be a single or twin screw extruder. The screws can have L/D ratios of >20 and compression ratios of 1 :2.0 to 1 :2.8. The melt temperatures can range from 190, 200, 210, 220, 230, 240, 250, 260, to 270 °C (including all values and ranges there between), depending on melt flow index (MFI) of the material, flow lengths, and part thickness. For applications where odor is important, low melt temperatures are preferable. To improve the transport of the granules the temperature of the cooled zone should not be too high; preferred temperature in the feed block can be 30, 40, 50, up to 60 °C, including all values and ranges there between. Although a broad mold temperature window is possible, low tool temperatures of 15, 16, 17, 18, 19, to 20 °C (including all values and ranges there between) in general yield faster cycle times. For surface aspect, texture clarity, or mold filling purposes it might be necessary to go to higher temperatures of 50 to 60 °C. Average temperatures of around 30 °C are widely used in the industry. With well-designed injection systems the effective injection-pressure is generally no more than 0.12 MPa (1.2 bar), including 0.1 MPa, 0.105, 0.11, or 0.115 to 0.12 MPa, including all values and ranges there between. In certain aspects, the mold-pressure can be about 25, 30, 35, 40, 45, 50, 55, up to 60 MPa (250, 300, 350, 400, 450, 500, 550, to 600 bar), including all values and ranges there between. The holding- pressure should generally be set to between 40, 45, 50 and 55, 60, 65, 70 % (including all values and ranges there between) of the maximum injection-pressure. The effective back-pressure should be between 10, 11, 12, 13, 14, or 15 MPa (100, 110, 120, 130, 140, or 150 bar), including all values and ranges there between. In one example, the lab-ware can be made using polypropylene.

C. Laboratory Consumables and Labware

[0082] Non-limiting examples of labware or laboratory consumables include, but are not limited to pipette tips; microplates (including 96 well plates); immunoassay products (such as lateral flow devices); centrifuge tubes (including microcentrifuge tubes); microtubes; specimen tubes; test tubes; blood collection tubes; flat based tubes; aseptically produced containers; general labware; IV. bags; burettes; cuvettes; nucleic acid, polypeptide, or protein-based drug delivery devices (e.g., needles, syringes, etc.); sample vials/bottles; screw cap containers; or weighing bottles. These can be made from a wide variety of thermosetting resins or thermoplastic resins. In certain aspects, both the inside surface and the outside surface have reduced binding surfaces as described herein. Some embodiments are directed to laboratory consumables configured to handle small volumes (less than 0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 or 1 mL, including all values and ranges there between) of sample or reagent, such as microtiter plates, microplates (including 96 well plates), centrifuge tubes (including microcentrifuge tubes) and microtubes. Some embodiments are directed to therapeutic labware, i.e., labware designed to store and/or deliver a polypeptide or polynucleotide in a therapeutic context. Such labware can be used as a depot to store polypeptides or polynucleotides and release them when appropriate at an appropriate rate. In one instance, such a labware can be a syringe or syringe plunger that can administer therapeutic drugs having polynucleotides or proteins (e.g., antibodies, vaccines, etc.) D. Polynucleotide or Polypeptide

[0083] As used herein, "polynucleotide" includes reference to a deoxyribopolynucleotide, ribopolynucleotide or analogs thereof that have the essential nature of a natural ribonucleotide in that they hybridize, under stringent hybridization conditions, to substantially the same nucleotide sequence as naturally occurring nucleotides and/or allow translation into the same amino acid(s) as the naturally occurring nucleotide(s). A polynucleotide can be full-length or a subsequence of a native or heterologous structural or regulatory gene. Unless otherwise indicated, the term refers to a specified sequence as well as the complementary sequence thereof. Thus, DNAs or RNAs (microRNA, messenger RNA, transfer RNA, etc.) with backbones modified for stability or for other reasons are "polynucleotides" as that term is intended herein. Moreover, DNAs or RNAs comprising unusual bases, such as inosine, or modified bases, such as tritylated bases, are polynucleotides as the term is used herein. It will be appreciated that a great variety of modifications have been made to DNA and RNA that serve many useful purposes known to those of skill in the art. The term polynucleotide embraces such chemically, enzymatically or metabolically modified forms of polynucleotides, as well as the chemical forms of DNA and RNA characteristic of viruses and cells.

[0084] The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to natural amino acid polymers and amino acid polymers in which one or more amino acid residue is an artificial chemical analog of a corresponding naturally occurring amino acid. The terms "residue" or "amino acid residue" or "amino acid" are used interchangeably herein to refer to an amino acid that is incorporated into a protein, polypeptide, or peptide (collectively "protein"). The amino acid may be a naturally occurring amino acid and, unless otherwise limited, may encompass known analogs of natural amino acids that can function in a similar manner as naturally occurring amino acids.

Claims

1. A labware having a reduced polypeptide or polynucleotide binding capacity, the labware comprising 80 wt. % to 99.99 wt. % of a base polymeric matrix and 0.01 wt. % to 20 wt. % of a surface modifying macromolecule (SMM) having a fluoro-oligomeric component comprised within the polymeric matrix, wherein at least a portion of the labware' s surface includes the SMM and has a polypeptide or a polynucleotide binding capacity of less than 80 nanograms (ng)/cm².

2. The labware of claim 1, wherein the polypeptide or polynucleotide binding capacity is less than 50 ng/cm², less than 20 ng/cm², or less than 10 ng/cm².

3. The labware of claim 1, wherein the SMM has a structure according to Formula I or Formula II:

FT-(oligo)-FT

Formula I

or

FT-[(L)](oligo)[(L)]-F_T

Formula II

where (oligo) is an oligomeric segment having a molecular weight of 500 to 3,000 Daltons, FT is a polyfluoroorgano group, and L is a linker molecule.

4. The labware of claim 3, wherein the oligomeric segment is a branched or non-branched oligomeric segment of fewer than 20 repeating units, preferably about 2 to 15 units, to 10 units, 3 to 15 units, or 3 to 10 units.

5. The labware of claim 4, wherein the oligomeric segment is selected from polyurethane, polyurea, polyamide, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl derivative, polypeptide, polysaccharide, polysiloxane, poly dimethyl siloxane, polyethylene-butylene, polyisobutylene, polybutadiene, polypropylene oxide, polyethylene oxide, polytetramethylene oxide, or polyethylenebutylene, and combinations thereof.

6. The labware of claim 3, wherein FT is a polyfluoroalkyl having a molecular weight between 100-1,500 Da.

7. The labware of claim 6, wherein FT is selected from the group consisting of CF3(CF₂)rCH₂CH2- wherein r is 2-20, and CF3(CF₂)_s(CH₂CH₂0)_y wherein y is 1-10 and s is 1-20.

8. The labware of claim 3, wherein FT is selected from 1H, lH,2H,2H-perfluoro-l-decanol; lH,lH,2H,2H-perfluoro-l-octanol; lH, lH,5H-perfluoro-l-pentanol; or ΙΗ,ΙΗ, perfluoro-l-butanol, and mixtures thereof.

9. The labware of claim 3, wherein FT is selected from (CF3)(CF2)sCH2CH20-, (CF3)(CF2)2CH₂CH₂0-, (CF3)(CF2)₅CH2CH₂0-, CHF2(CF₂)3CH₂0-, or

10. The labware of claim 1, wherein the base polymeric matrix is a thermoplastic polymer matrix or a thermoset polymer matrix.

11. The labware of claim 10, wherein the base polymeric matrix is a thermoplastic polymer matrix comprising polyethylene, polypropylene, polystyrene, polysulfone, polyetherimide, polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF), polycarbonate, polyamide, a polyethylene/polypropylene copolymer, or a blend thereof.

12. The labware of claim 1, wherein the at least a portion of the labware's surface has not been coated or plasma treated to reduce its polypeptide or polynucleotide binding capacity.

13. The labware of claim 1, wherein the labware is a tube, a microcentrifuge tube, a microtiter plate, a cartridge, a pipette tip, a filter cartridge, or a microfluidic device.

14. The labware of claim 13, wherein the microtiter plate is a polystyrene plate, a polypropylene plate, a polymethyl methacrylate plate, a 24-well plate, or a 96-well plate.

15. The labware of claim 1, wherein the at least a portion of the labware's surface is hydrophilic and/or the at least a portion of the labware's surface is hydrophobic.

16. The labware of claim 1 , wherein the labware comprises at least one containment portion configured to hold a material and having a volume of less than 1 mL.

17. The labware of claim 1, wherein the labware has a polypeptide or polynucleotide recovery percentage of at least 80, 85, 90, 95, 98, 99% and/or wherein the concentration of the SMM is greater at the labware's surface than in its interior volume.

18. A labware having a reduced polypeptide or polynucleotide binding capacity, the labware comprising 80 wt. % to 99.99 wt. % of a base polymeric matrix and 0.01 wt. % to 20 wt. % of a surface modifying macromolecule (SMM) having a fluoro-oligomeric component comprised within the polymeric matrix, wherein the labware has not been subjected to a post-molding or post-casting treatment or modification.

19. A method for reducing the loss of polypeptides and/or polynucleotides in an aqueous solution due to surface binding of polypeptides and/or polynucleotides to a labware, the method comprising:

(a) providing the labware of claim 1 for use in processing the aqueous solution,; and

(b) contacting the labware with the aqueous solution containing a polypeptide or polynucleotide.

20. A method of making the labware of claim 1, the method comprising:

(a) adding a surface modifying macromolecule (SMM) having a fluoro-oligomeric compound with a base polymer to form a blend, wherein the blend comprises 80 wt. % to 99.99 wt. % of the base polymer and 0.01 wt. % to 20 wt. % of the SMM; and

(b) casting or molding the blend into the labware having a polypeptide or a polynucleotide binding capacity of less than 80 nanograms (ng)/cm², wherein the SMM in the blend migrates to the surface of the casted or molded labware during the casting or molding step (b) such that the concentration of the SMM in the casted or molded labware is greater at its surface than in its interior volume.