WO/2007/036021 | BLOOD-BRAIN BARRIER EPITOPES AND USES THEREOF |
JPH11137263 | NEW COMPOUND |
WO/1991/006859 | ENZYME ASSAY AND ASSAY KIT TO MEASURE CELLULAR ACTIVATION |
ZHANG YU (US)
What Is Claimed Is: 1. A sensor system comprising: (A) a plurality of a shapes, wherein the shape comprises a length, width, and height, wherein the height is sufficient to allow the distribution of recognition molecules along the height of the shape; (B) one or more recognition molecules along with the height of the shape such that the recognition molecules are homogenously dispersed along the height of the shape; and (C) a surface, wherein the plurality of shapes is affixed onto a surface, wherein the surface is configured to fit to enclose one or more wells on a commercial well plate wherein the shape is formed using an additive manufacturing technique. 2. The sensor system of claim 1, wherein the surface is configured to enclose all of the wells on the commercial well plate. 3. The sensor system of either claim 1 or claim 2, wherein the commercial well plate is a 96 well plate. 4. The sensor system of either claim 1 or claim 2, wherein the commercial well plate is 384 well plate. 5. The sensor system of either claim 1 or claim 2, wherein the commercial well plate is a specially designed well plate. 6. The sensor system according to any one of claims 1-5, wherein the shapes are prepared using a biopolymer. 7. The sensor system of claim 6, wherein the biopolymer is further defined as: (i) a dimethacrylate monomer; (ii) a first PEGylated methacrylate monomer, wherein the PEG segment comprises an average molecular weight from about 600 to about 1,000; and (iii) a photoinitiator. 8. The sensor system of claim 7, wherein the biopolymer further comprises a second PEGylated methacrylate monomer, wherein the PEG segment comprises an average molecular weight from 100 to about 600. 9. The sensor system of either claim 7 or claim 8, wherein the biopolymer is used to prepare the shape and the surface. 10. The sensor system according to any one of claims 7-9, wherein the dimethacrylate monomer is joined by a linking group, wherein the linking group is an alkanediyl(C≤12), 37 4872-7531-9172, v. 1 substituted alkanediyl(C≤12), cycloalkanediyl(C≤12), substituted cycloalkanediyl(C≤12), alkenediyl(C≤12), substituted alkenediyl(C≤12), arenediyl(C≤12), substituted arenediyl(C≤12), heteroarenediyl(C≤12), substituted heteroarenediyl(C≤12), heterocycloalkanediyl(C≤12), substituted heterocycloalkanediyl(C≤12), a polymer of amino acid residues, a poly(ethylene glycol), a poly(propylene glycol), or a polycarbonate. 11. The sensor system of claim 10, wherein the linking group is alkanediyl(C≤12), substituted alkanediyl(C≤12), cycloalkanediyl(C≤12), substituted cycloalkanediyl(C≤12), heterocycloalkanediyl(C≤12), substituted heterocycloalkanediyl(C≤12), a poly(ethylene glycol), a poly(propylene glycol), or a polycarbonate. 12. The sensor system of either claim 10 or claim 11, wherein the linking group is alkanediyl(C≤12) or substituted alkanediyl(C≤12). 13. The sensor system according to any one of claims 10-12, wherein the linking group is alkanediyl(C≤12). 14. The sensor system according to any one of claims 10-13, wherein the linking group is 2,2,4-trimethylhexyl or 2,4,4-trimethylhexyl. 15. The sensor system according to any one of claims 10-14, wherein the linking group further comprises two joining groups. 16. The sensor system of claim 15, wherein each of the joining groups is −O−, −NRa−, −C(O)−, −C(O)O−, −OC(O)−, −OC(O)O−, −C(O)NRa−, −NRaC(O)−, −OC(O)NRa−, −NRaC(O)O−, −S(O)a−, −S(O)aO−, −OS(O)a−, −OS(O)aO−, wherein: Ra is hydrogen, alkyl(C≤6), or substituted alkyl(C≤6); and a is 0, 1, or 2. 17. The sensor system of either claim 15 or claim 16, wherein each of the joining groups is −C(O)O−, −OC(O)−, −OC(O)O−, −C(O)NRa−, −NRaC(O)−, −OC(O)NRa−, or −NRaC(O)O−. 18. The sensor system according to any one of claims 15-17, wherein each of the joining groups is −OC(O)NRa− or −NRaC(O)O−. 19. The sensor system according to any one of claims 15-18, wherein each of the joining group is −OC(O)NRa−. 20. The sensor system according to any one of claims 15-19, wherein each of the joining group is −OC(O)NH−. 38 4872-7531-9172, v. 1 21. The sensor system according to any one of claims 7-20, wherein the dimethacyrlate monomer is diurethane dimethacrylate. 22. The sensor system of claim 21, wherein the diurethane dimethacrylate is a mixture of multiple monomers. 23. The sensor system according to any one of claims 7-22, wherein the first PEGylated methacrylate monomer comprises an average molecular weight of the PEG unit from about 600 to about 800 Daltons. 24. The sensor system according to any one of claims 7-23, wherein the first PEGylated methacrylate monomer, wherein the average molecular weight of the PEG unit is about 700 Daltons. 25. The sensor system according to any one of claims 8-24, wherein the second PEGylated methacrylate monomer comprises an average molecular weight of the PEG unit from about 400 to about 600 Daltons. 26. The sensor system according to any one of claims 8-25, wherein the second PEGylated methacrylate monomer comprises an average molecular weight of the PEG unit from about 500 to about 600 Daltons. 27. The sensor system according to any one of claims 8-26, wherein the second PEGylated methacrylate monomer, wherein the average molecular weight of the PEG unit is about 575 Daltons. 28. The sensor system according to any one of claims 7-27, wherein the photoinitiator is a phosphorus based photoinitiator. 29. The sensor system according to any one of claims 7-28, wherein the photoinitiator is a phosphorus oxide based photoinitiator. 30. The sensor system according to any one of claims 7-29, wherein the photoinitiator is diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). 31. The sensor system according to any one of claims 7-30, wherein the biopolymer comprises from about 10 wt.% to about 65 wt.% of the dimethacrylate monomer in the pharmaceutical composition. 39 4872-7531-9172, v. 1 32. The sensor system according to any one of claims 7-31, wherein the biopolymer comprises from about 20 wt.% to about 40 wt.% of the dimethacrylate monomer in the biopolymer. 33. The sensor system according to any one of claims 7-32, wherein the biopolymer comprises from about 25 wt.% to about 35 wt.% of the dimethacrylate monomer in the pharmaceutical composition. 34. The sensor system according to any one of claims 7-33, wherein the biopolymer comprises from about 10 wt.% to about 55 wt.% of the first PEGylated methacrylate monomer in the biopolymer. 35. The sensor system according to any one of claims 7-34, wherein the biopolymer comprises from about 20 wt.% to about 40 wt.% of the first PEGylated methacrylate monomer in the biopolymer. 36. The sensor system according to any one of claims 7-35, wherein the biopolymer comprises from about 25 wt.% to about 35 wt.% of the first PEGylated methacrylate monomer in the biopolymer. 37. The sensor system according to any one of claims 8-36, wherein the biopolymer comprises from about 10 wt.% to about 55 wt.% of the second PEGylated methacrylate monomer in the biopolymer. 38. The sensor system according to any one of claims 8-37, wherein the biopolymer comprises from about 20 wt.% to about 40 wt.% of the second PEGylated methacrylate monomer in the biopolymer. 39. The sensor system according to any one of claims 8-38, wherein the biopolymer comprises from about 25 wt.% to about 35 wt.% of the second PEGylated methacrylate monomer in the biopolymer. 40. The sensor system according to any one of claims 7-39, wherein the biopolymer comprises from about 0.1 wt.% to about 5 wt.% of the photoinitiator in the biopolymer. 41. The sensor system according to any one of claims 7-40, wherein the biopolymer comprises from about 0.25 wt.% to about 3 wt.% of the photoinitiator in the biopolymer. 42. The sensor system according to any one of claims 7-41, wherein the biopolymer comprises from about 0.5 wt.% to about 2.5 wt.% of the photoinitiator in the biopolymer. 40 4872-7531-9172, v. 1 43. The sensor system according to any one of claims 7-42, wherein the biopolymer comprises a ratio of the dimethacrylate monomer to the first PEGylated methacrylate monomer from about 5:1 to about 1:5. 44. The sensor system according to any one of claims 7-43, wherein the biopolymer comprises a ratio of the dimethacrylate monomer to the first PEGylated methacrylate monomer from about 2:1 to about 1:2. 45. The sensor system according to any one of claims 7-44, wherein the biopolymer comprises a ratio of the dimethacrylate monomer to the first PEGylated methacrylate monomer is about 2:1, 1:1, or 2:3. 46. The sensor system according to any one of claims 8-45, wherein the biopolymer comprises a ratio of the dimethacrylate monomer to the second PEGylated methacrylate monomer from about 5:1 to about 1:5. 47. The sensor system according to any one of claims 8-46, wherein the biopolymer comprises a ratio of the dimethacrylate monomer to the second PEGylated methacrylate monomer from about 2:1 to about 1:2. 48. The sensor system according to any one of claims 8-47, wherein the biopolymer comprises a ratio of the dimethacrylate monomer to the second PEGylated methacrylate monomer is about 2:1, 1:1, or 2:3. 49. The sensor system according to any one of claims 8-48, wherein the biopolymer comprises a ratio of the first PEGylated methacrylate monomer to the second PEGylated methacrylate monomer from about 5:1 to about 1:5. 50. The sensor system according to any one of claims 8-49, wherein the biopolymer comprises a ratio of the first PEGylated methacrylate monomer to the second PEGylated methacrylate monomer from about 2:1 to about 1:2. 51. The sensor system according to any one of claims 8-50, wherein the biopolymer comprises a ratio of the first PEGylated methacrylate monomer to the second PEGylated methacrylate monomer is about 1:1 or 1:2. 52. The sensor system according to any one of claims 1-51, wherein the shape is a cylindrical shape. 53. The sensor system of claim 52, wherein the cylindrical shape comprises a height greater than its length or width. 41 4872-7531-9172, v. 1 54. The sensor system according to any one of claims 1-51, wherein the shape is a rectangular shape. 55. The sensor system of claim 54, wherein the rectangular shape comprises a height greater than its length or width. 56. The sensor system of either claim 54 or claim 55, wherein the rectangular shape comprises an equal length and width. 57. The sensor system according to any one of claims 1-51, wherein the shape is a ball shape. 58. The sensor system of claim 57, wherein the ball shape comprises a spherical end. 59. The sensor system of either claim 57 or claim 58, wherein the ball shape comprises a height longer than the width or length. 60. The sensor system according to any one of claims 57-59, wherein the ball shape comprise the spherical end on less than 50% of the height of the ball shape. 61. The sensor system according to any one of claims 1-51, wherein the shape comprises a first shape that is configured to bind to a second shape. 62. The sensor system of claim 61, wherein the first shape comprises a different recognition molecule than the second shape. 63. The sensor system according to any one of claims 1-51, wherein the shape is a custom shape for the application. 64. The sensor system according to any one of claims 1-51 and 63, wherein the shape is designed using CAD software. 65. The sensor system according to any one of claims 1-64, wherein the shape further comprises a biologic polymer. 66. The sensor system of claim 65, wherein the biologic polymer is a peptide, nucleic acid, or a polysaccharide. 67. The sensor system of claim 66, wherein the biologic polymer is a polysaccharide. 68. The sensor system according to any one of claims 65-67, wherein the biologic polymer comprises one or more amine groups. 69. The sensor system according to any one of claims 65-68, wherein the biologic polymer is a polysaccharide, wherein the sugar group comprises one or more amine groups. 70. The sensor system according to any one of claims 65-69, wherein the biologic polymer is chitosan. 71. The sensor system according to any one of claims 1-70, wherein the recognition molecule is covalently linked to the biologic polymer. 42 4872-7531-9172, v. 1 72. The sensor system according to any one of claims 1-71, wherein the covalent link between the biologic polymer and the recognition molecule is −Y1−A1−Y2−A2−Y3−, wherein: Y1 is the biologic polymer; Y2 is alkanediyl(C≤12), alkenediyl(C≤12), arenediyl(C≤12), or a substituted version of any of these groups; Y3 is the recognition molecule; and A1 and A2 are each independently selected from absent, −O−, −NRa−, −S−, −C(O)−, −CH(N−), −C(O)O−, −C(O)NH−, −OC(O)O−, −OC(O)NH−, −NHC(O)NH−, −C(NRa)O−, −C(NRa)NH−, −OC(NRa)O−, −OC(NRa)NH−, −NHC(NRa)NH−; wherein: Ra is hydrogen, alkyl(C≤6), or substituted alkyl(C≤6). 73. The sensor system of claim 72, wherein Y2 is alkanediyl(C≤12) or substituted alkanediyl(C≤12). 74. The sensor system of either claim 72 or claim 73, wherein Y2 is alkanediyl(C≤12). 75. The sensor system according to any one of claims 72-74, wherein Y2 is ethylene, propylene, or butylene. 76. The sensor system according to any one of claims 72-75, wherein Y2 is propylene. 77. The sensor system according to any one of claims 72-76, wherein A1 is −CH(N−). 78. The sensor system according to any one of claims 72-77, wherein A2 is −CH(N−). 79. The sensor system according to any one of claims 72-78, wherein A1 and A2 are −CH(N−). 80. The sensor system according to any one of claims 1-79, wherein the recognition molecule is a biologic molecule. 81. The sensor system of claim 80, wherein the biologic molecule is an antibody, a sugar or polysaccharide, an amino acid or a polypeptide, or a nucleic acid or polynucleotide. 82. The sensor system of either claim 80 or claim 81, wherein the biologic molecule is a polypeptide. 83. The sensor system of claim 82, wherein the polypeptide is a protein. 84. The sensor system of claim 83, wherein the protein is streptavidin. 85. The sensor system of either claim 80 or claim 81, wherein the biologic molecule is a nucleic acid. 43 4872-7531-9172, v. 1 86. The sensor system of claim 85, wherein the nucleic acid is an aptamer. 87. The sensor system of either claim 80 or claim 81, wherein the biological molecule is an antibody. 88. The sensor system according to any one of claims 1-79, wherein the recognition molecule is a small molecule. 89. The sensor system according to any one of claims 1-88, wherein the recognition molecule further comprises a second recognition molecule. 90. The sensor system of claim 89, wherein the second recognition molecule is an antibody, a signaling molecule, a nucleic acid or polynucleotide, an amino acid or a polypeptide, a sugar or polysaccharide, or a small molecule. 91. The sensor system of either claim 89 or claim 90, wherein the second recognition molecule is a small molecule. 92. The sensor system according to any one of claims 89-91, wherein the second recognition molecule is biotin. 93. The sensor system according to any one of claims 89-92, wherein the second recognition molecule is bound to a signaling molecule. 94. The sensor system of claim 93, wherein the signaling molecule is a dye. 95. The sensor system of either claim 93 or claim 94, wherein the signaling molecule is a fluorophore. 96. The sensor system according to any one of claims 1-95, wherein the recognition molecule binds to a macromolecule. 97. The sensor system of claim 96, wherein the macromolecule is a biologic molecule. 98. The sensor system of claim 97, wherein the biologic molecule is an antibody, a sugar or polysaccharide, an amino acid or a polypeptide, or a nucleic acid or polynucleotide. 99. The sensor system according to any one of claims 1-95, wherein the recognition molecule binds to a small molecule. 100. The sensor system of claim 99, wherein the small molecule is an active pharmaceutical ingredient, a co-factor, a vitamin, or a hormone. 101. The sensor system of claim 100, wherein the active pharmaceutical ingredient is a metabolite of the active pharmaceutical ingredient. 102. The sensor system according to any one of claims 1-101, wherein the sensor system comprises a detection limit of less than 1 µmol per well. 103. The sensor system of claim 102, wherein the detection limit is less than 100 nmol per well. 104. The sensor system of either claim 102 or claim 103, wherein the detection limit is less than 10 nmol per well. 44 4872-7531-9172, v. 1 105. The sensor system according to any one of claims 102-104, wherein the detection limit is less than 1 nmol per well. 106. The sensor system according to any one of claims 102-105, wherein the detection limit is less than 100 pmol per well. 107. The sensor system according to any one of claims 102-106, wherein the detection limit is less than 10 pmol per well. 108. The sensor system according to any one of claims 102-107, wherein the detection limit is less than 1 pmol per well. 109. The sensor system according to any one of claims 1-108, wherein the sensor system has a detection limit from about 0.5 pmols to about 2 µmols per well for a 96 well plate. 110. The sensor system according to any one of claims 1-108, wherein the sensor system has a detection limit from about 0.25 pmols to about 1 µmols per well for a 384 well plate. 111. A method of detecting the presence of an analyte in a solution comprising reacting a solution containing the analyte to a sensor system according to any one of claims 1- 110. 112. The method of claim 111, wherein the method further comprises reacting the sensor system with a detection modality. 113. The method of claim 112, wherein the detection modality is a dye labeled antibody. 114. The method of claim 113, wherein the dye is a fluorophore. 115. The method of claim 111, wherein the method further comprises allowing the analyte to displace a detection modality from the sensor system; and washing the sensor system to remove the detection modality. 116. The method according to any one of claims 111-115, wherein the solution further comprises a buffer. 117. The method of claim 116, wherein the buffer maintains the pH of the solution at from about 4 to about 10. 118. The method of claim 117, wherein the pH of the solution is from about 6 to about 9. 119. The method of either claim 117 or claim 118, wherein the pH of the solution is from about 7 to about 8. 120. The method according to any one of claims 117-119, wherein the pH of the solution is about 7.5. 121. The method according to any one of claims 116-120, wherein the buffer is a sulfonic acid-based buffer. 122. The method of claim 121, wherein the sulfonic acid-based buffer is HEPES or HEPBS. 123. The method according to any one of claims 116-122, wherein the buffer is HEPBS. 45 4872-7531-9172, v. 1 124. The method according to any one of claims 116-123, wherein the solution comprises a concentration of the buffer from about 0.1 mM to about 250 mM. 125. The method of claim 124, wherein the concentration of the buffer is from about 1 mM to about 100 mM. 126. The method of either claim 124 or claim 125, wherein the concentration of the buffer is about 20 mM. 127. The method according to any one of claims 111-126, wherein the solution further comprises a salt. 128. The method of claim 127, wherein the salt is a sodium salt. 129. The method of either claim 127 or claim 128, wherein the salt is sodium chloride. 130. The method according to any one of claims 127-129, wherein the solution comprises a concentration of the salt from about 1 mM to about 25 M. 131. The method of claim 130, wherein the concentration of the salt is from about 10 mM to about 10 M. 132. The method of either claim 130 or claim 131, wherein the concentration of the salt is about 1 M. 133. The method according to any one of claims 111-132, wherein the solution further comprises a surfactant. 134. The method of claim 133, wherein the surfactant is a non-ionic surfactant. 135. The method of either claim 133 or claim 134, wherein the surfactant is Tween. 136. The method according to any one of claims 133-135, wherein the surfactant is Tween 20. 137. The method according to any one of claims 133-136, wherein the solution comprises an amount of the surfactant from about 0.0001% to about 1%. 138. The method of claim 137, wherein the concentration of the surfactant is from about 0.001% to about 0.1%. 139. The method of either claim 137 or claim 138, wherein the concentration of the surfactant is about 0.01%. 140. The method according to any one of claims 111-139, wherein the solution further comprises a protein. 141. The method of claim 140, wherein the protein is a serum albumin. 142. The method of claim 141, wherein the serum albumin is bovine serum albumin. 143. The method according to any one of claims 111-142, wherein the solution further comprises a reducing agent. 144. The method of claim 143, wherein the reducing agent is a borohydride based reducing agent. 46 4872-7531-9172, v. 1 145. The method of either claim 143 or claim 144, wherein the reducing agent is sodium cyanoborohydride. 146. The method according to any one of claims 143-145, wherein the solution comprises a concentration of the reducing agent from about 1 mM to about 1 M. 147. The method of claim 146, wherein the concentration of reducing agent is from about 10 mM to about 500 mM. 148. The method of either claim 146 or claim 147, wherein the concentration of reducing agent is from about 50 mM to about 100 mM. 149. A method of determining the presence of absence of a disease state in a patient comprising exposing a sample from the patient to the sensor system according to any one of claims 1-110. 150. The method of claim 149, wherein the method determines the presence of a disease state. 151. The method of claim 149, wherein the method determines the absence of a disease state. 152. The method according to any one of claims 149-151, wherein the patient is a mammal. 153. The method of claim 152, wherein the mammal is human. 154. The method according to any one of claims 149-153, wherein the sample is saliva, blood, urine, mucous, plasma, serum, sputum, stool, or tears. 47 4872-7531-9172, v. 1 |
[0074] Chitosans may be obtained from any source known to those of ordinary skill in the art. For example, chitosans may be obtained from commercial sources. Chitosans may be obtained from chitin, the second most abundant biopolymer in nature. Chitosan is prepared by N-deacetylation of chitin. Chitosan is commercially available in a wide variety of molecular weight (e.g., 10-1000 kDa) and usually has a degree of deacetylation ranging between 70%- 90%. [0075] The chitosan used herein may have a molecular weight from about 1000 Daltons to about 100,000 Daltons. The weight may be from about 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10,000, 20,000, 25,000, 30,000, 40,000, 50,000, 60,000, 70,000, 75,000, 80,000, 90,000, to about 100,000 Daltons, or any range derivable therein. Chitosans of different molecular weights can be prepared by enzymatic degradation of high molecular weight chitosan using chitosanase or by the addition of nitrous acid. Both procedures are well known to those skilled in the art and are described in various publications (Li et al., 1995; Allan and Peyron, 1995; Domard and Cartier, 1989). The chitosan is water-soluble and may be produced from chitin by deacetylation to a degree of greater than 40%, preferably between 50% and 98%, and more preferably between 70% and 90%. [0076] Some methods of producing chitosan involve recovery from microbial biomass, such as the methods taught by U.S. Pat. No. 4,806,474 and U.S. Patent Application No.2005/0042735, herein incorporated by reference. Another method, taught by U.S. Pat. No. 4,282,351, teaches only how to create a chitosan-beta-glucan complex. 22 4872-7531-9172, v.1 [0077] The chitosan, chitosan derivative, or salt used herein is water soluble. Chitosan glutamate is water soluble. By “water soluble” it is meant that that the chitosan, chitosan derivative, or salt dissolves in water at an amount of at least 10 mg/ml at room temperature and atmospheric pressure. The chitosan, chitosan derivative, or salt used in the present invention has a positive charge. [0078] Additional information regarding chitosan and chitosan derivatives can be found in U.S. Patent App. Pub. Nos. 2007/0167400, 2007/0116767, 2007/0311468, 2006/0277632, 2006/0189573, 2006/0094666, 2005/0245482, 2005/0226938, 2004/0247632, and 2003/0129730, each of which is herein specifically incorporated by reference. II. Additive Manufacturing Methods [0079] Various additive manufacturing including additive systems are contemplated in the present disclosure. These additive manufacturing or additive systems represent machines used for additive manufacturing. These machines operate under various process categories and are used to refer to a category of machines rather than a particular commercial vendor variation of process methodology. Several examples of additive manufacturing process categories include: binder jetting, directed energy deposition, material extrusion, material jetting, powder bed fusion, sheet lamination, and vat photopolymerization. Vat photopolymerization refers to an additive manufacturing process in which liquid photopolymer in a vat is selectively cured by light-activated polymerization. Similarly, stereolithography is a vat photopolymerization process used to produce parts from photopolymer materials in a liquid state using one or more lasers to selectively cure to a predetermined thickness and harden the material into shape layer upon layers. In particular, stereolithography apparatus is an SLA additive machine. As a non-limiting example, SL additive machines are commercially available via various vendors, such as Envision Tec 3D, Formlabs, 3D systems corporation, etc. [0080] The devices described herein are cured products of the resin composition for stereolithography. Specifically, the flexible AM devices of the present invention are cured by irradiating the polymer composition for stereolithography with laser/light. While the hardness, tensile strength at break, tensile elongation at break, and compression of the flexible shaped biomedical devices made using the pharmaceutical composition may be set appropriately according to the mechanical properties required for the product. 23 4 872-7531-9172, v. 1 [0081] The flexible shaped biomedical devices made according to the methods described herein may be formed into any desired shapes by a stereolithography method. These flexible shaped biomedical devices may be produced by any known stereolithography methods, using the compositions described herein as raw material. [0082] The method for producing the flexible biomedical devices can be suitably performed by using the composition described herein, in a conventionally known stereolithography method that uses a liquid resin as a raw material, such as being used in various stereolithography methods including LCD (stereolithography liquid display method: Liquid Crystal Display), DLP (stereolithography projector (surface exposure) method: Digital Light Processing), and SLA (stereolithography laser method: Stereolithography Apparatus). [0083] In some aspects, the present disclosure provides composition that may be used to prepare biomedical devices described herein. These devices are prepared using a method including the steps of forming a first-layer cured product by supplying the compositions for stereolithography described herein onto a stereolithography platform, and irradiating the polymer composition for stereolithography with light/laser to cure the polymer composition for stereolithography; forming a second-layer cured product by supplying the composition described gereub for producing the second- layer cured product onto the first-layer cured product, and irradiating the compositions for stereolithography with laser/light to cure the polymer composition for stereolithography; and repeating the same step as the step of forming the second-layer cured product until a final layer is formed to devices (AM parts) with a three-dimensional shape. For a stereolithography method, any known 3D printer may be used and several types of 3D stereolithographic printer are commercially available. [0084] In a stereolithography method, the thickness of a single layer upon curing the composition described herein is, for example, from about 1 micron to about 1 mm, from about 10 to about 750 microns, from about 20 to about 500 microns, or from about 25 to about 300 microns. The size of the layers may be from about 1 µm, 2.5 µm, 5 µm, 10 µm, 15 µm, 20 µm, 25 µm, 50 µm, 75 µm, 100 µm, 150 µm, 200 µm, 250 µm, 300 µm, 350 µm, 400 µm, 450 µm, 500 µm, 600 µm, 700 µm, 800 µm, 900 µm, to about 1 mm, or any range derivable therein The irradiation light is typically ultraviolet light and preferably includes light with a wavelength of 405 nm. The wavelength of light may be from about 300 nm to about 800 nm, from about 350 nm to about 600 nm, or from about 400 nm to about 500 nm. Similarly, the laser used may have a power from about 10 mW to about 1 W, from about 50 nW to about 750 24 4 872-7531-9172, v. 1 mW, or from about 100 mW to about 500 mW. The irradiation laser power is 250 mW. The irradiation time for curing a single layer of the composition depends on the stereolithography method and may be adjusted appropriately. For example, in the DLP method, the irradiation time is about 1 to 60 seconds, but again depends on the specific formulation and method of stereolithography. These devices may be produced in an environment at about room temperature (e.g., 15 to 35 °C.). [0085] After the stereolithography, optionally, a general secondary treatment, such as high-pressure mercury lamp irradiation, metal halide lamp irradiation, UV-LED irradiation, or heating, may be additionally performed. The secondary treatment can modify the surface after stereolithography, improve the strength, or accelerate curing. The secondary treatment can be performed in combination with stereolithography, although the secondary treatment is not necessarily required, depending on the stereolithography conditions. [0086] In particular, when UV-LED irradiation is employed as a secondary treatment in the method of preparing a device described herein, any unreacted monomer contained in the AM parts can be cured by radicals generated from the photopolymerization initiator, which can further increase the mechanical strength. [0087] In other aspects, the biosensors described herein may also be used in an additive manufacturing platform. Some of the additive manufacturing platforms that may be used herein include 3D printing such as stereolithography may be used to obtain the final biosensor. [0088] In some aspects, the biosensors described herein are processed in a final dosage form instead of as a device. The granules that are produced by the process may be further processed into a capsule or a tablet. Before formulation into a capsule or tablet, the granule may be further milled before being compressed into the capsule or tablet. III. Definitions [0089] 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.” As used herein “another” may mean at least a second or more. 25 4 872-7531-9172, v. 1 [0090] As used herein, the terms “drug”, “pharmaceutical”, “active pharmaceutical ingredient”, “active agent”, “therapeutic agent”, and “therapeutically active agent” are used interchangeably to represent a compound which invokes a therapeutic or pharmacological effect in a human or animal and is used to treat a disease, disorder, or other condition. In some embodiments, these compounds have undergone and received regulatory approval for administration to a living creature. [0091] The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive. As used herein “another” may mean at least a second or more. [0092] The terms “sensor,” “biosensor,” “compositions,” “pharmaceutical compositions,” “formulations,” “pharmaceutical formulations,” “preparations”, and “pharmaceutical preparations” are used synonymously and interchangeably herein. [0093] As used herein, “SLA resin” refers to a stereolithographic resin. For example, SLA resins can be utilized as a building material and/or feedstock used in conjunction with vat polymerization and SLA. The conventional resin which can be applied to SLA equipment mainly focus on producing suitably elastic shaped part or devices. The mechanism properties were their top concerning properties to fit their industrial applications such as those described in WO 2017/154335. [0094] “Treating” or treatment of a disease or condition refers to executing a protocol, which may include administering one or more drugs to a patient, in an effort to alleviate signs or symptoms of the disease. Desirable effects of treatment include decreasing the rate of disease progression, ameliorating or palliating the disease state, and remission or improved prognosis. Alleviation can occur prior to signs or symptoms of the disease or condition appearing, as well as after their appearance. Thus, “treating” or “treatment” may include “preventing” or “prevention” of disease or undesirable condition. In addition, “treating” or “treatment” does not require complete alleviation of signs or symptoms, does not require a cure, and specifically includes protocols that have only a marginal effect on the patient. [0001] The term “therapeutic benefit” or “therapeutically effective” as used throughout this application refers to anything that promotes or enhances the well-being of the subject with respect to the medical treatment of this condition. This includes, but is not limited to, a 26 4 872-7531-9172, v. 1 reduction in the frequency or severity of the signs or symptoms of a disease. For example, treatment of cancer may involve, for example, a reduction in the size of a tumor, a reduction in the invasiveness of a tumor, a reduction in the growth rate of cancer, or prevention of metastasis. Treatment of cancer may also refer to prolonging the survival of a subject with cancer. [0002] “Subject” and “patient” refer to either a human or non-human, such as primates, mammals, and vertebrates. In particular embodiments, the subject is a human. [0095] As generally used herein “pharmaceutically acceptable” refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues, organs, and/or bodily fluids of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit/risk ratio. [0096] “Pharmaceutically acceptable salts” means salts of compounds disclosed herein which are pharmaceutically acceptable, as defined above, and which possess the desired pharmacological activity. Such salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or with organic acids such as 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, 2-naphthalenesulfonic acid, 3-phenylpropionic acid, 4,4′-methylenebis(3-hydroxy-2-ene- 1-carboxylic acid), 4-methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, acetic acid, aliphatic mono- and dicarboxylic acids, aliphatic sulfuric acids, aromatic sulfuric acids, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, carbonic acid, cinnamic acid, citric acid, cyclopentanepropionic acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, heptanoic acid, hexanoic acid, hydroxynaphthoic acid, lactic acid, laurylsulfuric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, muconic acid, o-(4-hydroxybenzoyl)benzoic acid, oxalic acid, p-chlorobenzenesulfonic acid, phenyl-substituted alkanoic acids, propionic acid, p-toluenesulfonic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, tartaric acid, tertiarybutylacetic acid, trimethylacetic acid, and the like. Pharmaceutically acceptable salts also include base addition salts which may be formed when acidic protons present are capable of reacting with inorganic or organic bases. Acceptable inorganic bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide, and calcium hydroxide. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine, and the 27 4 872-7531-9172, v. 1 like. It should be recognized that the particular anion or cation forming a part of any salt of this invention is not critical, so long as the salt, as a whole, is pharmacologically acceptable. Additional examples of pharmaceutically acceptable salts and their methods of preparation and use are presented in Handbook of Pharmaceutical Salts: Properties, and Use (P. H. Stahl & C. G. Wermuth eds., Verlag Helvetica Chimica Acta, 2002). [0097] The term “derivative thereof” refers to any chemically modified compound, wherein at least one of the compounds is modified by substitution of atoms or molecular groups or bonds. In one embodiment, a derivative thereof is a salt thereof. Salts are, for example, salts with suitable mineral acids, such as hydrohalic acids, sulfuric acid or phosphoric acid, for example, hydrochlorides, hydrobromides, sulfates, hydrogen sulfates or phosphates, salts with suitable carboxylic acids, such as optionally hydroxylated lower alkanoic acids, for example, acetic acid, glycolic acid, propionic acid, lactic acid or pivalic acid, optionally hydroxylated and/or oxo-substituted lower alkane dicarboxylic acids, for example, oxalic acid, succinic acid, fumaric acid, maleic acid, tartaric acid, citric acid, pyruvic acid, malic acid, ascorbic acid, and also with aliphatic, aromatic, heteroaromatic or araliphatic carboxylic acids, such as benzoic acid, nicotinic acid or mandelic acid, and salts with suitable aliphatic or aromatic sulfonic acids or N-substituted sulfamic acids, for example, methanesulfonates, benzenesulfonates, p-toluenesulfonates or N-cyclohexylsulfamates (cyclamates). [0098] The term “degradation” or “chemically sensitive” refers to a compound that is destroyed or rendered inactive and unacceptable for use. Degradation may include compounds which have one or more chemical bonds present in the compound has been broken. [0099] The term “dissolution” as used herein refers to a process by which a solid substance, such as the active ingredients or one or more excipients, is dispersed in molecular form in a medium. The dissolution rate of the active ingredients of the pharmaceutical dose of the invention is defined by the amount of drug substance that goes in solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition. [00100] The term “amorphous” refers to a noncrystalline solid wherein the molecules are not organized in a definite lattice pattern. Alternatively, the term “crystalline” refers to a solid wherein the molecules in the solid have a definite lattice pattern. The crystallinity of the active agent in the composition is measured by powder x-ray diffraction. 28 4 872-7531-9172, v. 1 [00101] A “poorly soluble drug” refers to a drug which meets the requirements of the USP and BP solubility criteria of at least a sparingly soluble drug. The poorly soluble drug may be sparingly soluble, slightly soluble, very slightly soluble or practically insoluble. In a preferred embodiment, the drug is at least slightly soluble. In a more preferred embodiment, the drug is at least very slightly soluble. As defined by the USP and BP, a soluble drug is a drug which is dissolved from 10 to 30 part of solvent required per part of the solute, a sparingly soluble drug is a drug which is dissolved from 30 to 100 part of solvent required per part of the solute, a slightly soluble drug is a drug which is dissolved from 100 to 1,000 part of solvent required per part of the solute, a very slightly soluble drug is a drug which is dissolved from 1,000 to 10,000 part of solvent required per part of the solute, and a practically insoluble drug is a drug which is dissolved from 10,000 part of solvent required per part of solute. The solvent may be water that is at a pH from 1-7.5, preferably physiological pH. [00102] 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. [00103] As used in this specification, the term “significant” (and any form of significance such as “significantly”) is not meant to imply statistical differences between two values but only to imply importance or the scope of the difference of the parameter. [00104] Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value or the variation that exists among the study subjects or experimental studies. Unless another definition is applicable, the term “about” refers to ±10% of the indicated value. [00105] As used herein, the term “substantially free of” or “substantially free” in terms of a specified component, is used herein to mean that none of the specified components has been purposefully formulated into a composition and/or is present only as a contaminant or in trace amounts. The total amount of all containments, by-products, and other material is present in that composition in an amount of less than 2%. The term “essentially free of” or “essentially free” is used to represent that the composition contains less than 1% of the specific 29 4 872-7531-9172, v. 1 component. The term “entirely free of” or “entirely free” contains less than 0.1% of the specific component. [00106] As used herein, the term “substantially intact” in terms of a specified component, is used herein to mean that the specified component has not been degraded or rendered inactive in an amount less than 5%. The term “essentially intact” is used to represent that less than 2% of the specific component has been degraded or rendered inactive. The term “entirely intact” contains less than 0.1% of the specific component that has been degraded or rendered inactive. [00107] The term “homogenous” is used to mean a composition in which the components are mixed in such a way that the components are uniformly distributed amongst the composition. In a preferred embodiment, the composition is uniformly distributed in such a manner that there are no regions of a single component that are greater than 1 µm or more preferably less than 0.1 µm. In one embodiment, the composition is so homogeneously mixed in such a manner that there are no atoms of the electromagnetic energy absorbing excipientsare adjacent to another atom of the electromagnetic energy absorbing excipients. [00108] The terms “substantially” or “approximately” as used herein may be applied to modify any quantitative comparison, value, measurement, or other representation that could permissibly vary without resulting in a change in the basic function to which it is related. [00109] A temperature, when used without any other modifier, refers to room temperature, preferably 23 °C unless otherwise noted. An elevated temperature is a temperature which is more than 5 °C greater than room temperature; preferably more than 10 °C greater than room temperature. [00110] The term “unit dose” refers to a formulation of the pharmaceutical composition such that the formulation is prepared in a manner sufficient to provide a single therapeutically effective dose of the active agent to a patient in a single administration. Such unit dose formulations that may be used include but are not limited to a single tablet, capsule, or other oral formulations, or a single vial with a syringeable liquid or other injectable formulations. In some forms, the final pharmaceutical composition that is produced is no longer a powder and is further produced as a homogenous final product. 30 4 872-7531-9172, v. 1 [00111] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements and parameters. [00112] Other objects, features, and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description. IV. Examples [00113] To facilitate a better understanding of the present disclosure, the following examples of specific embodiments are given. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the disclosure, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure. In no way should the following examples be read to limit or define the entire scope of the disclosure. Example 1 – Medical Devices Via Basic Biomedical SLA Resin [00114] During an additive manufacturing process, the energy source (e.g. laser) polymerizes the SLA resin in successive layers in an additive manufacturing build to form an additive manufacturing preform. When a layer is completed, a leveling blade is moved across the surface in order to smooth the surface before the next layer of additive manufacturing feedstock material is deposited. After the blade smooths the surface, the platform is lowered by a distance equal to the layer thickness of a build layer. Then the energy source again tracks the build pattern and cures the SLA resin in designated areas, adding another build layer to the additive manufacturing build. This process of tracing is repeated until the additive manufacturing build is complete, forming the additive manufacturing preform. After the 31 4 872-7531-9172, v. 1 additive manufacturing build is completed, then the additive manufacturing perform undergoes a post-cure step to finish the additive manufacturing part. [00115] The preferable viscosity of the resin ink for SLA is around 700 mPa·S or less, as measured using a rotational viscometer-Visco-Tester in an air environment at a temperature of 25 °C and relative humidity of 35 %. The viscosity of the purchased commercial DUDMA, PEGDA575, and PEGDA700 is ~2300 mPa·S, ~75 mPa·S, and ~95 mPa·S, respectively. [00116] The viscosity of the mixed resin (item 1) is approximately 600 mPa·S. The lower the processing temperature during printing, the higher the viscosity of the final resin ink. [00117] The thermal properties of the raw materials and physical mixtures were determined through a Mettler-Toledo TGA/DSC1 analyzer (Mettler-Toledo, Schwerzenbach, Switzerland). Pure TPO, DUDMA, PEGDA 575, and PEGDA 700, and all samples were ramped from 35 to 350 °C at a rate of 20 °C / min. The furnace was purged using ultra-purified nitrogen at a flow rate of 50 mL/min. The STAR software was used to operate the instrument and collect the data, while data were analyzed using Microsoft Excel software (Version 2007, Microsoft, Redmond, WA, USA). From the TGA data, it’s evident that all of our excipients and thus formulations are stable in the processing temperature used. [00118] Differential scanning calorimetry (DSC, DSC Q20, TA® instruments, New Castle, DE, USA) analysis was used to characterize the pure active functional ingredient (AFI), polymer, and AFI-polymer physical mixture. Approximately 7-12 mg of samples were weighed in standard DSC aluminum pans and sealed with standard aluminum lids (DSC consumables incorporated, Austin, MN, USA) using a calibrated balance. The prepared samples were subjected to a heat-cool-heat ramp circle heated from 25 °C to 200 °C with a ramp rate of 5 °C/min. A purge gas (Nitrogen) at a flow rate of 50 mL/min was used for all the experiments. The data were collected by TA advantage software (Q series, Version 2007 build 13029.20308) and analyzed by TA instruments Universal Analysis 2000. The results were presented as a plot of temperature (°C) versus reverse heat flow (mW). [00119] The DSC thermograms of bulk excipients demonstrated that TPO exhibited an endothermic thermal transition at 98 °C due to its melting. Our developed formulation didn’t exhibit any endotherm at around the range of processing temperature owing to the liquid nature of the polymeric substances used in the formulations. 32 4 872-7531-9172, v. 1 [00120] In order to additively build apart, the energy source traces out successive cross-sections of a three-dimensional object in a vat of liquid photosensitive polymer. The resin crosslinks to form a thermoset polymer, while the excess resin remains liquid resin adjacent to the additive manufacturing build. Once the additive manufacturing build is completed, the additive manufacturing build is elevated and drained to remove excess SLA resin. Once the draining is completed, the final cure is completed by placing the part (or parts) into a UV oven or conveyor and subjecting the additive manufacturing parts to a sufficient amount of light for a sufficient amount of time to cure the thermoset polymer. [00121] An SLA resin composition is prepared according to the above procedure. Optionally, the SLA resin is degassed by degassing sonication in a temperature-controlled water tank. The SLA resin is configured into an additive machine configured to utilize SLA resin as the AM build material. [00122] Examples of liquid resin compositions: liquid resin compositions were prepared by feeding the components shown in Table 1 to a container and stirring the mixture at room temperature for 5 mins. [00123] Test specimens of examples 1 to 3 were prepared from Table 1 listed resin compositions for evaluation according to the following method. Laser beams were selectively applied to the resin composition at a laser power at the irradiation surface of a 250 mW laser and a scanning speed at which the cure depth of each composition was 100 microns using a Form23D printer (manufactured by Formlabs, USA) to form a cured resin layer. This step was repeated to obtain a test specimen. Table 1: Basic SLA Resin Formulation Ingredients (wt.%) Example 1 Example 2 Example 3 33 4 872-7531-9172, v. 1 Example 2 – Preparation of Biosensors [00124] The Biosensor was prepared using FDA tested biomedical polymer di- urethane di-methacrylate (DUDMA), Polyethylene glycol diacrylate (PEGDA 575, PEGDA 700), and a photoinitiator (Diphenyl (2,4,6-trimethyl benzoyl) phosphine oxide (TPO) are selected for producing the structure of the Thinker biosensor. These compositions are used as described above. [00125] The overall schematic images of ideal designed biosensor are shown in FIG. 1 including film shape, cylinder shape, ball shape, assembled “Janus” shape Thinker biosensor. For the film biosensor, a bioprinter bioX was used to fabricate the biosensor. For the other complex 3D shaped biosensors, a stereolithography printer (Form2, FormLab int. USA) was used for the manufacture. [00126] FIG.2 illustrates a schematic for fabricating process of the film biosensors. First of all, to facilitate the subsequent covalent immobilization of DNA recognition element onto the 3D printed probe, via glutaraldehyde reaction with amine. The probes were first immerged into chitosan (CH) solution and then UV curved for 3 min at 60 °C. [00127] The curves analyses to test the sensitivity of biosensor is shown in FIG. 3. FIG.3A demonstrate the detection of the biosensor at large concentration range 40, 20, 10, 5, and 2.5 pmol/well. Then, FIG. 3B shows the detection of the biosensor at low concentration range from 2.5, 1.0, 0.5, 0.25, and 0.1 pmol/well. The results show that the biosensor shows good detection sensitivity start from 0.5 pmol/well of the biosensor at a surface area of biosensor at 4π. [00128] The images for fabricating process of ball biosensors are shown in FIG.4. Then, the chemical reaction scheme for biosensor surface modification is shown in FIG.5. The CH films were cross-linked by immersion in 0.5% (w/v) GA solution from Tris buffer at pH 7.5. The crosslinking procedure was allowed to continue for 24 h at 4 °C. Subsequently, these products were thoroughly washed with deionized water and finally dehydrated again by slow drying under a laminar flow hood. Some CH films without any crosslinking were taken as reference materials. FIG.6 shows the microscope images of Thinker from each reaction steps. [00129] The fluorescent microscope images of the ball biosensors are shown in FIG. 7. From left to the right in FIG. 7 show the ball biosensor without biotin fluorescent, with biotin FITC, and DNA-FAM, separately. 34 4 872-7531-9172, v. 1 [00130] Analysis of different methods are described and plotted as the fluorescent intensity vs concentration. The concentration was 20, 10, 5, 2.5, 1, 0.5, 0.25, and 0.1 pmol/well respectively. This data is shown in FIG. 8. It shows that method 1 has the lowest reading, method 2 has the highest reading and the method 3 is the optimized reading. [00131] Similarly, the use of different buffers was screened to control for different non-specific binding. The results of the screen are shown in FIG. 9. Buffer A: 500 mM NaCl in DI-water; Buffer B: 2 M NaCl in DI-water; Buffer C: 20 mM HEPBS with 1 M NaCl and 0.01% tween 20,and Buffer D Tris 0.1 M NaCl. pH of all buffers is around 7.5. Basic Buffer for washing: 20 mM HEPBS. Herein, the buffer C shows the optimized control for controlling the non-specific bindings. FIG. 10 shows the bar chart shows the binding percentage of Ball shape Thinker for 96 well plate. Buffer A-BSA/Buffer B-BSA with FAM-Biotin-DNA/FAM- DNA (1 pmol / per well). The binding percentage of the Thinker with the right parameters was able to reach 100%. [00132] Finally, the schematic process of assembling the “Janus” shaped Thinker biosensor is shown in FIG. 11. To analyze both large molecules and small molecules at the same time, the two parts of the Janus biosensors have different surface modifications process. After the surface treatment, the two parts were assembled by the process which is shown in FIG.11. [00133] Finally, the morphology of the sensors with each of the surface modifications is shown in FIG.12. * * * [00134] All of the compositions and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this disclosure have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit, and scope of the disclosure. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. 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