Drug screening systems, apparatuses, and methods

Abstract

A drug screening system automatically tests different potential drug molecules located within wells of a first microplate for interaction with a protein of interest. A first portion of individual chambers of a second microplate includes a sol-gel embedded with a first protein of interest and a second portion of the individual wells includes a sol-gel without the first protein of interest. Other portions may include a sol-gel embedded with a second protein of interest or a sol-gel embedded with both the first protein of interest and the second protein of interest. A robotic liquid handler is configured to aspirate a solution including the different potential drug molecules from the first microplate and dispense the solution into respective individual chambers of the second microplate such that the potential drug molecule passes through the sol-gel and is collected in a respective well of a third plate as an eluent for analysis.

Description

DRUG SCREENING SYSTEMS, APPARATUSES, AND METHODSCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority7to U.S. Provisional Application Number 63 / 512,735 titled “DRUG SCREENING SYSTEMS, APPARATUSES, AND METHODS,’’ filed July 10, 2023. which is assigned to the assignee hereof, and incorporated herein by reference in its entirety.INTRODUCTION

[0002] Aspects of the present disclosure generally relate to a system for drug screening, and particularly to screening drugs for interaction with a protein.BACKGROUND

[0003] A drug discovery process may involve determining how a potential drug molecule interacts with a protein of interest. For example, in order effectively travel to certain organs, a potential drug molecule must bind to proteins in plasma. Further, interactions between multiple drugs may affect the protein binding properties.

[0004] There remains an unmet need in the related art for techniques for screening binding properties of potential drugs.SUMMARY

[0005] The following presents a simplified summary of one or more aspects of the present disclosure in order to provide a basic understanding of such aspects. This summary is not an extensive overview of all contemplated aspects, and is intended to neither identify key or critical elements of all aspects, nor delineate the scope of any or all aspects. Its purpose is to present some concepts of one or more aspects in a simplified form as a prelude to the more detailed description that is presented later.

[0006] In some aspects, the techniques described herein relate to a drug screening system including: a first robotic handler configured to move a first plate into at least a first position and to move a second plate into at least a second position, wherein the first plate includes a first plurality of individual wells, each well including an initial amount of a solution including different potential drug molecules, wherein the second plate includes a second plurality of individual chambers, wherein a first portion of the second plurality of individualchambers are coated or filled with a sol-gel into which a protein of interest is embedded and a second portion of the plurality of individual chambers are coated or filled with a solgel having no protein of interest; a robotic liquid handler configured to perform a process of aspirating the solution from each of the first plurality of individual wells and dispensing the solution into a respective individual well of the second plurality of individual chambers such that the potential drug molecule passes through the sol-gel within the respective second individual chambers, and as respective eluent, into a respective well of a third microplate that includes a third plurality of individual wells, an analyzer configured to measure, for each well of the third plate, a final amount of drug molecule in each respective eluent received into the well, wherein a difference between the initial amount of the potential drug molecule and the final amount of drug molecule in the eluent indicates a drug molecule that interacted with the protein, and wherein no difference between the initial amount of the potential drug molecule and the final amount of drug molecule in the eluent indicates a drug molecule that does not interact with the protein; and a control system for the robotic handler, the robotic liquid handler, and the analyzer configured to correlate the potential drug molecules and protein in each well, and whether the potential drug molecule interacted with the protein.

[0007] In some aspects, the techniques described herein relate to a drug screening system, wherein the solution including different potential drug molecules includes an internal standard, wherein the analyzer is configured to compare the difference between the initial amount of the potential drug molecule and the final amount of drug molecule in the eluent to a difference in an amount of the internal standard.

[0008] In some aspects, the techniques described herein relate to a system, wherein the sol-gel is a sol-gel synthesized from silicon alkoxide.

[0009] In some aspects, the techniques described herein relate to a system, wherein the silicon alkoxide is tetraalkoxysilane or a mono-, di-, or tri-alkyl alkoxysilane, or a sodium silicate.

[0010] In some aspects, the techniques described herein relate to a system, wherein the sol-gel further includes a protein stabilizer selected from Ca2+, an organosilane, a polyethylene glycol (PEG), a graft copolymer, a charged polymer, a sugar, or an amino acid.

[0011] In some aspects, the techniques described herein relate to a system, wherein the protein of interest is a human protein, canine protein, feline protein, primate protein, equine protein, porcine protein, rodent protein, bacterial protein, or viral protein.

[0012] In some aspects, the techniques described herein relate to a system, wherein the protein of interest is an extracellular protein or an intracellular protein.

[0013] In some aspects, the techniques described herein relate to a system, wherein the protein of interest is human serum albumin.

[0014] In some aspects, the techniques described herein relate to a system, wherein the sol-gel is also embedded with alpha-acid glycoprotein.

[0015] In some aspects, the techniques described herein relate to a system, wherein the protein of interest is alpha-acid glycoprotein.

[0016] In some aspects, the techniques described herein relate to a system, wherein a concentration of the protein of interest is at least 30,000 parts per million.

[0017] In some aspects, the techniques described herein relate to a system, wherein each well of the first microplate includes the first solution of the initial amount of the potential drug molecule and a second initial amount of a second potential drug molecule, wherein the analyzer is configured to: measure and calculate a final amount of the second potential drug molecule in each respective analyte solution received into each well of the third microplate; and correlate the final amount of the second potential drug molecule in each well of the third microplate with the protein of interest in a corresponding well of the second microplate to determine whether the second potential drug molecule interacted with the protein of interest and / or the first potential drug molecule.

[0018] In some aspects, the techniques described herein relate to a system, wherein the robotic liquid handles is configured to: aspirate a second solution including a second potential drug molecule from the first microplate or a fourth microplate into a plurality of pipette tips; and dispense the second solution into the second microplate such that the second solution including the second potential drug molecules is placed into contact with the sol-gel and the first solution in the respective chamber such that the first solution and the second solution pass through the sol-gel thereby forming the analyte solution that exits the port into the third microplate.

[0019] In some aspects, the techniques described herein relate to a system, wherein the robotic liquid handles is configured to dispense a solvent into the second microplate such that the solvent passes through the sol-gel thereby forming a second analyte solution that exits the port into a fourth microplate, and wherein the analyzer is configured to measure and calculate a final amount of the first potential drug molecule in each respective second analyte solution received into each well of the fourth microplate.

[0020] In some aspects, the techniques described herein relate to a method for high throughput drug screening, including: transferring a first microplate to a first position with a robotic handler configured to move the first microplate, wherein the first microplate includes aplurality of individual chambers, each chamber including a body and a bottom surface forming a well, each well capable of holding an amount of a first solution including a first potential drug molecule, wherein each chamber is adapted to receive a pipette tip, and wherein each well includes the first solution of an initial amount of the first potential drug molecule; transferring a second microplate to a second position with the robotic handler, wherein the second microplate includes a second plurality of individual chambers, each chamber including a body and a bottom surface including a port, each chamber including a sol-gel, wherein the sol-gel in a first portion of the second plurality of individual chambers is embedded with a protein of interest and the sol-gel in a second portion of the second plurality' of individual chambers is not embedded with the protein of interest; aspirating the first solution including the first potential drug molecule from the first microplate into a plurality of pipette tips; dispensing the first solution into the second microplate such that the solution including the first potential drug molecule is placed into contact with the solgel in the respective chamber; passing the first solution through the sol-gel thereby forming an analyte solution that exits the port into a third microplate; measuring and calculating using an analyzer a final amount of first potential drug molecule in each respective analyte solution received into each well of the third microplate; and correlating final amount of first potential drug molecule in each w ell of the third microplate with the protein of interest in a corresponding w ell of the second microplate to determine whether the first potential drug molecule interacted with the protein of interest, wherein a difference between the initial amount of the first potential drug molecule and the final amount of the first potential drug molecule in the analyte solution indicates a drug molecule that interacts with the protein of interest, and wherein no difference between the initial amount of the first potential drug molecule and the final amount of the first potential drug molecule in the analyte solution indicates a drug molecule that does not interact with the protein of interest.

[0021] In some aspects, the techniques described herein relate to a method, wherein each w ell of the first microplate includes the first solution of the initial amount of the potential drug molecule and a second initial amount of a second potential drug molecule, the method further including: measuring and calculating using the analyzer a final amount of the second potential drug molecule in each respective analyte solution received into each w ell of the third microplate; and correlating final amount of the second potential drug molecule in each well of the third microplate with the protein of interest in a corresponding well of the second microplate to determine whether the second potential drug molecule interacted with the protein of interest and / or the first potential drug molecule.

[0022] In some aspects, the techniques described herein relate to a method, further including aspirating a second solution including a second potential drug molecule from the first microplate or a fourth microplate into a plurality of pipette tips; dispensing the second solution into the second microplate such that the second solution including the second potential drug molecules is placed into contact with the sol-gel and the first solution in the respective chamber; and passing the first solution and the second solution through the solgel thereby forming the analyte solution that exits the port into the third microplate.

[0023] In some aspects, the techniques described herein relate to a method, further including: dispensing a solvent into the second microplate; passing the solvent through the sol-gel thereby forming a second analyte solution that exits the port into a fourth microplate; and measuring and calculating using the analyzer a final amount of the first potential drug molecule in each respective second analyte solution received into each well of the fourth microplate.

[0024] In some aspects, the techniques described herein relate to a microplate for drug screening, including: a plurality’ of individual chambers, wherein a first portion of the individual chambers includes a sol-gel embedded with a protein of interest and a second portion of the individual chambers includes a sol-gel without the protein of interest; and a computer- readable tag indicating a location of the first portion of the individual chambers including the sol-gel with the protein of interest.

[0025] In some aspects, the techniques described herein relate to a microplate, wherein each chamber includes a body and a bottom surface including a port.

[0026] These and other aspects of the present disclosure will become more fully understood upon a review of the detailed description, which follows.BRIEF DESCRIPTION OF THE DRAWINGS

[0027] FIG. 1 is model of human serum albumin including drug binding sites.

[0028] FIG. 2 is a model of Alpha-acid Glycoprotein.

[0029] FIG. 3 is a diagram of an example sol-gel process, according to an aspect of the disclosure.

[0030] FIG. 4 is a diagram 600 of an example chamber including a sol-gel mixture.

[0031] FIG. 5 is a diagram of an example assay with a sol-gel with and without a protein of interest, according to an aspect of the disclosure.

[0032] FIG. 6 is diagram of an example microplate including filtered wells, according to an aspect of the disclosure.

[0033] FIG. 7 is a diagram of an example patern of filtered wells in a microplate, according to an aspect of the disclosure.

[0034] FIG. 8 is a diagram of an example patern of pipete tips, according to an aspect of the disclosure.

[0035] FIG. 9 is a diagram of an example patern of potential drug molecules in a microplate, according to an aspect of the disclosure.

[0036] FIG. 10 is a diagram of an example automated screening system, according to an aspect of the disclosure.

[0037] FIG. 11 is a flowchart of a first example method of screening drugs, according to an aspect of the disclosure.

[0038] FIG. 12 is a flowchart of an example method of screening drugs in a first competition study, according to an aspect of the disclosure.

[0039] FIG. 13 is a flowchart of an example method of screening drugs in a second competition study, according to an aspect of the disclosure.

[0040] FIG. 14 is a flowchart of an example method of screening drugs in a third competition study, according to an aspect of the disclosure.

[0041] FIG. 15 is a diagram of example results, according to an aspect of the disclosure.

[0042] FIG. 16 is a diagram of an example computer system, for use in accordance with aspects of the present disclosure.

[0043] FIG. 17 is a diagram of an example computer network, for use in accordance with aspects of the present disclosure.DETAILED DESCRIPTION

[0044] The detailed description set forth below in connection with the appended drawings is intended as a description of various configurations and is not intended to represent the only configurations in which the concepts described herein may be practiced. The detailed description includes specific details for the purpose of providing a thorough understanding of vanous concepts. However, it will be apparent to those skilled in the art that these concepts may be practiced without these specific details. In some instances, well known components are shown in block diagram form in order to avoid obscuring such concepts.

[0045] In an aspect, the disclosure provides for a high-throughput drug screening system. The drug screening system can automatically test different potential drug molecules located w ithin wells of a microplate for interaction with one or more proteins of interest. Many drug companies save every compound they have synthesized, or purchased, for everyproject they have addressed. Some companies have hundreds of thousands or millions of compounds in their libraries. A properly designed screen may quickly screen these compounds for interaction with a protein of interest

[0046] The high-throughput drug screening system may utilize a microplate containing the protein of interest immobilized in a sol-gel. Sol-gels allow an immobilized protein to act more like the protein does in a biological matrix compared to other methods of immobilizing proteins. This behavior is due to the way the protein is attached to some sort of support in the other methods. For example, proteins may be immobilized via covalent attachment to a solid support, non-covalent attachment to a solid support, or bioaffinity attachment (e.g., via an antibody that is attached to the support). Such immobilization techniques may affect the binding properties of the protein. In contrast, a sol-gel acts as a silicate cage around the protein, which remains fully in its natural state. Sol-gel nanoparticles are networks of metal oxide polymers that encase the protein and have small pores throughout the surface that allows small molecules to freely flow in and out of the network and interact with the protein. There are many reports in the literature demonstrating how protein binding affinities and enzyme kinetics mirror the biological system. That is, the protein may bind with molecules in the same manner as the protein would interact within plasma. Another way to think of this arrangement is in comparison to a microdialysis system in a single vessel. Normally, microdialysis is carried out in two adjacent wells separated by a permeable membrane. One well contains the protein and the other contains the molecule to be studied. Similarly, the sol-gel cages of protein are floating through the ligand solution, creating an effectively similar system in a single well.

[0047] In an aspect, a protein of interest may be human serum albumin (HSA). The choice of human serum albumin provides unique features of a screening process such as competition studies. Human serum albumin includes multiple binding sites. There are at least 5 binding sites identified on the protein, and different types of molecules bind to different sites at the same time.

[0048] In another aspect, a protein of interest may be Alpha-acid Glycoprotein, which is another protein present in human plasma. Alpha-acid Glycoprotein may bind with different drug molecules than human serum albumin. For example, neutral and acidic drugs bind to human serum albumin while basic drugs bind to Alpha-acid Glycoprotein.

[0049] In another aspect, the sol-gel may include both human serum albumin and Alpha-acid Glycoprotein.

[0050] In an aspect, a microplate containing the protein of interest immobilized in a sol-gel may be used to measure plasma protein binding of a potential drug molecule. We have tried this with several known drugs and can readily distinguish between low, medium and tight binding ligands. The assay simply involves mixing the product with ImL of a dilute solution of your ligand for 5 minutes. The difference in concentration of ligand, before and after mixing, indicates the level of binding.

[0051] In another aspect, a competition study using the one or more immobilized proteins of interest may be used to determine whether a first molecule binds more strongly to a protein than a second molecule. For example, the microplate containing the protein of interest immobilized in a sol -gel may receive a 50:50 mix of two molecules: Measuring the relative concentrations of the two ligands indicates relative binding affinity. Because the protein contains multiple binding sites, the result can provide additional information as to whether or not both molecules bind to the same site. For example, if both bind tightly, but to different sites, the measurements will show both ligand concentrations reduced.

[0052] . As another example, a competition study may determine whether one molecule displaces another molecule from the protein. For example, a second ligand may be added after mixing the first ligand: This approach potentially provides different information than the previous one. In this study, the measurements can indicate whether binding of the first drug allows the second one to bind. This study can be different than the initial experiment where all sites are initially empty.

[0053] In another example, the ligand may be washed off of the complex after running the above experiments: Once the ligand is bound to the protein, ImL of different solvents can be dispensed into the microplate to determine how ligand is stripped off the protein. The effect of pH and ionic strength, as well as different buffer solutions can be assessed.

[0054] In an aspect, a robotic liquid handler may be configured to dispense a solution including a potential drug molecule into a set of microplate wells including the sol-gel with one or more proteins of interest. The microplate may be configured with wells having different patterns of proteins of interest. The solution may be drawn through the wells, for example, by a filter press or vacuum nest. An eluent may be collected from each well in a second plate. An analyzer configured to measure, for each well of the second plate, a final amount of drug molecule in each respective eluent received into the well. A control system correlates the potential drug molecules and protein associated with each well to determine whether the potential drug molecule interacted with the protein

[0055] In an aspect, the present disclosure describes a new screening system that can be used to identify biologically active drugs. Generally, the disclosed techniques may involve immobilizing one or more proteins of interest in a plurality of chambers for high-throughput testing. In some implementations, the proteins of interest may include proteins present in the human plasma such as HSA and Alpha-acid Glycoprotein. Successful drugs may bind to these proteins and be carried through plasma and interstitial fluid to target cells. The protein of interest may be provided to a laboratory with access to a large compound library in a pre-fdled array such as a microplate. Some chambers in the array may be control chambers in which no protein of interest is present. Potential drugs may be applied to a plurality' of chambers in the array. After the potential drug is exposed to each chamber, an eluent may be collected in a second array of chambers. The eluent may be tested for an amount of the potential drug in the eluent. A difference in the amount of drug between the control chambers and the chambers with the protein of interest may indicate an interaction between the potential drug and the protein of interest. Potential drugs having an interaction may be identified for further testing. Accordingly, the present disclosure provides for a system for rapid testing of large compound libraries for drug discovery.

[0056] FIG. 1 is model 100 of human serum albumin (HSA) including drug binding sites. HSA is one of two major proteins that deliver drugs throughout the body. Generally, HSA binds more easily to neutral and acidic compounds. For example, known drugs that bind to HSA include barbiturates, benzodiazepines, NSAIDs, valpric acid, phenytoin, penicillins, sulfonamides, tetracyclines, tolbutamide, and warfarin. For a drug to be effective, the drug needs to bind to HSA to be transported to target cells. Further, if the drug binds too tightly to HSA, the drug may reach the target cell but may not function. Multiple drugs can bind to HSA at the same time (e.g., at different binding sites). It is also possible for one drug to displace less tight binding drugs.

[0057] FIG. 2 is a model 200 of Alpha-acid Glycoprotein, which is the other of the two major proteins that deliver drugs throughout the body. Alpha- acid Glycoprotein may also be referred to as Orosomucoid. Alpha-acid Glycoprotein preferentially binds with basic drugs (i.e., high pKa). For example, known drugs that bind to Alpha-acid Glycoprotein include P-blockers, Bupivacaine, Lidocaine, Disopyramide, Imipramine, Methadone, Prazosine, Quinidine, and Verapamil. Unlike HSA, Alpha-acid Glycoprotein only contains one binding site. Although Alpha-acid Glycoprotein is not as heavily studied as HSA, drug binding with Alpha-acid Glycoprotein may be important for a drug discovery program.

[0058] FIG. 3 is a diagram of an example sol-gel process 300 for forming a sol-gel immobilizing one or more proteins of interest. The one or more proteins of interest may be added to an initial solution of tetraethyl orthosilicate, water, and hydrochloric acid. The amount of the protein of interest may be controlled to produce a desired concentration. In some implementations, a concentration of approximately 30,000 ppm is desired. In some implementations, concentrations of 40,000 ppm is preferred and concentrations of 60,000 more preferred. In an aspect, a higher concentration that maintains the binding properties of the protein of interest is desirable to better detect the interaction of the protein of interest with potential drug molecules.

[0059] The solution undergoes hydrolysis and condensation to form a colloidal solution (sol). The sol may undergo various processes such as spinning, coating, or precipitation to form fibers, xerogel film, or powder. In an aspect, the sol undergoes a gelling process to produce a wet gel. The wet gel then undergoes an evaporation process to produce a xerogel, which may be pulverized to form a powdered gel.

[0060] FIG. 4 is a diagram 400 of an example chamber 410 including a sol-gel mixture 414. The sol-gel mixture 414 may include a protein of interest such as human serum albumin Alphaacid Glycoprotein . In some implementations, the sol-gel mixture 414 may made through a sol-gel process 300. The sol-gel mixture 414 may be a sol-gel synthesized from silicon alkoxide, preferably tetraalkoxysilane or mono-, di-, and tri-alkyl alkoxysilanes, or a sodium silicate. The sol-gel may further include a protein stabilizer selected from Ca2+, an organosilane, a polyethylene glycol (PEG), a graft copolymer, a charged polymer, a sugar, or an amino acid. In some implementations, the sol-gel mixture 414 may be a mixture of sol-gel and silica. The mixture may be prepared by grinding the silica and protein, in a cryogenic grinder, then forming the sol -gel through the sol-gel process. The silica may act as a diluent for the sol-gel, allowing better contact with an added solution. The sol-gel mixture 414 may protect the protein during storage and / or shipment. For example, the solgel mixture 414 may prevent denaturization of the protein. In some implementations, the sol-gel mixture 414 may be a mixture of sol-gel and other polymer materials that aid in the preservation of the embedded protein.

[0061] In some implementations, the chamber 410 may include a plug 416 in the port 412. The plug 416 may be, for example, a wad of fiber such as cotton or a material having high permeability. The plug 416 may prevent the sol-gel mixture 414 from exiting the port 412 during manufacture and / or shipping. The plug 416 may be removed prior to performing an assay.

[0062] The chamber 410 may be used for an assay. A buffer solution 430 including a potential drug molecule may be added to the chamber 410 above the sol-gel mixture 414. A filter press may apply pressure to the chamber 410 to push the buffer solution 430 through the sol-gel mixture 414. Eluent 422 may exit the chamber 410 via the port 412 and be received in a second chamber 420. If the potential drug molecule interacts with the protein embedded in the sol-gel mixture 414, an amount of drug molecule in the eluent 422 may be less than an amount of drug molecule in the buffer solution 430. The potential drug molecule may be indicated for further study. If the amount of drug molecule in the eluent 422 is approximately the same as the amount of drug molecule in the buffer solution 430, the potential drug molecule may not be indicated for further study.

[0063] FIG. 5 is a diagram 500 of an example assay using a sol-gel with and without a protein of interest. A first chamber 510 may include a sol-gel 512 having no protein. A second chamber 520 may include a sol-gel 522 having immobilized protein therein. The sol-gel 512 and sol -gel 522 may be the same except for the presence or absence of the one or more proteins of interest.

[0064] A buffer 502 including a molecule of interest (e.g., a potential drug) may be added to each of the chambers 510 and 520. In the chamber 510, most of the molecule of interest will pass through the sol-gel and be collected as eluent 516 in lower well 514. In the chamber 520, if the molecule of interest binds to the protein of interest, some of the molecule of interest will remain in the sol-gel 522. The eluent 526 collected in the chamber 524 will have a lower concentration of the molecule of interest than the eluent 516.

[0065] FIG. 6 is diagram of an example microplate 600 including filtered chambers 610. For example, the filtered chambers 610 may each be an example of the chamber 410. The chambers 610 may be arranged in an array. For example, in an implementation of a 96 well array, the chambers 610 may be arranged in 12 rows of 8 chambers.

[0066] FIG. 7 is a diagram of an example pattern 700 of filtered wells in a microplate. The pattern 700 may describe an example microplate such as the microplate 600. In an aspect, the microplate 600 may be preconfigured for high-throughput drug screening. In an example implementation, the chambers of each row of the microplate 600 may include a sol-gel mixture 414 with a different configuration of protein. For example, each sol-gel mixture 414 may include different proteins, different amounts of a protein, different combinations of proteins, different tag locations for the protein, or other characteristics that may affect interaction with a drug molecule. In an implementation with the illustrated pattern 700, the chambers in each column may have the same configuration of protein. For example, asillustrated, although the chambers in each row A-L include different configurations of proteins, each column 1-8 may include the same configuration of proteins. As discussed in further detail below, the pattern 700 may allow high throughput drug screening by adding a solution including a potential drug molecule to each chamber of a row. A solution with a different potential drug molecule may be added to each different row, or a subset of the chambers within each row (e.g., each half-row of 4 chambers).

[0067] In an example pattern for screening drugs for binding properties with plasma proteins, a first chamber in each row' may include a sol-gel with the HSA immobilized. A second chamber in each row' may include a sol-gel with Alpha-acid Glycoprotein immobilized. Other chambers in each row may include combinations of HSA and Alpha-acid Glycoprotein. One or more chambers in each row may include a sol-gel with no protein to serve as a control. Accordingly, for rapid throughput, a solution including a potential drug molecule may be added to each chamber in a row, and the resulting eluent may be analyzed to determine whether there is an interaction between the potential drug molecule and any of the proteins of interest.

[0068] In an example pattern for screening drugs for a virus, a first chamber in each row may include a sol-gel with a target protein of the drug immobilized. Other chambers in each row may include other plasma proteins or other target proteins. One or more chambers in each row may be empty, or may include a sol-gel with no protein to serve as a control. Accordingly, for rapid throughput, a solution including a potential drug molecule may be added to each chamber in a row; and the resulting eluent may be analyzed to determine w hether there is an interaction between the potential drug molecule and any of the proteins of interest.

[0069] FIG. 8 is a diagram of an example pattern 800 of chambers (e.g., in a microplate). In an implementation, the pattern 800 may include pairs of chambers. For example, each row may include alternating chambers with a first chamber in the pair being a chamber containing sol-gel immobilizing a protein of interest, and the second chamber in the pair containing sol-gel without a protein of interest. The first chamber may include the protein of interest and may be used to test a solution including a potential drug molecule. The second chamber may serve as a control.

[0070] FIG. 9 is a diagram of an example pattern 900 of potential drug molecules in a microplate. In an implementation, the pattern 900 may include pairs of wells including the same potential drug molecule. A drug library may be arranged in pattern 900 for high throughput screening using the chambers arranged in the pattern 800. Each pair of chambers in thepattern 800 may correspond to a pair of wells in the pattern 900. Accordingly, a pipettor may sample multiple wells at a time. For example, in an implementation, an 8 channel multi -pipettor may use a row of chambers (e.g., row A) to sample a row of potential drug molecules (e.g., row A). The sampling may include one or more aspirate and dispense cycles, where the solution including the potential drug molecule is aspirated into a pipette tip, then dispensed back into the upper chamber of the microplate. The solution may be drawn through the sol-gel in each chamber into the lower chamber 420 using a filter press or vacuum nest. The lower microplate including lower chamber 420 may then be provided to an analyzer (e.g., a liquid chromatography analyzer) including an autosampler that may analyze samples from the microplate and compare pairs of wells.

[0071] In an implementation, instead of the pattern 900, the potential drug molecules may be arranged in individual wells of a first microplate for each potential drug molecule. The well for a potential drug molecule may first be sampled and dispensed into a first chamber of a second microplate. The second microplate may follow the pattern 800. For example, the first sample may be dispensed into a chamber without the protein of interest. The well of the first microplate may then be sampled and dispensed into a different chamber of the second microplate (e.g., a chamber including the protein of interest) and the wells of the lower microplate with the same potential drug molecule may be paired for comparison.

[0072] In an aspect, the solution including the potential drug molecules may include an internal standard. The internal standard may be a molecule that is not expected to react with the protein of interest. For example, caffeine may be used as the internal standard in some implementations. The analyzer may detect an amount of the potential drug molecule and an amount of the internal standard for each well. Accordingly, a change in the amount of potential drug molecule may be detected via comparison with the amount of the internal standard.

[0073] FIG. 10 is a diagram of an example automated screening system 1000. The automated screening system 1000 may include a robotic handler 1010, a shelving system 1020, a liquid handler 1030, an analyzer 1040, and a control system 1050. In some implementations, the automated screening system 1000 may optionally include a filter press 1060. The control system 1050 may be a computer system including a computer memory and one or more computer processors. The control system 1050 may execute instructions stored on the computer memory (e.g., a control application) to control each of the robotic handler 1010, the shelving system 1020, the liquid handler 1030, the analyzer 1040, and the filter press 1060. In some implementations, each of the robotic handler 1010, the shelving system1020, the liquid handler 1030, the analyzer 1040, and the filter press 1060 may include a separate control system that provides an application programming interface (API) and / or a command interface that allows the control system 1050 to control the respective station.

[0074] The robotic handler 1010 may be an apparatus that moves one or more microplates. In one implementation, as illustrated, the robotic handler may include a robotic arm 1012. The robotic arm 1012 may rotate about a base between different stations (e.g., the shelving system 1020. the liquid handler 1030, and the analyzer 1040). The robotic arm 1012 may move vertically at either an elevator at the base or one or more joints. The robotic arm 1012 may move radially via telescoping segments and / or joints. The robotic arm 1012 may include an attachment for handling microplates. For example, the robotic arm 1012 may include opposing grippers for engaging opposite sides of the microplates and / or containers of pipettes. The attachment may maintain the microplates in a horizontal orientation while moving between stations. In some implementations, the robotic arm 1012 may include a scanner configured to scan a tag of an object such as a microplate. The tag may be used to determine that the robotic arm 1012 has acquired a correct object. In some implementations, the tag may provide input into the control system. For example, the tag may include an identifier of a pattern (e.g., pattern 700, 800, or 900).

[0075] The shelving system 1020 may include one or more racks 1022, 1024. The racks 1022, 1024 may be loaded with the microplates. As discussed above, the objects in the shelving system 1020 may be labelled with tags that can be read by the scanner of the robotic arm 1012.

[0076] The liquid handler 1030 may be an apparatus that dispenses liquids such as solutions including potential drug molecules. In some implementations, the liquid handler 1030 is an automated multi-channel pipettor. The liquid handler 1030 may operate on a microplate placed on a deck 1032. The liquid handler 1030 may acquire pipette tips from a pipette source 1034. The liquid handler 1030 may eject pipette tips once an operation is completed. The liquid handler 1030 may perform an aspirate operation. In an aspirate operation, the liquid handler 1030 may draw an amount of liquid from one or more chambers of a microplate on the deck 1032 into a respective pipette tip. The liquid handler 1030 may perform a dispense operation. In a dispense operation, the liquid handler 1030 may release an amount of liquid from one or more pipette tips into one or more corresponding chambers of the microplate on the deck 1032. In an aspect, the liquid handler may perform a sampling operation which may include one or more cycles of an aspirate operation and a dispenseoperation. The amount of liquid for each aspirate operation and each dispense operation may be configurable and may be controlled by the control system 1050.

[0077] The filter press 1060 may be an apparatus that applies pressure to samples in a microplate. In some implementations, where a filtered microplate such as the microplate 600 including the chambers 410 is used, the filter press 1060 may apply pressure to the microplate including the solution including the potential drug molecule in each well. The pressure may cause the solution to pass through the sol -gel and exit the chamber into a corresponding chamber in a lower microplate as eluent. Alternatively, the filter press 1060 may be a vacuum filtration nest that sucks the solution through the chambers 410. In an aspect, faster filtration may prevent drug molecules from coming off the protein of interest. For example, testing of 17.7ppm Propranolol, which is known to bind to bovine serum albumin (BSA), using slow filtration methods such as a filtering column, pipette, or syringe that take 30 minutes or more showed that approximately 80% of the drug molecule remained bound to the protein. In contrast, testing using a vacuum filtration nest resulted in more than 98% of remaining bound to the protein.

[0078] The analyzer 1040 may be an apparatus that detects an amount of one or more molecules in a sample. For example, the analyzer 1040 may be a liquid chromatography mass spectrometry (LCMS) analyzer or a gas chromatography mass spectrometry (CGMS) analyzer. In an implementation, the analyzer 1040 may include an autosampler configured to obtain a sample from each well of a microplate. In some implementations, the analyzer 1040 may be a UV -Vis spectrometer or plate reader. The analyzer 1040 may be configured to analyze each sample to produce a result. The results may be stored in a file based on the location within the microplate. The analyzer 1040 may provide the results to the control system 1050.

[0079] The control system 1050 may be configured to track the contents of microplates used in the system. The control system 1050 may receive an identifier of an object that is retrieved from the shelving system 1020. The control system 1050 may include a database that maps the identifier to a record of the object. For example, for a microplate 600, the record may indicate the pattern 800 including an indication of a protein embedded within each chamber. For a microplate including potential drug molecules, the record may indicate the pattern 900 indicating the potential drug molecule in each well. For each microplate including potential drug molecules, the control system 1050 may combine the record of potential drug molecule in each well with the record of protein containing sol-gel in each wells that is used to screen the potential drug molecules. The combined record may includean indication of the potential drug molecule and an indication of the protein of interest or control status. When the control system 1050 receives the results from the analyzer 1040, the control system 1050 may correlate the results for the microplate with the combined record for the microplate. Accordingly, for each well, the combined record may include the potential drug molecule, the protein of interest or control status, and the final amount of drug molecule. The control system 1050 may determine whether there is an interaction between the potential drug molecule and a protein of interest by comparing the final amount of drug molecule for a well with the control status to a well associated with the same potential drug molecule and the protein of interest. In some implementations where an internal standard is included in the solution, the amount of the internal standard may be used for reference. The control system may output an indication of potential drug molecules when there is an interaction between the potential drug molecule and a protein of interest. The indicated potential drug molecules may be subjected to further testing to determine whether the potential drug molecule may treat a disease associated with the protein of interest.

[0080] FIG. 11 is a flow diagram showing an example method 1100 of screening potential drug molecules, in accordance with aspects of the present disclosure. The method 1100 may be performed by automated screening system 1000 under the control of the control system 1050 of FIG. 10, for example.

[0081] In block 1110, the method 1100 may include transferring a first microplate to a first position with a robotic handler configured to move the first microplate. The first microplate includes a plurality of individual chambers, each chamber comprising a body and a bottom surface forming a well. For example, the robotic handler 1010 may transfer the first microplate from the rack 1022. In some implementations, the solutions comprising the initial amount of the potential drug molecules may be arranged in the first microplate according to the pattern 900. In some implementations, block 1110 may include scanning a tag of the first microplate and providing an identifier of the pattern and / or the drug molecules to the control system 1050.

[0082] In block 1120, the method 1100 may include transferring a second microplate to a second position with the robotic handler. For example, the robotic handler 1010 may transfer a second microplate to a second position with the robotic handler. The second microplate includes a second plurality of individual chambers, each chamber including a body and a bottom surface including a port. Each chamber includes a sol-gel. The sol-gel in a first portion of the second plurality of individual chambers is embedded with a protein of interestand the sol-gel in a second portion of the second plurality of individual chambers is not embedded with the protein of interest.

[0083] In block 1130, the method 1100 may include aspirating the solution comprising the potential drug molecule from the first microplate into a plurality of pipette tips. For example, the liquid handler 1030 may retrieve the at least two pipette tips from the pipette source 1034. The liquid handler 1030 may aspirate the solution comprising the potential drug molecule from the first microplate into the plurality of pipette tips.

[0084] In block 1 140, the method 1 100 may include dispensing the solution into the second microplate such that the solution comprising the potential drug molecules is placed into contact with the sol -gel in the respective chamber. For example, the liquid handler 1030 may dispense the solution into the second microplate such that the solution comprising the potential drug molecules is placed into contact with the sol-gel in the respective chamber. In some implementations, the block 1140 may including mixing the solution with the solgel. For example, mixing may include shaking the second microplate.

[0085] In block 1150. the method 1100 may include passing the solution through the sol -gel thereby forming an analyte solution that exits the port into a third microplate. In some implementations, the filter press 1060 or a vacuum nest may push or pull the solution through the sol-gel. For example, the robotic handler 1010 may move the first microplate from the deck 1032 to the filter press 1060, which may then pass the solution through the sol-gel.

[0086] In block 1160, the method 1100 may including measuring and calculating using an analyzer a final amount of drug molecule in each respective analyte solution received into each well of the third microplate. For example, the analyzer 1040 may measure and calculate a final amount of drug molecule in each respective analyte solution received into each well of the third microplate. In some implementations, the robotic handler 1010 may move the first microplate from the filter press 1060 to the analyzer 1040. For instance, the analyzer 1040 may be a UV-Vis spectrometer or plate reader that generates a spectrum analysis of the analyte solution. The final amount of drug molecule in each respective analyte solution may be calculated based on the UV-Vis absorbance of the analyte solution.

[0087] In block 1170, the method 1100 may include comparing the final amount of the potential drug molecule for the first well to the final amount of potential drug molecule for the second well. For example, the control system 1050 may compare the final amount of the potential drug molecule for the first well to the final amount of potential drug molecule for the second well. A difference between the initial amount of the potential drug molecule and the finalamount of drug molecule in the analyte solution indicates a drug molecule that interacts with the protein of interest. And no difference between the initial amount of the potential drug molecule and the final amount of drug molecule in the analyte solution indicates a drug molecule that does not interact with the protein of interest. The control system 1050 may identify a result from the analyzer for the first well and the second well. The control system 1050 may compare the final amount of the potential drug molecule. In some implementations, determining no difference between the final amounts may include determining that a difference in the final amounts is within a margin of error for the analyzer.

[0088] FIG. 12 is a flow diagram showing an example method 1200 of a competition study for screening potential drug molecules, in accordance with aspects of the present disclosure. The method 1200 may be performed by automated screening system 1000 under the control of the control system 1050 of FIG. 10, for example. The method 1200 may be performed in conjunction with the method 1100 of FIG. 11. In an aspect, the method 1200 may be performed when each well of the first microplate comprises the first solution of the initial amount of the potential drug molecule and a second initial amount of a second potential drug molecule.

[0089] In block 1210, the method 1200 may include measuring and calculating using the analyzer a final amount of the second potential drug molecule in each respective analyte solution received into each well of the third microplate. In block 1220, the method 1200 may include correlating final amount of the second potential drug molecule in each well of the third microplate with the protein of interest in a corresponding well of the second microplate to determine whether the second potential drug molecule interacted with the protein of interest and / or the first potential drug molecule.

[0090] FIG. 13 is a flow diagram showing an example method 1300 of a competition study for screening potential drug molecules, in accordance with aspects of the present disclosure. The method 1300 may be performed by automated screening system 1000 under the control of the control system 1050 of FIG. 10. for example. The method 1300 may be performed in conjunction with the method 1100 of FIG. 11 to detect whether a first potential drug molecule affects binding properties of a second potential drug molecule.

[0091] In block 1310, the method 1300 may include aspirating a second solution comprising a second potential drug molecule from the first microplate or a fourth microplate into a plurality of pipette tips. In block 1320, the method 1300 may include dispensing the second solution into the second microplate such that the second solution comprising the secondpotential drug molecules is placed into contact with the sol-gel and the first solution in the respective chamber. In block 1330, the method 1300 may include passing the first solution and the second solution through the sol-gel thereby forming the analyte solution that exits the port into the third microplate.

[0092] FIG. 14 is a flow diagram showing an example method 1400 of a competition study for screening potential drug molecules, in accordance with aspects of the present disclosure. The method 1400 may be performed by automated screening system 1000 under the control of the control system 1050 of FIG. 10, for example. The method 1400 may be performed in conjunction with the method 1100 of FIG. 11 to assess a strength of binding.

[0093] In block 1410, the method 1400 may include dispensing a solvent into the second microplate. In block 1420, the method 1400 may include passing the solvent through the sol-gel thereby forming a second analyte solution that exits the port into a fourth microplate. In block 1430, the method 1400 may include measuring and calculating using the analyzer a final amount of the first potential drug molecule in each respective second analyte solution received into each well of the fourth microplate.

[0094] FIG. 15 is a diagram of example results of an experimental procedure. The experimental procedure involved each chamber including sol-gel containing 18 pmols of BSA on the label. A 18 pmols solution of the drug candidate was prepared. The solution was mixed with the BSA for 30 minutes. The eluent was filtered off with a vacuum nest. A spectrum / chromatogram of the initial solution and the eluent was compared.

[0095] As illustrated in the results, tight binding ligands (e.g.. Propranolol) show very little material in the eluent. Medium binding ligands (e.g., Caffeine) show a significant reduction in the peaks. Weak binding ligands (e.g.. Fluconazole) give similar results, before and after treatment with the BSA.

[0096] Aspects of the present disclosure may be implemented using hardware, software, or a combination thereof and may be implemented in one or more computer systems or other processing systems. In one aspect, the disclosure is directed toward one or more computer systems capable of carrying out the functionality described herein. FIG. 16 presents an example system diagram of various hardware components and other features that may be used in accordance with aspects of the present disclosure. Aspects of the present disclosure may be implemented using hardware, software, or a combination thereof and may be implemented in one or more computer systems or other processing systems. In one example variation, aspects of the disclosure are directed toward one or more computersystems capable of carrying out the functionality described herein. An example of such a computer system 1600 is shown in FIG. 16.

[0097] Computer system 1600 includes one or more processors, such as processor 1604. The processor 1604 is connected to a communication infrastructure 1606 (e.g., a communications bus, cross-over bar, or network). Various software aspects are described in terms of this example computer system. After reading this description, it will become apparent to a person skilled in the relevant art(s) how to implement aspects of the disclosure using other computer systems and / or architectures.

[0098] Computer system 1600 may include a display interface 1602 that forwards graphics, text, and other data from the communication infrastructure 1606 (or from a frame buffer not shown) for display on a display unit 1630. Computer system 1600 also includes a main memory 1608, preferably random access memory (RAM), and may also include a secondary memoiy 1610. The secondary memory 1610 may include, for example, a hard disk drive 1612 and / or a removable storage drive 1614, representing a floppy disk drive, a magnetic tape drive, an optical disk drive, etc. The removable storage drive 1614 reads from and / or writes to a removable storage unit 1618 in a well-known manner. Removable storage unit 1618, represents a floppy disk, magnetic tape, optical disk, etc., which is read by and written to removable storage drive 1614. As will be appreciated, the removable storage unit 1618 includes a computer usable storage medium having stored therein computer software and / or data.

[0099] In alternative aspects, secondary memory 1610 may include other similar devices for allowing computer programs or other instructions to be loaded into computer system 1600. Such devices may include, for example, a removable storage unit 1622 and an interface 1620. Examples of such may include a program cartridge and cartridge interface (such as that found in video game devices), a removable memory chip (such as an erasable programmable read only memory (EPROM), or programmable read only memory (PROM)) and associated socket, and other removable storage units 1622 and interfaces 1620. which allow software and data to be transferred from the removable storage unit 1622 to computer system 1600.

[0100] Computer system 1600 may also include a communications interface 1624. Communications interface 1624 allows software and data to be transferred between computer system 1600 and external devices. Examples of communications interface 1624 may include a modem, a network interface (such as an Ethernet card), a communications port, a Personal Computer Memory Card International Association (PCMCIA) slot andcard, etc. Software and data transferred via communications interface 1624 are in the form of signals 1628, which may be electronic, electromagnetic, optical or other signals capable of being received by communications interface 1624. These signals 1628 are provided to communications interface 1624 via a communications path (e.g., channel) 1626. This path 1626 carries signals 1628 and may be implemented using wire or cable, fiber optics, a telephone line, a cellular link, a radio frequency (RF) link and / or other communications channels. In this document, the terms "computer program medium’7and "computer usable medium” are used to refer generally to media such as a removable storage drive 1614, a hard disk installed in hard disk drive 1612, and signals 1628. These computer program products provide software to the computer system 1600. Aspects of the disclosure are directed to such computer program products.

[0101] Computer programs (also referred to as computer control logic) are stored in main memory 1608 and / or secondary memory 1610. Computer programs may also be received via communications interface 1624. Such computer programs, when executed, enable the computer system 1600 to perform various features in accordance with aspects of the present disclosure, as discussed herein. In particular, the computer programs, when executed, enable the processor 1604 to perform such features. Accordingly, such computer programs represent controllers of the computer system 1600.

[0102] In variations where aspects of the disclosure are implemented using software, the software may be stored in a computer program product and loaded into computer system 1600 using removable storage drive 1614, hard disk drive 1612, or communications interface 1620. The control logic (software), when executed by the processor 1604, causes the processor 1604 to perform the functions in accordance with aspects of the disclosure as described herein. In another variation, aspects are implemented primarily in hardware using, for example, hardware components, such as application specific integrated circuits (ASICs). Implementation of the hardware state machine so as to perform the functions described herein will be apparent to persons skilled in the relevant art(s).

[0103] In yet another example variation, aspects of the disclosure are implemented using a combination of both hardware and software.

[0104] FIG. 17 is a block diagram of various example system components (e.g., on a network) that may be used in accordance with aspects of the present disclosure. The system 1700 may include one or more accessors 1760, 1762 (also referred to interchangeably herein as one or more "‘users”) and one or more terminals 1742, 1766. In one aspect, data for use in accordance with aspects of the present disclosure may, for example, be input and / oraccessed by accessors 1760, 1762 via terminals 1742, 1766, such as personal computers (PCs), minicomputers, mainframe computers, microcomputers, telephonic devices, or wireless devices, such as personal digital assistants (‘'PDAs”) or a hand-held wireless devices coupled to a server 1743, such as a PC, minicomputer, mainframe computer, microcomputer, or other device having a processor and a repository' for data and / or connection to a repository for data, via, for example, a network 1744, such as the Internet or an intranet, and couplings 1745, 1746, 1764. The couplings 1745. 1746, 1764 include, for example, wired, wireless, or fiber optic links. In another example variation, the method and system in accordance with aspects of the present disclosure operate in a stand-alone environment, such as on a single terminal.

[0105] The aspects of the disclosure discussed herein may also be described and implemented in the context of computer-readable storage medium storing computer-executable instructions. Computer-readable storage media includes computer storage media and communication media. For example, flash memory drives, digital versatile discs (DVDs), compact discs (CDs), floppy disks, and tape cassettes. Computer-readable storage media may include volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, modules or other data.

[0106] This written description uses examples to disclose aspects of the present disclosure, including the preferred embodiments, and also to enable any’ person skilled in the art to practice the aspects thereof, including making and using any devices or systems and performing any incorporated methods. The patentable scope of these aspects is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims. Aspects from the various embodiments described, as well as other known equivalents for each such aspect, can be mixed and matched by one of ordinary skill in the art to construct additional embodiments and techniques in accordance with principles of this application.

Claims

CLAIMS1. A drug screening system comprising: a first robotic handler configured to move a first plate into at least a first position and to move a second plate into at least a second position. wherein the first plate includes a first plurality of individual wells, each well comprising an initial amount of a solution comprising different potential drug molecules, wherein the second plate includes a second plurality of individual chambers, wherein a first portion of the second plurality of individual chambers are coated or filled with a sol -gel into which a protein of interest is embedded and a second portion of the plurality7of individual chambers are coated or filled with a sol-gel having no protein of interest; a robotic liquid handler configured to perform a process of aspirating the solution from each of the first plurality of individual wells and dispensing the solution into a respective individual well of the second plurality of individual chambers such that the potential drug molecule passes through the sol-gel within the respective second individual chambers, and as respective eluent, into a respective well of a third microplate that includes a third plurality of individual wells, an analyzer configured to measure, for each well of the third plate, a final amount of drug molecule in each respective eluent received into the well, wherein a difference between the initial amount of the potential drug molecule and the final amount of drug molecule in the eluent indicates a drug molecule that interacted with the protein, and wherein no difference between the initial amount of the potential drug molecule and the final amount of drug molecule in the eluent indicates a drug molecule that does not interact with the protein; and a control system for the robotic handler, the robotic liquid handler, and the analyzer configured to correlate the potential drug molecules and protein in each well, and whether the potential drug molecule interacted with the protein.

2. The drug screening system of claim 1. wherein the solution comprising different potential drug molecules includes an internal standard, wherein the analyzer is configuredto compare the difference between the initial amount of the potential drug molecule and the final amount of drug molecule in the eluent to a difference in an amount of the internal standard.

3. The system according to claim 1, wherein the sol-gel is a sol-gel synthesized from silicon alkoxide.

4. The system according to claim 3, wherein the silicon alkoxide is tetraalkoxysilane or a mono-, di-, or tri-alkyl alkoxysilane, or a sodium silicate.

5. The system according to claim 1, wherein the sol-gel further comprises a protein stabilizer selected from Ca2+, an organosilane, a polyethylene glycol (PEG), a graft copolymer, a charged polymer, a sugar, or an amino acid.

6. The system according to claim 1, wherein the protein of interest is a human protein, canine protein, feline protein, primate protein, equine protein, porcine protein, rodent protein, bacterial protein, or viral protein.

7. The system according to claim 1, wherein the protein of interest is an extracellular protein or an intracellular protein.

8. The system according to claim 1, wherein the protein of interest is human serum albumin.

9. The system according to claim 8, wherein the sol-gel is also embedded with alphaacid glycoprotein.

10. The system according to claim 1 , wherein the protein of interest is alpha-acid glycoprotein.

11. The system of claim 1, wherein a concentration of the protein of interest is at least 30,000 parts per million.

12. The system of claim 1, wherein each well of the first microplate comprises the first solution of the initial amount of the potential drug molecule and a second initial amount of a second potential drug molecule, wherein the analyzer is configured to: measure and calculate a final amount of the second potential drug molecule in each respective analyte solution received into each well of the third microplate; andcorrelate the final amount of the second potential drug molecule in each well of the third microplate with the protein of interest in a corresponding well of the second microplate to determine whether the second potential drug molecule interacted with the protein of interest and / or the first potential drug molecule.

13. The system of claim 1, wherein the robotic liquid handler is configured to: aspirate a second solution comprising a second potential drug molecule from the first microplate or a fourth microplate into a plurality of pipette tips; and dispense the second solution into the second microplate such that the second solution comprising the second potential drug molecules is placed into contact with the sol-gel and the first solution in the respective chamber such that the first solution and the second solution pass through the sol-gel thereby forming the respective eluent that exits a port into the third microplate.

14. The system of claim 1, wherein the robotic liquid handler is configured to dispense a solvent into the second microplate such that the solvent passes through the solgel thereby forming a second analyte solution that exits a port into a fourth microplate, and wherein the analyzer is configured to measure and calculate a final amount of the first potential drug molecule in each respective second analyte solution received into each well of the fourth microplate.

15. A method for high throughput drug screening, comprising: transferring a first microplate to a first position with a robotic handler configured to move the first microplate, wherein the first microplate includes a plurality of individual chambers, each chamber comprising a body and a bottom surface forming a well, each well capable of holding an amount of a first solution comprising a first potential drug molecule, wherein each chamber is adapted to receive a pipette tip, and wherein each w ell comprises the first solution of an initial amount of the first potential drug molecule; transferring a second microplate to a second position with the robotic handler,wherein the second microplate includes a second plurality of individual chambers, each chamber comprising a body and a bottom surface including a port, each chamber comprising a sol-gel, wherein the sol-gel in a first portion of the second plurality of individual chambers is embedded with a protein of interest and the sol-gel in a second portion of the second plurality of individual chambers is not embedded with the protein of interest; aspirating the first solution comprising the first potential drug molecule from the first microplate into a plurality of pipette tips; dispensing the first solution into the second microplate such that the solution comprising the first potential drug molecule is placed into contact with the sol-gel in the respective chamber; passing the first solution through the sol-gel thereby forming an analyte solution that exits the port into a third microplate; measuring and calculating using an analyzer a final amount of first potential drug molecule in each respective analyte solution received into each well of the third microplate; and correlating final amount of first potential drug molecule in each well of the third microplate with the protein of interest in a corresponding well of the second microplate to determine whether the first potential drug molecule interacted with the protein of interest, wherein a difference between the initial amount of the first potential drug molecule and the final amount of the first potential drug molecule in the analyte solution indicates a drug molecule that interacts with the protein of interest, and wherein no difference between the initial amount of the first potential drug molecule and the final amount of the first potential drug molecule in the analyte solution indicates a drug molecule that does not interact with the protein of interest.

16. The method of claim 15, wherein each well of the first microplate comprises the first solution of the initial amount of the potential drug molecule and a second initial amount of a second potential drug molecule, the method further comprising:measuring and calculating using the analyzer a final amount of the second potential drug molecule in each respective analyte solution received into each well of the third microplate; and correlating final amount of the second potential drug molecule in each well of the third microplate with the protein of interest in a corresponding well of the second microplate to determine whether the second potential drug molecule interacted with the protein of interest and / or the first potential drug molecule.

17. The method of claim 15, further comprising: aspirating a second solution comprising a second potential drug molecule from the first microplate or a fourth microplate into a plurality of pipette tips; dispensing the second solution into the second microplate such that the second solution comprising the second potential drug molecules is placed into contact with the sol-gel and the first solution in the respective chamber; and passing the first solution and the second solution through the sol-gel thereby forming the analyte solution that exits the port into the third microplate.

18. The method of claim 15, further comprising: dispensing a solvent into the second microplate; passing the solvent through the sol-gel thereby forming a second analyte solution that exits the port into a fourth microplate; and measuring and calculating using the analyzer a final amount of the first potential drug molecule in each respective second analyte solution received into each well of the fourth microplate.

19. A microplate for drug screening, comprising: a plurality of individual chambers, wherein a first portion of the individual chambers includes a sol-gel embedded with a protein of interest and a second portion of the individual chambers includes a sol-gel without the protein of interest; and a computer-readable tag indicating a location of the first portion of the individual chambers including the sol-gel with the protein of interest.

20. The microplate of claim 19, wherein each chamber comprises a body and a bottom surface including a port. 1

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