Digital Fluid Teleportation, Advanced Biological Virtualization, And Large Scale Integration Of Organ-On-Chips And Microphysiological Models

Abstract

A microphysiological platform described herein includes a fluidic synthesizer with a first fluid input selectively coupleable to a source of a first input fluid solution and a second fluid input selectively coupleable to a source of a second input fluid solution. The fluidic synthesizer further includes a fluid output. The microphysiological platform further includes a fluid addressing system with a fluid input fluidically coupled to the fluidic synthesizer fluid output. The fluid addressing system further includes a first fluid output and a second fluid output. The microphysiological platform further includes a first microphysiological device with a fluid input fluidically coupled to the first fluid output of the fluid addressing system and a second microphysiological device with a fluid input fluidically coupled to the second fluid output of the fluid addressing system.

1 - 53 . (canceled) 
     
     
         54 . A method for predicting a biological behavior of a target tissue, comprising:
 applying one or more first inputs to a statistical predictive model to predict the biological behavior of the target tissue,   wherein the statistical predictive model is created based on one or more second inputs provided to a cultured tissue within at least one microphysiological device and observational data of the cultured tissue acquired by one or more sensors, and   wherein the cultured tissue is the same tissue type as the target tissue.   
     
     
         55 . The method of  claim 54 , wherein the observational data include one or more of phenotypic data, morphological data, metabolic data, genotypic data, and proteomic data. 
     
     
         56 . The method of  claim 54 , wherein the observational data include a composition of a fluid output from the cultured tissue and a biological composition of the cultured tissue after exposure to a fluid input. 
     
     
         57 . The method of  claim 54 , wherein the cultured tissue is incubated within the at least one microphysiological device in a predetermined condition based on the one or more second inputs. 
     
     
         58 . The method of  claim 54 , wherein the one or more second inputs and the observational data are provided to train the virtual tissue model. 
     
     
         59 . The method of  claim 54 , wherein the observational data is used to assess biological efficacy or safety of at least one compound or condition on humans or animals. 
     
     
         60 . The method of  claim 54 , wherein the observational data is used for drug development or screening. 
     
     
         61 . The method of  claim 54 , wherein the statistical predictive model comprises a virtual tissue model. 
     
     
         62 . The method of  claim 54 , wherein the statistical predictive model comprises one or more of a neural network, a decision tree, and statistical inference. 
     
     
         63 . The method of  claim 54 , wherein applying the one or more first inputs to the statistical predictive model to predict the biological behavior of the target tissue further comprises
 applying a mathematical transformation to numerical values produced by the statistical predictive model.   
     
     
         64 . The method of  claim 54 , wherein the one or more sensors comprise at least one of an imager and a biosensor. 
     
     
         65 . The method of  claim 64 , wherein the biosensor comprises an analyte sensor. 
     
     
         66 . The method of  claim 64 , wherein the imager is configured to collect image information from the at least one microphysiological device. 
     
     
         67 . The method of  claim 64 , wherein the imager is configured to perform at least one of bright field imaging, optical microscopy, fluorescence microscopy, magnetic resonance imaging, and computed tomography (CT) scanning. 
     
     
         68 . The method of  claim 64 , wherein the biosensor comprises a chemical reaction or bioreaction recognition element configured to interact with the target analyte to produce a measurement of quantity or concentration of the target analyte, a recording system configured to record the measurement and an activity of the microphysiological device. 
     
     
         69 . The method of  claim 54 , wherein the target tissue includes one or more of a lung tissue, a bone marrow tissue, a bone tissue, a pancreatic tissue, an endocrine islet tissue, a liver tissue, a kidney tissue, a placenta tissue, an eye tissue, an intestinal tissue, a bladder tissue, a brain tissue, a mouth tissue, a tongue tissue, a tooth tissue, a nose tissue, a thymus tissue, a lymph node tissue, a lymphatic system tissue, a throat tissue, a specific human tissue, a specific human tissue undergoing a specific routine behavior, a lung tissue that is cyclically breathing, a specific human tissue undergoing an atypical condition, a lung tissue undergoing an asthma attack, a specific human tissue undergoing a specific interaction with an outside agent, a lung tissue being infected with bacteria, a lung tissue exposed to environmental factors, a lung tissue exposed to pollution, a lung tissue exposed to corrosive gas, a specific human tissue undergoing a specific interaction with an outside agent that is intended for use as a therapeutic, a specific human tissue undergoing a specific interaction with a drug, a specific human tissue undergoing a specific interaction with a biological antibody, a specific human tissue undergoing a specific interaction with a cellular therapy, or a lung tissue undergoing an asthma attack while being monitored for its interaction with a bronchodilator as therapy for asthma. 
     
     
         70 . The method of  claim 54 , wherein the one or more second inputs comprise one or more of a composition of a fluid input to the cultured tissue, a biological composition of the cultured tissue before exposure to the fluid input, and predetermined incubation conditions. 
     
     
         71 . The method of  claim 70 , wherein the composition of the fluid input to the cultured tissue comprises one or more of a predetermined culture medium, a chemical stimulus, and a biological stimulus. 
     
     
         72 . The method of  claim 70 , wherein the predetermined incubation conditions comprise one or more of temperature, a duration of incubation, and a gas composition. 
     
     
         73 . The method of  claim 70 , wherein the one or more second inputs are defined by a continuous function. 
     
     
         74 . The method of  claim 54 , further comprising:
 coupling the statistical predictive model to the cultured tissue within the at least one microphysiological device;   applying one or more third inputs to the statistical predictive model to predict the biological behavior of the cultured tissue; and   delivering, based on the predicted biological behavior of the cultured tissue, a synthesized fluidic solution as the fluid input to the cultured tissue within the at least one microphysiological device,   wherein the one or more third inputs are based on the cultured tissue within the at least one microphysiological device.   
     
     
         75 . The method of  claim 74 , further comprising:
 delivering the synthesized fluidic solution to the cultured tissue within the at least one microphysiological device through a fluid addressing system.   
     
     
         76 . The method of  claim 54 , wherein the biological behavior of the target tissue comprises phenotypic behavior, genotypic behavior, and proteomic behavior. 
     
     
         77 . The method of  claim 54 , wherein the statistical predictive model of the target tissue is based on off-chip observational data including one or more of measurements of biochemical secretion, metabolism, biochemical processes, electrophysiological measurements, and genomic, transcriptomic, and/or proteomic quantification of cells or a subset of cells in the cultured tissue. 
     
     
         78 . A system, comprising:
 a control system comprising a controller configured to:   apply one or more first inputs to a statistical predictive model to predict the biological behavior of the target tissue,   wherein the statistical predictive model is created based on one or more second inputs provided to a cultured tissue within at least one microphysiological device and observational data of the cultured tissue acquired by one or more sensors, and   wherein the cultured tissue is the same tissue type as the target tissue.   
     
     
         79 . The system of  claim 78 , wherein the at least one microphysiological device comprises materials configured for optical imaging. 
     
     
         80 . The system of  claim 78 , wherein the cultured tissue within the at least one microphysiological device is an organ-on-a-chip model. 
     
     
         81 . A method for predicting a biological behavior of a target tissue using a statistical predictive model, comprising:
 acquiring the statistical predictive model from a browsable statistical predictive model library; and   applying one or more first inputs to the statistical predictive model to predict the biological behavior of the target tissue,   wherein the statistical predictive model is based on one or more second inputs and observational data acquired by one or more sensors of a cultured tissue within at least one microphysiological device, and   wherein the cultured tissue is the same tissue type as the target tissue.   
     
     
         82 . A method of creating a statistical predictive model, comprising:
 providing one or more first inputs to a cultured tissue within at least one microphysiological device;   acquiring observational data from the cultured tissue; and   creating the statistical predictive model by correlating the first inputs and the observational data.