ABOUT US
TEAM
LEADERSHIP
Champion of Market Innovation
ADVISORY BOARD
SCIENTISTS & ASSOCIATES
Dr. Kumudu Madduma-Liyanage,
Lab Director
Dr. Mary Kathryn Sewell-Loftin,
Biomedical Scientist
Dr. Chelsea L. Crawford, Deputy Director of Research
Dr. Parmanand Ahirwar, Medicinal Chemist
Zeelu H. Patel,
Scientist
Dr. Seth E. Bollenbecker,
Scientist
Daniela D. De Nobrega,
Scientist
Urvi P. Rawal,
Scientist
Amr Mahmoud,
Scientist
Dr. M. Grace Albright,
Data Analytics
Logan C. Eiler,
Biomedical Engineer
Sonika Nallapu,
Scientist
Dr. Rachael E. Guenter,
Cancer Biologist
Shariq Khimani,
Scientist
Margaret L. Garner,
Administrative Coordinator
PARTNERS
SCIENCE
A hitchhiker’s guide to cancer models
Budhwani, KI; Patel, HK; Guenter, RE; Charania, AA.
Date: 05/2022
Journal: Trends in Biotechnology
Cancer deals a devastating one-two punch – every year – by claiming 8 million lives worldwide while cratering $2.5 trillion in economic impact. Over 40% of patients wipe out their entire life savings within two years of diagnosis. This is unsustainable.
Next generation cancer supermodels built on CerFlux ChipMux™ - including POET®, PEER®, POETRY, and PROPHET - can deliver a one-two counterpunch by enhancing our understanding of mechanisms of cancer and by deploying this knowledge to combat cancer at every stage: from protective measures to early diagnosis, optimal personalized therapy, and precision post treatment surveillance.
Each category – in vitro, in vivo, ex vivo, in silico – undergirding cancer models is in a state of renaissance resulting in a faster pace of new knowledge across the bench to bedside continuum.
Democratizing cancer innovation by reducing cost and complexity of cancer models
Punjani, Z; Bollenbecker, SE; Patel, ZH; Charania, AA; Patel, HK; Papachristou, G; Contreras, CM; Tsung, A; Budhwani, KI.
Date: 05/2022
Despite advances in high-throughput screening, combinatorial chemistry, databanks, and computational models, drug R&D remains expensive and slow, often over a decade. It is estimated that pharma companies spend nearly $90 billion annually on preclinical research and trials. Yet, 90% of drugs effective in pre-human studies fail in human trials. A reason for this dissonance is that most currently used methods for evaluating efficacy of treatments often fail to recapitulate in vivo microenvironments effectively, leading to failed trials and failed treatments resulting in considerable time and cost burden.
Our development of a patented “Lab-on-a-Brane” (LOB) successfully recapitulated in vivo tissue microenvironments, including barrier and transport functions, that laid the groundwork for modeling organ-capillary interfaces. We then expanded this to support an air-liquid interface to model in vivo sites such as lung microvasculature. Next, we extended this to a tumor-train to recapitulate migration and invasion of tumorous tissue. Finally, we transformed our platform into a scalable and clinically relevant ex vivo Simple Microchamber Array Technology (SMART), capable of concurrent assessment of multiple regimens directly on patient tissue.
Evaluating efficacy on tumor biopsy tissue ex vivo before treatment for equitable cancer care
Patel, HK; Bollenbecker, SE; Punjani, Z; Charania, AA; Patel, ZH; Papachristou, G; Contreras, CM; Tsung, A; Budhwani, KI.
Date: 05/2022
Nearly half the world will be diagnosed with cancer. Each year, over 1.7 million new cancers are diagnosed in the US. Worse, systemic therapy turns out to be ineffective in 70% of patients because those drugs do not match the patient’s tumor, imposing a substantial physical, emotional, and financial burden. Each tumor’s distinct composition and heterogeneity can result in diverse responses to the same treatment. A personalized medicine approach, based on efficacy observed on tissue directly from the patient’s own tumor, is fundamentally better than the current approach. There is a critical and urgent need for such ex vivo personalized cancer models that match patients with the right treatment – before treatment. Here we present findings from our low-cost ex vivo personalized solid tumor biopsy-on-a-chip to rapidly evaluate effectiveness of various therapeutics on intact core biopsy tissue obtained from a patient’s tumor. Core biopsies were generated from xenograft and human tumor tissue using 18-gauge and 20-gauge spring-loaded biopsy systems. Differential activity from anticancer agents compared to mock drugs was observed and quantitatively measured using custom image processing algorithms.
Preanalytical protocols for improving access to live tissue diagnostics in remote and low resource settings
Charania, AA; Bollenbecker, SE; Patel, HK; Punjani, Z; Patel, ZH; Papachristou, G; Contreras, CM; Tsung, A; Budhwani, KI.
Date: 05/2022
Nearly 70% of diagnostics lab test errors occur due to variability in preanalytical factors. Preanalytical factors comprise parameters from the time tissue is extracted from the patient to the time it is tested in the lab. For lack of standardized preanalytical protocols, integrity of collected specimens is often compromised. Establishing preanalytical protocols could serve as an important resource for remote collection sites and substantially reduce variability in the integrity of specimens thereby improving lab test rigor and reproducibility and promote innovation in live tissue diagnostic tests for personalized medicine. Here we present finding from our study analyzing impact of cold chain logistics on integrity of collected solid tumor tissue specimens. Specifically, duration in transit, container and wet ice packing, and composition of transport media were assessed.
Establishing preanalytical protocols would improve rigor and reproducibility in diagnostic lab tests by improving tissue viability and integrity. These would also enable next generation cancer models improve predictive capacity in translational research and subsequently in personalized medicine applications at the bedside.
-to-reduce-cost-and-acc.jpg)
Evaluating anticancer agents on 3D bioprinted organoid tumors (BOT) to reduce cost and accelerate therapeutic discovery
Patel, ZH; Bollenbecker, SE; Charania, AA; Punjani, Z; Patel, HK; Sewell-Loftin, MK; Saleh, MN; Budhwani, KI.
Date: 05/2022
Despite recent advances in therapeutics, cancer remains the second leading cause of death worldwide. Next generation cancer models hold the promise of breaking this stranglehold. However, extracting adequate tissue for precision and personalized medicine ex vivo models can be difficult depending on tumor type and tissue site. Mechanisms to expand tissue include patient derived xenografts and patient derived organoids. The former imposes a large time window to establish while the latter is constrained in space by sizescales. Here we present a novel mechanism to address space and time constrains with 3D bioprinted organoid tumors (BOT) that mimic core needle biopsy tissue to reduce both cost and time to market for novel therapeutics making effective cancer therapy more accessible and equitable. Here we present findings from our study to produce and use BOT core biopsy tissue in ex vivo precision and personalized medicine applications. Tissue 3D microarchitecture was validated using high-content fluorescence imaging and custom image processing applications. Diffusion of mock agents, small molecule, and nucleic acid stains was measured 200 μm deep in tissue. Differential activity in spatially distinct regions of intact BOT cores was quantified using advanced image processing modules.
Next generation cancer supermodel PROPHET and methods of using the same
Karim I. Budhwani
Date: 03/2022
Organization: US Patent and Trademark Office
Simple Microchamber Array Technology (SMART) and method of use. The present disclosure generally pertains to a biomimetic array device and methods of using the device to expose biological samples to an array of fluids. The presently disclosed apparatus may be used to test therapeutics; to study disease; to monitor disease; to predict compound efficacy; to collect generalizable data; and model external environmental conditions. The multiplexing capability of the platform allows for simultaneous evaluation of multiple compounds on a single intact tissue sample.
%20to%20Improve%20Breast%20Cancer%20(BC)%20Treatm.jpg)
Predictive Personalized Oncology Efficacy Test (POET®) to Improve Breast Cancer (BC) Treatment Outcomes
Karim I. Budhwani
Date: 12/2021
Organization: Breast Cancer Research Foundation of Alabama
Simple Microchamber Array Technology (SMART) and method of use. The present disclosure generally pertains to a biomimetic array device and methods of using the device to expose biological samples to an array of fluids. The presently disclosed apparatus may be used to test therapeutics; to study disease; to monitor disease; to predict compound efficacy; to collect generalizable data; and model external environmental conditions. The multiplexing capability of the platform allows for simultaneous evaluation of multiple compounds on a single intact tissue sample.
Biomimetic array device and methods of using same (US 11,097,274 B2)
Karim I. Budhwani
Date: 08/2021
Organization: US Patent and Trademark Office
Simple Microchamber Array Technology (SMART) and method of use. The present disclosure generally pertains to a biomimetic array device and methods of using the device to expose biological samples to an array of fluids. The presently disclosed apparatus may be used to test therapeutics; to study disease; to monitor disease; to predict compound efficacy; to collect generalizable data; and model external environmental conditions. The multiplexing capability of the platform allows for simultaneous evaluation of multiple compounds on a single intact tissue sample.
Biomimetic Interface Device and Methods of Using the Same (US 10,969,383 B1)
Karim I. Budhwani
Date: 04/2021
Organization: US Patent and Trademark Office
Continuing from US 10,114,010 B1. The present disclosure generally pertains to a biomimetic apparatus configured to simulate physiological conditions by, in part, providing for both barrier and transport interfaces. The presently disclosed apparatus may be used to test therapeutics for different diseases; to study transport; form a substrate for any organ tissue with a barrier and/or transport function; provide a closed-loop assembly for fluid flow; mimic underlying and enveloped tissue; and model external environmental conditions.
CerFlux POET®
matches treatment to tumors.
Development of Personalized Oncology Efficacy Test (POET®) for Breast Cancer
Karim I. Budhwani
Date: 12/2020
Organization: Breast Cancer Research Foundation of Alabama
Cancer is pervasive; nearly half the world will be diagnosed with cancer. Each year, >1.7 million patients are diagnosed with cancer in the United States alone; of these, about 300,000 cases are breast cancer (BC). Worse, about 70% of those receiving systemic therapy will be treated with drugs that do not work for them because those drugs do not match the patient’s tumor, imposing a substantial physical, emotional, and financial burden. This is because BC is heterogeneous; tumors differ greatly from patient to patient both in makeup and in response even to the same treatment. And yet, for lack of clinically relevant therapeutic efficacy predictive tools, treatment is based on generalized parameters, potentially exposing patients to several rounds of ineffective therapy with potentially life-threatening toxicities. Timely effective treatment can increase overall survival. There is a critical, unmet, and urgent need to match the right treatment to the right patient prior to treatment to reduce unnecessary morbidity, expense, and loss of time from failed therapy. CerFlux is developing innovative ex vivo technology to bridge this gap. Our proposed Personalized Oncology Efficacy Test (POET®) will rapidly match patient tumor tissue with various therapeutics simultaneously – before treatment – to identify the right treatment for each patient on an individualized basis which is fundamentally better than the current nonselective approach.
Development of Personalized Ex Vivo Predictive Technology for Rapidly Matching Patient Tumors with Chemotherapy Regimens Before Treatment.
Karim I. Budhwani
Date: 09/2020
Organization: National Institutes of Health
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers with <9% five-year survival rate and an estimated 60,000 deaths/year by 2030. PDAC is often diagnosed at an advanced stage thereby precluding surgical resection for most patients. While new systemic therapy regimens have improved survival, availability of multiple options, without tools to select an optimal regimen from these (on an individualized basis), has created a frustrating paradox in clinical decision-making. Due to a lack of personalized predictive tools, current standard of care treatment strategy is based on prognostic factors such as age, stage, performance status, serum albumin, etc. There is a critical, urgent and unmet need to develop predictive tools that can identify optimal systemic therapy regimens and eliminate from consideration ineffective options, on an individualized basis, to improve quality of life and reduce overtreatment. CerFlux, Inc. is developing such predictive technology with its low-cost and rapid Personalized Oncology Efficacy Test (POET®) to match each patient with the right treatment – before treatment – to transform pancreatic cancer treatment in the near term and make a difference in the lives of patients and providers around the world. Our personalized medicine approach is unique and further enhanced by a commercial-academic collaboration between CerFlux, Inc. and the James Comprehensive Cancer Center at the Ohio State University. The proposed project will build on recent work by our team including a patented (US 10,114,010B1) biomimetic in vitro platform for pharmacological transport and pancreatic microtissue tumor models. The commercial goal of this proposal is to identify best practices for using POET® in personalized therapy. Our hypothesis is that response to treatment observed in POET® will approximate the response in the corresponding patient. Our objective is to predict both effective and ineffective treatments for each patient prior to initiating treatment. We envision substantial continuing commercial-academic collaboration between CerFlux, Inc. and the James Comprehensive Cancer Center at the Ohio State University including the integration of machine learning to derive a “POET Score” – a personalized quantitative efficacy score – based on a combination of factors. Data from POET® and the POET® Score will help clinical teams rank treatments for individual patients before the first drug infusion. If successful, this SBIR-driven study has the potential to transform pancreatic cancer treatment in the near-term and make a positive impact around the world.
Evaluating Population Density as a Parameter for Optimizing COVID-19 Testing: Statistical Analysis
Karim I. Budhwani, Henna Budhwani, Ben Podbielski
Date: 08/2020 (preprint) 03/2021 (print)
Journal: JMIRx | Med
Background: SARS-CoV-2 transmission risk generally increases with the proximity of those shedding the virus to those susceptible to infection. Thus, this risk is a function of both the number of people and the area they occupy. However, the latter continues to evade the COVID-19 testing policy. Objective: The aim of this study is to analyze per capita COVID-19 testing data reported for Alabama to evaluate whether testing realignment along population density, rather than density agnostic per capita, would be more effective. Methods: Descriptive statistical analyses were performed for population, density, COVID-19 tests administered, and positive cases for all 67 Alabama counties. Results: Tests reported per capita appeared to suggest widespread statewide testing. However, there was little correlation (r=0.28, P=.02) between tests per capita and the number of cases. In terms of population density, new cases were higher in areas with a higher population density, despite relatively lower test rates as a function of density. Conclusions: Increased testing in areas with lower population density has the potential to induce a false sense of security even as cases continue to rise sharply overall.
Measuring Surface and Interfacial Tension In Situ in Microdripping Mode for Electrohydrodynamic Applications
Karim I. Budhwani, Gerald M. Pekmezi, Mohamed M. Selim
Date: 07/2020
Journal: Micromachines
Walking on water is made possible, at least for tiny insects, by molecular interaction at the interfaces of dissimilar materials. Impact of these interactions—surface tension (SFT) and, more broadly, interfacial tension (IFT)—is particularly evident at micro and nano sizescales. Thus, implications of walking on water can be significant for SFT or IFT (S/IFT)-driven nanofabrication technologies, such as electrohydrodynamic atomization (EHDA), in developing next-generation biomimetic microphysiological systems (MPS) and drug delivery systems (DDS). However, current methods for estimating S/IFT, based on sessile drops or new surface formation on a ring or plate, are unsuitable for integration with EHDA assemblies used in electrospinning and electrospraying. Here, we show an in situ method for estimating S/IFT specifically devised for EHDA applications using signal processing algorithms that correlate the frequency and periodicity of liquid dispensed in EHDA microdripping mode with numerical solutions from computational fluid dynamics (CFD). Estimated S/IFT was generally in agreement with published ranges for water–air, 70% ethanol–air, chloroform–air, and chloroform–water. SFT for solutions with surfactants decreased with increasing concentrations of surfactant, but at relatively higher than published values. This was anticipated, considering that established methods measure SFT at boundaries with asymmetrically high concentrations of surfactants which lower SFT.
Bridging the Gap in Training and Clinical Practice in Sub-Saharan Africa
Mansoor Saleh, Gurudatta Naik, Anne Mwirigi, Asim Jamal Shaikh, Saleem Sayani, Munir Ghesani, Sheemain Asaria, Aliyah R. Sohani, Shahin Sayed, Zahir Moloo, Karim I. Budhwani, Zohray Talib
Date: 08/2019
Journal: Current Breast Cancer Reports
As medical knowledge and innovation reach new heights, there is a growing gap in medical advancements between low- and middle-income countries (LMICs) and high-income countries (HICs). The former has a lack of basic health care and preventive or diagnostic services for early cancer while the latter has access to novel diagnostic and therapeutic modalities. The key to overcoming this disparity is finding ways to bridge this divide across distances and continental divides through innovative technology and sharing of knowledge by committed individuals and through public-private partnerships. Many initiatives that include onsite and online training programs for regional healthcare providers have shown that the gap in medical training between HICs and LMICs can be narrowed. The following article shines a light on this disparity and provides exemplary case studies of ways in which this gap between LMICs and HICs can be bridged.
Lab-on-a-Brane: Biomimetic interface device and methods of using the same (US 10,114,010 B1)
Karim I. Budhwani
Date: 10/2018
Organization: US Patent and Trademark Office
The present disclosure generally pertains to a biomimetic apparatus configured to simulate physiological conditions by, in part, providing for both barrier and transport interfaces. The presently disclosed apparatus may be used to test therapeutics for different diseases; to study transport; form a substrate for any organ tissue with a barrier and/or transport function; provide a closed-loop assembly for fluid flow; mimic underlying and enveloped tissue; and model external environmental conditions.
Novel Biomimetic Microphysiological Systems for Tissue Regeneration and Disease Modeling
Karim I. Budhwani, Patsy G. Oliver, Donald J. Buchsbaum, Vinoy Thomas
Date: 10/2018
Journal: Novel Biomaterials for Regenerative Medicine
Biomaterials engineered to closely mimic morphology, architecture, and nanofeatures of naturally occurring in vivo extracellular matrices (ECM) have gained much interest in regenerative medicine and in vitro biomimetic platforms. Similarly, microphysiological systems (MPS), such as lab-chip, have drummed up momentum for recapitulating precise biomechanical conditions to model the in vivo microtissue environment. However, porosity of in vivo scaffolds regulating barrier and interface functions is generally absent in lab-chip systems, or otherwise introduces considerable cost, complexity, and an unrealistic uniformity in pore geometry. We address this by integrating electrospun nanofibrous porous scaffolds in MPS to develop the lab-on-a-brane (LOB) MPS for more effectively modeling transport, air-liquid interface, and tumor progression and for personalized medicine applications.