Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery.United States. Army Research Office (Grant W911NF-12-2-0039

Electromagnetic pump and hardware development for organs-on-chips

Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2018.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 255-260).MicroPhysiological Systems (MPS), also called organs-on-chips, attempt to mimic the relevant human multi-organ physiology in-vitro. They have potential applications in drug development and personalized medicine by enabling more accurate testing of physiological drug response earlier in the development cycle. On-platform pumps provide greater flexibility and design freedom and are a key feature of such platforms. One approach to multi-organ MPS platforms has been developed in our lab and uses an open-well system to culture tissues of various organs. A common fluid-media circulates between the organs using on-platform pneumatic diaphragm micro-pumps. These pumps require significant effort in setup and depend on external pressure and vacuum sources. An independent, portable pump with low power consumption is desirable. There are also on-going efforts in the field to make sterile platform components low-cost and single use, to reduce user setup time and sterilization effort. This thesis describes a scaled-up version of an ElectroMagnetic (EM) pump. The pump uses a teeter-totter EM actuator having a low energy consumption of about 1 mJ/stroke. The EM actuator minimizes energy by a latching design that requires a short pulse of energy only to switch its state and its springs store energy which is recovered in the reverse stroke. This thesis also describes injection-molded, single-use platforms with onboard pneumatic diaphragm micro-pumps. It describes various valve and pump geometries and a model to predict large deflections of polymer diaphragms. We integrate the EM actuators with these platforms, demonstrating temperature rise of less than 0.1 'C, valve sealing up to 60 kPa, and a pumping frequency of 1 Hz, limited by diaphragm behavior. In addition, we improve platform features using spillways which allow for better passive leveling of fluid height between MPSes. This thesis also presents the selection of polymer tubing to resolve condensation issues in pneumatic channels of an MPS platform inside a cell culture incubator.by Brij M. Bhushan.S.M

Electrostatically Levitated Object Handoff to Minimize Wear and Particle Generation

In semiconductor photolithography, feature sizes are reducing towards low nanometers using extreme ultraviolet (EUV) light, which requires exposure in vacuum. Even a few particles on surfaces in the optical path (such as reticles, lenses, and mirrors) pose critical limits on performance, yield, and machine availability. In the semiconductor manufacturing process, object handoff between stages is one of the significant particle generation mechanisms. Vibrations in the handoff and pickup stages generate impact forces on the object and cause relative sliding between contact surfaces, leading to wear and particle generation. Unlike in air, non-contact handling techniques such as Bernoulli grippers do not work in vacuum. We have developed the concept of object handoff by electrostatic levitation, establishing a small upward bow shape to make first contact at the object center and then flattening outward. Our research solution converts the transfer problem from a three-body contact (handoff stage, object, and pickup stage) to a phased two-body contact by electrostatically levitating the object from the handoff to the pickup stage. This thesis describes the design and modeling of a proof-of-concept handoff system and presents the experimental results. We levitate a 152 by 152 mm square, 400 μm thick aluminum sheet (object) across a 200 μm air gap. We explore various sensing and actuation patterns, develop control strategies, and evaluate methods to avoid electrostatic discharge during stable levitation and handoff. The prototype suspends and stabilizes the object in six degrees-of-freedom (6-DOF) below the pickup stage electrodes. 3-DOF (Z, ₓ, and ᵧ) are actively controlled and the other 3-DOF in horizontal directions (X, Y, and subscript z) are passively stabilized. The flexible Bow shape of the object is also controlled. The achieved steady-state object positioning noise is < 200 nm-pp in the Z-direction, and < 0.2 mdeg-pp in ₓ, ᵧ directions, with a 150 Hz maximum bandwidth. The horizontal positions are repeatable to < 0.5 mm in X and Y, and ±0.2 deg in subscript z. We demonstrate pickup-clamp and unclamp-placedown sequences by levitating the object from the resting pins (handoff stage) to the pickup stage electrodes and back. This methodology for object handoff by levitation could be extended, using electrostatic, electromagnetic, acoustic, and pneumatic force fields, to other situations in which wear and particle generation during object handoff are critical.Ph.D

Nano-Conjugated Food-Derived Antimicrobial Peptides As Natural Biopreservatives: A Review of Technology and Applications

In recent years, microbial food safety has garnered a lot of attention due to worldwide expansion of the food industry and processed food products. This has driven the development of novel preservation methods over traditional ones. Food-derived antimicrobial peptides (F-AMPs), produced by the proteolytic degradation of food proteins, are emerging as pragmatic alternatives for extension of the shelf-life of food products. The main benefits of F-AMPs are their wide spectrum antimicrobial efficacy and low propensity for the development of antibiotic resistance. However, direct application of F-AMPs in food limits its efficacy during storage. Therefore, the development of nanocarriers for the conjugation and distribution of potential AMPs may hold great potential to increase their bioactivity. This review highlights the significance of F-AMPs as a feasible and sustainable alternative to conventional food preservatives. The most recent developments in production, characterization, and mode of action of these AMPs against planktonic and biofilm forming pathogens are thoroughly discussed in this work. Moreover, nano-conjugation of F-AMPs with different nano-carriers and potential future application in food packaging are emphasized. This review may aid in comprehending the nano-conjugation of F-AMPs and offer insightful recommendations for further exploration and potential uses in the food processing industry

Nature of V<SUP>n+</SUP> ions in SnO<SUB>2</SUB>: EPR and photoluminescence studies

SnO<SUB>2</SUB> and 5 at.% V doped SnO<SUB>2</SUB> samples were prepared by citrate-gel method. From Raman study on vanadium doped SnO<SUB>2</SUB>, the existence of phase separated V<SUB>2</SUB>O<SUB>5</SUB> clusters has been established. EPR study on the V doped sample clearly revealed the existence of V<SUP>4+</SUP> ions, which are incorporated in SnO<SUB>2</SUB> lattice and the existence of conduction electrons with g=1.993. For vanadium doped SnO<SUB>2</SUB> sample, there is a decrease in luminescence at 400 nm and an increase in activation energy of electrical conduction compared to undoped SnO<SUB>2</SUB>, and this has been attributed to the decrease in oxygen vacancies brought about by the incorporation of V<SUP>5+</SUP> in the SnO<SUB>2</SUB> lattice