SLAS Technology Authors Talk Tech

Volume 25 Issue 3, June 2020

Dave Pechter discusses with Georges Muller & Yann Barrandon their two featured research articles, "Traceable Impedance-Based Dispensing and Cloning of Living Single Cells" and "Impedance-Based Single-Cell Pipetting."

Traceable Impedance-Based Dispensing and Cloning of Living Single Cells: Single-cell cloning is essential in stem cell biology, cancer research, and biotechnology. Regulatory agencies now require an indisputable proof of clonality that current technologies do not readily provide. Here, we report a one-step cloning method using an engineered pipet combined with an impedance-based sensing tip. This technology permits the efficient and traceable isolation of living cells, stem cells, and cancer stem cells that can be individually expanded in culture and transplanted.

Impedance-Based Single-Cell Pipetting: Many biological methods are based on single-cell isolation. In single-cell line development, the gold standard involves the dilution of cells by means of a pipet. This process is time-consuming as it is repeated over several weeks to ensure clonality. Here, we report the modeling, designing, and testing of a disposable pipet tip integrating a cell sensor based on the Coulter principle. We investigate, test, and discuss the effects of design parameters on the sensor performances with an analytical model. We also describe a system that enables the dispensing of single cells using an instrumented pipet coupled with the sensing tip. Most importantly, this system allows the recording of an impedance trace to be used as proof of single-cell isolation. We assess the performances of the system with beads and cells. Finally, we show that the electrical detection has no effect on cell viability.

Volume 25 Issue 2, April 2020

Dave Pechter discusses with Agata Blasiak & Theodore Kee regarding their article, "CURATE.AI: Optimizing Personalized Medicine with Artificial Intelligence." 

The clinical team attending to a patient upon a diagnosis is faced with two main questions: what treatment, and at what dose? Clinical trials’ results provide the basis for guidance and support for official protocols that clinicians use to base their decisions upon. However, individuals rarely demonstrate the reported response from relevant clinical trials, often the average from a group representing a population or subpopulation. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual’s response to the treatment varies over time with the changes in his or her condition, whether via the indication or physiology. In practice, the drug and the dose selection depend greatly on the medical protocol of the healthcare provider and the medical team’s experience. As such, the results are inherently varied and often suboptimal. Big data approaches have emerged as an excellent decision-making support tool, but their application is limited by multiple challenges, the main one being the availability of sufficiently big datasets with good quality, representative information. An alternative approach—phenotypic personalized medicine (PPM)—finds an appropriate drug combination (quadratic phenotypic optimization platform [QPOP]) and an appropriate dosing strategy over time (CURATE.AI) based on small data collected exclusively from the treated individual. PPM-based approaches have demonstrated superior results over the current standard of care. The side effects are limited while the desired output is maximized, which directly translates into improving the length and quality of individuals’ lives.

Volume 25 Issue 1, February 2020

Dave Pechter discusses with Hideaki Tsutsui & Peter Lillehoj regarding February's Special Issue. Over the last decade, flexible analytical devices have received considerable attention in both academia and industry. Compared to conventional analytical devices which are generally made from rigid materials, such as silicon, glass, and plastics, flexible devices offer several unique advantages, such as simplified fabrication, lower costs, enhanced portability and disposability, and compliance to curved or deforming surfaces. For these reasons, flexible analytical devices are well suited for many diagnostic applications, including wearable and in vivo sensing, and point-of-care testing for disease detection and health monitoring. This special issue showcases a comprehensive review and exciting original research on topics ranging from wearable sensors for human motion monitoring and disease diagnosis, flexible electrochemical sensor arrays for human cell culture monitoring, paper-based sensors and immunoassays for diagnostic testing, a paper-based biological solar cell for power generation and storage, and a 3D printing strategy for rapid prototyping of flexible microfluidic devices.

Volume 24 Issue 6, December 2019

Dave Pechter discusses with Chao Li the article, "Automated System for Small-Population Single-Particle Processing Enabled by Exclusive Liquid Repellency." 

Lossless processing and culture of rare cells (e.g., circulating tumor cells, drug-persistent microorganisms) at single-cell level is of great significance in understanding the heterogeneity of carcinogenesis or human pathogenesis caused by microbial infection. Current single-cell isolation techniques like fluorescence-activated cell sorting (FACS) require relatively large sample volume and cell number to work with, and inflict sample loss and reduced cell viability from the processing. While microfluidic and single-cell printing techniques allow the handling of minute amounts of cellular samples, they either come with limited physical access to the sample of interest due to the closed-channel design (e.g., droplet microfluidics) or sample loss during aspiration, transfer, and sample retrieval from culture.

Recently, we reported an extreme wettability phenomenon, named exclusive liquid repellency or ELR. ELR is observed in solid-liquid-liquid three phase systems, where a solid surface shows complete repellency to a liquid (with Young’s contact angle, CA = 180o) when exposed to a second immiscible liquid. This phenomenon is observed when a particular thermodynamic boundary condition is satisfied (i.e., γS/Lcp + γLdp/Lcp ≤ γS/Ldp, where γ - interfacial tension, S - solid, Lcp - liquid of continuous phase, and Ldp - liquid of dispersed phase). Neither surfactant nor flow condition is required, e.g., compared with droplet microfluidics. ELR enables additional fluidic control, robust on-chip cell culture, and improved processing of rare cell samples in open aqueous fluid under oil. ELR is distinct from other liquid repellent systems with CA < 180o (i.e., non-ELR), showing no compromise of liquid adhesion on solid surfaces and enabling unique applications.

In this work, we developed an automated platform using ELR microdrops for lossless single-particle (or single-cell) isolation, identification, and retrieval. It features the combined use of a robotic liquid handler, an automated microscopic imaging system, and real-time image-processing software for single-particle identification. The automated ELR technique enables rapid, hands-free, and robust isolation of microdrop-encapsulated rare cellular samples, and further on-chip cell culture or down-stream analysis (e.g., RNA extraction and RT-qPCR).

SLAS Technology 24.5 October 2019

Professors at Johns Hopkins University, Claire Hur and Deok-Ho Kim, discuss their special issue, "Engineering Innovations for Fundamental Biology and Translational Medicine."

In this special issue of SLAS Technology, the editors showcase reviews and original research reports addressing the accuracy in diagnostic and prognostic tests performed on the patient-derived specimen, an emerging technology demand for personalized medicine.

Soojung Claire Hur, Ph.D., is Clare Boothe Luce Assistant Professor in the Department of Mechanical Engineering at Johns Hopkins Whiting School of Engineering, and an expert in microfluidics. Deok-Ho Kim, Ph.D., is faculty in the Department of Biomedical Engineering and Department of Medicine at the Johns Hopkins University School of Medicine.

Topics include the role of microfluidic technology in patient-specific information collection and endeavors to integrate innovative technologies with existing clinical workflows through automation and miniaturization for expedited translation.

Volume 24 Issue 4, August 2019

UCLA Professor, Dino Di Carlo, discusses his review paper, "Technologies for the Directed Evolution of Cell Therapies." 

The next generation of therapies is moving beyond the use of small molecules and proteins to using whole cells. Compared with the interactions of small-molecule drugs with biomolecules, which can largely be understood through chemistry, cell therapies act in a chemical and physical world and can actively adapt to that world, amplifying complexity but also the potential for truly breakthrough impact. Although there has been success in introducing targeting proteins into cells to achieve a therapeutic effect, for example, chimeric antigen receptor (CAR) T cells, our ability to engineer cells is generally limited to introducing proteins, but not modulating large-scale traits or structures of cellular “machines,” which play critical roles in disease. Example traits include the ability to secrete compounds, deform through tissue, adhere to surrounding cells, apply force to phagocytose targets, or move through extracellular matrix. There is an opportunity to increase the efficacy of cell therapies through the use of quantitative automation tools, to analyze, sort, and select rare cells with beneficial traits. Combined with methods of genetic or epigenetic mutagenesis to create diversity, such approaches can enable the directed cellular evolution of new therapeutically optimal populations of cells and uncover genetic underpinnings of these optimal traits.

SLAS Technology 24.1 February 2019

Guest Editor Richard M. Eglen of Corning Life Sciences (Tewksbury, MA, USA) talks about a new collection of reviews and original research reports that illustrate how the combination of human iPS cells and 3D cell culture technology provide powerful new approaches to the development of novel and more effective therapies. Free access to the published collection is sponsored by Corning Life Sciences.

SLAS Technology 23.6 December 2018

University of Kansas researchers Yangjie Wei and Nicholas Larson talk about how they used a steady-state/lifetime fluorescence-based, high-throughput platform to develop a general workflow for direct formulation optimization under analytically challenging but commercially relevant conditions.

SLAS Technology 23.5 October 2018

Guest Editor James M. Gill, II, Ph.D., of BFL Consulting (Madison, CT) talks about how the October 2018 issue of SLAS Technology showcases life sciences researchers who are pioneering the use of powerful yet accessible and low-cost IoT technologies in their laboratories. Ten articles illustrate how IoT is being used to optimize factors such as throughput, cost, uptime and result quality.

SLAS Technology 23.4 August 2018

UCLA’s Coleman Murray, Ph.D., talks about his contribution to the August 2018 special issue of SLAS Technology on Enabling Technology in Cell-Based Therapies by guest editor Chris Puleo and his associates at General Electric Global Research. Murray’s article illustrates an important example of how new technologies are changing automation and processing in cell therapy manufacturing.