MTIF & Hamamatsu Photonics collaboration

Presented below are two main applications based on our collaboration using our FDSS/μCELL:

Drug Discovery

Development of new, safe and effective medicines is enhanced when drug discovery research can be done faster and more precisely. Hamamatsu’s FDSS®/μCELL - our highly reliable screening system for functional cell-based assays - facilitates testing of a large number of compounds at high speed. The FDSS®/μCELL monitors calcium flux and membrane potential change when adding compounds, specialized for GPCR and ion channel research. The FDSS®/μCELL advances early-stage innovative discoveries and accelerates research into drug solutions.

FDSS/μCELL in the Drug Discovery process

The process of first finding drug targets, then the development of these drugs to increase efficacy, metabolic stability, affinity and selectivity to reduce potential side effects, can be both lengthy and costly. The FDSS®/μCELL identifies active compounds that play a significant role in disease at high speed in the early stages of the drug discovery process:

Target identification and validation
Screening and hit identification
Lead identification and optimization

The system can also be used during the toxicity evaluation stage of the drug discovery process. Using iPS (induced Pluripotent Stem) cell-derived cardiomyocytes and neurons, the FDSS/μCELL can electrically stimulate cells and monitor Ca2+ transient and membrane potential measurements using Electric Field Stimulation (EFS) to predict a diverse range of toxicities.

FDSS/μCELL features for Drug Discovery

The FDSS®/μCELL is an easy to use, purpose-built kinetic plate reader that screens various compounds at high throughput. The FDSS®/μCELL dispenses in 96 / 384 wells while fluorescence or luminescence measurements are taken simultaneously in 96 / 384 / 1536 wells using a highly sensitive Hamamatsu camera, which captures cell dynamics under the same conditions with no time lag between wells. The FDSS®/μCELL is simple to connect to an external robotic system for easy automation of assays.

Additional features of the FDSS/μCELL making it the best solution for drug discovery:

High speed acquisition – high speed reading (up to 200kHz) is a key factor to detect changes in wells accurately.
Temperature control – temperature can be maintained at physiological sample temperature +35 °C to 37 °C for all wells in a plate.
CO2 supply – the CO2 concentration can be maintained to keep intracellular pH in the medium constant.
Analysis of waveform - Ca2+ transient waveforms can be analyzed using the FDSS Waveform Analysis software.
Electric Field Stimulation (EFS) - EFS system adds electric field stimulation to all 96 wells simultaneously during fluorescence measurement.

FDSS/μCELL Drug Discovery applications

The FDSS/μCELL uses cell-based models to screen for drug targets across a variety of different applications. Key applications include looking at important membrane receptors:

GPCRs (G-protein-coupled receptors)
Ion channels

Other drug discovery applications include:

Protein-Protein Interaction (PPI) or BRET/FRET
Antibody Functional Assays
Enzymatic assays
Optogenetics
In-vitro toxicity assay

Please tell us more about your latest Drug Discovery research

Hamamatsu’s specialist engineers work collaboratively with members of the drug discovery community across the world to develop numerous different techniques to meet customers’ needs. The new partnership between Hamamatsu Photonics UK Ltd and Medical Technologies Innovation Facility (MTIF) will enable researchers the ability to view and utilize the FDSS®/μCELL at MTIF’s new research and development site. Hamamatsu’s team of experts will be working alongside MTIF to provide guidance to help accelerate the development of new medical and pharmaceutical therapies.

Please contact Jack Bennett, Hamamatsu FDSS Sales Engineer, at jbennett@hamamatsu.co.uk to discuss how your research could benefit from the FDSS/μCELL.

Resources

https://fdss.hamamatsu.com/jp/en/index.html

https://fdss.hamamatsu.com/resources/pdf/sys/SBIS0007E_FDSS_ap03.pdf

https://fdss.hamamatsu.com/resources/pdf/sys/SBIS0128E_FDSS_ap28.pdf

Biocompatibility

By formal consensus, biocompatibility is defined as the ability of a biomaterial to perform with an appropriate host response. A biomaterial is either a biological or synthetic material which can be introduced into direct contact with body tissue as part of a medical device to repair, replace or regenerate a bodily function. Biocompatibility and safety evaluation studies involve the identification of the host response to a biomaterial. This is important as it evaluates the placement of differing materials in defined anatomical locations as treatments, with the therapeutic requirements of each location differing significantly. One size certainly does not fit all when it comes to biomaterials and host response versus location, even before cell-based approaches are considered. The goal is to develop practical and reproducible approaches for the identification of biocompatibility and safety that ultimately deliver successful patient cell therapies.

MTIF’s FDSS/μCELL in Biocompatibility

The interaction of a patient’s immune defense mechanisms with an implanted material is important in determining the performance of such a material. Following implantation leukocytes will infiltrate the implantation wound site, initiated by acute inflammation, that includes the formation and release of reactive free radical species (RS) as part of the innate immune response. When an intervention induces a high degree of cell activation and RS formation is triggered, this can correspond to accelerated degradation rates of the material and when it is severe, sustained acute phase inflammation. With conventional biocompatibility testing only, it is difficult to predict the exact nature of the innate immune reaction when a therapy is implanted, with such a reaction often patient specific. RS are very important in wound healing; however, often overlooked during biocompatibility testing, with the required tests specialized and requiring fresh primary derived relevant samples.

MTIF’s FDSS®/μCELL can carry out assays for measuring real time production of RS as an indicator of cell health or signaling events in Biocompatibility. In the system, fresh primary derived patient samples can be incubated and then triggered with a biomaterial of choice. The cellular response is measured using screening techniques such as Luminol or ROS-Glo to detect changes in fluorescence / luminescence. This test will assess the level of innate immune response that a patient will have to a biomaterial, thus determining the safety and performance of the material.

FDSS/μCELL features for Biocompatibility

The FDSS®/μCELL is an easy to use, purpose-built kinetic plate reader that screens various biomaterials at high throughput. The FDSS®/μCELL dispenses in 96 / 384 wells while fluorescence or luminescence measurements are taken simultaneously in 96 / 384 / 1536 wells using a highly sensitive Hamamatsu camera. Capturing cell dynamics in vitro under the same conditions as in vivo is key to replicating a patient’s response to biomaterials.

Additional features of the FDSS®/μCELL making it the best solution for Biocompatibility research:

High-speed acquisition – high-speed reading (up to 200kHz) is a key factor to detect changes in wells accurately.
Temperature control – temperature can be maintained at physiological sample temperature +35 °C to 37 °C for all wells in a plate.
Electric Field Stimulation (EFS) - EFS system adds electric field stimulation to all 96 wells simultaneously during fluorescence measurement.

Please tell us about your latest Biocompatibility research

The MTIF team have over 50 years’ experience in implanted devices and cellular therapies, developing and implementing both in vitro and in vivo biocompatibility studies. MTIF will provide required technical advice to ensure success of its customers’ product development and the necessary regulatory expertise to support international regulatory submissions. All testing will be conducted in MTIF’s ISO 10993 testing facility. It is crucial that more relevant 3D human tissue analogues are utilized going forward, with host response precisely tested and identified for each individual patient.

Please contact Max Bardwell ( max.bardwell@ntu.ac.uk) within the MTIF team to discuss how your research could benefit from the MTIF FDSS/μCELL.

Resources

In determining the innate immune response, key publications include: