Automated Liquid Handling for
Assay Development and Optimization

Flap endonuclease FEN is a long-standing target of interest in the DNA damage response DDR field due to its therapeutic potential in BRCA mutant cancers To-date there have only been a handful of FEN inhibitors reported in the literature most of which display modest selectivity and or weak cellular activity ...More |Related Solutions: Tempest^®

Flap endonuclease 1 (FEN1) is a long-standing target of interest in the DNA damage response (DDR) field due to its therapeutic potential in BRCA mutant cancers. To-date there have only been a handful of FEN1 inhibitors reported in the literature, most of which display modest selectivity and/or weak cellular activity. As such, there is a need for more advanced pharmacological tools to probe the biology of FEN1. Here, we report the discovery of MSC778, the first potent, selective, and orally bioavailable FEN1 inhibitor. We describe our metal-chelating fragment screening approach and structure-based optimization to identify MSC778, using structural insights to drive design. Consistent with FEN1 inhibition, MSC778 selectively kills BRCA2-deficient cells and potentiates the activity of PARPi niraparib in vivo to induce tumor stasis in a BRCA2 KO DLD-1 mouse xenograft. Furthermore, we illustrate how development of this approach has the potential for addressing nucleases as a target class. Less |Related Solutions: Tempest^®

Liquid dispensing technologies that enhance experimental efficiency and deliver high accuracy across multiple volume ranges are critically important in high-throughput experimentation HTE workflows for reaction exploration and optimization The Mantis liquid handler stands out as a compact highly modular system featuring a wide array of input options and near plug-and-play ...More |Related Solutions: Mantis^®

Liquid dispensing technologies that enhance experimental efficiency and deliver high accuracy across multiple volume
ranges are critically important in high-throughput experimentation (HTE) workflows for reaction exploration and optimization. The
Mantis liquid handler stands out as a compact, highly modular system featuring a wide array of input options and near plug-and-play
functionality with carousels, all while employing positive displacement dispensing technology for precise liquid delivery that is largely
independent of liquid properties. However, the system was originally designed to handle aqueous-based biological media at low
volumes (1−5 μL/dispense), limiting its applications in nonaqueous chemistry. Herein, we report a hardware development effort
from a cross-industry collaboration aimed at enhancing Mantis’ capabilities to handle organic solvents and chemical reagents, even at
larger deliverable volumes (up to 50 μL/dispense). Various chemistry examples are provided to demonstrate the implementation of
newly developed chip designs, which allow the acquisition of accurate, reproducible, and robust data, enabling more efficient
workflows for new reaction discovery, reaction optimization, and data set production. Most importantly, by implementing the Mantis
liquid handler from the outset, an increase of 77% in HTE execution efficiency relative to a manual workflow incorporating
traditional liquid handling operations was achieved in an amide coupling demonstration. Less |Related Solutions: Mantis^®

Microbial production of target molecules has advanced significantly in recent years driven by innovations in enzyme engineering DNA synthesis and genomic editing However to access the massive potential of microbial production a vast parametric space remains to be investigated to optimize these biobased processes for a robust bioeconomy Here we ...More |Related Solutions: Mantis^®

Microbial production of target molecules has advanced significantly in recent years driven by innovations in enzyme engineering, DNA synthesis, and genomic editing. However, to access the massive potential of microbial production, a vast parametric space remains to be investigated to optimize these biobased processes for a robust bioeconomy. Here, we review the current state of the art, some key challenges and possible solutions. We see a critical role of automation, high-throughput technologies, self-driving and cloud labs, and data management to enable Artificial Intelligence/Machine Learning and mechanistic models to overcome the design space challenges and accelerate the development of novel bio-based solutions. Accurate models will expedite the development and scale-up of engineered microbes for a range of final products from many starting materials. Less |Related Solutions: Mantis^®

Physical activity improves health yet the molecular mechanisms remain partially understood This study presents a high-resolution time-resolved atlas profiling proteins across plasma saliva and urine from healthy adults post-acute exercise Exercise regulated over proteins revealing distinct fluid-specific temporal dynamics By integrating fluid-specific exercise signatures with tissue and disease atlases we ...More |Related Solutions: F.A.S.T.^™

Physical activity improves health, yet the molecular mechanisms remain partially understood.
This study presents a high-resolution, time-resolved atlas profiling 10,127 proteins across
plasma, saliva, and urine from healthy adults post-acute exercise. Exercise regulated over
3,000 proteins, revealing distinct, fluid-specific temporal dynamics. By integrating fluid-specific
exercise signatures with tissue and disease atlases, we delineated the contribution of tissues
and associations to various diseases. Network analysis across body fluids elucidated
coordinated remodeling in the extracellular matrix and immune activation orchestrating
exercise-induced networks. Many exercise-responsive plasma proteins were robust across
age, sex, and exercise modalities, indicating a conserved systemic signature. Integration with
genetic data established exercise-regulated proteins as modulators of metabolic traits and
identified over 200 targeted by approved drugs, highlighting their impact on disease-relevant
pathways. This comprehensive atlas, available as an open-access resource
https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/, advances our
molecular insight into exercise adaptations and enables exerkine discovery, biomarker
development, and pharmacological exercise-mimetic strategies. Less |Related Solutions: F.A.S.T.^™

Mobile phones contaminated with pathogenic microorganisms have the potential to act as trojan horses The microbial signatures present on their surfaces most probably vary across different geographical regions As a result mobile phones belonging to international conference attendees may serve as a model for global microbial dissemination posing potential risks ...More |Related Solutions: Mantis^®

Mobile phones, contaminated with pathogenic microorganisms, have
the potential to act as “trojan horses”. The microbial signatures present on their surfaces most probably vary across different geographical regions. As a result, mobile phones belonging to
international conference attendees may serve as a model for global microbial dissemination,
posing potential risks to public health and biosecurity. This study aimed to profile the microbes present on mobile phones belonging to delegates
attending an international scientific conference through use of metagenomic shotgun DNA
sequencing. Results: A total of 2204 microbial hits were accumulated across 20 mobile phones inclusive of
882 bacteria, 1229 viruses, 88 fungi and 5 protozoa. Of particular concern was the identification of 65 distinct antibiotic resistance genes and 86 virulence genes. Plant, animal and human
pathogens, including ESKAPE and HACEK bacteria were found on mobile phones Less |Related Solutions: Mantis^®