scholarly journals Novel Electrochemiluminescent Assays for Drug Discovery

Author(s):  
Maura C. Kibbey ◽  
David MacAllan ◽  
James W. Karaszkiewicz

IGEN's ORIGEN® technology, which is based on electrochemiluminescence, has been adopted by a number of research and bioanalytical laboratories who have recognized its exquisite sensitivity, high precision, wide dynamic range, and flexibility in formatting a wide variety of applications. IGEN's M-SERIES™ marks the introduction of the second generation of detection systems employing the ORIGEN technology specifically repackaged to address the needs of the high throughput laboratories involved in drug discovery. Assays are formatted without wash steps. Users realize the high performance of a heterogeneous technology with the convenience of a homogeneous format. The M-SERIES platform can address enzymatic assays (kinases, proteases, helicases, etc.), receptor-ligand or protein-protein assays, immunoassays, quantitation of nucleic acids, as well as other applications. Recent assay formats will be explored in detail.

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (2) ◽  
pp. 74-84 ◽  
Author(s):  
Shenaz Bunally ◽  
Robert J Young

During the early phase of drug discovery, it is becoming increasingly important to acquire the full physicochemical profile of molecules. For this purpose, there is a strong interest in developing efficient and cost-effective platforms for fast and reliable measurements of physicochemical properties. We have developed an automated physchem platform which ensures that consistent, comprehensive, and high-quality physicochemical property measurements and derived property information for 100's of compounds per week are available alongside potency data at the right time to guide compound progression decisions. We discuss the routine assessments of biomimetic properties using high throughput automated high-performance liquid chromatography (HPLC) platforms, with details of the methods and hardware employed, also with illustrations of the quality and impact of the data generated.


2019 ◽  
Author(s):  
Jarrod J Sandow ◽  
Giuseppe Infusini ◽  
Laura F Dagley ◽  
Rune Larsen ◽  
Andrew I Webb

AbstractRecent advances in mass spectrometry technology have seen remarkable increases in proteomic sequencing speed, while improvements to dynamic range have remained limited. An exemplar of this is the new timsTOF Pro instrument, which thanks to its trapped ion mobility, pushes effective fragmentation rates beyond 100Hz and provides accurate CCS values as well as impressive sensitivity. Established data dependent methodologies underutilize these advances by relying on long analytical columns and extended LC gradients to achieve comprehensive proteome coverage from biological samples. Here we describe the implementation of methods for short packed emitter columns that fully utilize instrument speed and CCS values by combining rapid generation of deep peptide libraries with enhanced matching of single shot data dependent sample analysis. Impressively, with only a 17 minute gradient separation (50 samples per day), the combination of high performance chromatography and CCS enhanced library based matching resulted in an average of 6,690 protein identifications within individual samples, and 7,797 proteins cumulatively across replicates from HeLa cell tryptic digests. Additionally, an ultra-high throughput setup utilizing 5 min gradients (180 samples per day) yielded an average of 2,800 protein identifications within individual samples and 4,254 proteins cumulatively across replicates. These workflows are simple to implement on available technology and do not require complex software solutions or custom made consumables to achieve high throughput and deep proteome analysis from biological samples.


1992 ◽  
Vol 41 (1) ◽  
pp. 40-44 ◽  
Author(s):  
S. Shinohara ◽  
H. Yoshida ◽  
H. Ikeda ◽  
K. Nishide ◽  
M. Sumi

Biosensors ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 99 ◽  
Author(s):  
Tory Schaaf ◽  
Ang Li ◽  
Benjamin Grant ◽  
Kurt Peterson ◽  
Samantha Yuen ◽  
...  

We have developed fluorescence resonance energy transfer (FRET) biosensors with red-shifted fluorescent proteins (FP), yielding improved characteristics for time-resolved (lifetime) fluorescence measurements. In comparison to biosensors with green and red FRET pairs (GFP/RFP), FPs that emit at longer wavelengths (orange and maroon, OFP/MFP) increased the FRET efficiency, dynamic range, and signal-to-background of high-throughput screening (HTS). OFP and MFP were fused to specific sites on the human cardiac calcium pump (SERCA2a) for detection of structural changes due to small-molecule effectors. When coupled with a recently improved HTS fluorescence lifetime microplate reader, this red-shifted FRET biosensor enabled high-precision nanosecond-resolved fluorescence decay measurements from microliter sample volumes at three minute read times per 1536-well-plate. Pilot screens with a library of small-molecules demonstrate that the OFP/MFP FRET sensor substantially improves HTS assay quality. These high-content FRET methods detect minute FRET changes with high precision, as needed to elucidate novel structural mechanisms from small-molecule or peptide regulators discovered through our ongoing HTS efforts. FRET sensors that emit at longer wavelengths are highly attractive to the FRET biosensor community for drug discovery and structural interrogation of new therapeutic targets.


2013 ◽  
Vol 321-324 ◽  
pp. 724-727
Author(s):  
Lei Li ◽  
Jun Li Liu ◽  
Cheng Xing Lv

A high-precision marine ambient noise sound pressure monitoring system is developed based on the Michelson interference, a method of improving the measurement accuracy is presented by signal modulation and compensation. Experiments show that the monitoring system has a wide dynamic range and high accuracy especially in low-frequency.


2012 ◽  
Vol 605-607 ◽  
pp. 873-877
Author(s):  
Lei Li ◽  
Zhong Hai Zhou ◽  
Cheng Xing Lv ◽  
Bo Liu ◽  
He Chao Zang ◽  
...  

A low frequency and high-precision microbarograph monitoring system is developed based on the Michelson interference of unequal-arm type, a method of signal modulation and compensation is presented, it improves the system’s anti-jamming capability and measurement accuracy. Experiments show that the monitoring system has a high accuracy and a wide dynamic range, especially for monitoring low-frequency signal.


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