Services

We specialize in high throughput affinity selection mass spectrometry (ASMS) screens using the Automated Ligand Identification System (ALIS) on an Agilent 2D-HPLC system interfaced to an Agilent Time-of-Flight MS.

ASMS offers several distinct advantages over legacy high throughput screening (HTS) methods:

• ASMS is binding site agnostic, enabling clients to identify potential leads acting through a variety of mechanisms, including degradation and disruption of protein-protein or protein-oligonucleotide interactions.
• ASMS is compatible with a range of targets. Protein, RNA, and Protein Complexes can be screened without the need for tagging or surface immobilization, ensuring the results are physiologically relevant.
• ASMS requires very little target (~1mg) to screen hundreds of thousands of potential compounds.
• ASMS assay development is limited to buffer optimization and therefore much faster than traditional biochemical HTS methods like FRET and enzymatic assays, enabling identification of leads in half the time.
• ASMS is much faster to run than other biophysical assays such as SPR, interferometry, DSF, Mesoscale, ITC, and NMR.
• ASMS allows compounds to be screened in pools of 250: 100,000 test compounds can be screened in a single day.
• ASMS covers broad chemical space as positive mode electrospray ionization is compatible with 95% of drug-like test compounds.
• ASMS is immune to false positives resulting from active impurities and breakdown products by identifying the exact compound based on molecular formula.

We have extensive experience using ASMS screens to study hundreds of targets tested against tens of millions of compounds.

We can our in-house library, third-party libraries, and internal client libraries. While we typically screen Rule of Five compliant chemical libraries, we can also screen macrocyclics. We offer target QC on proteins and RNA to ensure accurate screens.

Following ASMS primary, pooled screens:

• We recommend clients run a secondary screen to confirm hits in small pools of one to five compounds.
• We can also rank order hits by competitive binding, give quantitative information on target occupancy, and determine binding affinity for Structure-Activity Relationship (SAR) studies.

Next day data delivery may be possible with couriered samples to our Billerica location.

Our team developed a covalent binding assay that enables screening of electrophilic test compounds that irreversibly modify protein targets on a RapidFire coupled to an Agilent Quadrupole Time-of-Flight MS.

• We have the capacity to screen up to 4,500 compounds per day from internal client libraries, a 12,000 compound electrophile library from Wuxi AppTec, or a third-party library.

We offer ICP-MS analysis for several applications depending on the needs of our clients’ specific programs. We have used ICP-MS to test for trace metals in CGT and biologics media, perform pharmacokinetic studies on metallodrugs, quantify biomarkers for rare diseases (Ex. Wilson’s Disease), and characterize zinc finger proteins.

• We understand that ICP-MS results are crucial to go-forward decision making in CGT and biologics development, so we strive to turn around data as fast as possible. We can analyze hundreds of samples daily.

Next day data delivery may be possible with couriered samples to our Billerica location.

We offer assay development and analysis for small molecule quantification on both HPLC-MS and Rapid-Fire-MS. We can perform biomarker quantification, potency assays, and pharmacokinetic studies depending on your need.

• We have extensive experience measuring lipids, amino acids, sugars, and metabolites in lysosomal storage diseases such as Gaucher, Fabry, Hunter, Metachromatic leukodystrophy (MLD), and Muco-polysaccharidoses (MPS); urea cycle disorders such as Ornithine transcarbamylase deficiency (OTC) and Citrullinemia; Phenylketonuria (PKU); and Hypertryptophanemia.

Next day data delivery may be possible with couriered samples to our Billerica location.

We provide functional cell-based and biochemical screening, and have the capacity to generate upwards of 20,000 datapoints per day.

• As the inventors of the RapidFire-MS platform, we have 20 years of experience in RapidFire analytical method development and biochemical assay development.

Next day data delivery may be possible with couriered samples to our Billerica location.

We offer quality control services on oligonucleotides using high-resolution MS paired with multiple interfaces (HPLC, UHPLC, RapidFire) ranging from 12s to 20m cycle times to support client throughput requirements. We can work on DNA/RNA samples with both standard and modified chemistries to provide:

• Intact mass determination/confirmation
• Target purity
• Component profiling
• RNA cap and tail analyses
• Sequence confirmation

Our techniques offer several advantages over other methods including:

• Excellent mass accuracy
• Detection and identification of low abundance components
• Targeted and untargeted profiling
• High quality results on oligos > 100 nucleotides in length

Data delivery is typically 1-2 business days after sample receipt at our Billerica, MA location.