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Order](https://www.sigmaaldrich.com/US/en/quick-order) Cart0 [Home](https://www.sigmaaldrich.com/US/en)[Solid Phase Microextraction (SPME)](https://www.sigmaaldrich.com/US/en/applications/analytical-chemistry/sample-preparation/solid-phase-microextraction)Sample Cleanliness Using BioSPME # Sample Cleanliness Using BioSPME __M. James Ross, Senior R&D Scientist, Olga Shimelis, R&D Manager__ MilliporeSigma - [Phospholipids Removal Efficiency: BioSPME Vs. Acetonitrile Protein Precipitation](https://www.sigmaaldrich.com#phospholipids-removal) - [Albumin Protein Removal from Plasma](https://www.sigmaaldrich.com#albumin-protein-removal) - [Measuring Overall Sample Cleanliness by LC-MS/MS](https://www.sigmaaldrich.com#cleanliness) - [Results & Discussion: Supel™ BioSPME 96-PIN Device Outperforms Acetonitrile Based Sample Preparation](https://www.sigmaaldrich.com#results-discussion) - [Conclusion: Effective Sample Preparation with BioSPME](https://www.sigmaaldrich.com#conclusion) [See Products](https://www.sigmaaldrich.com#materials) Sample preparation is performed to prepare the sample for analysis and to eliminate matrix effects. Matrix effects are exerted by endogenous species that may impede the signal of the desired analyte(s) from analysis.1 One analysis that is sensitive to matrix effects is LC-MS/MS. Plasma is a complex matrix that contains proteins, lipids, salts and carbohydrates which requires some sample preparation. Failure to address these concerns not only leads to potential matrix effects but also to increased analysis time, investment in new columns, or increased instrument maintenance time. In this study, we report the effectiveness of solid phase microextraction and the use of the [Supel™ BioSPME](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/solid-phase-microextraction/supel-biospme-96-pin-devices) C18 96-pin tool in preparing samples for analysis by LC-MS/MS. Previous work has demonstrated the ability of BioSPME in the preparation of samples for determination of protein binding values.2 ## [](https://www.sigmaaldrich.com)PHOSPHOLIPIDS REMOVAL EFFICIENCY: BioSPME Vs. ACETONITRILE PROTEIN PRECIPITATION The amount of phospholipids remaining in samples after extraction using the BioSPME 96-pin tool (__Figure 1__) was compared to the amount of phospholipids remaining after acetonitrile assisted protein precipitation. The BioSPME procedure is outlined in __Figure 2__. Briefly, the pin tool is conditioned in isopropanol, followed by a short rinse in water. At this point, the pin tool is ready for extraction. After extraction, the pin tool is rinsed briefly to remove any proteins that may remain on the pin’s surface before the analyte is desorbed and is then ready for analysis. Protein precipitation was performed by using 100 µL human plasma and mixing with 300 µL of acetonitrile. The mixture was stored at 4 °C for 20 minutes before centrifugation at 5,000 rpm for 10 minutes. The supernatant was transferred and dried at 45 °C under a flow of nitrogen at 10 psi. The sample was then resuspended in 200 µL of the starting mobile phase.  [](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/solid-phase-microextraction/supel-biospme-96-pin-devices) __Figure 1.__View of the Supel™ BioSPME C18 96-pin tool. | | | | | | | | | | | | |-----------|------|------|------|------------|------|------|------|------------|------|---------| | Condition | > | Wash | > | Extraction | > | Wash | > | Desorption | > | Analyze | Figure 2.Overview of the steps for BioSPME. Five samples from the two methods were analyzed on an AB Sciex-3200 Q Trap mass spectrometry with an Agilent 1290 LC using the method described in __Table 1__. The phospholipids that were monitored are listed in __Table 2__. Column:Ascentis® Express C8 column, 10 cm x 2.1 mm, 2.7 µm ([53832-U](https://www.sigmaaldrich.com/US/en/product/supelco/53832u))   Mobile Phase:\[A] 5 mM Ammonium acetate, 0.1% acetic acid in water \[B] 5 mM Ammonium acetate, 0.1% acetic acid in 95% acetonitrile and 5% water Gradient:80% A, 20% B held for 1.5 min; to 100% B in 1.5 min; the flow is increased to 0.6 mL/min in 0.1 min and held at 100% B for 12 min; in 0.1 min the flow is decreased back to 0.4 mL/min and 20% B, and held for 3 min. Flow Rate:0.4 to 0.6 mL/min (see Gradient) Column Temp:40 °C Detector:MS, ESI(+) Scheduled MRM (See __Table 1__ and __2__) Injection:2 or 5 µL Table 1.LC-MS/MS conditions for monitoring phospholipids | | | | | | | |----------|-----------|---------|-----------------|-----|----| | Analyte | Precursor | Product | Dwell Time (ms) | DP | CE | | Choline | 184.1 | 104.1 | 40 | 120 | 80 | | LPC 16:0 | 496.4 | 184.1 | 40 | 120 | 80 | | LPC 18:0 | 524.4 | 184.1 | 40 | 120 | 80 | | PC 30:1 | 704.4 | 184.1 | 40 | 120 | 80 | | PC 34:2 | 758.4 | 184.1 | 40 | 120 | 80 | | PC 36:2 | 786.4 | 184.1 | 40 | 120 | 80 | | PC 38:6 | 806.4 | 184.1 | 40 | 120 | 80 | | LPC 18:2 | 520.4 | 184.1 | 40 | 120 | 80 | | LPC 18:1 | 522.4 | 184.1 | 40 | 120 | 80 | | PC 36:1 | 788.4 | 184.1 | 40 | 120 | 80 | | PC 38:5 | 804.4 | 184.1 | 40 | 120 | 80 | | PC 34:1 | 760.4 | 184.1 | 40 | 120 | 80 | | PC 36:3 | 784.4 | 184.1 | 40 | 120 | 80 | Table 2.Phospholipids monitored (LPC – lysophosphatidylcholine; PC – phosphatidylcholine) ## [](https://www.sigmaaldrich.com)ALBUMIN PROTEIN REMOVAL FROM PLASMA The amount of protein remaining in the extracted sample via non-specific retention on the pins was determined using a NanoOrange™ kit. The pins (eight) were conditioned for 20 minutes in 800 µL of isopropanol in a well-plate under static conditions. The pins were then washed for 10 seconds in 800 µL of water. Extraction of pooled human plasma (800 µL) took place from a 96-well plate while shaking at 1200 rpm, 3 mm orbital radius, and the thermo adapter set at 37 °C. Following extraction, the pins were washed for one minute in water. Another well plate was prepared with 1 mL of the working solution (dye for protein staining) loaded into the appropriate wells of a well plate as described in the product directions. The pins used for bovine serum albumin (BSA) extraction were exposed to the working solution and allowed to react at 90-96 °C for 10 minutes while shaking at 300 rpm. The well plate was covered with foil to protect the samples from light. The samples were then cooled to room temperature. The samples were analyzed on a Thermo Scientific Dionex HPLC instrument using fluorescence detector with direct flow (no column), see __Table 3__ for full details. Samples were quantified using the peak height using an external calibration in the range of 0.1 – 5.0 µg/mL of BSA.  | | | |---------------|------------------------------| | Column: | None (Direct injection) | | Mobile Phase: | Water, 100% | | Flow Rate: | 1 mL/min | | Temp: | 5 °C sample, 30 °C flow cell | | Detector: | Fluorescence, 485/590 nm | | Injection: | 50 µL | Table 3.LC-Fluorescence conditions for monitoring fluorescent signals from tagged proteins. ## [](https://www.sigmaaldrich.com)MEASURING OVERALL SAMPLE CLEANLINESS BY LC-MS/MS The cleanliness of the sample was determined by measuring the total ion chromatogram, TIC, for three sets of conditions: a control of the 80:20 desorption solution (methanol:water v/v), an extracted spiked plasma sample by BioSPME, and an acetonitrile assisted protein precipitated serum sample. The acetonitrile assisted protein precipitated sample was prepared as followed. An aliquot of the spiked plasma corresponding to the plasma used in the extracted sample was diluted 3x with acetonitrile (v/v). This sample was then centrifuged for 10 minutes at 10,000 rpm at 4 °C. Upon completion, the supernatant was removed and dried under nitrogen at 10 psi and resuspended in the desorption solution to keep solvent effects to a minimum and better reflect sample cleanliness. All three samples were analyzed as described in __Table 1,__ using a 2 µL injection with a Q1 scan between 100 to 900 m/z. Multiple methanol injections followed each sample of interest to remove carry over between samples. ## [](https://www.sigmaaldrich.com)RESULTS & DISCUSSION: Supel™ BioSPME 96-PIN DEVICE OUTPERFORMS ACETONITRILE BASED SAMPLE PREPARATION Phospholipid amounts in the BioSPME prepared samples were compared to those of acetonitrile assisted protein precipitation prepared samples. As can be seen in __Table 4__, less than 0.1% of phospholipids remained in the final extracted sample using BioSPME compared to the acetonitrile assisted protein precipitated control. A sample chromatogram comparing the two conditions is shown in __Figure 3__.  | | | | | |---------|---------------|----------------------------------|----------| | Method | \# of samples | Average % Phospholipid Remaining | RSD | | BioSPME | 5 | <0.1 | <0.01 | Table 4.Phospholipid remaining in analyte by method.  __Figure 3.__Representative chromatograms (2 µL injections) for phospholipids in control sample (acetonitrile protein precipitated, purple) and the BioSPME sample (green). From the NanoOrange™ studies, the pin tools accumulated approximately 1.2 µg of protein, quantified against BSA, on the surface of the pin. A representative chromatogram from a pin compared to a calibrator can be seen in __Figure 4__. Albumin accounts for over half of the total proteins in plasma (between 35 mg/mL to 50 mg/mL).3 This value correlates to less than 0.01% of proteins being in the final extracted sample as shown in __Table 5__ across the eight pins tested. | | | | | | |-------------------------------------------------------------|---------------|-----------|-----|---------------------------------| | | \# of samples | Amount µg | RSD | % Protein retained from plasmaa | | Pin | 8 | 1.2 | 24 | <0.01% | | a Based-on concentration of 35,000 µg/mL albumin in plasma2 | | | | | Table 5.Summary of protein extracted from pin tools.  __Figure 4.__Representative chromatogram for albumin protein, extracted pin (blue), and 2.5 µg/mL standard (black). To demonstrate that the sample is cleaner compared to a standard preparation, a full TIC was collected for a protein precipitated plasma sample, BioSPME extracted plasma sample, and desorption solution (see __Figure 5)__. As seen, the BioSPME extracted sample is significantly closer to the desorption solution than the acetonitrile precipitated sample. The peaks that are observed in the desorption solution correspond to the deuterated carbamazepine present (RT ~4.5 min).   __Figure 5.__TIC chromatograms (5 µL injections) of phospholipids in protein precipitated sample (green), BioSPME extracted sample (pink), and desorption solution (blue). The chromatograms are adjusted to the same relative counts. ## [](https://www.sigmaaldrich.com)CONCLUSION: EFFECTIVE SAMPLE PREPARATION WITH BioSPME This [BioSPME 96-pin tool](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/solid-phase-microextraction/supel-biospme-96-pin-devices) provides a quick and efficient means to deliver a clean sample with minimal matrix effects for analysis from human plasma.  ## Materials Sorry, an unexpected error has occurred Response not successful: Received status code 500 ### References 1\. Fang N, Yu S, Ronis MJ, Badger TM. 2015. Matrix effects break the LC behavior rule for analytes in LC-MS/MS analysis of biological samples. Exp Biol Med (Maywood). 240(4):488-497. [https://doi.org/10.1177/1535370214554545](https://doi.org/10.1177/1535370214554545) 2\. Roy KS, Nazdrajić E, Shimelis OI, Ross MJ, Chen Y, Cramer H, Pawliszyn J. 2021. Optimizing a High-Throughput Solid-Phase Microextraction System to Determine the Plasma Protein Binding of Drugs in Human Plasma. Anal. Chem.. 93(32):11061-11065. [https://doi.org/10.1021/acs.analchem.1c01986](https://doi.org/10.1021/acs.analchem.1c01986) 3\. Merlot AM, Kalinowski DS, Richardson DR. Unraveling the mysteries of serum albuminâ—more than just a serum protein. Front. Physiol. 5 [https://doi.org/10.3389/fphys.2014.00299](https://doi.org/10.3389/fphys.2014.00299) __Related Articles__ - [Supel™ BioSPME 96-Pin Devices](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/solid-phase-microextraction/supel-biospme-96-pin-devices) - [Protein Binding Determination - Comparison Study of Techniques & Devices](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/solid-phase-microextraction/protein-binding-determination-comparison-study-of-techniques-devices) - [BioSPME for Plasma Protein Binding Assay: Details of Method Development and Optimization](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/analytical-chemistry/solid-phase-microextraction/biospme-plasma-protein-binding-assay) - [Protein Binding Determination Using Supel™ BioSPME C18 Pin Device as Part of the Manual Methodology With and Without Shaking](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/pharmaceutical-and-biopharmaceutical-manufacturing/small-molecules-analysis-quality-control/protein-binding-determination-using-supel-biospme-c18-pin-device) __Related Product Categories__ - [Solid Phase Micro-Extraction (SPME)](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/analytical-sample-preparation/spme-fibers-and-accessories) - [HPLC Columns](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/analytical-chromatography/hplc-columns) - [HPLC Buffers](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/analytical-chromatography/hplc-buffers) - [Solvents](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/analytical-chromatography/solvents) - [Chromatography & Spectroscopy Reagents](https://www.sigmaaldrich.com/US/en/products/analytical-chemistry/analytical-reagents/chromatography-spectroscopy-reagents) - [Biological Buffers](https://www.sigmaaldrich.com/US/en/products/chemistry-and-biochemicals/biochemicals/biological-buffers) Top __Sign In To Continue__ To continue reading please sign in or create an account. 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[Enhanced Validation Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/enhanced-validation-ab) - [Flow Cytometry Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/flow-cytometry-antibodies) - [Prestige Antibodies^®](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/prestige-antibodies) - [Primary Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/primary-antibodies) - [Secondary Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/secondary-antibodies) - [Small Pack Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/small-pack-antibodies) - [ZooMAb^® Recombinant Antibodies](https://www.sigmaaldrich.com/US/en/products/protein-biology/antibodies/zoomab-antibodies) - [Bioactive Small Molecules](https://www.sigmaaldrich.com/US/en/products/protein-biology/bioactive-small-molecules) - [Structural Genomics Consortium](https://www.sigmaaldrich.com/US/en/products/protein-biology/bioactive-small-molecules/structural-genomics-consortium) - 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[Transfer Membranes & Kits](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/transfer-membranes-and-kits) - [Immunodetection Reagents & Substrates](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/immunodetection-reagents-and-substrates) - [Membrane Immunodetection Devices](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/membrane-immunodetection-devices) - [Protein Electrophoresis Gels & Buffers](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/protein-electrophoresis-gels-and-buffers) - [Protein Electrophoresis Gel Stains](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/protein-electrophoresis-gel-stains) - [Protein Markers](https://www.sigmaaldrich.com/US/en/products/protein-biology/protein-electrophoresis-and-western-blotting/protein-markers) - 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[Primary Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type/primary-cell-culture) - [Stem Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-cell-type/stem-cell-culture) - [Cell Culture by Technique](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique) - [3D Cell Culture](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/3d-cell-culture) - [Cell Culture Media Preparation](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/cell-culture-media-preparation) - [Cell Growth & Maintenance](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/cell-growth-and-maintenance) - [Transfection & Gene Editing](https://www.sigmaaldrich.com/US/en/applications/cell-culture-and-cell-culture-analysis/cell-culture-by-technique/transfection-and-gene-editing) - 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[Biotech Resource Hub](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub) - [Discovery](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/discovery) - [Pre-clinical](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/pre-clinical) - [Phase I-II](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/phase-i-ii) - [Phase III and Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/phase-iii-and-manufacturing) - [Regulatory](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/regulatory) - [Startup Programs](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/biotech-resource-hub/startup-programs) - 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[Sterile Filtration Strategies](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/classical-pharma-manufacturing/sterile-filtration-strategies) - [Gene Therapy Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing) - [Viral Vector Upstream Processing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-upstream-processing) - [Viral Vector Downstream Processing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-downstream-processing) - [Viral Vector Formulation & Final Fill](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-formulation-and-final-fill) - [Viral Vector Characterization & Biosafety Testing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/gene-therapy-manufacturing/viral-vector-characterization-and-biosafety-testing) - 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[Viral-like Particles Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/viral-like-particles-vaccine-manufacturing) - [Viral Vector Vaccine Manufacturing](https://www.sigmaaldrich.com/US/en/applications/pharmaceutical-and-biopharmaceutical-manufacturing/vaccine-manufacturing/viral-vector-vaccine-manufacturing) - [Protein Biology](https://www.sigmaaldrich.com/US/en/applications/protein-biology) - [ELISA](https://www.sigmaaldrich.com/US/en/applications/protein-biology/elisa) - [Enzyme Activity Assays](https://www.sigmaaldrich.com/US/en/applications/protein-biology/enzyme-activity-assays) - [Flow Cytometry](https://www.sigmaaldrich.com/US/en/applications/protein-biology/flow-cytometry) - [Gel Electrophoresis](https://www.sigmaaldrich.com/US/en/applications/protein-biology/gel-electrophoresis) - [Immunohistochemistry](https://www.sigmaaldrich.com/US/en/applications/protein-biology/immunohistochemistry) - [Interrogation of Protein Pathways](https://www.sigmaaldrich.com/US/en/applications/protein-biology/interrogation-protein-pathways) - [Lysis & Protein Extraction](https://www.sigmaaldrich.com/US/en/applications/protein-biology/lysis-and-protein-extraction) - [Protein & Nucleic Acid Interactions](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-and-nucleic-acid-interactions) - [Protein Concentration & Buffer Exchange](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-concentration-and-buffer-exchange) - [Protein Expression](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-expression) - [Protein Labeling & Modification](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-labeling-and-modification) - [Protein Pulldown](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-pulldown) - [Protein Purification](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-purification) - [Protein Quantitation](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-quantitation) - [Protein Structural Analysis](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-structural-analysis) - [Western Blotting](https://www.sigmaaldrich.com/US/en/applications/protein-biology/western-blotting) - [Protein Mass Spectrometry](https://www.sigmaaldrich.com/US/en/applications/protein-biology/protein-mass-spectrometry) - [Research & Disease Areas](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas) - [Cancer Research](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/cancer-research) - [Cell & Developmental Biology Research](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/cell-and-developmental-biology-research) - [Cell Signaling](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/cell-signaling) - [Glycobiology](https://www.sigmaaldrich.com/US/en/applications/research-disease-areas/glycobiology) - 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Services - [Contract Manufacturing](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing) - [ADC & Bioconjugation](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/adc-bioconjugation) - [Diagnostic OEM & CMO Services](https://www.sigmaaldrich.com/US/en/services/ivd-development-manufacturing/diagnostic-oem-cmo) - [mRNA & LNP](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/mrna-and-lnp-formulation-ctdmo-services) - [Lipids CDMO Services](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/mrna-and-lnp-formulation-ctdmo-services/lipids-cdmo-services) - [Lipid Nanoparticle CDMO Service](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/mrna-and-lnp-formulation-ctdmo-services/lipid-nanoparticle-cdmo-services) - [Small Molecule](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/small-molecule) - [Activated Polyethylene Glycol (PEGs)](https://www.sigmaaldrich.com/US/en/services/contract-manufacturing/peg) - 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