Bioanalytical ServicesWhat we do
Proteins for early disease diagnostics
Protein biomarkers are optimal for early phenotypic diagnosis or monitoring treatment response. Protein markers offer a significantly higher degree of differentiated information compared to genomic markers and will immediately mirror the state of the biological system. In addition, proteins provide the direct functionality which makes them essential in understanding disease pathology and other biological phenomena.
Sample types for protein analysis
The majority of protein biomarkers are low abundant proteins found in minimally-invasive samples such as blood serum, urine, saliva and other accessible body fluids. However, understanding disease pathology often requires more insight, therefore we offer biomarker studies on a wealth of sample types, for example tissue biopsies, plasma, cerebrospinal fluids, microvesicles, cell lysates etc. Most of our assays are developed to human samples but can be used with success for a variety of other species.
Using Proximity Extension Assay (Olink Proteomics) we can provide disease-focused screening of 92 protein biomarkers measured simultaneously using only 1µL sample. Each panel of 92 biomarkers are targeted at a specific disease or key biological process. The panels cover a total of 1165 clinically relevant proteins, divided into 15 different focused biomarker panels, e.g. oncology, immuno-oncology, inflammation, immune response, cardiovascular disease, neurology, cell regulation and development, metabolism, organ damage and a translational mouse panel.
Digital protein quantification
Using nCounter® (nanoString Technologies) we offer digital single molecule detection. The analyses have a high multiplex level with approximately 30 biomarkers in each panel. The panels are focused to immune cell profiling, cell signalling, solid tumor lysate with focus on phosphorylated proteins and a hematology panel for lysate and FFPE samples. The technology is fully automated to ensure precise and reproducible measurements, across many sample types, including low-quality samples and FFPE tissue.
The nCounter® system also permits simultaneous quantification of DNA, RNA and protein, allowing you to compare genotype with gene and protein expression.
Technologies for protein biomarker screening:
What is microRNA?
MicroRNAs (miRNAs) are a group of small non-coding RNAs that are involved in regulating a range of developmental and physiological processes; their dysregulation has been associated with development of diseases. Circulating miRNAs and exosomal miRNAs have also been proposed as being useful in diagnostics as biomarkers for diseases and for monitoring treatment.
MicroRNA as diagnostic biomarkers
MicroRNA (miRNA) biomarker screening is targeted for the investigation of regulatory functions related to cell growth, development, differentiation and a variety of human diseases. Depending on the application and the purpose of the analysis BioXpedia offers different miRNA profiling techniques.
Multiplex miRNA profiling using Fluidigm
Using the Fluidigm Biomark HD system we provide miRNA expression profiling and experimental validation in a variety of sample types. The Biomark system ensures efficient, high-throughput processing of miRNA samples with increased speed and reproducibility. The technology is fast and only requires small sample volumes in the nanoliter scale, making it ideal for miRNA profiling.
Digital detection and quantification of miRNA
With the nCounter® miRNA Expression Assays from NanoString Technologies we perform highly multiplexed, direct digital detection and quantification of miRNAs in a single reaction. The assays are optimized for robust performance across a variety of sample types and in a wide range of biological areas of research, including cell signalling, neuroscience, stem cell research, autophagy, infectious disease, and immunology. The nCounter® technology allows simultaneous measurement of miRNA and mRNA from the same sample, making it ideal to study the impact of miRNAs on their target mRNAs.
Technologies for miRNA biomarker screening:
What is Single Nucleotide Polymorphism (SNP) variation
SNPs (single nucleotide polymorphisms) or point mutations are the most common types of genetic variation determining a major part of the phenotypic diversity between individuals. Causal point mutations change the amino acid sequence of the encoded protein and hence such SNPs can be used as markers for development of companion diagnostics and stratification of patients.
SNP variation analysis
BioXpedia offers SNP genotyping for investigation of genetic associations, structural changes, copy number variations or loss of heterozygosity (LOH). Additionally, we provide SNP tracing for standardized authentication and quality control check of biobank samples and cell lines. We offer different genotyping technologies depending on the application and the purpose of the analysis, the number of SNPs per sample and the number of samples in the study.
SNP genotyping using Fluidigm Biomark
We provide gene-wide SNP genotyping, e.g. fine mapping or haplotyping of candidate regions including the analysis of <500 SNPs using the Fluidigm Biomark HD. The Fluidigm System enables efficient, high-throughput processing of SNP genotyping samples with increased speed and reproducibility, and with small quantities of DNA required, which makes it ideal for precious sample analysis.
Digital DNA analysis – high quality performance on FFPE samples
Especially suited to FFPE samples is the nCounter® DNA Assays to investigate mutational status. These assays are highly optimized for robust performance on FFPE samples and provides simple multiplexing of genetic and copy number variation (CNV) while providing precise, accurate, and robust results. With the shortest hands-on time of any DNA analysis platform, the nCounter® Analysis System is ideal for translation and routine screening applications.
Technologies for SNP genotyping:
Gene expression biomarkers
RNA expression analysis to study molecular regulation
Analysis of changes in gene expression levels is the first level of exploration for any regulation at the molecular and cellular levels. Transcription of genes is a very dynamic process, allowing cells to adapt rapidly to external, environmental or physiological changes. Therefore, gene expression profiling is a very powerful way of identifying biomarkers that describe a given physiological state, disease or exposure to drugs.
High throughput gene expression profiling
BioXpedia provides gene expression biomarker screening using technologies that are time-, cost-, and sample-effective, allowing profiling of the RNA content at single cell level.
High multiplex level and low sample requirement
With the Fluidigm BioMark HD technology rapid and reproducible results are ensured with an automated workflow on Integrated Fluidic Circuits (chips) with reaction chambers of less than 10nl. The high capacity, multiplex level system enables simultaneous detection of 96 assays in 96 samples creating 9.216 data points in a single run. Therefore, the technology offers production scale throughput and exquisite single cell sensitivity with a wide range of genomic applications, making it flexible to your own design.
Targeted direct digital gene expression detection
Using the nCounter Gene Expression Panels from nanoString Technologies, we perform highly multiplexed, direct digital detection and quantification of mRNA molecules in a single reaction. The assays are optimized for robust performance across a variety of sample types and in a wide range of biological areas of research. The nanoString technology can detect target molecules as small as 100 base pairs with less than 100ng of input material. This enables multiplex gene expression profiling with single cell worth of input.
Technologies for screening of RNA biomarkers:
Extraction and isolation of biomarkers
BioXpedia offers sample preparation and high-quality extraction of the molecules of interest – DNA, RNA species and proteins – for any downstream analysis.
Sample types for biomarker isolation
We provide extraction from plasma, serum, whole blood, tissue biopsies and FFPE tissue along with any other biofluid sample such as urine, cerebrospinal fluid, saliva, and tear fluid. Furthermore, cultured cells and medium from cell cultures can be used as a source for extraction of the biomarker molecules of interest.
Our extraction methods are suitable for mRNA extraction and small RNA species such as miRNA. Additionally, we offer isolation of RNA from extravesicular vesicles like exosomes derived from plasma, serum and other biofluid samples.
Extraction of protein biomarkers is optimized for the specific sample type, for example cells or tissue, to ensure extraction of native proteins and avoid degradation of proteins prior to analysis.
Quantification and integrity (RIN) analysis of extracted RNA and DNA
The concentration and quality of extracted DNA and RNA is assessed by state-of-the-art technologies (4200 TapeStation, QIAxpert) to assure high quality input material for our downstream analyses. Automated workflow and robotic pipetting is used whenever possible to ensure maximum reproducibility and efficacy.
If your research is specifically focused on a sample type not mentioned above, please do not hesitate to contact us for a discussion.
Statistics and bioinformatic analysis
Analysing multi-marker data often requires advanced biostatistical methods to translate raw output data into credible and substantiated interpretation and biological knowledge.
BioXpedia offer statistical analysis of your data, for example gene expression or protein screening data. We can provide a standard statistical service, or you can choose a customized biostatistical analysis for more complex project designs and analyses. The biostatistical analyses are performed by bioinformatic professionals experienced in handling data output from the technologies that BioXpedia offers. Our biostatistical analysis and consultancy ensure that you acquire the maximal value and information output from the bioanalytical data of your project.
Standard biostatistical service
The standard statistical service includes an investigation of which biomarkers are significantly different between groups of interest, for example between a disease and control group of patients. A fast and reliable way to get the most out of your experiment!
The standard biostatistical service includes:
- Test for normal distribution of data to investigate assumptions for statistical tests.
- Hierarchical cluster analysis or Principal Component Analysis (PCA) to investigate how the profile of all samples group together.
- Identification of significant differential markers between groups, either by parametric or non-parametric tests. Correction for multiple testing is performed using false discovery rate.
- Visual presentation of all significant markers and fold change in a Volcano plot for each group comparison.
- Standard report including detailed description of statistical analysis, boxplots of significant markers and a table listing significance and fold change of all markers.
Tailored biostatistical service
If you have a project with a more complex experimental design, for example time-series data, or need additional statistical analyses and bioinformatics, we can tailor our biostatistical service targeted specifically to your project.
We also offer analyses to support decision on project and experimental design, for example power analysis and sample size calculation.
Customized biostatistical analysis is for example:
- Univariate and multivariate statistical analyses, for example ANOVA, T-test, Principal Component Analysis (PCA), Partial Least Squares etc.
- Cluster analysis, for example heat-map, K-means clustering for response profile clustering to identify markers that respond similar for example during a time course.
- Network analysis for visualization of the correlation, interaction or association among markers in a complex biological system.
- Gene Ontology annotation and enrichment analysis for example of KEGG pathways.
- Model development and fitting for identification of predictive markers and validation of discovered markers.
Open Olink Proteomic panels
Each Olink Proteomic protein biomarker panel (PEA technology) provide disease-focused screening of 92 protein biomarkers. The PEA technology is run using Fluidigm 96.96 IFC chip, thus each run (chip) has space for 90 patient samples plus assay controls.
However, if you have a small project or need to run a pilot project before initiating a large-scale study including many clinical samples, it is possible to team up with other researchers to share costs.
Pilot projects running on shared chips will await a sufficient number of samples for the panel, thus a longer delivery time can be expected. We will of course keep you updated on the timeline for your project.
More information on the Proximity Extension Assay from Olink Proteomics here
Joint R&D projects – Scientific excellence together
BioXpedia is eager to participate in national and international biomarker research and development projects. We may contribute to innovative research as service provider or as SME-partner in grant proposals or research consortia. BioXpedia is ready to establish true research collaboration by exchanging knowledge, data and research expertise for shared research projects, developing scientific and commercial innovations.
BioXpedia participates actively in international funding programs such as H2020 and Eureka-Eurostars and Danish research programs run by Innovation Fund Denmark, the Lundbeck Foundation and the Novo Nordisk Foundation.
A background with many years of scientific research and experience from several successful R&D projects, makes BioXpedia the ideal partner for establishing partnerships for biomarker discovery and validation.
If you are interested in exploring collaboration opportunities, please contact us
BioXpedia is in all aspects committed to operate under controlled conditions and under the highest level of quality.