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BioMark™ HD System
Key Applications:  Gene Expression, Single-Cell Gene Expression, SNP Genotyping, Protein Expression, Copy Number Variation, Sample Quantification for Sequencing

The BioMark™ HD System stands alone in the world of analytical instrumentation as a multi-application platform without compromise—providing high quality results for every experimental approach. Today’s biological research requires a systems approach and the BioMark HD System now has even greater impact on your understanding of your biological system by producing high quality data from RNA, miRNA, DNA, and proteins. Leading this biological insight is the system’s proven and published capabilities to uncover gene expression at the single-cell level.

  • Get a new level of insight—Reproducible results from cell populations down to a single cell
  • Save time and money—Fluidigm nanofluidic technology produces more data at drastically less cost in a shorter time
  • Expand your possibilities—Use multiple reagents and different sample and assay configurations
  • Perform analysis of protein expression, gene expression, SNP genotyping, digital PCR, mutant detection, and use real-time PCR to qualify and quantitate samples prior to next-generation sequencing
  • Accept only the best—Highest quality results from multiple applications from a single instrument

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Streamline your analysis

The SINGuLAR™ Analysis Toolset 3.0 is an intuitive, easy-to-use tool to analyze Fluidigm Single-Cell DNA sequencing, Gene Expression, miRNA Profiling, and mRNA sequencing data sets. Based on the popular statistical programming language, R, you can quickly and easily analyze, visualize and compare transcriptional or variant profiles. You can use an automated analysis command and advanced functions to perform unbiased hierarchical clustering and principal component analysis (PCA), ANOVA, and much more.

Get Started >>

 

BioMark™ System

The BioMark™ HD System provides you with the ability to use a wide variety of sample types, multiple chemistry choices, and an industry leading degree of flexibility with no compromise in performance. The system offers unparalleled throughput for real-time PCR and digital PCR, integrating thermal cycling and fluorescence detection on integrated fluidic circuits (IFCs).

Integrated fluidic circuits significantly improve productivity in life science research through the automation of PCR reactions in nanoliter volumes. This is made possible by miniaturizing and integrating liquid handling components on a single microfluidic device. The BioMark HD System consists of a real-time PCR instrument, Dynamic Array™ IFCs for multiplexing samples and reagents, as well as an IFC loader to load the Dynamic Array IFCs.

Find out how the BioMark HD System can help you to go from discovery to validation with one easy platform.

BioMark instrumentation consists of a real-time PCR instrument and a variety of chip loading platforms customized for your throughput research requirements.


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BioMark™ HD Reader

The BioMark Reader is a real-time PCR instrument designed to run Fluidigm Integrated Fluidic Circuits (IFCs) in either real-time or end-point read modes.

The reader is equipped with features that enhance throughput and ease-of-use:

     
  • Collect dozens to 147,456 data points with a single system and single technician in one day.
  • Easy-to-use acquisition software module starts a chip run in less than one minute.
  • Multiplex capability supports multiple reporter dyes.
  • Accommodates multiple IFC configurations to match your experimental and throughput needs.
  • Integrated barcode scanner avoids errors, identifies each chip type and tracks results.
  • Setup and acquisition software that easily interfaces with liquid-handling workstations.

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BioMark™ HD Reader

IFC Controllers

Fluidigm's IFC Controllers are designed to prime, load, and clean (reusable IFCs only) Dynamic Array™ and Digital Array™ IFCs.

Key advantages

     
  • Automated setup of Dynamic Array and Digital Array IFCs
  • Significantly fewer liquid handling steps when compared to conventional platforms
  • Self-contained and fully integrated design
  • Touch screen interface
                                                     
IFC Controller Dynamic Array IFCs Digital Array IFCs
  FLEXsix 48.48 96.96 192.24 FR48.48 12.765 48.770
MX   x       x x
HXx x    
RX   x   
WX    x  


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IFC Controller HX


Dynamic Array™ IFCs

Fluidigm Dynamic Array integrated fluidic circuits (IFCs) deliver a new level of efficiency and throughput for real-time PCR and genotyping applications. Dynamic Array IFCs have an on-chip network of microfluidic channels, chambers and valves that automatically assemble individual PCR reactions, decreasing the number of pipetting steps required by up to 100 fold. Reusable chip formats have also been developed to dramatically decrease costs and increase throughput. The available chip formats are:

  • 192.24 - 192 samples x 24 assays (single use)
  • FR48.48 – 48 samples x 48 assays (reusable, SNP Genotyping use only)
  • 48.48 – 48 samples x 48 assays (single use)
  • 96.96 – 96 samples x 96 assays (single use)
  • FLEXsix – Six 12 samples x12 assays single use partitions
    (unused partitions can be used over 3 months from first run)

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96.96 Dynamic Array IFC

Digital Array™ IFCs

The Fluidigm Digital Array integrated fluidic circuit (IFC) enables users to conduct digital PCR experiments. The digital array partitions a sample, premixed with PCR reagents, into hundreds of individual PCR reactions. This partitioning of the mixture allows the absolute quantification of target sequences. Digital PCR is a novel technique for PCR applications demanding extremely accurate determination of copy number variation.

Using the Fluidigm digital PCR technology, there are just five easy steps from setup to analysis to discovery. See how it's done


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qdPCR 37K IFC

PreAmp Master Mix & Reverse Transcription Master Mix

Fluidigm’s Reverse Transcription and PreAmp Master Mixes provide exceptional data results in convenient and optimized configurations. These products are provided in single tubes for 96 reactions, matching the configurations of Fluidigm IFCs. These kits are provided with optimized and validated protocols that ensure reproducible, high-quality data when used on the BioMark HD. See how it's done.


PreAmp Master Mix & Reverse Transcription Master Mix

PreAmp Master Mix &
Reverse Transcription Master Mix


DELTAgene™ Assays

Take full advantage of your BioMark™ HD System with Fluidigm DELTAgene Assays. Flexible groups of biologically-related genes are available for your specific requirements; there is no need to use fixed content. Simply provide us with your genes of interest (via RefSeq IDs) and the target species. All assays are ready-to-use via Fluidigm standard protocols.

Benefits include:

  • High quality—Sensitivity and linearity similar to probe-based assays
  • MIQE compliant—Assay primer sequences provided
  • Cost savings—Low startup and running costs

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Cq difference between 1, 10 and 100 cells easily distinguished

SNPtype™ Assays

Take full advantage of your EP1™ or BioMark HD Systems with Fluidigm SNPtype Assays. The assays provide a high-throughput, low-cost single nucleotide polymorphism (SNP) genotyping solution which enables rapid assay design and polymorphism screening. They are based on allele-specific PCR SNP detection chemistry. SNPtype Assays combine the advantages of minimum experimental setup time and flexible assay choices.

Benefits include:

  • Cost savings—Low startup and running costs
  • Confidence—Locus-specific primer sequences provided
  • Flexibility—Change targets on demand

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Cluster plot for a typical SNPtype Assay


Each software application is designed to be intuitive and easy-to-use, with the industry’s best graphical user interface. The Fluidigm software features include pipetting templates, easy import/export functionality, predefined experiment layouts, and multiple data viewing options.

The SINGuLAR™ Analysis Toolset

The SINGuLAR™ Analysis Toolset is a powerful analysis tool based on the programming language R, for analyzing and visualizing single-cell DNA sequencing and gene expression data. It includes:

  • Identify and evaluate novel mutations — Perform Fisher’s Exact test and display Manhattan plots to select for significant variants
  • Compare gene expression levels — Convert Ct values to Log2 gene expression using LoD method to assign unexpressed genes
  • Sort and filter function — Sort by gene expression and rapidly exclude low variance genes
  • Scalable computing — Process individual or multiple data sets in parallel
  • Multivariant analysis — Analyze data in hierarchical clustering or PCA to compare factors
  • Visualization tools — View data in violin plot, scatter plot, or heat map to rapidly identify major
    classes of individual cells


Download the scripts and sample data >


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Visualization Tools - Violin Plot
Results are easily viewed in multiple plots or map views.

Real-Time PCR Analysis

The Fluidigm Real-Time PCR Analysis software includes:

  • Standard curve view—Easily calculate the standard curve by identifying dilutions samples
  • Delta delta Ct calculation—Get delta delta Ct in just three easy steps
  • Automated threshold setting—Automatically determine the ideal threshold setting for each chip run
  • Automatic curve quality score—Quickly and efficiently sort through real-time PCR curves and exclude those that do not meet your  criteria

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Table and Amplification Curve Views

Results are easily viewed in table and amplification curve formats.

Genotyping Analysis

The Fluidigm Genotyping Analysis software includes additional features specific to genotyping applications including:

  • Automatic cluster calling—Automatically increase accuracy while processing more using a highly accurate cluster-calling algorithm that ranks among the best in the industry
  • Multiple chip scoring—Combines and scores multiple experiments to decrease the analysis time and improve scoring accuracy for rare  genotypes
  • Confidence score—Automatically determines the confidence level of cluster calls
  • Real time or end point—View real-time data that aids in assay design while using end-point imaging for high-throughput applications

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Allele Map

Automatic cluster calling results are easily viewed in multiple formats.

Digital PCR Analysis

The Fluidigm Digital PCR software includes features specific to digital PCR, including:

  • Real-time digital PCR—Use real-time analysis to confirm specificity of digital PCR
  • Multiplex capability—Quantitate up to four targets per sample  in each reaction by using up to four reporter dyes
  • Copy number variation—Automatically apply statistical correction and determine the ratio of your targets of interest
  • End-point analysis—Use end-point image for analysis, greatly increasing the throughput of the system

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Heat Map and Call/No-Call Map

Automatic counts and reports for the number of positives for each reporter dye are easily viewed in multiple formats.




Bibliography

Brochures

Specification Sheet

Data Sheets

Application Notes

Customer Focus


News

  • July 10, 2010
    Leading INRA Facility Reports Robust Genetic Analysis Results from Fluidigm Biomark™ System
    Number One Agricultural Institute in Europe Brings World-leading Integrated Fluidic Circuit Technology to All European Researchers

Featured Publications

Featured Posters

ISSCR 2013: ASCB 2012: AMN 2011:

Gene Expression and SNP Genotyping Workflow

  • Prime. Prime the Dynamic Array IFC to close the interface valves, preventing premature mixing of samples and assays.
  • Transfer. Pipette samples, premixed with master mix, into separate sample inlets and primer-probe sets into separate primer-probe inlets on the frame of the chip.
  • Load. Place the Dynamic Array IFC on the IFC Controller, and use the software interface to pressure load the assay components into reaction chambers. Assay components are automatically combined on-chip.
  • Run. Place the Dynamic Array IFC on the BioMark System for thermal cycling and end-point or real-time fluorescence detection.
  • Analyze. Use the analysis software to view and analyze color-coded allele maps and cluster diagrams for one or more chip runs.

  

Digital PCR Workflow

  • Prime. Prime the Digital Array IFC to prepare it for transferring samples.
  • Transfer. Pipette each of the samples, premixed with master mix and primer-probe sets, into separate inlets on the frame of the chip.
  • Load. Place the Digital Array IFC on the IFC Controller, and use the software interface to pressure load the assay components into separate panels of reactions.
  • Run. Place the Digital Array IFC on the BioMark System for thermal cycling and fluorescence detection.
  • Analyze. Use the analysis software to view and analyze amplification curves and color-coded heat maps for one or more chip runs.

  


Instrument Specifications 
Performance
Throughput 2,304 reactions per run with the 48.48 Dynamic Array IFC
9,216 reactions per run with the 96.96 Dynamic Array
IFC
9,180 reactions per run with the 12.765 Digital Array IFC
36,960 reactions per run with the 48.770 Digital Array IFC
Components
LED Excitation Sources
(center, in nm)
475-41, 530-16, 575-31
Optional: 632-27
Emission Filters
(center, in nm)
525-25, 570-30, 630-30
Optional: 700-30
Detection CCD camera; 9MPixel, 12 µm; 12 µm pixel size
Thermal Control Peltier-based, ranging from 4ºC - 99ºC
Max heating rate: > 5ºC/sec
Max cooling rate:  > 5ºC/sec
Chip Compatibility Dynamic Array IFCs (48.48, 96.96, FR48.48)
Digital Array IFCs (12.765, 48.770)
Software Fluidigm Real-Time PCR Analysis Software
Fluidigm SNP Genotyping Analysis Software
Fluidigm Digital PCR Analysis Software
Fluidigm Data Collection Software
Computer and Accessories Windows XP PRO, having at least 2 GB memory, 300 GB hard drive, 4 USB ports, LCD flat screen monitor, keyboard and mouse
Data Storage Options 1 GB/sec Ethernet connection; 40 GB hard disk space; USB port for memory stick
Startup Support
Installation Installation kit; On-site installation and training

TaqMan is a registered trademark of Roche Molecular Systems, Inc

Integrated Fluidic Chip (IFC) Specifications

                                                                                                                       
Parameter 96.96
Dynamic
Array IFC
192.24 Dynamic Array IFC 48.48 Dyanmic Array IFC FR 48.48 Dynamic Array IFC 48.770
Digital
Array IFC
FLEXsix Gene Expression IFC   12.765
Digital
Array IFC
qdPCR 37K
IFC
Sensitivity of detection Single-copy per 6.75 nl reaction Single-copy per 9 nl reaction Single-copy per 10 nl reaction Single-copy per 8 nl reaction Single-copy per 0.85 nl reaction Single-copy per 9 nl reaction Single-copy per 6 nl reaction Single-copy
per 0.85 nl reaction
Sample wells 96 192 48 48 48 12 per partition (x6) 12 48
Reagent (primers/probes) wells 96 24 48 48 Combined with Sample 12 per partition (x6) Combined with Sample Combined with Sample
Input volume per well5 µl      (minimum)3 µl (minimum)5 µl (minimum)5 µl (minimum)8 µl      (minimum)3 µl (minimum)4 µl (minimum)8 µl     (minimum)
Liquid-transfer steps19221696964824 per partition1248
Reactions per chip9,216
(96 x 96)
46082,304
(48 x 48)
2,304
(48 x 48)
36,960
(48 x 770)
144
per partition
9,180
(12 x 765)
36,960
(48 x 770)
Experiment trackingChip-specific barcodesChip-specific barcodesChip-specific barcodesChip-specific barcodesChip-specific barcodesChip-specific barcodesChip-specific barcodesChip-specific barcodes
Setup and valve controlIFC Controller HXIFC Controller RXIFC Controller MXIFC Controller WXIFC Controller MXIFC Controller HXIFC Controller MXIFC Controller MX
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