Caren B. Les, firstname.lastname@example.org
LOS ANGELES – Molecular diagnostics is the fastest growing segment of the in vitro diagnostics
market, according to a study by DeciBio, a Los Angeles-based market analysis firm.
Stéphane Budel, a partner in the company, said the market size, estimated at
$4.8 billion in 2010, has experienced a growth rate of approximately 15 percent
over the past few years, driven by the increased availability of tests, the rising
incidence of chronic diseases related to the aging population, and pharmacogenomics/personalized
DeciBio published its report Molecular Dx: Market Segmentation
and Opportunities in October 2010.
“The market for photonics-based molecular diagnostic tools
has been attractive and will remain so in the foreseeable future,” Budel said.
The vast majority of molecular diagnostic tests rely on detection of nucleic acids
and use some form of photonics-based tool, primarily fluorescence, for sequencing
and real-time polymerase chain reaction (PCR), chemiluminescence for transcription-mediated
amplification, or a chromogenic method such as in situ hybridization.
The LightCyler, an instrument for rapid online PCR-based applications,
is undergoing tests.
In addition, a number of new automated photonics-based platforms,
including the San Diego-based Gen-Probe Inc.’s Tigris DTS direct-tube sampling
system, have supported the growth and adoption of legacy tests, he said.
Molecular diagnostic tests identify biological markers in the
form of nucleic acids such as DNA or RNA. These nucleic acids can be genetic material
of foreign organisms, as in the case of an HIV infection, or markers that distinguish
normal from abnormal tissue, such as in the case of overexpression of the breast
cancer receptor Her-2.
Molecular diagnostic tests do not include microbiology ones that
detect whole organisms by culturing them in a dish or immunochemistry tests that
detect protein, typically using antibodies.
“Current technologies are well understood, but establishing
growth figures for rising photonics-based molecular diagnostics test markets, such
as next-generation sequencing or bead-based multiplex technologies, can be difficult,
as current utilization is small, making current market size hard to estimate,”
Budel said. “Moreover, key customers are still gauging their forecasted level
of adoption for the next few years.”
He estimated the real-time PCR market at $2 billion, the transcription-mediated
amplification market at $1 billion, the combined in situ hybridization and fluorescence
in situ hybridization (FISH) market at $700 million and the sequencing market at
“Each of these technologies depends on an instrument with
photonics-based elements,” he said. “The key trends affecting these
instruments are increased automation, work-flow simplification and multiplexing.
“Multiplexing – the ability to look at multiple analytes
in a single sample – is of particular relevance to photonics-based tools,
as it depends on the availability of instruments with the right set of excitation
sources and filters as well as the existence of appropriate dyes.
“Currently, growth in the molecular diagnostics test market
is driven in large part by adoption of multiplex tests because these assays tend
to be more comprehensive, only require smaller sample volumes and can eliminate
intrasample variability. Advances in personalized medicine necessitate the analysis
of multiple analytes in a single sample in order to make a diagnosis; for example,
the Oncotype DX from Genomic Health Inc. of Redwood City, Calif., examines the activity
of 12 genes in a patient’s tumor. Limiting factors in multiplexing technologies
are often linked to cross-reactivity, higher costs and spectral differentiation
for signal detection.”
Budel cited four photonics-based molecular diagnostic tools that
have gained traction or that are on the horizon: point-of-care readers, next-generation
sequencing platforms, low-density bead-based microarray readers and digital anatomical
Although current point-of-care readers rely primarily on simple
tests often based on chemistry/immunochemistry, some companies are beginning to
develop molecular diagnostics-based tests because of their higher sensitivity and
“This evolution is motivated by the increased number of
genetic biomarkers found each year and rendered possible by the development and
uptake of molecular diagnostic test techniques that do not require thermal cycling,
thereby facilitating instrument development,” Budel said. “Some of the
key applications for point-of-care readers include infectious-disease testing in
the field, such as for HIV, or in hospitals, such as for MRSA [Methicillin-resistant
Staphylococcus aureus] infection, where an immediate response is critical for patient
triage. The key challenge for these readers is photonics miniaturization.”
Next-generation sequencing platforms enable an entire human genome
or transcriptome to be sequenced in about a week for a few thousand dollars, he
added. It is starting to be used in clinical settings, in centers of excellence
and by companies such as GeneDx Inc. of Gaithersburg, Md. The technology seems poised
to revolutionize health care and affect a broad range of stakeholders, with the
$1000 genome right around the corner, Budel said.
“These sequencing instruments promise to be a key platform
for optics in the next few years,” he added. “One of their key applications
will be repeat sequencing of patient tumors to identify mutations in cancer cells
that create resistance to drug treatment. The main challenges for this technology
are higher sensitivity and resolution of signal from higher picture density.”
Low-density bead-based microarrays also are expected to play an
increasingly important role in molecular diagnostic testing.
“These laser-based instruments can measure 50 to 500 analytes
in a single sample at a throughput appropriate for clinical settings – especially
for hospital-based laboratories,” Budel said. This technology promises to
have applications ranging from genetic mutation panels to respiratory viral panels
such as flu strains and other viruses. The challenges for bead-based microarrays
are higher sensitivity and discrimination of spectral overlaps.
“Digital anatomical pathology may be the future of histology,”
Budel noted, and it is used in less than 10 percent of US hospitals and clinical
labs. “The technology allows health care providers to digitally capture, store
and share images of biopsies from patient tissues on slides. Software can perform
some of the work done by a pathologist and help with data interpretation and reflex
testing. The key hurdles for this technology are clearer pictures with a 3-D feeling,
faster image acquisition and downstream analysis.”
An employee of Roche, based in
Basel, Switzerland, works on the production of PCR (Master Mix) reagents for diagnosing
the hepatitis C virus. The balance control panel is shown in the background. Images
courtesy of Roche.
Roche, Abbott Molecular, Siemens and Qiagen are the major PCR/real-time
PCR companies, Budel said. Applied Biosystems and Roche offer two of the most popular
laser-based instruments to perform these tests in clinical settings, he said, adding
that Gen-Probe offers large-volume tests used for blood screening based on transcription-mediated
amplification and hybrid capture technology, while Dako, Vysis (Abbott Molecular)
and Ventana Medical Systems (Roche) are key developers of in situ hybridization
“Within the latest instrument-based technology, Illumina,
Life Technologies and Roche (454 Life Sciences) are top sequencing companies,”
he said. “For bead-based technologies, Luminex is the current company of choice.
Key digital anatomical pathology suppliers include Roche (BioImagene) and Aperio.”