Making room for robotics in molecular labs
August 2003 William Check, PhD
Which of us has not pondered at least once that recurrent dilemma:
Should I upgrade my computer now or wait six months for the next
generation? Sure, there are bargains to be had among current models.
And the new models will sell at a premium. But the newer computers
will be blazingly fast. And who knows what spiffy features they
will offer?
A similar conundrum
is shaping up in molecular diagnostics. Nucleic acid extraction
has long been a tedious, repetitive manual operation, with little
more in the way of instrumentation than pipetting robots—for
those who could afford them. However, over the past few years truly
automated nucleic acid extraction devices have become available
from Roche, Qiagen, and Gentra. In the next year, several more options
will reach the market, with offerings from Abbott and Cepheid as
well as advanced models from Roche and Gentra. Should a laboratory
that hasn’t yet invested in automated extraction technology
buy what’s available now? Or should it wait for the next round
of instruments? And what about laboratories that already have an
instrument—should they consider trading up?
For a discipline
that has struggled with manual procedures for too long, this is
a welcome dilemma. Semiautomated extraction instruments based on
organic methods were available more than a decade ago, notes Daniel
H. Farkas, PhD, associate professor of pathology at Baylor College
of Medicine and director of molecular diagnostics at Methodist Hospital,
Houston. “When improved, nonorganic chemistries were introduced,
the field moved away from automation for a time,” Dr. Farkas
says. “In only the past two to three years has automated nucleic
acid extraction started to come around again, based on these same
nonorganic chemistries. Now the field is really mushrooming.”
Gradual evolution
of technology has played a part in this advance. Another major impetus
has come from widespread adoption of real-time PCR cyclers. “Everyone
has been moving to real-time instrumentation,” says Karen
Kaul, MD, PhD, director of molecular diagnostics at Evanston (Ill.)
Northwestern Healthcare and professor of pathology and urology at
Northwestern University Feinberg School of Medicine, Chicago. Real-time
cyclers combine amplification and detection in a single vessel.
“Real-time cyclers offer huge time and labor savings,”
Dr. Kaul says. For the first time, molecular diagnostics has a “black
box” like those in clinical chemistry—samples go in
and results come out with no human manipulation. “Real-time
PCR took a lot of post-amplification processing out of the picture,
so now most labor and time is expended in sample preparation,”
Dr. Kaul says. “And we are finally seeing strides in automated
sample preparation.”
Real-time PCR
cyclers are “the first part of this whole revolution,”
agrees Frank Cockerill, MD, chair of the Division of Clinical Microbiology
at Mayo Clinic and professor of microbiology and medicine at Mayo
Medical School. Because they are closed systems, real-time cyclers
lessen the chance for amplicon carryover without the need for special
air-controlled PCRlaboratories. They also have a rapid turnaround
time, with some analyses completed in about 30 minutes. And in many
cases, real-time PCR is more sensitive than culture-based methods.
Dr. Cockerill has found that real-time PCR increases the sensitivity
of detection of herpes simplex virus by 23 percent, varicella-zoster
virus by 90 percent, Bordetella pertussis by 219 percent,
and vancomycin-resistant enterococcus from stool by 100 percent
(Espy MJ, et al. J Clin Microbiol. 2000; 38: 795–799,
3187–3189; Sloan LM, et al. J Clin Microbiol. 2002;
40: 96–100). “We currently offer 15 tests that use this
technology and have probably 20 more in development,” Dr.
Cockerill says.
“Because
of the revolution in real-time detection by PCR or other amplification
methods, there is a huge need for automated extraction technology,”
says David Hillyard, MD, director of molecular infectious disease
testing at ARUP Laboratories. Continuing increases in test volume,
too, have augmented the need for robotic extraction in all areas
of molecular diagnostics. “As the first entry-level platforms
have proven successful, many new robotic platforms are coming to
market,” Dr. Hillyard notes.
Specialists
in molecular diagnostics suggest that laboratorians who are considering
purchasing an automated extraction device evaluate many dimensions
besides technical specifications. “I look for flexibility
more than number,” Dr. Kaul says. She wants an instrument
that can handle blood, plasma, swab samples in medium, urine, even
tissue. Throughput must be matched to each laboratory’s circumstances.
“A laboratory that does large volumes of HIV or HCV has needs
that are significantly different from a laboratory like mine, which
does smaller volumes of a wider range of tests and sample types,”
Dr. Kaul says. “One of the challenges for companies is to
create instruments that will answer needs on both ends of the spectrum.”
As Dr. Hillyard
puts it, “The notion that one size does not fit all is certainly
true in this field.”
Automation
could bring structural and other changes to molecular diagnostics
laboratories, Dr. Kaul says: “At one point we thought we would
be much more like clinical chemistry. And to some extent that is
the case.” Will automated instruments combined with commercial
kits reduce the need for laboratory directors experienced in molecular
technology? “Certainly having automated equipment reduces
the degree of expertise needed by the technical staff,” she
says. “But you still need a significant amount of expertise.”
Equipment expense
is another factor. At Dr. Kaul’s hospital, it has driven centralization
and sharing of equipment. “Right now we are mostly seeing
consolidation of equipment and platforms,” she says. On the
other hand, at some hospitals microbiology, medical genetics, and
molecular hematopathology might have sufficient volumes to justify
molecularly equipped and staffed laboratories in each of these areas.
Eventually, when reagents are in kit form, making validation unnecessary,
and instrumentation is automated, it may become the norm to have
equipment in every area. For now, she says, “we are still
in a transition period.”
Mayo Clinic’s
Division of Clinical Microbiology combines decentralization and
centralization, Dr. Cockerill says. Twelve real-time cyclers are
divided along traditional lines—bacteriology, virology, and
parasitology—while six automated nucleic acid extraction instruments
handle all samples centrally, in the same area as accession and
culture.
Bringing in
an instrument that costs $150,000 to $200,000 requires putting several
assays on it to justify its purchase. “For the first time,
in the last year I started thinking about what assays we can put
on these platforms, something other clinical laboratories have had
to think about for years,” Dr. Kaul says. “If we are
going to run CF, do we want to go with [Third Wave’s] Invader
because we also do factor V? Or are we better off going with ABI
and switching other assays to that platform?” Manufacturers
are going to have to address this question too, she says.
Then there is
stat testing and around-the-clock staffing. “As we move into
analytes needed around the clock, such as group B strep on women
who are about to deliver or bacterial resistance testing, when are
we going to have to staff our laboratory three shifts and weekends?”
Dr. Kaul asks. Right now she is facing that question with regard
to detecting methicillin-resistant Staphylococcus aureus.
In most places MRSA testing is done by culture and takes two to
three days. With a molecular assay, screening for MRSA can be done
in two to three hours, detecting patients who are carriers and possibly
preventing nosocomial infections. “If we want to do that test
in the time frame that clinicians need, we will have to look at
evening and weekend hours, which is a real shift from how we have
been running the molecular laboratory,” Dr. Kaul says. She
recently instituted Sunday coverage for MRSA by real-time PCR.
Contamination
is another concern. “Many people worried about contamination
from these fairly open robotic instruments,” Dr. Hillyard
says, “especially people in infectious diseases.” The
rate of contamination with manual extraction is very low. “Comparing
that very low rate to hopefully another very low rate would be quite
difficult,” he says. Perhaps the most compelling current evidence
is lookback data—tracking experience over months and years
of use. “What many people report, and our experience is the
same, is that there is no evidence for a higher rate of contamination
with robotic instruments,” says Dr. Hillyard. “Probably
the opposite is true, since they take a lot of human errors out
of the picture.” As an extra precaution, ARUP keeps its robotic
extraction instrument in a separate room from its cyclers.
And will it
be necessary to revalidate your method? “These instruments
run a particular chemistry,” Dr. Hillyard says. “When
we set up a clinical test, we validate that test for a specific
chemistry. So one thing that needs to be carefully considered as
you progress to a next-generation instrument is whether you are
going to have to use a different chemistry that might necessitate
revalidating your methodology.” He cites as an example ARUP’s
Qiagen 9604 robot, developed for R&D work but adapted by ARUP
and others to clinical samples. ARUP is now replacing it with a
more advanced walkaway Qiagen extractor. Since the newer instrument
uses the same chemistry as the 9604, less extensive revalidation
is necessary.
Then there is
the step in which the robot presents the extracted nucleic acid
to the amplification/detection device, sequencer, or other analytical
instrument. For this, liquid handling is required. “MagnaPure
is one instrument that does that very well,” Dr. Hillyard
says. “Other platforms are doing a great job of moving in
that direction too.”
Raymond Tubbs,
DO, professor of pathology at the Cleveland Clinic Lerner College
of Medicine and chair of the Department of Clinical Pathology and
section head of molecular genetic pathology at the Cleveland Clinic
Foundation, raises other strategic issues. “We need to be
thinking differently about laboratory operations,” he says.
Most laboratories still focus on batch testing once or more per
week, he notes. “Instead,” he says, “we need to
be moving toward continuous-flow operations wherever possible to
improve throughput and leverage automation.” LightCycler-based
assays, for example, have high throughput. “If one links automated
extraction to real-time PCR,” he says, “one can convert
a labor-intensive three-day assay to automated closed platforms
that can reduce turnaround time from days to hours and improve safety
for laboratory personnel.” Factor V Leiden mutational analysis,
as one example, is readily amenable to coupled automated extraction
and real-time PCR analysis, says Dr. Tubbs.
Second, he says,
“Molecular methods have been very much a part of clinical
microbiology, but molecular applications for disorders other than
infectious diseases have lagged behind.” Now he sees more
molecular genetics, molecular oncology, and molecular hematopathology
applications as prime candidates for automation as well. “So
the scope and utility of automation in those areas need to catch
up with what has been much more readily available for molecular
microbiology.”
Finally, he
highlights the need for a skilled workforce. “As in all areas
of clinical pathology,” Dr. Tubbs says, “there is a
tremendous need for skilled molecular technologists.” In practice,
he finds, technologists who have experience in other areas must
be hired and trained in molecular skills on the job.
Turning
to specific automated nucleic acid extraction instruments,
Roche’s MagnaPure is most widely used in clinical laboratories,
even though it was designed for research labs. “One issue
in adapting the MagnaPure to the clinical laboratory is that its
manufacturing processes and documentation are not up to what we
are used to,” says Frederick Nolte, PhD, professor of pathology
and laboratory medicine at Emory University School of Medicine and
director of the clinical microbiology and molecular diagnostic laboratories
of Emory Medical Laboratories, Atlanta. Even so, says Dr. Nolte,
who was one of the first to see the clinical potential of this instrument
and to adapt it for clinical use, “in practice it has not
made a difference.”
In automating
sample preparation, Dr. Nolte puts a premium on versatility. “It
doesn’t do any good to have automation that serves only one
test in the laboratory,” he says. “You ought to be able
to have a couple of extraction protocols that handle most of your
specimens.” For his lab, MagnaPure meets that need. His laboratory
uses it mostly for extracting viral nucleic acid and human genomic
DNA for a number of formats—Amplicor kits and tests developed
in the lab—and a variety of platforms—ABI Prism, LightCycler,
and Cobas Amplicor (Clin Chem. 2002; 48: 613; J Clin
Microbiol. 2003; 41: 2062). “At 32 samples in 1.5 hours,
it fits our volume and workflow,” Dr. Nolte says.
Their only problem
is that they use the instrument for so many samples that it has
become a bottleneck and he has to buy another one. “We keep
bringing new tests online, so it is a coping mechanism,” he
says. “It allows us to do more things with the same number
of people.” Dr. Nolte calls buying the MagnaPure “one
of the few popular decisions I have made in the laboratory.”
“As exciting
as it is conceptually,” he says, “molecular diagnostics,
in practice, involves a lot of repetitive manual steps. It gives
great answers, but performance is basically repetitive pipetting.
Anything you can do to alleviate manual sample preparation, which
is now the most labor-intensive aspect, will be appreciated.”
Dr. Cockerill
was also an early adopter—and adapter—of the MagnaPure.
“Extraction is the last part of this whole process to be automated,”
he says. “Infectious agents frequently occur in low counts
in various body fluids or tissues, so we need efficient extraction
methods.” Some previous manual techniques have been efficient
but have taken several hours to carry out. With MagnaPure, extraction
has been done in about 1.5 hours for a full run of 32 samples.
Although the
MagnaPure is almost completely automated, and will even load cuvettes
containing extracted samples into the rotor used for LightCycler,
Dr. Cockerill has found that manual loading saves time. Likewise,
he finds that not all samples need to be extracted by an automated
instrument. “We put herpesvirus samples on MagnaPure,”
he says, “but for group A strep automated extraction would
actually take longer.” Dr. Cockerill considers MagnaPure cost-efficient
because of its rapid turnaround time and higher sensitivity.
Dr. Tubbs uses
the MagnaPure for most high-volume, high-throughput assays in molecular
genetic pathology, including 1,500 factor V Leiden tests per year.
A second instrument will be installed in molecular microbiology.
“MagnaPure is relatively easily incorporated into laboratory
operations,” Dr. Tubbs says. “My impression is that
it has allowed us to absorb volume increases that would have been
very difficult to handle manually.”
Roche is in
clinical trials now with a second automated extraction instrument,
the Cobas AmpliPrep system, which provides an automated front end
to the Cobas TaqMan 96 and 48 analyzers, says Ronnie Andrews, senior
vice president for marketing and commercial business development
for Roche Molecular Diagnostics. The aim is to provide laboratories
with an FDA-cleared front and back end for hepatitis and HIV PCR
assays. AmpliPrep is in clinical use at more than 300 sites outside
the United States.
Dr. Nolte says
Cobas AmpliPrep works only for laboratories that are doing high-volume
testing of analytes that Roche chooses to put on the Cobas. “That
is not the bulk of small to medium clinical laboratories,”
he points out.
Roche’s TaqPrep biorobot, a higher-volume, higher-throughput,
open-architecture system, will enter clinical trials in the fourth
quarter of this year. TaqPrep will be two to three times faster
than MagnaPure and AmpliPrep, Andrews says. It has one manual step—transferring
the DNA-rich amplicon to TaqMan. The FDA has recommended a closed
architecture for HIV testing; thus, the combination will go through
rigorous clinical trials and be validated from start to finish for
HIV.
Qiagen
offers a range of automated nucleic acid extraction instruments,
including those developed in-house and those acquired in the purchase
of Genovision. Dr. Farkas bought five Qiagen instruments in the
process of setting up from scratch a molecular diagnostics laboratory
at Methodist Hospital. “The Methodist Hospital has been sending
almost all molecular testing to a large reference laboratory,”
Dr. Farkas says, “and we need to bring that in-house. Any
hospital with a reasonably sized pathology laboratory and without
an in-house molecular service is likely sending out hundreds of
thousands of dollars of tests.”
Dr. Farkas surveyed
all available instruments. “I thought Qiagen’s experience
in nucleic acid extraction chemistries clinched it,” he says.
“And the breadth of equipment Qiagen provided was a huge plus.
They were able to package for us a nice combination of robots at
an attractive price.”
He bought two
EZ-1s, which he calls “incredible machines that can generate
high-quality DNA from six blood samples in 20 minutes.” Dr.
Farkas believes the EZ-1 is appropriate for relatively low-volume
tests, such as prothrombin mutation analysis, herpes simplex virus,
Epstein-Barr virus, and factor V Leiden. It processes only blood
now, but Qiagen is adding new protocols to accommodate additional
specimens. The EZ-1 is programmed with a protocol card that looks
like a credit card and is inserted into a slot in the instrument.
Dr. Farkas bought
one MDX, which he calls “a workhorse that is ideally suited
for HIV and HCV RNA extraction for viral load testing.” The
MDX processes 96 samples in 2.5 hours. “It generates high-quality
nucleic acid straight from blood tubes with no aliquotting or pouring,”
he says. “It has higher throughput than the MagnaPure, which
would have been sufficient for my current needs. But I am planning
to grow this operation.” One advantage of MagnaPure over MDX
is that MDX requires extracted samples to be transferred manually
to a real-time cycler. “If we get to such high volumes for
HCV and HIV that transferring samples becomes a bottleneck, that
would be a good problem,” he says. “In the meantime,
MDX’s higher processing volume relative to MagnaPure trumps
that potential obstacle.”
Dr. Farkas also
purchased a Biorobot 3000, which will be used in the HLA laboratory
for medium-volume DNA extractions, and a Biorobot M48, which will
be shared for PCR setup and liquid reagent handling.
How is he staffing
the new molecular laboratory? “Everything in prospect is difficult,
everything in retrospect is easy,” he says. Initially, he
thought that getting qualified personnel would be his biggest hurdle.
Now, however, the laboratory is working with two technologists with
more than 20 person-years’ experience in molecular assays
between them. “At this point,” Dr. Farkas says, “I
am trying to get things so automated that in the future I can add
FTEs who are not necessarily molecularly oriented but who are simply
excellent in the laboratory, so my more molecularly oriented technologists
can develop esoteric tests.”
“We’re
getting to the point in molecular diagnostics that unless the lab
is going to delve into something more esoteric than the top five
or six molecular tests,” he believes, “you may not absolutely
need molecularly oriented technologists, as long as excellent med
techs work with a laboratory director who is molecularly experienced
and can provide troubleshooting skills.”
Gentra
Systems already offers an automated extraction instrument,
Autopure LS, that prepares large amounts of DNA, suitable for archiving,
from whole blood or buccal samples. It does not handle RNA. Gentra
has now developed a higher-throughput, smaller-volume sample platform,
Versapure 1000, that will process DNA and RNA and is expected to
be in production in 2004. Esoterix Molecular Genetics, Austin, Tex.,
will be one of the beta sites.
Molecular diagnostics
has gone through a “point of divergence” in the past
year, says Ronald McGlennen, MD, Esoterix’s medical director.
“Traditionally, the lion’s share of testing has been
done on DNA extracted from blood or bone marrow,” he says.
“Now we are seeing rapidly growing opportunities to look at
other tissue sources.” Dr. McGlennen likes the Versapure 1000
because it has unique steps that allow it to handle fixed tissue
samples, thanks in part to discussions he had with Gentra during
its design.
Working with
serum or blood will remain important for infectious disease testing,
Dr. McGlennen acknowledges. But for molecular genetics he sees fixed
tissue as “an emerging market.” In his laboratory, the
most notable nonblood specimens are cervical cells in Pap specimens.
Gonorrhea, chlamydia, and human papillomavirus have previously been
tested in urine and swab samples using large volumes from blind
collections. However, in its new recommendations for Pap smears,
the American College of Obstetricians and Gynecologists recommends
that Pap specimens from women 25 years and younger be routinely
screened for Neisseria and Chlamydia. As a result,
Dr McGlennen says, “volumes of testing on cervical cells are
increasing and we are approaching a decision point—can we
continue to manage these samples through manual DNA extraction?”
Obtaining good
DNA from fixed cells such as cervical smears is difficult and requires
partially unfixing them. “What we have learned,” Dr.
McGlennen says, “is that you need to go through an obligate
number of washes to get cells on which routine extraction chemistry
can be applied. So there are additional steps in this automated
instrument that we don’t see in blood cell extraction.”
Another issue
unique to fixed cells is nonuniformity. Adjusting concentrations
of blood samples to get optimal yields of nucleic acid is easy.
With tissue, however, Dr. McGlennen says, “the quantity and
quality of material in the collection is very wide. To make the
PCR setup more efficient, we have to make calibrations on the front
end before we do extraction, so we don’t have to spend so
much time after DNA extraction trying to create a uniform DNA concentration.”
Ruth Shuman,
PhD, president and CEO of Gentra Systems, explains that Versapure’s
name derives from the fact that it “handles anything—whole
blood, cultured cells, buccal cells, and tissue homogenates.”
Gentra anticipates that protocols for additional sample types such
as CSF, sputum, and fixed tissues will be developed for Versapure.
In addition,
Versapure uses both liquid-phase and solid-phase chemistries. Using
solid-phase chemistry, the instrument processes two 96-well plates
in approximately one hour; with liquid-phase chemistry, one plate
takes about two hours.
Dr. Shuman predicts
that Versapure will appeal to laboratories with a need for faster
purification and more samples than MagnaPure can handle. Fixed tissue
can’t be handled by current Qiagen or Roche systems, she adds.
Abbott
Diagnostics will enter the automatic extraction market
with an instrument that it calls the m1000, which was launched first
in Europe this summer. It will be launched in the United States
several months later, says Howard Rood, worldwide marketing manager
in new product development for molecular diagnostics. “The
m1000 is an open nucleic acid sample preparation system designed
to work on a wide variety of sample types,” Rood says. It
has been studied on whole blood, plasma, serum, urine, swabs, and
buffy coats and uses a novel and proprietary nontarget-specific
magnetic particle chemistry. Additional sample types were to be
studied this summer. With multiple protocols, the m1000 will handle
samples from 200 µL to 1 mL. Throughput for 1-mL samples is
about 48 samples in just under two hours, Rood says. Smaller samples
are processed faster.
The first version
of the m1000 platform is a sample preparation instrument. With additional
hardware it will become the m2000, which adds pipetting and reagent
handling as well as linkage to a real-time thermal cycler/reader.
In closed mode, the m1000 will be specific to Abbott’s assays;
in Europe, after receiving the appropriate registration approvals,
it will be launched with protocols for HIV and HCV assays on the
LCx. In open mode, users can make adaptations such as changing sample
input size. Samples will have to be transferred manually in both
modes.
The m1000’s
price will be “very competitive,” says Rood. He projects
its list price as between that of the MDX, $150,000 to $170,000,
and the MagnaPure, $84,000.
Cepheid’s
GeneXpert, in development now, is a closed system that
integrates automated sample extraction with real-time PCR, says
Ted Fong, strategic marketing manager. GeneXpert is a random-access
unit with four bays that can be programmed independently. The user
introduces minimally prepared specimens and puts in extraction buffers,
Fong says. All PCR reagents come dried preloaded in cartridges.
Four samples can be processed in less than one hour.
With GeneXpert,
Cepheid is looking at “niche markets and unmet needs,”
says Fong. “We are working on a list of clinical disease offerings,
starting with a viral meningitis panel followed by nosocomial infection
control panels, including MRSA and VRE. Down the line, we’re
looking at viral respiratory and bacteremia assays.” GeneXpert
will be geared toward point-of-care and CLIA-waived tests. “Realistically,
in the short term we will try to achieve at least moderate complexity,”
Fong says. For instance, Cepheid has developed an assay for tumor
marker detection in sentinel lymph nodes that takes less than one
hour and helps the surgeon decide whether further dissection is
needed and what adjuvant therapy is required. This assay has to
be done in the surgical suite, so it still has guidance from pathologists
and laboratorians.
Even large laboratories
may be able to use GeneXpert, Fong suggests. “High-throughput
reference laboratories may have tests that are lower in volume and
come in on a stat basis, such as group B strep for pregnant women,”
he says. With GeneXpert, such tests can be done singly, allowing
rapid turnaround.
Cepheid tells
customers to budget about $50,000 for GeneXpert. Test cartridges
for infectious diseases will cost $25 to $50, Fong says, while oncology
tests will “run in the hundreds of dollars.”
Perhaps GeneXpert
will accommodate some tests in an analyte-specific reagent type
of configuration, Fong says: “We are looking to an intermediate
solution because it takes time to get FDA approval for all tests.”
If laboratories use their own probes and primers, then, of course,
they will be responsible for validating tests.
Dr. Kaul thinks
GeneXpert will potentially be useful outside the molecular laboratory,
though she visualizes it more in a small clinic with trained staff
than as a bedside or POC tool. Dr. Farkas, too, says GeneXpert “looks
promising.”
“I’m
waiting to get my hands on one,” he says. Cepheid says that
will be possible sometime next year.
Some
laboratories have cobbled together extraction and analysis
systems from components. At Specialty Laboratories in Santa Monica,
Calif., DNA extraction of whole blood is done with the combination
of a Beckman Coulter Biomek FX biorobot and the Gentra Generation
Capture 96-well microplate system. “We use the Biomek because
of its flexible format,” says Christian Riley, BS, CLS, operations
coordinator for molecular genetics. This biorobot gets one type
of flexibility from its Span-8 pipetting arrangement, which consists
of eight individual tips capable of pipetting variable volumes into
or out of 96- or 384-well microtiter plates. To accommodate different
plates, the Span-8 unit varies its volume from 0.2 mL to 5 mL and
alters the spread between pipette tips.
The Biomek FX
in Specialty’s molecular genetics department handles perhaps
500 specimens per week, well below its capacity. Genetic tests for
which DNA is prepared by the Biomek-Generation hybrid include factor
V Leiden, prothrombin, methylene tetrahydrofolate reductase, hereditary
hemochromatosis, and others. In addition to DNA isolation, other
processes set up on the Biomek include Third Wave’s Invader
SNP detection assays, HCV genotyping, and soon HIV genotyping.
Riley explains
that the decision to combine the FX with the Gentra Generation Capture
plate system was partly due to Specialty’s experience and
satisfaction with the Gentra method in cystic fibrosis testing.
“In addition,” Riley says, “we were unable to
find an open platform for both DNA extraction and assay setup that
met our precision and flexibility needs. So we developed our own.”
Similarly, a
laboratory can put together an extraction system—for RNA,
at least—by combining ABI’s 6700, an automated large-scale
robot designed primarily for the research market, or its lower-throughput
semiautomated 6100, with the company’s RNA extraction chemistry.
“In the future, we expect to support genomic DNA extraction
for DNA sequencing or genotyping as well,” says John West,
vice president for DNA platforms in the Applied Biosystems division
of Applera Corp.
As more
automated nucleic acid extraction instruments enter the
market, how many will become financially rewarding? “Market
space is limited,” says Dr. McGlennen. For these instruments
to become profitable, he believes, “we need to increase the
number of laboratories doing molecular diagnostics.” In his
view: “A test like HPV creates the opportunity for entry because
test volumes are already there. A laboratory just has to decide
whether to take it in-house or outsource.”
Dr. Farkas thinks
the expansion of molecular diagnostics applications beyond the centralized
laboratory lies in starting with smaller, less expensive instruments,
such as a Qiagen EZ-1 in tandem with a real-time PCR cycler. Such
a setup might require 0.5 FTE, cost $60,000 to $80,000, and provide
“a great little molecular pathology service for starter laboratories
who want to put a toe in the water instead of jumping in,”
he says.
To facilitate
the rise of molecular diagnostics laboratories, vendors must be
more aware of users’ needs. After going through the multi-year
process of adapting the MagnaPure to clinical applications, Dr.
Nolte’s verdict is this: “The instrument works well,
but we had to go through a lot of trial and error to get it to work
well for kits. Manufacturers need to take greater responsibility
for effective solutions for automation.”
William Check
is a medical writer in Wilmette, Ill. Vendors whose instruments are
discussed in this article will exhibit at the Association for Molecular
Pathology annual meeting in Orlando, Fla., Nov. 21–23.
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