Edwin En-Te Hwu1, Anja Boisen1. 1. Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN), Department of Micro- and Nanotechnology , Technical University of Denmark , Lyngby 2800 , Denmark.
Abstract
The optical pickup unit (OPU) within a CD/DVD/Blu-ray drive integrates 780, 650, and 405 nm wavelength lasers, diffraction-limited optics, a high-bandwidth optoelectronic transducer up to 400 MHz, and a nanoresolution x-, z-axis, and tilt actuator in a compact size. In addition, the OPU is a remarkable piece of engineering and could enable different scientific applications such as sub-angstrom displacement sensing, micro- and nanoimaging, and nanolithography. Although off-the-shelf OPUs can be easily obtained, manufacturers protect their datasheets under nondisclosure agreements to impede their availability to the public. Thus, OPUs are black boxes that few people can use for research, and only experienced researchers can access all their functions. This review details the OPU mechanism and components. In addition, we explain how to utilize three commercially available triple-wavelength OPUs from scratch and optimize sensing quality. Then, we discuss scientific research using OPUs, from standard optical drive-based turnkey-biomarker array reading and OPU direct bioapplications (cytometry, optical tweezing, bioimaging) to modified OPU-based biosensing (DNA chip fluorescence scanning, biomolecular diagnostics). We conclude by presenting future trends on optical storage devices and potential applications. Hacking low-cost and high-performance OPUs may spread micro- and nanoscale biosensing research from research laboratories to citizen scientists around the globe.
The optical pickup unit (OPU) within a CD/DVD/Blu-ray drive integrates 780, 650, and 405 nm wavelength lasers, diffraction-limited optics, a high-bandwidth optoelectronic transducer up to 400 MHz, and a nanoresolution x-, z-axis, and tilt actuator in a compact size. In addition, the OPU is a remarkable piece of engineering and could enable different scientific applications such as sub-angstrom displacement sensing, micro- and nanoimaging, and nanolithography. Although off-the-shelf OPUs can be easily obtained, manufacturers protect their datasheets under nondisclosure agreements to impede their availability to the public. Thus, OPUs are black boxes that few people can use for research, and only experienced researchers can access all their functions. This review details the OPU mechanism and components. In addition, we explain how to utilize three commercially available triple-wavelength OPUs from scratch and optimize sensing quality. Then, we discuss scientific research using OPUs, from standard optical drive-based turnkey-biomarker array reading and OPU direct bioapplications (cytometry, optical tweezing, bioimaging) to modified OPU-based biosensing (DNA chip fluorescence scanning, biomolecular diagnostics). We conclude by presenting future trends on optical storage devices and potential applications. Hacking low-cost and high-performance OPUs may spread micro- and nanoscale biosensing research from research laboratories to citizen scientists around the globe.
Entities:
Keywords:
Blu-ray; DNA chip; compact disc (CD); cytometer; digital versatile disc (DVD); fluorescence; medical diagnostics; nanobio imaging; optical tweezer; pptical pickup-unit (OPU)
Some years
ago, the global market
of digitized music, video, and data storage pushed the capacity and
speed of optical drives to their limits, with a huge amount of R&D
investment. From compact discs (CDs), digital versatile discs (DVDs),
to the most recent Blu-ray discs, the data capacity evolved from the
megabyte (MB) to the gigabyte (GB). Likewise, mass production and
outstanding sales dramatically reduced the cost of optical storage
drives while maintaining high quality and performance. Nowadays, Blu-ray
players (12× speed, 432 Mb/s) are affordable devices that reliably
read 150 nm data pits from a spinning disc at 10,000 rpm.Optical
drive components have been used for research over the past
decades, as they adopt an accessible standard of CD/DVD/Blu-ray disc,
and the spindle motor can be used for centrifugal lab-on-disc applications.[1,2] Most of this research relies on either commercially available optoelectrical
sensing systems or customized sensing mechanisms.[3−8] A seldom considered component inside optical drives is the optical
pickup unit (OPU), which is essential for converting physical data
pits into electric signals. A CD/DVD/Blu-ray drive OPU equips at least
one triple-wavelength laser and optimized optical components to achieve
the diffraction limit of light for high-density data-pit reading.
To focus the laser spot perfectly on a spinning and wobbling disc,
an objective lens is actuated by a high-bandwidth triple-axis precision
actuator. The light intensity signal reflected from the data pits
is then transduced by a specialized high-bandwidth optoelectrical
component. These functions are compactly integrated within an eraser-sized
box, representing a low-cost and high-performance engineering achievement.Although off-the-shelf OPUs can be unrestrictedly purchased, accessing
their full functions can be much more challenging. In fact, every
manufacturer protects the OPU datasheets and hardware pin assignment
under secrecy, and hence any researcher needs to either sign a nondisclosure
agreement or reverse engineer the OPU to access its functions. This
technical barrier has prevented researchers, especially those without
an engineering background, from utilizing OPUs with research purposes,
and only few groups have managed to access all the OPU functions for
its use in applications such as sub-angstrom displacement sensing,[9] micro- and nanoimaging,[10] and nanolithography.[11] Interestingly,
an OPU-based low-cost atomic force microscope (AFM) has already democratized
nanoimaging up to the point that even children can perform nanoscale
measurements by themselves.[12,13]Before exploiting
the full potential of the OPU in a CD/DVD/Blu-ray
drive, we must understand its mechanism and main components. We distinguish
the types of OPUs that are flexible for scientific research and explain
how to increase the signal-to-noise ratio and couple external optical
sensors to enhance sensing quality. Then, we further describe how
to control the OPU in practice, by using either specific software
tools or customized circuits. We dedicate another part of the review
to surveying biosensing studies using OPUs, including standard optical
drive-based turnkey biosensing, OPU direct bioimaging, and modified
OPU-based systems for advanced bioapplications.
Opening the Black Box:
The OPU Mechanism
From CDs and DVDs to Blu-ray discs, higher
data capacity requires
smaller data pits on the same 12-cm-diameter disc, as illustrated
in Figure .[14] Likewise, higher data density demands shorter
laser wavelength λ (CD: 780 nm, DVD: 650 nm, Blu-ray disc: 405
nm) and higher numerical apertures (NAs) of objective lenses (CD:
∼0.5, DVD: ∼0.63, Blu-ray disc: 0.85) to focus the laser
on nanoscale data pits (CD: 800 nm, DVD: 400 nm, Blu-ray disc: 150
nm). The OPU focuses a polarized laser to the diffraction limit of
light, with full width at half-maximum being approximately 800 nm
for CD, 530 nm for DVD, and 250 nm for Blu-ray disc.[15] In addition, each data pit has a depth of λ/4, and
when the laser hits the pit, the reflection is destructively interfered
and the OPU receives a low reflection corresponding to the digital
signal “0”, whereas if no pit is hit, the higher intensity
reflection is translated as the digital signal “1”.
Figure 1
CD/DVD/Blu-ray
disc data pit, pitch, and laser spot dimensions.[14]
CD/DVD/Blu-ray
disc data pit, pitch, and laser spot dimensions.[14]A transparent hard-coat polycarbonate
cover layer[16] (CD: 1.1 mm, DVD: 0.6 mm,
Blu-ray: 0.1 mm in thickness)
protects the data pits from being destroyed by scratching and has
a refractive index of 1.6. This layer is an essential optical component
of the storage system, as its absence could cause spherical aberration,
creating an optical path difference which could exceed 0.2 of the
light wavelength. Consequently, the optical path difference could
reduce in more than 20% the reflected laser intensity.[17]Figure illustrates
the structure of a typical CD/DVD/Blu-ray OPU.[18] A triple-wavelength semiconductor laser diode, its most
expensive component, emits a laser beam that is collimated, linearly
polarized, and focused on a disc by a collimator, a polarized beam
splitter, and an objective lens, respectively. The reflected laser
from the disc passes through the same optical path back to an astigmatic
lens and impinges onto a photodiode integrated circuit (PDIC).
Figure 2
Diagram of
the optical path in a typical triple-wavelength OPU.[18]
Diagram of
the optical path in a typical triple-wavelength OPU.[18]To achieve better signal integrity
and lower relative intensity
noise, the laser diode is modulated within a frequency from 300 to
500 MHz to mitigate laser coherence.[19] Next
to the laser diode, a diffraction grating splits the laser into three
beams to generate data tracking feedback control signals.[20,21] Then, the collimator lens, which is linearly driven by a miniature
stepper motor along the laser beam direction, adjusts its position
to accurately vary the OPU focal distance. This fine-tuning compensates
the effect from both the different disc cover layer thicknesses and
the switching target data layers (for single-sided dual-layer DVDs
and Blu-ray discs) while reading the disc. The objective lens integrates
aspherical and diffractive optical design to focus 780, 650, and 405
nm laser beams to the diffraction limit of light.[22] A dichroic filter reflects the laser light to the objective
lens, which has reflective coatings for the OPU operation wavelengths.
Some OPUs have a clear aperture in the back of the dichroic filter
to allow external optical access, despite being preferable to avoid
the OPU operation wavelengths. This aperture enables the external
coupling of optical components for applications such as optical imaging[23] and fluorescence light sensing.[24]While reading data pits on a fast-spinning disc,
an x-, z-axis and tilt electromagnetic
actuator, known
as voice coil motor (VCM), allows focusing the laser on the data layer.
Three pairs of suspension wires mechanically suspend an objective
lens holder and electrically conduct driving signals to the x-, z-axis, and tilt coils inside the holder.
The VCM has an operation bandwidth of 20 kHz for moving the objective
lens along the z-axis (±1000 μm) for data
layer focusing and the x-axis (±350 μm)
for following spiral data tracks, whereas tilting (±1°)
compensates the data layer angular variation due to disc wobbling.
The x- and z-axes usually have a
sensitivity of 1 μm/mV to achieve nanoscale resolution with
precise diving signals that can be used in various applications.[25−27]The PDIC consists of current preamplifiers for photodiodes
A to
H in Figure (CXA2875GA,
Sony Co., Tokyo, Japan), which have an operation bandwidth up to 400
MHz. Given the laser splitting grating, there are three laser spots
reflected onto the PDIC, and photodiodes A to H monitor the laser
spots and provide signals SA to SH, respectively.Figure shows the
center laser spot shape according to the laser focusing, which is
described as an astigmatic method.[28] When
the laser is focused on an object (z = 0), the laser
spot on the PDIC projects a circular shape. When the focal point is
off-center, the laser spot projects an elliptical shape with the major
axis along photodiodes A–C (SFE > 0) or B–D (SFE < 0).
This
changing shape can be expressed as focus error signal SFE = (SA + SC) – (SB + SD), which is used to control the VCM for focusing
the laser precisely on a target and has been proven to exhibit subatomic
resolution for AFM applications.[28,29]
Figure 3
Focusing detected
by astigmatic method. (A) Astigmatic optics inside
OPU. (B) Focus error signal SFE according
to defocus distance. Reprinted with permission from ref (28). Copyright 2007 AIP Publishing.
Focusing detected
by astigmatic method. (A) Astigmatic optics inside
OPU. (B) Focus error signal SFE according
to defocus distance. Reprinted with permission from ref (28). Copyright 2007 AIP Publishing.OPUs can feature different functions
(reading and writing) and
sizes (half height, slim type). From our experience, CD/DVD/Blu-ray
OPUs can provide flexibility for scientific research given the characteristics
shown in Table , which
summarizes the core components from ten different types of OPUs.
Table 1
Characteristics of Main Components
from Different CD/DVD/Blu-ray OPUs
component
characteristic
type
value
unit
Objective lens
Lens NA
CD
0.47–0.53
-
DVD
0.6–0.66
Blu-ray
0.85
Laser spot size (full width at half-maximum)
CD
∼800
nm
DVD
∼530
Blu-ray
∼250
S-curve linear region
CD
∼15
μm
DVD
∼6
Blu-ray
∼0.3
Working distance (lens to disc)
CD
0.55–0.86
mm
DVD
0.63–1.25
Blu-ray
0.27–0.61
Semiconductor laser diode
Wavelength
CD
770–790
nm
DVD
645–660
Blu-ray
400–410
Power (Average)
CD
160–1130
mW
DVD
170–830
Blu-ray
340–450
VCM
Working distance
x-axis
±350
μm
z-axis
±1000
μm
Tilt
±1
°
PDIC
Operation
bandwidth
CD
25–90
MHz
DVD
50–130
Blu-ray
110–400
Driving OPUs
from Scratch
The easiest way to gain access to the OPU for
biosensing is by
using an optical disc diagnostic software, which can be downloaded
online for free. There are at least four diagnostic software tools:
PlexUtilities v 1.3.3 (Plextor, USA), K-Probe2, QpxTool by Gennady
Kozlov, and Opti Drive Control by Erik Deppe. PlexUtilities offers
more diagnostic tools, whereas Opti Drive Control has enhanced hardware
compatibility.[30] Furthermore, a Linux-based
software allows one to burn and analyze data sectors on the disc.[31] This type of software can read logical error
correction codes (ECCs) on the disc including detect parity inner
errors and parity inner failures, where the former indicate correctable
reading/data errors of a logical ECC block on the disc, and the latter
determines whether an ECC block contains uncorrectable errors. The
Blu-ray utilizes more powerful ECCs which contains long distance code
and burst-indicating subcode to protect the data on the disc.[32] The ECCs can indicate scratches or polluted
parts on the disc surface. We can exploit these features to drive
almost every kind of OPU inside optical drives and perform certain
biosensing applications as described later.Inside the CD/DVD
optical drives, it is relatively easy to gain
access to the OPU. A very efficient method to determine the input/output
pin assignment and operating parameters of the OPU laser, PDIC, and
VCM is by measuring the voltage and current of each component during
operation. Then, the retrieved parameters can be used to drive the
OPU for different applications. Unfortunately, it is much more difficult
to reverse engineer triple-wavelength OPUs and determine their pin
assignment using this method, because most of them have built-in microcontrollers
that receive and deliver digital commands for operation.Supporting Information of this review
provides three controller circuit designs with their parameters for
the widely available OPUs PHR-803T (Toshiba Co., Tokyo, Japan) inside
the XBOX 360 (Microsoft Co., Redmond, WA, USA), KEM 410 with dual
objective lens (Play Station 3; Sony Co., Tokyo, Japan), and SF-BC620L
(Sanyo Electric Co., Ltd., Osaka, Japan). The customized controllers
grant access to all the functions of these OPUs, including CD/DVD/Blu-ray
laser switching and power adjustment, modulation frequency control,
VCM x-, z-axis and tilt actuation,
PDIC filter, gain and modes switching, and miniature stepper motor
control.
Recommendations for OPU-Based Applications
It is recommended
to keep the cover layer, whose thickness depends
on the operation wavelength, in front of the OPU objective lens to
guarantee optimal laser focusing. Microscopy cover glasses provide
a similar refractive index (1.47 to 1.5) as the cover layer or one
can simply use the disc hard-coat polycarbonate cover layer. Furthermore,
the cover layer can be used for sealing microfluidic channels. OPU-based
imaging or sensing through different media, such as liquid or gas,
demands the optimization of the distance between the cover layer and
measurement target.[33] Moreover, removing
the laser splitting grating can increase the laser intensity up to
25% for improved signal-to-noise ratio in sensing applications.Compared with CD/DVD laser, the Blu-ray 405 nm laser has a focal
point of approximately 250 nm, thus being suitable for high-resolution
fluorescence imaging. However, the Blu-ray laser may destroy live-cell
samples while imaging depending on the dose. Likewise, the Blu-ray
phototoxicity might cause plasma membrane permeabilization, cytoskeleton
destruction,[34] and DNA damage.[35] These aspects should be thoroughly considered
when using Blu-ray technology for biosensing and imaging.
OPU-Based Biosensing
Turnkey
Biosensing
The above-mentioned software tools
can turn standard CD/DVD/Blu-ray optical drives into turnkey biosensing
instruments.[30] Besides custom-made bio-CD
for multiplexing DNA microarray detection,[36] biomolecular complex assay spots can be inject-printed onto the
cover layer of a standard CD.[31] Then, a
diagnostic analysis of ECCs can be performed while the OPU reads data
through the bioassays to quantitatively extract colorimetric characteristics
of different assay spots on the cover layer. Figure illustrates the typical ECC-based method
for biotin–streptavidin binding, DNA hybridization, and protein–protein
interaction sensing.[37] In addition, this
method can be employed to detect DNAzyme assay at the part-per-billion
level.[38]
Figure 4
(A) Preparation of disc-based bioassay
and signal amplification
using gold/silver staining. (1) UV/ozone activation to generate carboxylic
acid groups on CD surface; (2) immobilization of amino-tethered DNA
probe strands via amide coupling; (3) hybridization with biotinylated
DNA target strands; (4) binding of gold nanoparticle–streptavidin
conjugates; (5) reductive precipitation of silver particles for signal
enhancement. (B) Digital reading of bioassay using CD drive. The biomolecule/nanoparticle
conjugates block the reading laser and generate errors. (C) Optical
image of DNA microarray formed on a regular CD-R according to the
above surface reaction and signal amplification. Reprinted with permission
from ref (37). Copyright
2008 American Chemical Society.
(A) Preparation of disc-based bioassay
and signal amplification
using gold/silver staining. (1) UV/ozone activation to generate carboxylic
acid groups on CD surface; (2) immobilization of amino-tethered DNA
probe strands via amide coupling; (3) hybridization with biotinylated
DNA target strands; (4) binding of gold nanoparticle–streptavidin
conjugates; (5) reductive precipitation of silver particles for signal
enhancement. (B) Digital reading of bioassay using CD drive. The biomolecule/nanoparticle
conjugates block the reading laser and generate errors. (C) Optical
image of DNA microarray formed on a regular CD-R according to the
above surface reaction and signal amplification. Reprinted with permission
from ref (37). Copyright
2008 American Chemical Society.The ECC-based method has been extended for applications such
as
onsite pregnancy test,[39] multiplexed drug
abuse diagnostics,[40] heavy metal detection,[41] and acute myocardial infarction monitoring.[41] Furthermore, Blu-ray optical drives have been
shown to increase the resolution and sensitivity for biosensing,[42,43] reaching a sensitivity and selectivity comparable to standard enzyme-linked
immunosorbent assays.A professional CD/DVD/Blu-ray disc testing
or quality control platform,
which is normally used during optical disc production, can be repurposed
to monitor on-disc biotin–streptavidin binding at a linear
speed of 4.0 m/s. Unlike ECC-based biosensing, such platforms provide
an analog reflection intensity signal from the disc.[44] Following that approach, a commercially available optical
drive can connect the OPU PDIC analog output to a data acquisition
device, thus enabling more flexibility for biosensing applications,
such as reading on-disc biochemical films to determine Ca2+ concentrations with a detection limit of ±5 ppm,[45,46] measuring on-disc multiplexed microimmunoassays (e.g., pesticides,
antibiotics),[47] detecting Haemagglutinin
of influenza virus,[48] and sensing RNA aptamers
generated against reverse transcriptase interaction.[49] Furthermore, the OPU can be extracted from the drive for
C-reactive protein measurement with a detection limit of 1 pM.[50]
Cytometer and Optical Trap
Blood
cell count and sizing
can provide insightful information during AIDS, sepsis, anemia, and
leukemia diagnoses. A conventional CD modified with a polydimethylsiloxane
microfluidic channel can be read by a standard optical drive for counting
microparticles and living cells and determining concentrations based
on ECCs.[51]Figure illustrates a conventional and an OPU-based
cytometer, which integrates a lab-on-chip device. The OPU-based cytometer
has been used to count individual polystyrene beads between yeast
cells,[52] erythrocytes,[53] Chinese hamster ovary,[54] and
cattle erythrocytes[55] by analyzing focus
error signal SFE as depicted in Figure .
Figure 5
(A) Conventional optical
flow cytometer. (B) Mirror measurement
setup using DVD OPU. The laser beam is reflected to the OPU. Reprinted
with permission from ref (54). Copyright 2008 Elsevier.
Figure 6
Erythrocytes and beads cause focus error signal SFE to rise and drop, respectively. Consequently, the number
of cells or beads can be determined from SFE analysis. (A) OPU SFE readings for erythrocytes
(left) and polystyrene beads (right). (B) Histogram of the measurements
in (A) considering the minimum and maximum intensities of the peaks.
The plot shows two clusters containing erythrocytes at the rightmost
region in blue and beads at the leftmost region in green. Reprinted
with permission from ref (54). Copyright 2008 Elsevier.
(A) Conventional optical
flow cytometer. (B) Mirror measurement
setup using DVD OPU. The laser beam is reflected to the OPU. Reprinted
with permission from ref (54). Copyright 2008 Elsevier.Erythrocytes and beads cause focus error signal SFE to rise and drop, respectively. Consequently, the number
of cells or beads can be determined from SFE analysis. (A) OPU SFE readings for erythrocytes
(left) and polystyrene beads (right). (B) Histogram of the measurements
in (A) considering the minimum and maximum intensities of the peaks.
The plot shows two clusters containing erythrocytes at the rightmost
region in blue and beads at the leftmost region in green. Reprinted
with permission from ref (54). Copyright 2008 Elsevier.A DVD burner OPU equips a laser with approximate power of
200 mW
and can generate tens of piconewtons of force at the focal point.
This force is enough to trap colloid or red blood cells.[56] Furthermore, the VCM can precisely steer the
cells to different channels. This setup has been used to isolate microparticles
and red blood cells nondestructively by controlling the OPU with an
Arduino board (Arduino LLC, USA) in a gravity-driven microfluid device,[57] as shown in Figure .
Figure 7
(A) Arduino board-controlled OPU generates an
optical trap that
isolates single microparticles inside the microfluidic device and
delivers them as free-falling droplets to 96 well plates. (B) Particles
flowing into this section follow streamlines into the waste channel,
unless translated by the optical trap into the sample channel that
leads into a droplet section. Reprinted with permission from ref (57). Copyright 2014 Royal
Society of Chemistry.
(A) Arduino board-controlled OPU generates an
optical trap that
isolates single microparticles inside the microfluidic device and
delivers them as free-falling droplets to 96 well plates. (B) Particles
flowing into this section follow streamlines into the waste channel,
unless translated by the optical trap into the sample channel that
leads into a droplet section. Reprinted with permission from ref (57). Copyright 2014 Royal
Society of Chemistry.
Direct Bioimaging
The OPU laser focus to the diffraction
limit of light has been used as principle for a high-resolution laser
scanning microscope to monitor morphological changes in astrocytes
and investigate apoptosis triggered by Toxocara canis larval excretory-secretory antigens.[58] The OPU-based direct bioimaging system setup is similar to that
shown in Figure B,
except for the microchannel. The OPU laser focuses on astrocytes incubated
on a reflective substrate. Then, the substrate is raster scanned by
a piezoelectric scanner while the OPU reads out the focus error signal.
The astrocytes can be represented by mapping the focus error array
into a grayscale image. Figure shows the images obtained using a conventional high-end optical
microscope (Figure A; magnification 1000×, phase contrast mode) and a laser imaging
system based on a DVD OPU (Figure B; λ: 650 nm, NA: 0.6). The OPU-based system
reveals detailed filament structures of the astrocytes and retrieves
a higher contrast than the conventional optical microscope.
Figure 8
Astrocytes
imaged by (A) high-end optical microscope in phase contrast
mode (contrast: 0.143) and (B) OPU-based laser bioimaging system (contrast:
0.224) Reprinted with permission from ref (58). Copyright 2013 Japan Society for Analytical
Chemistry.
Astrocytes
imaged by (A) high-end optical microscope in phase contrast
mode (contrast: 0.143) and (B) OPU-based laser bioimaging system (contrast:
0.224) Reprinted with permission from ref (58). Copyright 2013 Japan Society for Analytical
Chemistry.
Biosensing Using Transducers
Microelectromechanical
systems (MEMS) cantilever-based biosensors are traditionally monitored
using optical beam deflection,[59] which
implies a complicated configuration. In contrast, OPUs provide submicron
laser spots and subatomic sensing resolution[9] to monitor MEMS[28,29] and even nanoelectromechanical
systems.[60] These cantilevers can be functionalized
with receptor molecules as label-free biomolecular transducers that
are immersed in an analyte and monitored by the OPU[61] using static bending and frequency changes,[62] as shown in Figure .
Figure 9
(A) SU-8 cantilever bending monitored by a DVD
OPU.[61] (B) Excited and thermal noise spectrum
of a
MEMS SU-8 cantilever monitored using the OPU.[62] Reprinted with permission from refs (61) and (62). Copyright 2010 Elsevier and 2012 Hindawi, respectively.
(A) SU-8 cantilever bending monitored by a DVD
OPU.[61] (B) Excited and thermal noise spectrum
of a
MEMS SU-8 cantilever monitored using the OPU.[62] Reprinted with permission from refs (61) and (62). Copyright 2010 Elsevier and 2012 Hindawi, respectively.In addition, a Blu-ray OPU-based
vibrometer combining MEMS resonators
inside microfluidic chips has been used to characterize biopolymer
degradation under the action of enzymes in a controlled flow condition.
An algorithm enables the OPU to measure 12 resonators within 4 min,
thus dramatically reducing the degradation measurement time from 6
weeks to 8 h.[63]Furthermore, the
OPU has a high sensing tolerance of ±5°
to the cantilever initial angular tilt, allowing to scan cantilever-based
biosensors on a rotating disc. This scanning system has a theoretical
throughput of 500,000 cantilevers per second.[64] Moreover, the OPU scanning data has been used to reconstruct 3D
topography and surface roughness of each cantilever to provide extra
physical information for detection of pesticide derivative 2,6-dichlorobenzamide,[65] as shown in Figure . OPU cantilever-based biosensing has also
been used in applications such as detection of vapor and liquid phase
of 2,4-dinitrotoluene,[66] platelet derived
growth factor proteins,[67] and soluble urokinase
plasminogen activator receptor inflammatory biomarker.[68]
Figure 10
(A) Photograph of a DVD platform with integrated cantilever
chips.
The disc is fabricated from glass and SU-8 polymer. Scanning electron
microscope images of gold-coated silicon microcantilevers using three
data acquisition modes: (B) deflection, (C) surface 3D reconstruction,
and (D) resonant frequency. Reprinted with permission from ref (65). Copyright 2011 Royal
Society of Chemistry.
(A) Photograph of a DVD platform with integrated cantilever
chips.
The disc is fabricated from glass and SU-8 polymer. Scanning electron
microscope images of gold-coated silicon microcantilevers using three
data acquisition modes: (B) deflection, (C) surface 3D reconstruction,
and (D) resonant frequency. Reprinted with permission from ref (65). Copyright 2011 Royal
Society of Chemistry.Interestingly, an OPU can be used for nanoscale biomolecule
imaging
beyond the diffraction limit by monitoring a MEMS AFM probe (Figure A),[9,10,28,32] which has a tip with a typical radius of 10 nm. This OPU-based AFM
is capable of imaging DNA in air or solution environments,[33] as shown in Figure B.
Figure 11
(A) Diagram of OPU-based AFM for bioimaging
in liquid environment.
(B) DNA sample with approximate height of 1.5 nm on a mica substrate
immersed in an aqueous solution. Reprinted with permission from ref (33). Copyright 2013 AIP Publishing.
(A) Diagram of OPU-based AFM for bioimaging
in liquid environment.
(B) DNA sample with approximate height of 1.5 nm on a mica substrate
immersed in an aqueous solution. Reprinted with permission from ref (33). Copyright 2013 AIP Publishing.
Modified OPU for Biosensing
A conventional DNA microarray
scanner requires microscale precision for xy positioning,
laser excitation, precise optics for focusing, and optical sensing.
Consequently, the resulting system is expensive and bulky. By replacing
the OPU components with a single-mode optical fiber and attaching
an external sensing setup, the OPU can be used as the head of a scanning
confocal microscope to enable fluorescent-based biosensing.[69]Figure shows an OPU-based DNA microarray scanner. The OPU
is coupled to a photomultiplier tube (PMT) detector through a dichroic
filter, such as that shown in Figure . The OPU–PMT setup can acquire signals from
fluorescent dyes excited by the OPU laser of 650 nm.[24] The OPU VCM provides dynamic autofocusing that enables
higher detection performance than conventional microarray scanners,
as shown in Figure . The OPU–PMT-based DNA microarray scanner has been successfully
used to measure a commercial bacterial artificial chromosome oligonucleotide
DNA chip and a 32 12 Cy5 fluorescent dye calibration slide (DS01).[70] Combined with microfluidic chips, OPU–PMT
fluorescence detection can measure 2.5 μm fluorescent beads
inside a microchannel,[71,72] as shown in Figure .
Figure 12
Diagram of OPU–PMT-based
DNA microarray scanner. Reprinted
with permission from ref (24). Copyright 2007 Springer Nature.
Figure 13
Detection image of a 32 12 Cy5 fluorescent dye calibration slide
(A) with and (B) without VCM autofocusing. Reprinted with permission
from ref (70). Copyright
2008 Elsevier.
Figure 14
(A) Two-dimensional
image of a microchannel cross-section containing
multiple 6 μm fluorescent beads. (B) Detection of two 2.5 μm
beads within the microchannel. Reprinted with permission from ref (72). Copyright 2012 Royal
Society of Chemistry.
Diagram of OPU–PMT-based
DNA microarray scanner. Reprinted
with permission from ref (24). Copyright 2007 Springer Nature.Detection image of a 32 12 Cy5 fluorescent dye calibration slide
(A) with and (B) without VCM autofocusing. Reprinted with permission
from ref (70). Copyright
2008 Elsevier.(A) Two-dimensional
image of a microchannel cross-section containing
multiple 6 μm fluorescent beads. (B) Detection of two 2.5 μm
beads within the microchannel. Reprinted with permission from ref (72). Copyright 2012 Royal
Society of Chemistry.To reduce the cost of using triple-wavelength laser diodes,
some
OPUs are endowed with dual-optics 780 and 650 nm lasers for CD/DVD,
and a 405 nm laser for Blu-ray disc reading. These dual-optics OPUs
have two objective lenses driven by the same VCM and can perform two
separate optical sensing tasks while the objective lenses move synchronously. Figure shows a diagram
of a Blu-ray scanning microscope (BSM) comprising a dual-optics OPU
coupled with a PMT sensor. The BSM uses the Blu-ray optical path to
excite fluorescent light and capture a cell fluorescence image. Simultaneously,
the DVD optical path is focused on an address-patterned area to monitor
the xy scanning area and z-axis
focusing.[73] This BSM setup has been successfully
used to measure monkey-derived kidney epithelial cells and fibroblast
cells stained with fluorophore phalloidin CF405 (Biotum, Inc., Fremont,
CA, USA),[74] as shown in Figure . Moreover, the compact size
of the BSM allows embedding it into a cell culture chamber.
Figure 15
Diagram of
BSM. The fluorescence signal passes through multimode
fiber B7 and is collimated by collimator lens B8 and narrowband emission
filter B9. D1, laser diode; D2, beam splitter; D3, collimator lens;
D4, dichroic filter; D5, photodiode; D6, objective lens (NA: 0.6);
D7, Al-coated address pattern; B1, blue laser diode; B2, B3, beam
splitters; B4, collimator lens; B5, dichroic filter; B6, 4.34 mm focal
lens; B10, objective lens (NA: 0.85); B11, lens holder. B12, cover
glass; B13, collimator astigmatic plate; B14, photodetector. Reprinted
with permission from ref (74). Copyright 2014 The Optical Society.
Figure 16
Fluorescence (A) HA22T/VGH (B) and VERO cell images stained with
phalloidin CF405 and Alexa Fluor 488. Collimator lens B4 position
of (C) 0, (D) 1, and (E) 2.5 mm. Reprinted with permission from ref (75). Copyright 2015 The Japan
Society of Applied Physics.
Diagram of
BSM. The fluorescence signal passes through multimode
fiber B7 and is collimated by collimator lens B8 and narrowband emission
filter B9. D1, laser diode; D2, beam splitter; D3, collimator lens;
D4, dichroic filter; D5, photodiode; D6, objective lens (NA: 0.6);
D7, Al-coated address pattern; B1, blue laser diode; B2, B3, beam
splitters; B4, collimator lens; B5, dichroic filter; B6, 4.34 mm focal
lens; B10, objective lens (NA: 0.85); B11, lens holder. B12, cover
glass; B13, collimator astigmatic plate; B14, photodetector. Reprinted
with permission from ref (74). Copyright 2014 The Optical Society.Fluorescence (A) HA22T/VGH (B) and VERO cell images stained with
phalloidin CF405 and Alexa Fluor 488. Collimator lens B4 position
of (C) 0, (D) 1, and (E) 2.5 mm. Reprinted with permission from ref (75). Copyright 2015 The Japan
Society of Applied Physics.The Blu-ray objective lens can also be replaced by a 488
nm optimized
lens for imaging HA22T/VGH and VERO cell stained with phalloidin CF405
and Alexa Fluor 488 (Thermo Fisher Scientific, Waltham, MA, USA).
The imaging depth can be adjusted in a range of ±20 μm
through collimator lens B4 (Figure ) inside the OPU.[75] Besides
the PMT, the OPU can also equip an avalanche photodiode for Cy5 detection
of stained cell fluorescence on a spinning disc.[76]Nanoparticle labeling can enhance the biomolecule
signals up to
100 times.[77] Using this labeling technique,
OPUs can scan the DNA microarray with an external photodiode, which
is much less expensive than a PMT. Figure shows an OPU–photodiode-based DNA
microarray scanner to measure human papillomavirus with Ag-deposited
Au nanoparticle labels.[78]
Figure 17
(A) Diagram for human
papillomavirus genotyping microarray preparation.
(B) Scanned image and calculated signal-to-noise ratio of human papillomavirus
genotyping DNA with low-risk 6, 11, 16, and 18 types. Reprinted with
permission from ref (78). Copyright 2014 The Optical Society.
(A) Diagram for human
papillomavirus genotyping microarray preparation.
(B) Scanned image and calculated signal-to-noise ratio of human papillomavirus
genotyping DNA with low-risk 6, 11, 16, and 18 types. Reprinted with
permission from ref (78). Copyright 2014 The Optical Society.Besides labeling, functionalized magnetic nanoparticle (MNP)-based
antigen and antibody assay reactions can be opto-magnetically[79] monitored using a Blu-ray OPU (objective lens
removed) instead of the expensive and bulky superconducting quantum
interference devices.[80] Specifically, the
Blu-ray OPU–MNP sensing shines a 405 nm parallel laser through
a solution contains the MNPs, then acquiring reflection via a mirror.
In addition, the Blu-ray OPU PDIC monitors the reflected laser frequency,
phase, and amplitude while two coils apply an oscillating magnetic
field to the MNPs. Combining Blu-ray OPU–MNP sensing with the
lab-on-disc technique can carry out microliter-scale whole blood separation
and antibody sensing[81] in few minutes (Figures and 19).
Figure 18
(A) Disk for magneto-optical measurements of protein biomarkers
in full blood. (B) Platform comprising a motor, modified Blu-ray OPU,
magnetic coils, reflection mirror, and customized electronic board
for signal extraction. Reprinted with permission from ref (81). Copyright 2014 The Chemical
and Biological Microsystems Society.
Figure 19
(A) Detection mechanism of biotinylated IgG (antistreptavidin)
antibodies using streptavidin coated 100 nm MNPs. (B) Magneto-optical
spectra measured on different pools with varying amount of IgG spiked
into blood. Reprinted with permission from ref (81). Copyright 2014 The Chemical
and Biological Microsystems Society.
(A) Disk for magneto-optical measurements of protein biomarkers
in full blood. (B) Platform comprising a motor, modified Blu-ray OPU,
magnetic coils, reflection mirror, and customized electronic board
for signal extraction. Reprinted with permission from ref (81). Copyright 2014 The Chemical
and Biological Microsystems Society.(A) Detection mechanism of biotinylated IgG (antistreptavidin)
antibodies using streptavidin coated 100 nm MNPs. (B) Magneto-optical
spectra measured on different pools with varying amount of IgG spiked
into blood. Reprinted with permission from ref (81). Copyright 2014 The Chemical
and Biological Microsystems Society.Blu-ray OPU–MNP biosensing has also been applied on Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa,[82,83] NS1 antigen of dengue,[84] and adenosine
triphosphate.[85] This system features a
compact size and can be integrated with commercial bioimaging systems
to study the aptamer-conjugated MNPs[86] and
the action mechanism of type 2 diabetes drugs.[87]
Conclusions and Future Perspectives
CD/DVD/Blu-ray OPUs provide outstanding characteristics such as
light weight, low cost, compact size, and high performance, which
could be exploited to democratize and spread micro- and nanoscale
biotechnology research for institutes in developing countries and
citizen scientists. This review shows the possibility to open the
black box of commercial OPUs and describes its mechanism, component
characteristics, and several OPU-based bioapplications. We place special
attention on gaining access to the OPU functions for various biosensing
applications, and describe this access using circuits for three commercially
available triple-wavelength OPUs in the Supporting Information.High-speed Internet and solid-state drives
have overcome optical
drives for digital data transference and storage, with optical disc
drives being discontinued from devices such as notebooks. Still, operative
optical storage drives can be found in some music players and gaming
consoles such as triple-wavelength Blu-ray OPUs are equipped in the
Sony’s Play Station 4 (Sony Co., Tokyo, Japan) and XBOX One
X (Microsoft Co., Redmond, WA, USA), which are devices that can operate
for over 10 years. Moreover, repair assistance for OPUs can guarantee
sustained scientific research for years and maybe decades to come.Optical storage devices have a low cost, high durability, zero-energy
storage, and compactness, which helps end users keep their information
safe and private from enterprises (e.g., social networks), which can
misuse sensitive information, and avoid big data cloud storage. Moreover,
the femtosecond laser-based 360 TB with 13.8-billion-year storage
time data recording technique proposed in ref (88) suggests an exciting future
for optical storage technology. Of course, successful engineering,
commercialization, and mass production processes will determine the
future of this technology and reduce the costs for potential applications
in further scientific research.
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