CD-Based Microfluidics for Primary Care in Extreme Point-of-Care Settings
Abstract
:1. The Need for Extreme Point-of-Care
2. Fluidic Approaches
3. Introduction to CD-Based Microfluidics
3.1. Theory of Operation
3.2. Recent Advances in CD Fluidics
3.2.1. Mixing
3.2.2. Valving and Timing Control
3.2.3. Cell Handling
4. Centrifugal-Based Systems for Extreme Point-of-Care
4.1. Lab on a CD
Laboratory EquipmentFunction | Implementation Method | Example Applications |
---|---|---|
Centrifuge | Motor for spinning disc. High speed for centrifuge action. Motor speed can be varied accurately. | Blood plasmaseparation [85]. |
Vortex | Motor for spinning disc clockwise or counter-clockwise. Turbulence created causing vortex effect. Rotation direction changes vary acceleration, causing turbulence. | RotaPrep, Inc. [103], cell culture [104], vortexing [47]. |
Mixer | Ceramic beads incorporated into disc. Mixing of fluids using beads when turbulence created. Changes in spin direction cause turbulence and mixing. | Mixing of different reagents [47]. |
Lysis | Magnets and glass beads incorporated into disc. Lysis of cells as a result of mechanical impaction and shear forces. Rotational dual magnetic field moves magnet and beads inside chambers. | Lysis of bacteria [105,106], RotaPrep, Inc. [103]. |
Microscope | CD or DVD player. System components used as laser scanning microscope. Photodetector module detects absorbance of objects, images reconstructed. | Detection of cells [107,108]. |
x-y table/spotter | CD or DVD player. Rotational and linear motors for positioning. Microarrays applied onto disc using piezoelectric inkjet applicator and positioning system. | Immunoassay microarrays [109]. |
Sample concentration | Pneumatic pressure chambers on a disc. Reciprocation pump implemented. Fluid flushed back and forth, concentration/capture of analyte. | Immunoassays [49]. |
Cell counter | CD or DVD player. Locating and counting of cells, microparticles, biomolecules. Laser in drive detects errors on disc where particles are located. | Counting of cells, microparticles [107,110]. |
Thermal cycler | Peltier elements. Thermal treatment of small chambers. Current direction changes mode from heating to cooling. | DNA amplification via PCR [111]. |
Hypergravity simulation | Spinning microfluidic disc. Chambers containnutrients for cultivation. Centrifugal force simulateshigh g-forces on live samples trapped in fluidic chambers. | C. elegans stress response cultivation platform [112]. |
4.2. Innovative Centrifugal Approaches for Extreme Point-of-Care
4.2.1. Sensing and Detection
Parameter | Optical Sensors | Electrochemical Sensors |
---|---|---|
Instrument cost and size | Often expensive and bulky | Inexpensive and compact |
Sensor cost | Fair | Low |
Optically transparent substrate | Required | Not required |
Selectivity | Good | Fair |
Limit of detection (LOD) | Very good | Good and very good (using redox amplification |
Response time | Long (up to tens of seconds) | Less than a second |
Simplicity of the method | Often simple | Simple |
Analysis of turbid solutions | Sometimes problematic | Not problematic |
Electromagnetic interface | No | Yes |
Resistance to radiation and corrosion | Yes | No |
Cross-talk | No | Yes |
Ambient light | Problematic | Not problematic |
Response curve | Sigmoidal | Nernstian (potentiometric or linear) |
Sensitivity enhancement | Complicated | Nernstian (potentiometric or linear) |
4.2.2. Energy for Operation
Module | Power (mW) |
---|---|
Qi transmitter: Transmitted power | 5000 |
On-disc power: Received power (80% efficiency) | 4000 |
Arduino microcontroller consumption | 190 |
Bluetooth and SD Card consumption | 200 |
Energy available for application | 3610 |
4.2.3. Biomimetic Approaches for Environmental Control
4.3. Evolution of the CD Platform
4.3.1. Four Generations of Spin Stands
Parameter | Slip Ring | Wireless Power Transfer with Qi | Energy Harvesting |
---|---|---|---|
Wear | − contacts wear | + no wear | + no wear |
Direct analog output | + signals can be coupled in and out directly | − only digital signals can be sent to and from the disc | − only digital signals can be sent to and from the disc |
Energy level | + high voltages and currents can be sent to disc | +/− 5–20 W of power can be transferred (limited power) | +/− 100–500 mW of power can begenerated (relatively low power) |
Constant energy | + available energy does not depend on spinning frequency | + available energy does not depend on spinning frequency | − induced power depends on the spinning frequency and is zero when stationary |
Energy storage needed | + no storage is needed since power is always available | + no storage is needed since power is always available | − storage is needed, otherwise there is no power before spinning |
Weight | + the rotational part can be made to be light weight | + the rotating disk is light weight | − the coils are heavy; hence, a high−torque motor is needed |
Maintenance | +/− moderate maintenance | + low maintenance | + low maintenance |
Price | +/− electrical brushes and contacts are mechanically complex | + low cost, below EUR 50 | + low cost, below EUR 50 |
Interaction with surrounding | + no effect on the surrounding | +/− RF might disturb some applications, but frequency can be adapted | − magnets on the lower disk inhibit magnetic sorting applications |
Applicable to standard spin stands | − can only be integrated with a special spin stand head | +/− has only a few geometrical demands to enable integration | +/− has only a few geometrical demands to enable integration |
Power source | − additional power source required | − additional power source required | + no need for additional power source |
4.3.2. Scale-Up of CD-Based Microfluidic Systems
4.3.3. Examples of Existing Centrifugal Systems for Point-of-Care
5. Ideal Panel of Tests for Extreme Point-of-Care
Critical Test for Under-Resourced POC | Lab-on-Disc Implementation? | Methods and References |
---|---|---|
Complete blood count | Yes | Cell capture and counting [94]. Blood fractionation, density gradient tests [87,88,89]. Hemoglobin [163] and Hematocrit [164]. From these tests, all remaining complete blood count values can be calculated. |
Blood group (ABO and rhesus) | Yes | Agglutination of cells [165]. |
Blood sugar (F and PP ), urea, creatinine, uric acid | Yes | Colorimetric glucose assay [116]. Uric acid, glucose and lactate tests using whole blood and electrochemistry [166]. Urine analysis [167]. |
Serum sodium, potassium | Yes | Plasma separation and automated assay [155]. Commercially available: Abaxis Picollo Xpress. |
Liver function test: bilirubin, liver enzymes (SGOT, SGPT, SAKP) | Yes | Liver function on a disc [117]. |
HbA1C (diabetes) | Yes | Commercially available: Roche Cobas b 101. |
HbsAG (hepatitis B) | Yes | Integrated ELISA for detecting antigens and antibodies of hepatitis B virus, HBsAg and anti-HBs in parallel using whole blood [168]. |
HIV | Yes | CD4+ cell counts [154,169]. |
TB | In progress, some existing components. | Bacterial pathogen detection [170]. |
Urine-routine and microscopic, culture | In progress, some existing components. | Individual cell capture: counting can be performed using microscopy [94]. ELISA from cell culture [121]. |
6. Summary and Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Smith, S.; Mager, D.; Perebikovsky, A.; Shamloo, E.; Kinahan, D.; Mishra, R.; Torres Delgado, S.M.; Kido, H.; Saha, S.; Ducrée, J.; et al. CD-Based Microfluidics for Primary Care in Extreme Point-of-Care Settings. Micromachines 2016, 7, 22. https://doi.org/10.3390/mi7020022
Smith S, Mager D, Perebikovsky A, Shamloo E, Kinahan D, Mishra R, Torres Delgado SM, Kido H, Saha S, Ducrée J, et al. CD-Based Microfluidics for Primary Care in Extreme Point-of-Care Settings. Micromachines. 2016; 7(2):22. https://doi.org/10.3390/mi7020022
Chicago/Turabian StyleSmith, Suzanne, Dario Mager, Alexandra Perebikovsky, Ehsan Shamloo, David Kinahan, Rohit Mishra, Saraí M. Torres Delgado, Horacio Kido, Satadal Saha, Jens Ducrée, and et al. 2016. "CD-Based Microfluidics for Primary Care in Extreme Point-of-Care Settings" Micromachines 7, no. 2: 22. https://doi.org/10.3390/mi7020022