Analog Devices ICs for In Vitro Diagnostics Equipment

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Analog Devices ICs for In Vitro Diagnostics
Equipment
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Agenda

• In Vitro Diagnostics Overview
• Example Application Flow Cytometry
• General block diagram
• Detectors Sensors
• Amplifying signals from photodiodes
• Digitizing the analog signals
• Digital processing
• Steering cells into collection chambers
• Additional Information Resources

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In Vitro Diagnostics Overview

• Testing tissue or fluid samples
• Used in diagnosis and monitoring applications in
  humans and animals
• Example applications
• Cellular analysis hematology, flow cytometry
• Chemistry glucose, cholesterol, electrolytes,
  proteins, enzymes
• Immunoassay determines concentration of a
  substance by measuring reaction of an antibody
• Electrophoresis protein, DNA, RNA analysis

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Flow Cytometry

• Flow Cytometry is a process through which cells
  are differentiated according to cell
  characteristics
• Size, Granularity, Structures present, Reaction
  to a compound
• Application
• Separate specific cell types from heterogeneous
  mixture
• Determine cell reaction to compounds
• Development and testing of new drugs
• Detect presence of cells in small quantities
• Benefits of Flow Cytometry
• Detection of biological agents in minutes
• Capable of detecting agents at low concentrations

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How does Flow Cytometry work?

• Sorting cells, one by one
• Stained cells pass in front of light source
• Deflection plates can steer charged cells into
  different containers

• Amp Requirements
• Wide BW for fast signals
• Low bias current
• Low input capacitance
• Fast Settling Time

• DAC Requirements
• Applies charge to each cell
• Multiplies pulses must have wide BW to
  accommodate different cell velocities (500kHz
  2MHz)
• High Speed Interface

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Flow Cytometry Detectors/Sensors

• Photomultiplier tubes (PMTs) Avalanche
  photodiodes (APDs)
• Fluorescence detection in 400-1000 nm wavelength
  range
• high sensitivity
• high internal gain (106)
• fast response (10-7 to 10-9 s)
• yield a large S/N due to their internal gain
• Next generation Solid-state lasers and PIN-based
  photodetectors
• a few nA of current in the PIN photodiodes, a
  lock-in amplification technique is applied to
  increase the signal to noise ratio
• lock-in circuit parameters such as the time
  constant and sensitivity are selected to maximize
  signal to noise ratio at the given modulation
  frequency

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Amplifying Signals from High Speed Photodiodes
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Photodiode Preamp Example using AD8067
C2
0.35pF
CD 4pF, CIN 4pF C1 CD CIN
33.2k?
33.2k?
33.2k?
12V
D1

AD8067
C1 8pF
10V

fu 350MHz
D2
D1,D2 IF-D91
33.2k?
12V
C3 0.35pF
Bandwidth 7MHz Output Noise 725µV RMS, 21MHz
550µV RMS, 10MHz
33.2k?
33.2k?
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Comparison of Op Amps for Photodiode Preamps
Unity GBW fu, MHz 25 65 40 350 24
Input Capacitance CIN, pF 23 6.6 4 4 2.5
fu/CIN MHz/pF 1.1 9.85 10 87 9.6
Ib pA 2 2 1.5 2 lt1
VN_at_10kHz nV/?Hz 6 7 11 7 7
AD8610/20 AD8065/66 AD8033/34 AD8067 G gt 9
Stable AD8615/6/8
Ideal low frequency precision preamps for large
area photodiodes operated in photovoltaic
mode (zero volt bias)
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ADC Requirements SNR Sample Rate

• Bench-top Equipment
• Good SNR (typically 12 ENOBs 72 dB of SNR)
• Low power to minimize heat
• Larger Equipment
• Excellent SNR (16 ENOBs 96 dB of SNR)
• Frequently use over-sampling to increase SNR in
  digital domain
• Can average many samples to reduce noise.
• New SNR SNRDATASHEET 10Log(FSAMPLE/2BW)
• ExampleAD9446 SNR 82dB at 80MspsCustomer BW
  is 2 MHzEffective SNR of AD9446 will be82dB
  10Log(80MHz/4MHz) 82dB 13dB 95dB
• The right ADC choice depends on
• Power
• SNR
• Sample Rate

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Some Recommended ADCs

• Benchtop Equipment (low power, multi-channel)
• AD9252 AD9259 14 bits, 8 4 channel ADCs
  with serial LVDS output
• AD7621 16 bits, 1 channel ADC with very low
  power (86mW)
• Large Equipment (best performance, highest SNR)
• AD9446 82dB SNR at 80Msps
• AD7625 90dB SNR at 5Msps
• Higher Resolution Lower Sampling Rate ADCs

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Digital Processing in Flow Cytometry

• Each cell produces a Gaussian distribution of a/d
  conversions as it passes the sensors
• FPGA Tasks
• Take each sample above a threshold. 50Mhz
  converter.
• Do a numerical integration (rectangle addition),
  this is the Area
• Determine Base Width based on threshold
• Pass to the DSP
• DSP Tasks
• Receive FPGA dispersion
• Convert to floating point
• Compensate for filter overlap
• Compare to desired cell type
• Steer cell (desired or non desired) via high
  voltage

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Steering the Cells into ContainersGenerating
pulsed voltage to charge cell

• DAC Requirements
• Very fast throughput
• gt10MHz Bandwidth
• Fast digital interface
• Support Low voltage designs
• 10V Reference with 2.5V to 5.5V supply
• Current output convert to voltage with op amp
• Extended temperature range

Pulsed voltage
CellCharger
-

DeflectionPlates
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Additional Information Resources

• Motor Control Solutions
• Current Sense Amplifiers
• Gate Drivers
• Resolver-to-Digital Converters
• Digital Potentiometers
• Temperature Sensing and Thermal Management
• Analog Temperature Sensors
• Thermocouple Conditioners
• Digital Temperature Sensors
• Fan Control
• Other Medical Solutions from ADI