1 00:00:10,520 --> 00:00:12,150 PROFESSOR: So, as an aside for more 2 00:00:12,150 --> 00:00:15,000 advanced students, let's try to fill 3 00:00:15,000 --> 00:00:17,700 in some mathematical details to provide a theory 4 00:00:17,700 --> 00:00:21,360 to support or interpret the Lin-Marr hypothesis 5 00:00:21,360 --> 00:00:23,760 of disinfection kinetics having to do 6 00:00:23,760 --> 00:00:27,450 with the concentration of solutes during drying 7 00:00:27,450 --> 00:00:31,830 and their effect on deactivating viruses. 8 00:00:31,830 --> 00:00:33,700 So, to put it in mathematical terms, 9 00:00:33,700 --> 00:00:36,870 if we have a certain number of viruses Nv in a droplet, 10 00:00:36,870 --> 00:00:40,140 then we'll postulate that d Nv dt is 11 00:00:40,140 --> 00:00:43,410 minus lambda v0, the deactivation 12 00:00:43,410 --> 00:00:46,680 rate per solute virion collision, 13 00:00:46,680 --> 00:00:50,790 times the volume fraction of disinfecting solutes 14 00:00:50,790 --> 00:00:52,950 we'll call phi d, which is time dependent, 15 00:00:52,950 --> 00:00:57,270 having to do with the size of the droplet, times Nv. 16 00:00:57,270 --> 00:01:00,450 The volume fraction of disinfecting 17 00:01:00,450 --> 00:01:04,319 solutes we'll write as alpha D, a constant, times phi 18 00:01:04,319 --> 00:01:08,430 s, which is the total volume fraction of solutes present. 19 00:01:08,430 --> 00:01:11,070 And that might be, for example, the fraction of solutes 20 00:01:11,070 --> 00:01:14,060 that are sodium chloride or some other salt that 21 00:01:14,060 --> 00:01:16,950 might be causing the damage to the virus, as opposed 22 00:01:16,950 --> 00:01:20,430 to the mucins or other macromolecules that 23 00:01:20,430 --> 00:01:22,380 may be present. 24 00:01:22,380 --> 00:01:27,990 Then we can-- as the droplet is shrinking with a radius R of t, 25 00:01:27,990 --> 00:01:30,440 then it's simply the volume of phi s 26 00:01:30,440 --> 00:01:32,880 that is getting re-scaled relative to the initial value, 27 00:01:32,880 --> 00:01:35,910 phi 0, as R0, the initial radius, 28 00:01:35,910 --> 00:01:37,259 divided by R of t cubed. 29 00:01:37,259 --> 00:01:40,690 So that's just simply the changing of the volume. 30 00:01:40,690 --> 00:01:42,750 Now let's recall some of our results 31 00:01:42,750 --> 00:01:47,190 from the past earlier part of this chapter 32 00:01:47,190 --> 00:01:49,650 having to do with Wells' theory of evaporation. 33 00:01:49,650 --> 00:01:51,570 So, if we consider diffusion-limited droplets, 34 00:01:51,570 --> 00:01:56,550 we've shown that the radius of the droplet versus time 35 00:01:56,550 --> 00:01:58,860 relative to the initial radius R0 36 00:01:58,860 --> 00:02:02,070 is square root of 1 minus t over tau e, where 37 00:02:02,070 --> 00:02:05,640 tau e is the evaporation time, R0 squared divided 38 00:02:05,640 --> 00:02:09,539 by d bar, a constant with units of diffusivity, times 1 39 00:02:09,539 --> 00:02:12,630 minus RH, the relative humidity. 40 00:02:12,630 --> 00:02:15,120 Now that predicts pure liquid droplets 41 00:02:15,120 --> 00:02:17,940 that shrink all the way to nothing and evaporate away, 42 00:02:17,940 --> 00:02:19,650 but, when there's solute present, there's 43 00:02:19,650 --> 00:02:21,770 a cutoff, which we've also discussed that gives you 44 00:02:21,770 --> 00:02:25,260 an equilibrium stable size of the drop, 45 00:02:25,260 --> 00:02:30,360 R equilibrium, relative to R0, which is given by phi s0, 46 00:02:30,360 --> 00:02:32,730 the solid volume fraction-- or solute volume fraction 47 00:02:32,730 --> 00:02:37,980 initially divided by 1 minus RH raised to the 1/3 power. 48 00:02:37,980 --> 00:02:41,700 By writing that as square root of 1 minus tau over tau e, 49 00:02:41,700 --> 00:02:45,210 we can also define the time tau when you reach the equilibrium 50 00:02:45,210 --> 00:02:48,250 size by a diffusion-limited evaporation process. 51 00:02:48,250 --> 00:02:52,420 So that's sort of the time to form a stable droplet nucleus. 52 00:02:52,420 --> 00:02:54,750 Now let's start combining all these equations, 53 00:02:54,750 --> 00:02:58,590 and we can write what is the volume fraction of disinfecting 54 00:02:58,590 --> 00:03:01,380 solutes, phi d of t. 55 00:03:01,380 --> 00:03:04,650 Well, from this equation here, it'll be alpha d times 56 00:03:04,650 --> 00:03:10,050 phi s of t, which is phi s0, times 57 00:03:10,050 --> 00:03:13,230 this ratio, R0 over R cubed. 58 00:03:13,230 --> 00:03:16,560 So, using this expression for diffusion-limited kinetics, 59 00:03:16,560 --> 00:03:24,220 this would give me a 1 minus t over tau e to the 3/2. 60 00:03:24,220 --> 00:03:27,700 And, if we look at the ultimate limit 61 00:03:27,700 --> 00:03:33,390 here that they'll get from when it's a solute, when tau goes-- 62 00:03:33,390 --> 00:03:35,550 or when t goes to tau, the evaporation time, 63 00:03:35,550 --> 00:03:37,600 so when you've reached the droplet nucleus stage, 64 00:03:37,600 --> 00:03:43,340 we're left with just alpha d times 1 minus RH. 65 00:03:43,340 --> 00:03:47,150 So that tells us sort of the fraction of solutes which 66 00:03:47,150 --> 00:03:50,510 are present as a function of relative humidity, 67 00:03:50,510 --> 00:03:54,750 but, also, as a function of time, as drying is going on. 68 00:03:54,750 --> 00:03:57,770 So now let's go back to this dynamical equation. 69 00:03:57,770 --> 00:03:59,250 And let's go ahead and solve it. 70 00:03:59,250 --> 00:04:02,810 So this is a first-order, separable-order differential 71 00:04:02,810 --> 00:04:03,930 equation. 72 00:04:03,930 --> 00:04:11,090 So what we can do is write this as minus d Nv over lambda v0. 73 00:04:11,090 --> 00:04:16,440 Nv is equal to phi d of t dt. 74 00:04:16,440 --> 00:04:18,410 So we've put all the N's on one side 75 00:04:18,410 --> 00:04:20,200 and the t's on the other side. 76 00:04:20,200 --> 00:04:23,110 And so we can actually then integrate this equation. 77 00:04:23,110 --> 00:04:27,750 And so the integral of dN over N is the natural log of N. 78 00:04:27,750 --> 00:04:31,560 So we can write this as minus 1 over lambda v0 79 00:04:31,560 --> 00:04:35,909 natural log of Nv over Nv0, which 80 00:04:35,909 --> 00:04:37,990 is the initial value of Nv. 81 00:04:37,990 --> 00:04:40,200 And, in time, we're integrating from the initial time 82 00:04:40,200 --> 00:04:51,030 0 up to the droplet nucleus time tau of phi d of t dt. 83 00:04:51,030 --> 00:04:54,120 So, substituting our expression right here, 84 00:04:54,120 --> 00:04:58,830 we then see that we have alpha d phi s0 times 85 00:04:58,830 --> 00:05:07,890 the integral from 0 to tau dt over 1 minus t over tau e 86 00:05:07,890 --> 00:05:10,650 to the 3/2. 87 00:05:10,650 --> 00:05:16,340 And we can do that integral and get alpha d phi s0. 88 00:05:16,340 --> 00:05:17,140 And then let's see. 89 00:05:17,140 --> 00:05:19,580 To get the integration variable, we 90 00:05:19,580 --> 00:05:24,230 need to have a tau e here and write that as dt over tau e. 91 00:05:24,230 --> 00:05:28,580 And, doing the integral, we would get 2 times 1 92 00:05:28,580 --> 00:05:34,440 over square root of 1 minus tau over tau e minus 1, 93 00:05:34,440 --> 00:05:37,220 evaluating at the two limits of integration, 94 00:05:37,220 --> 00:05:39,560 taking into account the integral of the-- antiderivative 95 00:05:39,560 --> 00:05:45,320 of integrand there is 1 over 1 minus t over tau e 96 00:05:45,320 --> 00:05:49,490 to the 1/2 power times 2. 97 00:05:49,490 --> 00:05:51,290 So, putting all this together then, 98 00:05:51,290 --> 00:05:55,020 we can write the viability. 99 00:05:55,020 --> 00:06:05,140 So we can write the log of Nv over Nv0 as minus-- 100 00:06:05,140 --> 00:06:06,350 we have all this stuff here-- 101 00:06:06,350 --> 00:06:13,510 2 alpha d phi s0 lambda v0, putting the lambda 102 00:06:13,510 --> 00:06:16,340 v0 back on the other side with the minus sign. 103 00:06:16,340 --> 00:06:21,330 And then we have times two factors. 104 00:06:21,330 --> 00:06:24,140 So, first, there's the factor, which 105 00:06:24,140 --> 00:06:30,620 we know has units of time, which is R0 squared over d bar. 106 00:06:30,620 --> 00:06:35,180 So that's, essentially, kind of a water vapor diffusion time 107 00:06:35,180 --> 00:06:38,210 that comes into the evaporation time, tau e. 108 00:06:38,210 --> 00:06:40,409 So that sets the timescale here. 109 00:06:40,409 --> 00:06:42,080 But then what we're really interested in 110 00:06:42,080 --> 00:06:44,490 is the relative humidity effect. 111 00:06:44,490 --> 00:06:47,370 So that would be-- 112 00:06:47,370 --> 00:06:48,000 let's see here. 113 00:06:48,000 --> 00:06:56,520 So we have this factor, and then we also have the-- 114 00:06:56,520 --> 00:06:57,020 let's see. 115 00:06:57,020 --> 00:07:00,980 The 1 minus RH is coming in where? 116 00:07:00,980 --> 00:07:03,110 Sorry, so, 1 over square root of tau, this one 117 00:07:03,110 --> 00:07:04,640 is from right here. 118 00:07:04,640 --> 00:07:08,640 That's R over R of tau. 119 00:07:08,640 --> 00:07:12,120 And R of tau is, by definition, R equilibrium. 120 00:07:12,120 --> 00:07:13,770 So it's this factor here. 121 00:07:13,770 --> 00:07:25,010 So we get 1 minus RH over phi s0 to the 1/3 minus 1. 122 00:07:25,010 --> 00:07:31,130 And then we also have this factor 123 00:07:31,130 --> 00:07:40,080 of 1 minus RH that comes, yes, from the tau e 124 00:07:40,080 --> 00:07:42,890 because the tau e has this sort of basic timescale, 125 00:07:42,890 --> 00:07:45,920 but there's also a factor of 1 minus RH that I've included. 126 00:07:45,920 --> 00:07:47,600 So the point of all this theory was 127 00:07:47,600 --> 00:07:50,090 to try to understand what is the dependence 128 00:07:50,090 --> 00:07:53,060 on relative humidity, which is what I've shown here in white. 129 00:07:53,060 --> 00:07:57,550 And, if you plot this function, then what you find 130 00:07:57,550 --> 00:07:59,330 is a function of relative humidity. 131 00:08:06,590 --> 00:08:12,320 Then, if you do here log of Nv over Nv0-- 132 00:08:12,320 --> 00:08:18,640 so this is our relative viability of the virus, 133 00:08:18,640 --> 00:08:22,870 and the 0 here corresponds to Nv0, the initial-- 134 00:08:22,870 --> 00:08:24,910 then, this white function, what this looks like 135 00:08:24,910 --> 00:08:27,580 is something, which decays like this. 136 00:08:27,580 --> 00:08:29,500 It kind of reaches a minimum around 80 137 00:08:29,500 --> 00:08:31,960 or in this range from sort of 60 to 80, 138 00:08:31,960 --> 00:08:36,010 depending on what the values of this parameter phi s0 139 00:08:36,010 --> 00:08:37,270 is in fact. 140 00:08:37,270 --> 00:08:39,650 And then it goes back up again. 141 00:08:39,650 --> 00:08:41,650 So, basically, we get a shape for the dependence 142 00:08:41,650 --> 00:08:44,070 of the relative humanity that nicely matches 143 00:08:44,070 --> 00:08:48,690 the experimental data and is consistent with the hypothesis 144 00:08:48,690 --> 00:08:53,050 of disinfection kinetics that was postulated by Lin and Marr.